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Norditropin

Norditropin(somatropin rdna origin) – Novo Nordisk

OTHER BRAND NAMES

Norditropin FlexPro (Novo Nordisk)Norditropin Nordiflex (Novo Nordisk)

THERAPEUTIC CLASS

Recombinant human growth hormone

INDICATIONS

Treatment of growth failure in pediatrics due to inadequate secretion of endogenous growth hormone (GH). Treatment of short stature in pediatrics associated with Noonan syndrome, Turner syndrome (TS), and pediatric patients born small for gestational age (SGA) with no catch-up growth by age 2-4 yrs. Replacement of endogenous GH in adults with adult-onset or childhood-onset GH deficiency (GHD).

ADULT DOSAGE

Adults: GHD: Weight-Based: Initial: Not more than 0.004mg/kg/day SQ. Titrate: May increase to not more than 0.016mg/kg/day after 6 weeks according to individual requirements. Non-Weight Based: Initial: 0.2mg/day SQ (range, 0.15-0.30mg/day). Titrate: May increase gradually every 1-2 months by increments of 0.1-0.2mg/day based on response and serum insulin-like growth factor-I (IGF-I) concentrations. Maint: Individualize dose. Elderly: Start at lower end of dosing range and consider smaller dose increments. Estrogen-replete women may need higher doses than men.

PEDIATRIC DOSAGE

Pediatrics: Individualize dose. GHD: 0.024-0.034mg/kg/day SQ 6-7X/week. Noonan Syndrome: Up to 0.066mg/kg/day SQ. TS/SGA: Up to 0.067mg/kg/day SQ. Refer to PI for further details.

HOW SUPPLIED

Inj: 5mg/1.5mL, 15mg/1.5mL [cartridge]; (FlexPro) 5mg/1.5mL, 10mg/1.5mL, 15mg/1.5mL [prefilled pen]; (Nordiflex) 5mg/1.5mL, 10mg/1.5mL, 15mg/1.5mL, 30mg/3mL [prefilled pen]

CONTRAINDICATIONS

Acute critical illness due to complications following open heart surgery, abdominal surgery, multiple accidental trauma, or with acute respiratory failure. Patients with Prader-Willi syndrome (PWS) who are severely obese, with history of upper airway obstruction or sleep apnea, or with severe respiratory impairment. Pediatrics with growth failure due to genetically confirmed PWS. Active malignancy, or progression or recurrence of underlying intracranial tumor. Active proliferative or severe non-proliferative diabetic retinopathy, pediatrics with closed epiphyses.

WARNINGS/PRECAUTIONS

Increased mortality reported with acute critical illness. Fatalities reported in pediatrics with PWS. Evaluate PWS patients for signs of upper airway obstruction and sleep apnea before treatment; d/c therapy if these signs occur (eg, new/increased snoring). Implement effective weight control in patients with PWS and treat respiratory infections aggressively. Examine for progression/recurrence of underlying disease process in those with preexisting tumors or GHD secondary to intracranial lesion. Monitor for malignant transformation of skin lesions. May decrease insulin sensitivity, as well as unmask undiagnosed impaired glucose tolerance and overt diabetes mellitus (DM). New-onset type 2 DM reported; monitor glucose levels. Intracranial HTN with papilledema, visual changes, headache, N/V reported; perform funduscopic exam before and during therapy and d/c if papilledema occurs. Fluid retention in adults may occur. Undiagnosed/untreated hypothyroidism may prevent optimal response. Hypothyroidism may become evident/worsen in patients with GHD; perform periodic thyroid function tests. Monitor other hormonal replacement treatments in patients with hypopituitarism. Slipped capital femoral epiphysis and progression of scoliosis may occur. Increased risk of ear/hearing disorders and cardiovascular disorders reported in TS patients. Tissue atrophy may occur when administered at the same site over prolonged periods; rotate inj site. Local/systemic allergic reactions may occur. Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and IGF-I may increase. Pancreatitis rarely reported. Caution in elderly.

ADVERSE REACTIONS

Edema, infection, arthralgia, headache, increased sweating, leg edema, myalgia, bronchitis, flu-like symptoms, HTN, gastroenteritis, paresthesia, skeletal pain, laryngitis, otitis media.

DRUG INTERACTIONS

Use with glucocorticoid therapy may attenuate growth-promoting effects in children; carefully adjust glucocorticoid replacement dosing. May inhibit 11β-hydroxysteroid dehydrogenase type 1, resulting in reduced serum cortisol concentrations; may need glucocorticoid replacement or dose adjustments of glucocorticoid therapy (eg, cortisone acetate, prednisone). May alter clearance of compounds metabolized by CYP450 liver enzymes (eg, corticosteroids, sex steroids, anticonvulsants, cyclosporine). May increase clearance of antipyrine. May require larger dose with PO estrogen replacement. May need to adjust dose of insulin and/or PO/inj hypoglycemic agents and thyroid hormone replacement therapy.

PREGNANCY

Category C, caution in nursing.

MECHANISM OF ACTION

Recombinant human GH; binds to dimeric GH receptor in cell membrane of target cells resulting in intracellular signal transduction.

PHARMACOKINETICS

Absorption: Tmax=4-5 hrs; Cmax=13.8ng/mL (4mg), 17.1ng/mL (8mg). Elimination: T1/2=7-10 hrs.

ASSESSMENT

Assess for PWS, preexisting DM or impaired glucose tolerance, diabetic retinopathy, active malignancy, history of scoliosis, hypothyroidism, hypopituitarism, otitis media/other ear disorders in TS, any other conditions where treatment is contraindicated or cautioned, pregnancy/nursing status, and possible drug interactions. Perform funduscopic exam. Assess for short stature in patients with Noonan syndrome.

MONITORING

Monitor for growth, clinical response, compliance, malignant transformation of skin lesions, fluid retention, allergic reactions, pancreatitis, and slipped capital femoral epiphysis and progression of scoliosis in pediatrics. Perform periodic thyroid function tests, funduscopic exam, and monitoring of glucose levels. In patients with PWS, monitor weight as well as signs of respiratory infections, sleep apnea, and upper airway obstruction. In patients with preexisting tumors or GHD secondary to intracranial lesion, monitor for progression/recurrence of underlying disease process. In patients with TS, monitor for ear/hearing/cardiovascular disorders.

PATIENT COUNSELING

Inform about potential benefits and risks of therapy, proper administration, usage and disposal, and caution against any reuse of needles and syringes.

ADMINISTRATION/STORAGE

Administration: SQ route. Refer to PI for preparation and administration instructions. Storage: Unused: 2-8°C (36-46°F). Do not freeze. Avoid direct light. In-use: 5mg, 10mg: 2-8°C (36-46°F) and use within 4 weeks or store at ≤25°C (77°F) for up to 3 weeks. Discard unused portion. 15mg, 30mg: 2-8°C (36-46°F) and use within 4 weeks; discard unused portion after 4 weeks.


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    Norditropin

    Norditropin

    Generic Name: somatropin (rDNA origin)

    Dosage Form: injection, solution

    For ProfessionalsSide EffectsInteractionsMore…

    Indications and Usage for Norditropin

    Pediatric Patients

    Norditropin [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH).

    Norditropin [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients with short stature associated with Noonan syndrome.

    Norditropin [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients with short stature associated with Turner syndrome.

    Norditropin [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients with short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years.

    Adult Patients

    Norditropin [somatropin (rDNA origin) injection] is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:

    Adult Onset (AO): Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
    Childhood Onset (CO): Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

    Patients who were treated with somatropin for GHD in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for GHD adults. According to current standards, confirmation of the diagnosis of adult GHD in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

    Norditropin Dosage and Administration

    For subcutaneous injection.

    Therapy with Norditropin should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with GHD, Noonan syndrome, Turner syndrome or SGA, and adult patients with either childhood onset or adult onset GHD.

    Dosing of Pediatric Patients

    General Pediatric Dosing Information

    The Norditropin dosage and administration schedule should be individualized based on the growth response of each patient. Serum insulin-like growth factor I (IGF-I) levels may be useful during dose titration.

    Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human GH (rhGH).

    Treatment with Norditropin for short stature should be discontinued when the epiphyses are fused.

    Pediatric Growth Hormone Deficiency (GHD)

    A dosage of 0.024 to 0.034 mg/kg/day, 6 to 7 times a week, is recommended.

    Pediatric Patients with Short Stature Associated with Noonan Syndrome

    Not all patients with Noonan syndrome have short stature; some will achieve a normal adult height without treatment. Therefore, prior to initiating Norditropin for a patient with Noonan syndrome, establish that the patient does have short stature.

    A dosage of up to 0.066 mg/kg/day is recommended.

    Pediatric Patients with Short Stature Associated with Turner Syndrome

    A dosage of up to 0.067 mg/kg/day is recommended.

    Pediatric Patients with Short Stature Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2 to 4 Years

    A dosage of up to 0.067 mg/kg/day is recommended.

    Recent literature has recommended initial treatment with larger doses of somatropin (e.g., 0.067 mg/kg/day), especially in very short children (i.e., HSDS < -3), and/or older/pubertal children, and that a reduction in dosage (e.g., gradually towards 0.033 mg/kg/day) should be considered if substantial catch-up growth is observed during the first few years of therapy. On the other hand, in younger SGA children (e.g., approximately < 4 years) (who respond the best in general) with less severe short stature (i.e., baseline HSDS values between -2 and -3), consideration should be given to initiating treatment at a lower dose (e.g., 0.033 mg/kg/day), and titrating the dose as needed over time. In all children, clinicians should carefully monitor the growth response, and adjust the rhGH dose as necessary.

    Dosing of Adult Patients

    Adult Growth Hormone Deficiency (GHD)

    Either of two approaches to Norditropin dosing may be followed: a non-weight-based regimen or a weight-based regimen.

    Non-weight based — based on published consensus guidelines, a starting dose of approximately 0.2 mg/day (range, 0.15-0.30 mg/day) may be used without consideration of body weight. This dose can be increased gradually every 1 to 2 months by increments of approximately 0.1-0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor I (IGF-I) concentrations. The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-I concentrations above the age- and gender-specific normal range. Maintenance dosages vary considerably from person to person, and between male and female patients.

    Weight-based — based on the dosing regimen used in the original adult GHD registration trials, the recommended dosage at the start of treatment is not more than 0.004 mg/kg/day. The dose may be increased to not more than 0.016 mg/kg/day after approximately 6 weeks according to individual patient requirements. Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-I concentrations should be used as guidance in dose titration.

    A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger individuals. In addition, obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. In order to reach the defined treatment goal, estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.

    Preparation and Administration

    Norditropin®FlexPro® 5 mg/ 1.5 mL, 10 mg/1.5 mL and 15 mg/1.5 mL:

    Instructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the Norditropin FlexPro prefilled pen.

    NorditropinNordiFlex® 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL and 30 mg/3 mL:

    Instructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the Norditropin NordiFlex prefilled pen.

    Norditropin Cartridges must be administered using the NordiPen delivery systems. Each cartridge size has a corresponding, color-coded pen which is graduated to deliver the appropriate dose based on the concentration of Norditropin in the cartridge.

    Norditropin® Cartridges 5 mg/1.5 mL and 15 mg/1.5 mL:

    Each cartridge of Norditropin must be inserted into its corresponding NordiPen delivery system. Instructions for delivering the dosage are provided in the NordiPen INSTRUCTION booklet.

    Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Norditropin MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless.

    Injection sites should always be rotated to avoid lipoatrophy.

    Dosage Forms and Strengths

    Norditropin is available preloaded in the Norditropin FlexPro or Norditropin NordiFlex pens or in cartridges for use with the corresponding NordiPens:

    5 mg/1.5 mL (orange): Norditropin FlexPro and Norditropin NordiFlex prefilled pens, and cartridges
    10 mg/1.5 mL (blue): Norditropin FlexPro and Norditropin NordiFlex prefilled pens
    15 mg/1.5 mL (green): Norditropin FlexPro and Norditropin NordiFlex prefilled pens, and cartridges
    30 mg/3 mL (purple): Norditropin NordiFlex prefilled pen only

    Contraindications

    Acute Critical Illness

    Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo [see Warnings and Precautions (5.1)].

    Prader-Willi Syndrome in Children

    Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment [see Warnings and Precautions (5.2)]. There have been reports of sudden death when somatropin was used in such patients [see Warnings and Precautions (5.2)]. Norditropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

    Active Malignancy

    In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor.

    Diabetic Retinopathy

    Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.

    Closed Epiphyses

    Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.

    Hypersensitivity

    Norditropin is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Localized reactions are the most common hypersensitivity reactions.

    Warnings and Precautions

    Acute Critical Illness

    Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications (4.1)]. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients experiencing acute critical illnesses should be weighed against the potential risk.

    Prader-Willi Syndrome in Children

    There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If, during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [see Contraindications (4.2)]. Norditropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

    Neoplasms

    Patients with preexisting tumors or GHD secondary to an intracranial lesion should be monitored routinely for progression or recurrence of the underlying disease process. In pediatric patients, clinical literature has revealed no relationship between somatropin replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors. However, in childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm. Intracranial tumors, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence.

    Patients should be monitored carefully for potential malignant transformation of skin lesions, i.e. increased growth of preexisting nevi.

    Impaired Glucose Tolerance and Diabetes Mellitus

    Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New onset type 2 Diabetes Mellitus has been reported in patients. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral/injectable agents) may require adjustment when somatropin therapy is instituted in these patients.

    Intracranial Hypertension

    Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose.

    Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome may be at increased risk for the development of IH.

    Fluid Retention

    Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention are usually transient and dose dependent.

    Hypothyroidism

    Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

    In patients with hypopituitarism (multiple hormone deficiencies), standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered.

    Slipped Capital Femoral Epiphysis in Pediatric Patients

    Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.

    Progression of Preexisting Scoliosis in Pediatric Patients

    Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated patients with Turner syndrome and Noonan syndrome. Scoliosis is also commonly seen in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy.

    Otitis Media and Cardiovascular Disorders in Turner Syndrome

    Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

    Confirmation of Childhood Onset Adult GHD

    Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated according to the criteria in Indications and Usage (1.2) before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults.

    Local and Systemic Reactions

    When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.3)].

    As with any protein, local or systemic allergic reactions may occur. Parents/Patients should be informed that such reactions are possible and that prompt medical attention should be sought if allergic reactions occur.

    Laboratory Tests

    Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and IGF-I may increase after somatropin therapy.

    Pancreatitis

    Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin-treated patient, especially a child, who develops persistent severe abdominal pain.

    Adverse Reactions

    Most Serious and/or Most Frequently Observed Adverse Reactions

    This list presents the most seriousb and/or most frequently observeda adverse reactions during treatment with somatropin:

    bSudden death in pediatric patients with Prader-Willi syndrome with risk factors including severe obesity, history of upper airway obstruction or sleep apnea and unidentified respiratory infection [see Contraindications (4.2) and Warnings and Precautions (5.2)]
    bIntracranial tumors, in particular meningiomas, in teenagers/young adults treated with radiation to the head as children for a first neoplasm and somatropin [see Contraindications (4.3) and Warnings and Precautions (5.3)]
    a,bGlucose intolerance including impaired glucose tolerance/impaired fasting glucose as well as overt diabetes mellitus [see Warnings and Precautions (5.4)]
    bIntracranial hypertension [see Warnings and Precautions (5.5)]
    bSignificant diabetic retinopathy [see Contraindications (4.4)]
    bSlipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.8)]
    bProgression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.9)]
    aFluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias [see Warnings and Precautions (5.6)]
    aUnmasking of latent central hypothyroidism [see Warnings and Precautions (5.7)]
    aInjection site reactions/rashes and lipoatrophy (as well as rare generalized hypersensitivity reactions) [see Warnings and Precautions (5.12)]
    Pancreatitis [see Warnings and Precautions (5.14)]

    Clinical Trials Experience

     Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

    Clinical Trials in Children with Noonan Syndrome

    Norditropin was studied in a two-year prospective, randomized, parallel dose group trial in 21 children, 3-14 years old, with Noonan syndrome. Doses were 0.033 and 0.066 mg/kg/day. After the initial two-year randomized trial, children continued Norditropin treatment until final height was achieved; randomized dose groups were not maintained. Final height and adverse event data were later collected retrospectively from 18 children; total follow-up was 11 years. An additional 6 children were not randomized, but followed the protocol and are included in this assessment of adverse events.

    Based on the mean dose per treatment group, no significant difference in the incidence of adverse events was seen between the two groups. The most frequent adverse events were the common infections of childhood, including upper respiratory infection, gastroenteritis, ear infection, and influenza. Cardiac disorders was the system organ class with the second most adverse events reported. However, congenital heart disease is an inherent component of Noonan syndrome, and there was no evidence of somatropin-induced ventricular hypertrophy or exacerbation of preexisting ventricular hypertrophy (as judged by echocardiography) during this study. Children who had baseline cardiac disease judged to be significant enough to potentially affect growth were excluded from the study; therefore the safety of Norditropin in children with Noonan syndrome and significant cardiac disease is not known. Among children who received 0.033 mg/kg/day, there was one adverse event of scoliosis; among children who received 0.066 mg/kg/day, there were four adverse events of scoliosis [see Warnings and Precautions (5.9)]. Mean serum IGF-I standard deviation score (SDS) levels did not exceed +1 in response to somatropin treatment. The mean serum IGF-I level was low at baseline and normalized during treatment.

    Clinical Trials in Children with Turner Syndrome

    In two clinical studies wherein children with Turner syndrome were treated until final height with various doses of Norditropin as described in Clinical Studies (14.2), the most frequently reported adverse events were common childhood diseases including influenza-like illness, otitis media, upper respiratory tract infection, otitis externa, gastroenteritis and eczema. Otitis media adverse events in Study 1 were most frequent in the highest dose groups (86.4% in the 0.045-0.067-0.089 mg/kg/day group vs. 78.3% in the 0.045-0.067 mg/kg/day group vs. 69.6% in the 0.045 mg/kg/day group) suggesting a possible dose-response relationship. Of note, approximately 40-50% of these otitis media adverse events were designated as “serious” [see Warnings and Precautions (5.10)]. No patients in either study developed clearcut overt diabetes mellitus; however, in Study 1, impaired fasting glucose at Month 48 was more frequent in patients in the 0.045-0.067 mg/kg/day group (n=4/18) compared with the 0.045 mg/kg/day group (n=1/20). Transient episodes of fasting blood sugars between 100 and 126 mg/dL, and, on occasion, exceeding 126 mg/dL also occurred more often with larger doses of Norditropin in both studies [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)]. Three patients withdrew from the 2 high dose groups in Study 1 because of concern about excessive growth of hands or feet. In addition, in Study 1, exacerbation of preexisting scoliosis was designated a serious adverse reaction in two patients in the 0.045 mg/kg/day group [see Warnings and Precautions (5.9)].

    Clinical Trials in Children Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2-4 Years

    Study 1 (Long-Term)

    In a multi-center, randomized, double-blind study, 53 non-GHD children with short stature born SGA with failure to catch-up were treated with 2 doses of Norditropin (0.033 or 0.067 mg/kg/day) to final height for up to 13 years (mean duration of treatment 7.9 and 9.5 years for girls and boys, respectively). The most frequently reported adverse events were common childhood diseases including influenza-like illness, upper respiratory tract infection, bronchitis, gastroenteritis, abdominal pain, otitis media, pharyngitis, arthralgia, and headache. Adverse events possibly/probably related to Norditropin were otitis media, arthralgia, headaches (no confirmed diagnoses of benign intracranial hypertension), gynecomastia, and increased sweating. One child treated with 0.067 mg/kg/day for 4 years was reported with disproportionate growth of the lower jaw, and another child treated with 0.067 mg/kg/day developed a melanocytic nevus [see Warnings and Precautions (5.3)]. There were no clear cut reports of exacerbation of preexisting scoliosis or slipped capital femoral epiphysis. No apparent differences between the treatment groups were observed. In addition, the timing of puberty was age-appropriate in boys and girls in both treatment groups. Therefore, it can be concluded that no novel adverse events potentially related to treatment with Norditropin were reported in long-term Study 1.

    Study 2 (Short-Term)

    In a multi-center, randomized, double-blind, parallel-group study, 98 Japanese non-GHD children with short stature born SGA with failure to catch-up were treated with 2 doses of Norditropin (0.033 or 0.067 mg/kg/day) for 2 years or were untreated for 1 year. The most frequently reported adverse events were common childhood diseases almost identical to those reported above for Study 1. Adverse events possibly/probably related to Norditropin were otitis media, arthralgia and impaired glucose tolerance. No apparent differences between the treatment groups were observed. However, arthralgia and transiently impaired glucose tolerance were only reported in the 0.067 mg/kg/day treatment group. Therefore, it can also be concluded that no novel adverse events potentially related to treatment with rhGH were reported in short-term Study 2.

    As with all protein drugs, some patients may develop antibodies to the protein. Eighteen of the 76 children (~24%) treated with Norditropin developed anti-rhGH antibodies. However, these antibodies did not appear to be neutralizing in that the change from baseline in height SDS at Year 2 was similar in antibody positive and antibody negative children by treatment group.

    In both Study 1 and Study 2, there were no clear cut cases of new onset diabetes mellitus, no children treated for hyperglycemia, and no adverse event withdrawals due to abnormalities in glucose tolerance. In Study 2, after treatment with either dose of Norditropin for 2 years, there were no children with consecutive fasting blood glucose levels between 100 and 126 mg/dL, or with fasting blood glucose levels > 126 mg/dL. Furthermore, mean hemoglobin A1c levels tended to decrease during long-term treatment in Study 1, and remained normal in Study 2. However, in Study 1, 4 children treated with 0.067 mg/kg/day of Norditropin and 2 children treated with 0.033 mg/kg/day of Norditropin shifted from normal fasting blood glucose levels at baseline to increased levels after 1 year of treatment (100 to 126 mg/dL or > 126 mg/dL). In addition, small increases in mean fasting blood glucose and insulin levels (within the normal reference range) after 1 and 2 years of Norditropin treatment appeared to be dose-dependent  [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

    In both Study 1 and Study 2, there was no acceleration of bone maturation. A dose-dependent increase in mean serum IGF-I SDS levels within the reference range (but including a substantial number of children with serum IGF-1 SDS > +2) was observed after both long-term (Study 1) and short-term (Study 2) Norditropin treatment.

    Clinical Trials in Adult GHD Patients

    Adverse events with an incidence of ≥5% occurring in patients with AO GHD during the 6 month placebo-controlled portion of the largest of the six adult GHD Norditropin trials are presented in Table 1. Peripheral edema, other types of edema, arthralgia, myalgia, and paraesthesia were common in the Norditropin-treated patients, and reported much more frequently than in the placebo group. These types of adverse events are thought to be related to the fluid accumulating effects of somatropin. In general, these adverse events were mild and transient in nature. During the placebo-controlled portion of this study, approximately 5% of patients without preexisting diabetes mellitus treated with Norditropin were diagnosed with overt type 2 diabetes mellitus compared with none in the placebo group [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)]. Anti-GH antibodies were not detected.

    Of note, the doses of Norditropin employed during this study (completed in the mid 1990s) were substantially larger than those currently recommended by the Growth Hormone Research Society, and, more than likely, resulted in a greater than expected incidence of fluid retention- and glucose intolerance-related adverse events. A similar incidence and pattern of adverse events were observed during the other three placebo-controlled AO GHD trials and during the two placebo-controlled CO GHD trials.

    Table 1 – Adverse Reactions with ≥5% Overall Incidence in Adult Onset Growth Hormone Deficient Patients Treated with Norditropin During a Six Month Placebo-Controlled Clinical Trial
    Norditropin

    (N=53)

    Placebo

    (N=52)

    Adverse Reactions

    n

    %

    n

    %

    Peripheral Edema

    22

    42

    4

    8

    Edema

    13

    25

    0

    0

    Arthralgia

    10

    19

    8

    15

    Leg Edema

    8

    15

    2

    4

    Myalgia

    8

    15

    4

    8

    Infection (non-viral)

    7

    13

    4

    8

    Paraesthesia

    6

    11

    3

    6

    Skeletal Pain

    6

    11

    1

    2

    Headache

    5

    9

    3

    6

    Bronchitis

    5

    9

    0

    0

    Flu-like symptoms

    4

    8

    2

    4

    Hypertension

    4

    8

    1

    2

    Gastroenteritis

    4

    8

    4

    8

    Other Non-Classifiable Disorders

    (excludes accidental injury)

    4

    8

    3

    6

    Increased sweating

    4

    8

    1

    2

    Glucose tolerance abnormal

    3

    6

    1

    2

    Laryngitis

    3

    6

    3

    6

    The adverse event pattern observed during the open label phase of the study was similar to the one presented above.

    As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Norditropin with the incidence of antibodies to other products may be misleading. In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.

    In clinical trials, GHD pediatric patients receiving Norditropin for up to 12 months were tested for induction of antibodies, and 0/358 patients developed antibodies with binding capacities above 2 mg/L. Amongst these patients, 165 had previously been treated with other somatropin formulations, and 193 were previously untreated naive patients.

    Post-Marketing Experience

    Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The adverse events reported during post-marketing surveillance do not differ from those listed/discussed above in Sections 6.1 and 6.2 in children and adults.

    Leukemia has been reported in a small number of GH deficient children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, if any, remains to be established [see Contraindications (4.3) and Warnings and Precautions (5.3)].

    The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and pancreatitis (children and adults [see Warnings and Precautions (5.14)])..

    New-onset type 2 diabetes mellitus has been reported.

    Drug Interactions

    Inhibition of 11ß-Hydroxysteroid Dehydrogenase Type 1 (11ßHSD-1)

    The microsomal enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH and somatropin inhibit 11βHSD-1. Consequently, individuals with untreated GHD have relative increases in 11βHSD-1 and serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11ßHSD-1.

    Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment

    Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of somatropin in children. Therefore, glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth.

    Cytochrome P450-Metabolized Drugs

    Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)- mediated antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes. However, formal drug interaction studies have not been conducted.

    Oral Estrogen

    Because oral estrogens may reduce the serum IGF-1 response to somatropin treatment, girls and women receiving oral estrogen replacement may require greater somatropin dosages [see Dosage and Administration (2.2)].

    Insulin and/or Oral/Injectable Hypoglycemic Agents

    In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral/injectable agent may require adjustment when somatropin therapy is initiated [see Warnings and Precautions (5.4)].

    USE IN SPECIFIC POPULATIONS

    Pregnancy

    Pregnancy Category C. Animal reproduction studies have not been conducted with Norditropin. It is not known whether Norditropin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Norditropin should be given to a pregnant woman only if clearly needed.

    Nursing Mothers

    It is not known whether Norditropin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Norditropin is administered to a nursing woman.

    Geriatric Use

    The safety and effectiveness of Norditropin in patients aged 65 and over has not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of somatropin, and therefore may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments should be considered for older patients [see Dosage and Administration (2.2)].

    Overdosage

    Short-Term

    Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, overdose with somatropin is likely to cause fluid retention.

    Long-Term

    Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone [see Dosage and Administration (2)].

    Norditropin Description

    Norditropin is a polypeptide hormone of recombinant DNA origin. The hormone is synthesized by a special strain of E. coli bacteria that has been modified by the addition of a plasmid which carries the gene for human growth hormone. Norditropin contains the identical sequence of 191 amino acids constituting the naturally occurring pituitary human growth hormone with a molecular weight of about 22,000 Daltons.

    Norditropin cartridges are supplied as sterile solutions for subcutaneous injection in ready-to-administer cartridges or prefilled pens with a volume of 1.5 mL or 3 mL.

    Each Norditropin Cartridge contains the following (see Table 2):

    Table 2
    Component

    5 mg/1.5 mL

    10 mg/1.5 mL

    15 mg/1.5 mL

    30 mg/3 mL

    Somatropin

    5 mg

    10 mg

    15 mg

    30 mg

    Histidine

    1 mg

    1 mg

    1.7 mg

    3.3 mg

    Poloxamer 188

    4.5 mg

    4.5 mg

    4.5 mg

    9.0 mg

    Phenol

    4.5 mg

    4.5 mg

    4.5 mg

    9.0 mg

    Mannitol

    60 mg

    60 mg

    58 mg

    117 mg

    HCl/NaOH

    as needed

    as needed

    as needed

    as needed

    Water for Injection

    up to 1.5 mL

    up to 1.5 mL

    up to 1.5 mL

    up to 3.0 mL

    Norditropin – Clinical Pharmacology

    Mechanism of Action

    Somatropin (as well as endogenous GH) binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by IGF-I produced in the liver and also locally (e.g., skeletal growth, protein synthesis), while others are primarily a consequence of the direct effects of somatropin (e.g., lipolysis) [see Clinical Pharmacology (12.2)].

    Pharmacodynamics

    Tissue Growth

    The primary and most intensively studied action of somatropin is the stimulation of linear growth. This effect is demonstrated in children with GHD.

    Skeletal Growth

    The measurable increase in bone length after administration of somatropin results from its effect on the cartilaginous growth areas of long bones. Studies in vitro have shown that the incorporation of sulfate into proteoglycans is not due to a direct effect of somatropin, but rather is mediated by the somatomedins or insulin-like growth factors (IGFs). The somatomedins, among them IGF-I, are polypeptide hormones which are  synthesized in the liver, kidney, and various other tissues. IGF-I levels are low in the serum of hypopituitary dwarfs and hypophysectomized humans or animals, and increase after treatment with somatropin.

    Cell Growth

    It has been shown that the total number of skeletal muscle cells is markedly decreased in children with short stature lacking endogenous GH compared with normal children, and that treatment with somatropin results in an increase in both the number and size of muscle cells.

    Organ Growth

    Somatropin influences the size of internal organs, and it also increases red cell mass.

    Protein Metabolism

    Linear growth is facilitated in part by increased cellular protein synthesis. This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion and blood urea nitrogen following the initiation of somatropin therapy.

    Carbohydrate Metabolism

    Hypopituitary children sometimes experience fasting hypoglycemia that may be improved by treatment with somatropin. In healthy subjects, large doses of somatropin may impair glucose tolerance. Although the precise mechanism of the diabetogenic effect of somatropin is not known, it is attributed to blocking the action of insulin rather than blocking insulin secretion. Insulin levels in serum actually increase as somatropin levels increase. Administration of human growth hormone to normal adults and patients with growth hormone deficiency results in increases in mean serum fasting and postprandial insulin levels, although mean values remain in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1C levels remain in the normal range.

    Lipid Metabolism

    Somatropin stimulates intracellular lipolysis, and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides. Untreated GHD is associated with increased body fat stores, including increased abdominal visceral and subcutaneous adipose tissue. Treatment of growth hormone deficient patients with somatropin results in a general reduction of fat stores, and decreased serum levels of low density lipoprotein (LDL) cholesterol.

    Mineral Metabolism

    Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium. This retention is thought to be the result of cell growth. Serum levels of phosphate increase in children with GHD after somatropin therapy due to metabolic activity associated with bone growth. Serum calcium levels are not altered. Although calcium excretion in the urine is increased, there is a simultaneous increase in calcium absorption from the intestine. Negative calcium balance, however, may occasionally occur during somatropin treatment.

    Connective Tissue Metabolism

    Somatropin stimulates the synthesis of chondroitin sulfate and collagen, and increases the urinary excretion of hydroxyproline.

    Pharmacokinetics

    A 180-min IV infusion of Norditropin (33 ng/kg/min) was administered to 9 GHD patients. A mean (±SD) hGH steady state serum level of approximately 23.1 (±15.0) ng/mL was reached at 150 min and a mean clearance rate of approximately 2.3 (±1.8) mL/min/kg or 139 (±105) mL/min for hGH was observed. Following infusion, serum hGH levels had a biexponential decay with a terminal elimination half-life (T1/2) of approximately 21.1 (±5.1) min.

    In a study conducted in 18 GHD adult patients, where a SC dose of 0.024 mg/kg or 3 IU/m2 was given in the thigh, mean (±SD) Cmax values of 13.8 (±5.8) and 17.1 (±10.0) ng/mL were observed for the 4 and 8 mg Norditropin vials, respectively, at approximately 4 to 5 hr. post dose. The mean apparent terminal T1/2 values were estimated to be approximately 7 to 10 hr. However, the absolute bioavailability for Norditropin after the SC route of administration is currently not known.

    Nonclinical Toxicology

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenicity, mutagenicity, and fertility studies have not been conducted with Norditropin.

    Clinical Studies

    Short Stature in Children with Noonan Syndrome

    A prospective, open label, randomized, parallel group trial with 21 children was conducted for 2 years to evaluate the efficacy and safety of Norditropin treatment for short stature in children with Noonan syndrome. An additional 6 children were not randomized, but did follow the protocol. After the initial two-year trial, children continued on Norditropin until final height. Retrospective final height and adverse event data were collected from 18 of the 21 subjects who were originally enrolled in the trial and the 6 who had followed the protocol without randomization. Historical reference materials of height velocity and adult height analyses of Noonan patients served as the controls.

    The twenty-four (24) (12 female, 12 male) children 3 – 14 years of age received either 0.033 mg/kg/day or 0.066 mg/kg/day of Norditropin subcutaneously which, after the first 2 years, was adjusted based on growth response.

    In addition to a diagnosis of Noonan syndrome, key inclusion criteria included bone age determination showing no significant acceleration, prepubertal status, height SDS <-2, and HV SDS <1 during the 12 months pre-treatment. Exclusion criteria were previous or ongoing treatment with growth hormone, anabolic steroids or corticosteroids, congenital heart disease or other serious disease perceived to possibly have major impact on growth, FPG >6.7 mmol/L (>120 mg/dL), or growth hormone deficiency (peak GH levels <10 ng/mL).

    Patients obtained a final height (FH) gain from baseline of 1.5 and 1.6 SDS estimated according to the national and the Noonan reference, respectively. A height gain of 1.5 SDS (national) corresponds to a mean height gain of 9.9 cm in boys and 9.1 cm in girls at 18 years of age, while a height gain of 1.6 SDS (Noonan) corresponds to a mean height gain of 11.5 cm in boys and 11.0 cm in girls at 18 years of age.

    A comparison of HV between the two treatment groups during the first two years of treatment for the randomized subjects was 10.1 and 7.6 cm/year with 0.066 mg/kg/day versus 8.55 and 6.7 cm/year with 0.033 mg/kg/day, for Year 1 and Year 2, respectively.

    Age at start of treatment was a factor for change in height SDS (national reference). The younger the age at start of treatment, the larger the change in height SDS.

    Examination of gender subgroups did not identify differences in response to Norditropin.

    Not all patients with Noonan syndrome have short stature; some will achieve a normal adult height without treatment. Therefore, prior to initiating Norditropin for a patient with Noonan syndrome, establish that the patient does have short stature.

    Short Stature in Children with Turner Syndrome

    Two randomized, parallel group, open label, multicenter studies were conducted in the Netherlands to evaluate the efficacy and safety of Norditropin for the treatment of children with short stature associated with Turner syndrome. Patients were treated to final height in both studies [height velocity (HV) < 2 cm/year]. Changes in height were expressed as standard deviation scores (SDS) utilizing reference data for untreated Turner syndrome patients as well as the national Dutch population.

    In Study 1 (the primary study), 68 euthyroid Caucasian patients stratified based on age and baseline height SDS were randomized in a 1:1:1 ratio to three different Norditropin treatment regimens: 0.045 mg/kg/day (Dose A) for the entire study; 0.045 mg/kg/day for the first year and 0.067 mg/kg/day thereafter (Dose B); or 0.045 mg/kg/day for the first year, 0.067 for the second year, and 0.089 mg/kg/day thereafter (Dose C). Overall, at baseline, mean age was 6.5 years, mean height SDS (National standard) was -2.7, and mean HV during the previous year was 6.5 cm/year. Patients also received estrogen therapy after age 12 and following four years of Norditropin treatment if they did not have spontaneous puberty.

    Patients were treated for a mean of 8.4 years. As seen in Table 3, overall mean final height was 161 cm in the 46 children who attained final height. Seventy percent of these children reached a final height within the normal range (height SDS > -2 using the National standard). A greater percentage of children in the two escalated dose groups reached normal final height. The mean changes from baseline to final height in height SDS after treatment with Dose B and Dose C were significantly greater than the mean changes observed after treatment with Dose A (utilizing both the National and Turner standards). The mean changes from baseline to final height in height SDS (Turner standard) in Table 3 correspond to mean height gains of 9.4, 14.1 and 14.4 cm after treatment with Doses A, B and C, respectively. The mean changes from baseline to final height in height SDS (National standard) in Table 3 correspond to mean height gains of 4.5, 9.1 and 9.4 cm after treatment with Doses A, B and C, respectively. In each treatment group, peak HV was observed during treatment Year 1, and then gradually decreased each year; during Year 4, HV was less than the pre-treatment HV. However, between Year 2 and Year 6, a greater HV was observed in the two dose escalation groups compared to the 0.045 mg/kg/day group.

    Table 3 – Final Height-Related Results After Treatment of Patients with Turner Syndrome with Norditropin in a Randomized, Dose Escalating Study
    *
    Unadjusted (raw) means
    Adjusted (least squares) means based on an ANCOVA model including terms for treatment, duration of treatment, age at baseline, bone age at baseline, height SDS at baseline, age at onset of puberty and mid-parental target height SDS
    p=0.005 vs. Dose A
    §
    p=0.006 vs. Dose A
    p=0.008 vs. Dose A
    Dose A

    0.045 mg/kg/day

    (n=19)

    Dose B

    up to 0.067 mg/kg/day

    (n=15)

    Dose C

    up to 0.089 mg/kg/day

    (n=12)

    Total

    (n=46)

    Baseline height (cm)*

    105 (12)

    108 (12.7)

    107 (11.7)

    106 (11.9)

    Final height (cm)*

    157 (6.7)

    163 (6.0)

    163 (4.9)

    161 (6.5)

    Number (%) of patients reaching normal height (height SDS >-2 using National standard)

    10 (53%)

    12 (80%)

    10 (83%)

    32 (70%)

    Height SDS (Turner standard)†

    Final [95% CI]

    1.7 [1.4, 2.0]

    2.5 [2.1, 2.8]‡

    2.5 [2.1, 2.9]§

    NA

    Change from baseline [95% CI]

    1.5 [1.2, 1.8]

    2.2 [1.9, 2.5]‡

    2.2 [1.9, 2.6]§

    NA

    Height SDS (National standard)†

    Final [95% CI]

    -1.9 [-2.2, -1.6]

    -1.2 [-1.5, -0.9]§

    -1.2 [-1.6, -0.8]¶

    NA

    Change from baseline [95% CI]

    0.7 [0.4, 1.0]

    1.4 [1.1, 1.7]§

    1.4 [1.1, 1.8]¶

    NA

    Values are expressed as mean (SD) unless otherwise indicated. SDS: Standard deviation score.

    In Study 2 (a supportive study), 19 euthyroid Caucasian patients (with bone age ≤13.9 years) were randomized to treatment with 0.067 mg/kg/day of Norditropin as a single subcutaneous dose in the evening, or divided into two doses (1/3 morning and 2/3 evening). All subjects were treated with concomitant ethinyl estradiol. Overall, at baseline, mean age was 13.6 years, mean height SDS (National standard) was -3.5 and mean HV during the previous year was 4.3 cm/year. Patients were treated for a mean of 3.6 years. In that there were no significant differences between the two treatment groups for any linear growth variables, the data from all patients were pooled. Overall mean final height was 155 cm in the 17 children who attained final height. Height SDS changed significantly from -3.5 at baseline to -2.4 at final height (National standard), and from 0.7 to 1.3 at final height (Turner standard).

    Short Stature in Children Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2-4 Years

    A multi-center, randomized, double-blind, two-arm study to final height (Study 1) and a 2-year, multi-center, randomized, double-blind, parallel-group study (Study 2) were conducted to assess the efficacy and safety of Norditropin in children with short stature born SGA with no catch-up growth. Changes in height and height velocity were compared to a national reference population in both studies.

    Study 1

    The pivotal study included 53 (38 male, 15 female) non-GHD, Dutch children 3-11 years of age with short stature born SGA with no catch-up growth. Catch-up growth was defined as obtaining a height of ≥ 3rd percentile within the first 2 years of life or at a later stage. These prepubertal children needed to meet the following additional inclusion criteria: birth length < 3rd percentile for gestational age, and height velocity (cm/year) for chronological age < 50th percentile.  Exclusion criteria included chromosomal abnormalities, signs of a syndrome (except for Silver-Russell syndrome), serious/chronic co-morbid disease, malignancy, and previous rhGH therapy. Norditropin was administered subcutaneously daily at bedtime at a dose of approximately 0.033 (Dose A) or 0.067 mg/kg/day (Dose B) for the entire treatment period. Final height was defined as a height velocity below 2 cm/year. Treatment with Norditropin was continued to final height for up to 13 years. Mean duration of treatment was 9.5 years (boys) and 7.9 years (girls).

    38 out of 53 children (72%) reached final height. Sixty-three percent (24 out of 38) of the children who reached final height were within the normal range of their healthy peers (Dutch national reference). For both doses combined, actual mean final height was 171 (SD 6.1) cm in boys and 159 (SD 4.3) cm in girls.

    As seen in Table 4, for boys and girls combined, both mean final height SDS (Dose A, -1.8 vs. Dose B, -1.3), and increase in height SDS from baseline to final height (Dose A, 1.4 vs. Dose B, 1.8), were significantly greater after treatment with Dose B (0.067 mg/kg/day). A similar dose response was observed for the increase in height SDS from baseline to Year 2 (Table 4).

    Overall mean height velocity at baseline was 5.4 cm/y (SD 1.2; n=29). Height velocity was greatest during the first year of Norditropin treatment and was significantly greater after treatment with Dose B (mean 11.1 cm/y [SD 1.9; n=19]) compared with Dose A (mean 9.7 cm/y [SD 1.3; n=10]).

    Table 4 – Study 1: Results for Final Height SDS and Change from Baseline to Final Height in Height SDS Using National Standard After Long-Term Treatment of SGA Children with Norditropin
    *
    Adjusted (least-squares) means based on an ANCOVA model including terms for treatment, gender, age at baseline, height SDS at baseline, and pubertal status.
    Adjusted (least-squares) means based on an ANCOVA model including terms for treatment, gender, age at baseline, bone age at baseline, height SDS at baseline, duration of treatment, peak GH after stimulation and baseline IGF-1.
    Raw Mean + SD (N)

    Dose A

    0.033 mg/kg/day

    Dose B

    0.067 mg/kg/day

    Total

    Baseline Height SDS

    -3.2 + 0.7 (26)

    -3.2 + 0.7 (27)

    -3.2 + 0.7 (53)

    Adjusted least-squares mean + standard error (N) and [95% confidence intervals]

    Height SDS: Change from Baseline at Year 2*

    1.4 + 0.1 (26)

    [1.1, 1.6]

    1.8 + 0.1 (26)

    [1.5, 2.0]

    Treatment Diff = 0.4

    [0.2, 0.7]

    p-value = 0.002

    Height SDS: Change from Baseline at Final Height†

    1.4 + 0.2 (19)

    [0.9, 1.8]

    1.8 + 0.2 (19)

    [1.4, 2.2]

    Treatment Diff = 0.5

    [0.0, 0.9]

    p-value = 0.045

    Final Height SDS†

    -1.8 + 0.2 (19)

    [-2.2, -1.4]

    -1.3 + 0.2 (19)

    [-1.7, -0.9]

    Final Height SDS > -2

    13/19 (68%)

    11/19 (58%)

    24/38 (63%)

    SDS: Standard deviation score.

    Study 2

    In this study, 84 randomized, prepubertal, non-GHD, Japanese children (age 3-8) with short stature born SGA with no catch-up growth were treated for 2 years with 0.033 or 0.067 mg/kg/day of Norditropin subcutaneously daily at bedtime or received no treatment for 1 year. Additional inclusion criteria included birth length or weight SDS ≤ -2 or < 10th percentile for gestational age, height SDS for chronological age ≤ -2, and height velocity SDS for chronological age < 0 within one year prior to Visit 1. Exclusion criteria included diabetes mellitus, history or presence of active malignancy, and serious co-morbid conditions.

    As seen in Table 5, for boys and girls combined, there was a dose-dependent increase in height SDS at Year 1 and Year 2. The increase in height SDS from baseline to Year 2 (0.033 mg/kg/day, 0.8 vs. 0.067 mg/kg/day, 1.4) was significantly greater after treatment with 0.067 mg/kg/day. In addition, the increase in height SDS at Year 1 was significantly greater in both active treatment groups compared to the untreated control group.

    Table 5 – Study 2: Results for Change from Baseline in Height SDS At Year 1 and Year 2 Using National Standard After Short-Term Treatment of SGA Children with Norditropin
    *
    Adjusted (least-squares) means based on an ANCOVA model including terms for treatment, gender, age at baseline, and height SDS at baseline. All children remained prepubertal during the study.
    Raw Mean + SD (N)

    No Treatment

    0.033

    mg/kg/day

    0.067

    mg/kg/day

    Total

    Height SDS: Baseline

    -2.9 + 0.5 (15)

    -3.0 + 0.6 (35)

    -2.9 + 0.7 (34)

    -2.9 + 0.6 (84)

    Height SDS: Year 1

    -2.8 + 0.5 (15)

    -2.4 + 0.6 (33)

    -2.0 + 0.8 (34)

    -2.3 + 0.7 (82)

    Height SDS: Year 2

    NA

    -2.2 + 0.7 (33)

    -1.4 + 0.7 (32)

    -1.8 + 0.8 (65)

    Adjusted least-squares mean + standard error (N) and [95% confidence intervals]

    Height SDS: Change from Baseline at Year 1*

    0.1 + 0.1 (15)

    [-0.1, 0.2]

    0.6 + 0.1 (33)

    [0.5, 0.7]

    0.9 + 0.1 (34)

    [0.8, 1.0]

    0.033 vs. No Treatment: Treatment Diff = 0.5, [0.3, 0.7], p < 0.0001

    0.067 vs. No Treatment: Treatment Diff = 0.8, [0.6, 1.0], p < 0.0001

    0.067 vs. 0.033: Treatment Diff = 0.3, [0.2, 0.5], p-value < 0.0001

    Height SDS: Change from Baseline at Year 2*

    NA

    0.8 + 0.1 (33)

    [0.7, 0.9]

    1.4 + 0.1 (32)

    [1.3, 1.6]

    0.067 vs. 0.033: Treatment Diff = 0.6, [0.5, 0.8], p-value < 0.0001

    SDS: Standard deviation score.

    Adult Growth Hormone Deficiency (GHD)

    A total of six randomized, double-blind, placebo-controlled studies were performed. Two representative studies, one in adult onset (AO) GHD patients and a second in childhood onset (CO) GHD patients, are described below.

    Study 1

    A single center, randomized, double-blind, placebo-controlled, parallel-group, six month clinical trial was conducted in 31 adults with AO GHD comparing the effects of Norditropin  [somatropin (rDNA origin) for injection] and placebo on body composition. Patients in the active treatment arm were treated with Norditropin 0.017 mg/kg/day (not to exceed 1.33 mg/day). The changes from baseline in lean body mass (LBM) and percent total body fat (TBF) were measured by total body potassium (TBP) after 6 months.

    Treatment with Norditropin produced a significant (p=0.0028) increase from baseline in LBM compared to placebo (Table 6).

    Table 6 – Lean Body Mass (kg) by TBP
    Norditropin

    (n=15)

    Placebo

    (n=16)

    Baseline (mean)

    50.27

    51.72

    Change from baseline at 6 months (mean)

    1.12

    -0.63

    Treatment difference (mean)

    95% confidence interval

    p-value

    1.74

    (0.65, 2.83)

    p=0.0028

    Analysis of the treatment difference on the change from baseline in percent TBF revealed a significant decrease (p=0.0004) in the Norditropin-treated group compared to the placebo group (Table 7).

    Table 7 – Total Body Fat (%) by TBP
    Norditropin

    (n=15)

    Placebo

    (n=16)

    Baseline (mean)

    44.74

    42.26

    Change from baseline at 6 months (mean)

    -2.83

    1.92

    Treatment difference (mean)

    95% confidence interval

    p-value

    -4.74

    (-7.18, -2.30)

    p=0.0004

    Fifteen (48.4%) of the 31 randomized patients were male. The adjusted mean treatment differences on the increase in LBM and decrease in percent TBF from baseline were larger in males compared to females.

    Norditropin also significantly increased serum osteocalcin (a marker of osteoblastic activity).

    Study 2

    A single center, randomized, double-blind, placebo-controlled, parallel-group, dose-finding, six month clinical trial was conducted in 49 men with CO GHD comparing the effects of Norditropin and placebo on body composition. Patients were randomized to placebo or one of three active treatment groups (0.008, 0.016, and 0.024 mg/kg/day). Thirty three percent of the total dose to which each patient was randomized was administered during weeks 1-4, 67% during weeks 5-8, and 100% for the remainder of the study. The changes from baseline in LBM and percent TBF were measured by TBP after 6 months.

    Treatment with Norditropin produced a significant (p=0.0079) increase from baseline in LBM compared to placebo (pooled data) (Table 8).

    Table 8 – Lean Body Mass (kg) by TBP
    Norditropin

    (n=36)

    Placebo

    (n=13)

    Baseline (mean)

    48.18

    48.90

    Change from baseline at 6 months (mean)

    2.06

    0.70

    Treatment difference (mean)

    95% confidence interval

    p-value

    1.40

    (0.39, 2.41)

    p=0.0079

    Analysis of the treatment difference on the change from baseline in percent TBF revealed a significant decrease (p=0.0048) in the Norditropin-treated groups (pooled data) compared to the placebo group (Table 9).

    Table 9 – Total Body Fat (%) by TBP
    Norditropin

    (n=36)

    Placebo

    (n=13)

    Baseline (mean)

    34.55

    34.07

    Change from baseline at 6 months (mean)

    -6.00

    -1.78

    Treatment difference (mean)

    95% confidence interval

    p-value

    -4.24

    (-7.11, -1.37)

    p=0.0048

    Norditropin also significantly reduced intraabdominal, extraperitoneal and total abdominal fat volume, waist/hip ratio and LDL cholesterol, and significantly increased serum osteocalcin.

    Forty four men were enrolled in an open label follow up study and treated with Norditropin for as long as 30 additional months. During this period, the reduction in waist/hip ratio achieved during the initial six months of treatment was maintained.

    How Supplied/Storage and Handling

     NorditropinFlexPro prefilled pens [somatropin (rDNA origin) injection] 5 mg/1.5 mL, 10 mg/1.5 mL, and 15 mg/1.5 mL:

    Norditropin FlexPro is individually cartoned in 5 mg/1.5 mL, 10 mg/1.5 mL, or 15 mg/1.5 mL prefilled pens.

    Norditropin FlexPro 5 mg/1.5 mL (orange) NDC 0169-7704-21
    Norditropin FlexPro 10 mg/1.5 mL (blue) NDC 0169-7705-21
    Norditropin FlexPro 15 mg/1.5 mL (green) NDC 0169-7708-21

     

    NorditropinNordiFlex prefilled pens [somatropin (rDNA origin) injection] 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL and 30 mg/3 mL:

    NorditropinNordiFlex is individually cartoned in 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL or 30 mg/3 mL prefilled pens.

    Norditropin NordiFlex 5 mg/1.5 mL (orange)  NDC 0169-7704-11
    Norditropin NordiFlex 10 mg/1.5 mL (blue)    NDC 0169-7705-11
    Norditropin NordiFlex 15 mg/1.5 mL (green)  NDC 0169-7708-11
    Norditropin NordiFlex 30 mg/3 mL (purple) NDC 0169-7703-11

    Unused Norditropin NordiFlex and FlexPro prefilled pens  must be stored at 2-8°C/36-46°F (refrigerator). Do not freeze. Avoid direct light.

    5 mg/1.5 mL (orange) and 10 mg/1.5 mL (blue) prefilled pens:

    After the initial injection, a Norditropin FlexPro or Norditropin NordiFlex (5 mg/1.5 mL or 10 mg/1.5 mL) prefilled pen may be EITHER stored in the refrigerator (2-8ºC/36-46ºF) and used within 4 weeks OR stored for up to 3 weeks at not more than 25ºC (77ºF). Discard unused portion.

    15 mg/1.5 mL (green) and 30 mg/3 mL (purple) prefilled pens:

    After the initial injection, a Norditropin FlexPro 15 mg/1.5 mL or Norditropin NordiFlex (15 mg/1.5 mL or 30 mg/3 mL) prefilled pen  must be stored in the refrigerator (2-8ºC/36-46ºF) and used within 4 weeks. Discard unused portion after 4 weeks.

    Norditropin Cartridges [somatropin (rDNA origin) injection] 5 mg/1.5 mL and 15 mg/1.5 mL:

    Norditropin is individually cartoned in 5 mg/1.5 mL or 15 mg/1.5 mL cartridges which must be administered using the corresponding color-coded NordiPen delivery system.

    Norditropin Cartridges 5 mg/1.5 mL (orange) NDC 0169-7768-11
    Norditropin Cartridges 15 mg/1.5 mL (green) NDC 0169-7770-11

    Unused Norditropin cartridges must be stored at 2-8°C/36-46°F (refrigerator). Do not freeze. Avoid direct light.

    5 mg/1.5 mL (orange) cartridges:

    After a Norditropin cartridge (5 mg/1.5 mL) has been inserted into its NordiPen delivery system (NordiPen 5), it may be EITHER stored in the pen in the refrigerator (2-8ºC/36-46ºF) and used within 4 weeks OR stored for up to 3 weeks at not more than 25ºC (77ºF). Discard unused portion.

    15 mg/1.5 mL (green) cartridges:

    After a Norditropin cartridge (15 mg/1.5 mL) has been inserted into its NordiPen delivery system (NordiPen 15), it must be stored in the pen in the refrigerator (2-8ºC/36-46ºF) and used within 4 weeks. Discard unused portion after 4 weeks.

    Table 10 – Storage Options
    Norditropin Product Formulation

    Before Use

    In-use (After 1st injection)

    Storage requirement

    Storage Option 1

    (Refrigeration)

    Storage Option 2

    (Room temperature)

    5 mg

    2-8 ºC/

    36-46 ºF

    Until exp date

    2-8 ºC/36-46 ºF

    4 weeks

    Up to 25ºC/77ºF

    3 weeks

    10 mg

    2-8 ºC/36-46 ºF

    4 weeks

    Up to 25ºC/77ºF

    3 weeks

    15 mg

    2-8 ºC/36-46 ºF

    4 weeks

    Does Not Apply

    30 mg

    2-8 ºC/36-46 ºF

    4 weeks

    Does Not Apply

    Patient Counseling Information

    See FDA-approved patient labeling.

    Patients being treated with Norditropin FlexPro or Norditropin NordiFlex prefilled pens, or Norditropin Cartridges, (and/or their parents) should be informed about the potential risks and benefits associated with somatropin treatment [in particular, see Adverse Reactions (6.1) for a listing of the most serious and/or most frequently observed adverse reactions associated with somatropin treatment in children and adults]. This information is intended to better educate patients (and caregivers); it is not a disclosure of all possible adverse or intended effects.

    Patients and caregivers who will administer Norditropin FlexPro or Norditropin NordiFlex prefilled pens, or Norditropin Cartridges, should receive appropriate training and instruction on proper use from the physician or other suitably qualified health care professional. A puncture-resistant container for the disposal of used needles should be strongly recommended. Patients and/or parents should be thoroughly instructed in the importance of proper disposal, and cautioned against any reuse of needles. This information is intended to aid in the safe and effective administration of the medication.

    If patients are prescribed Norditropin Cartridges (to be inserted into color-coded NordiPen delivery systems), physicians should instruct patients to read the NordiPen INSTRUCTION booklet provided with the NordiPen delivery systems.

    If patients are prescribed Norditropin FlexPro or Norditropin NordiFlex, physicians should instruct patients to read the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets provided with the Norditropin FlexPro and Norditropin NordiFlex prefilled pens.

    Date of Issue: May 25, 2011

    Version: 14

     Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

    Norditropin®, FlexPro®,   NordiPen® and NorditropinNordiFlex® are registered trademarks of Novo Nordisk Health Care AG.

    © 2002-2011 Novo Nordisk Health Care AG

    For information contact:

    Novo Nordisk Inc.

    100 College Road West

    Princeton, New Jersey 08540, USA

    1-888-NOVO-444 (1-888-668-6444)

    Manufactured by:

    Novo Nordisk A/S

    DK-2880 Bagsvaerd, Denmark

    PATIENT INFORMATION

     Norditropin® (Nor-dee-tro-pin)

    (somatropin [rDNA origin]) injection

    Read the Patient Information that comes with Norditropin before you start to take it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.

    What is Norditropin?

    Norditropin is a prescription medicine given by injection under the skin (subcutaneous) that contains human growth hormone, identical to the growth hormone produced in the human body, used to treat:

    children who are not growing because of low or no growth hormone
    children who are short (in stature) and who have Noonan syndrome or Turner syndrome
    children who are short (in stature) because they were born small (small for gestational age-SGA) and have not caught-up in growth by age 2 to 4 years
    adults who do not make enough growth hormone

    Who should not use Norditropin?

    Do not use Norditropin if:

    you have a critical illness caused by certain types of heart or stomach surgery, trauma or breathing (respiratory) problems
    you are a child with Prader-Willi syndrome who is severely obese or has breathing problems including sleep apnea  
    you have cancer or other tumors
    your healthcare provider tells you that you have certain types of eye problems caused by diabetes
    you are a child with closed bone growth plates (epiphyses)
    you are allergic to any of the ingredients in Norditropin. See the end of this leaflet for a complete list of ingredients in Norditropin. 

    What should I tell my healthcare provider before I start Norditropin?

    Before you take  Norditropin, tell your healthcare provider if you:

    have diabetes
    had cancer or any tumor
    have any other medical condition
    are pregnant or plan to become pregnant. It is not known if Norditropin will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
    are breast-feeding or plan to breast-feed. It is not known if Norditropin passes into your breast milk. You and your healthcare provider should decide if you will take Norditropin while you breast-feed.

    Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Norditropin may affect how other medicines work, and other medicines may affect how Norditropin works.

    Especially tell your healthcare provider if you take:

    glucocorticoid medication
    thyroid hormone
    insulin or other medicine for diabetes
    medicines that are metabolized by the liver
    estrogen replacement medicines

    Ask your healthcare provider if you are not sure if any of your medicines are the kind listed above. Keep a list of your medicines with you and show it to your healthcare provider and pharmacist when you get a new medicine.

    How should I use Norditropin?

    Read the detailed Instructions for Use that come with Norditropin. Your healthcare provider will show you how to inject Norditropin.
    Take Norditropin exactly as prescribed.
    NorditropinFlexPro pens, NordiFlex pens and cartridges are for use by one person only.
    Novo Nordisk disposable needles are designed to be used with Norditropin for each injection.
    Always keep the pen cap closed on Norditropin when you are not using it.
    Norditropin comes in 3 dose strengths for FlexPro prefilled color coded pens, 4 dose strengths for NordiFlex prefilled color coded pens, and 2 dose strengths for color coded cartridges.
    If you inject too much Norditropin, call your healthcare provider.
    If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take 2 doses at the same time unless your healthcare provider tells you to. If you are not sure about your dosing, call your healthcare provider.
    Throw away Norditropin when the cartridge is empty.
    Refer to the Instructions for Use about what to do if you have less than a full dose left in your pen.

    What are the possible side effects of Norditropin?

    Norditropin can cause serious side effects, including:

    high risk of death in people who have critical illnesses because of heart or stomach surgery, trauma or serious breathing (respiratory) problems
    high risk of death in children with Prader-Willi syndrome who are severely obese or have breathing problems, including sleep apnea
    return of tumor or cancerous growths
    high blood sugar (hyperglycemia)
    increase in pressure in the skull (intracranial hypertension). If you have headaches, eye problems, nausea or vomiting, contact your healthcare provider right away.
    swollen hands and feet due to fluid retention
    decrease in thyroid hormone levels. Your healthcare provider will do blood tests to check your thyroid hormone levels.
    hip and knee pain or a limp in children (slipped capital femoral epiphysis)
    worsening of curvature of the spine (scoliosis)
    middle ear infection, hearing problems or ear problems in patients with Turner syndrome
    redness, itching and tissue weakness in the area you inject
    increase in phosphorus, alkaline phosphatase and parathyroid hormone levels in your blood. Your healthcare provider will do blood tests to check this.

    The most common side effects of Norditropin include:

    headaches
    muscle pain
    joint stiffness
    high blood sugar (hyperglycemia)
    sugar in your urine (glucosuria)
    swollen hands and feet due to fluid retention
    redness and itching in the area you inject

    Talk to your healthcare provider if you have any side effect that bothers you or that does not go away.

    These are not all the possible side effects of Norditropin. For more information, ask your healthcare provider or pharmacist.

    Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 (1-800-332-1088). You may also report side effects to Novo Nordisk at 1-888-NOVO-444 (1-888-668-6444).

    How do I store Norditropin?

    Unused NorditropinFlexPro and NordiFlexpens, and cartridges:

    Keep in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC).
    Do not freeze or expose Norditropin to heat.
    Keep Norditropin away from direct light.
    Do not use Norditropin that has been frozen or in temperatures warmer than 77ºF (25ºC).
    Do not use Norditropin after the expiration date printed on the carton and the pen or cartridge.

    After the first injection

    Norditropin FlexPro, NordiFlex and cartridge 5 mg/1.5 mL (orange):
    either store in the refrigerator between 36ºF to 46ºF (2ºC to 8ºC) and use within 4 weeks
    orkeep for up to 3 weeks at no warmer than 77ºF(25ºC).
    Throw away any unused medicine.
    Norditropin FlexPro and NordiFlex 10 mg/1.5mL (blue):
    either store in the refrigerator between 36ºF to 46ºF (2ºC to 8º C) and use within 4 weeks.
    or keep for up to 3 weeks at no warmer than 77 ºF (25ºC).
    Throw away any unused medicine.
    Norditropin FlexPro, NordiFlex and cartridge 15 mg/1.5 mL (green):
    store in the refrigerator between 36ºF to 46ºF (2ºC to 8ºC) and use within 4 weeks
    Throw away any unused medicine after 4 weeks.
    Norditropin NordiFlex pens 30 mg/3 mL (purple):
    store in the refrigerator between 36ºF to 46ºF (2ºC to 8ºC) and use within 4 weeks
    Throw away any unused medicine after 4 weeks

    General Information about Norditropin.

    Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use Norditropin for a condition for which it was not prescribed. Do not give Norditropin to other people, even if they have the same symptoms that you have. It may harm them.

    This Patient Information summarizes the most important information about Norditropin. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Norditropin that is written for healthcare professionals.

    What are the ingredients in Norditropin?

    Active ingredient: somatropin (rDNA origin)

    Inactive ingredients: Histidine, Poloxamer 188, Phenol, Mannitol, HCl/NaOH (as needed) and Water for Injection

    Date of Issue: March 2, 2010

    Version: 7

    For assistance or further information, write to:

    Novo Nordisk Inc.

    100 College Road West

    Princeton, NJ 08540, USA

    1-888-NOVO-444 (1-888-668-6444)

    Norditropin-us.com

    US Patent Nos. 6,235,004; 6,004,297; 6,582,404; 6,716,198; 6,899,699; 5,849,704; 5,691,169; 5,618,697 and other patents pending.

    Norditropin®, FlexPro®, NorditropinNordiFlex® and NordiFlexPenMate® are registered trademarks of Novo Nordisk Health Care AG.

    Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

    © 2004-2010 Novo Nordisk Health Care AG

    Manufactured by:

    Novo Nordisk A/S

    DK-2880 Bagsvaerd, Denmark

    INSTRUCTIONS FOR USE

    NorditropinNordiFlex®

    Somatropin (rDNA origin) injection

    30 mg/3 mL Prefilled Pen

    Using the disposable NorditropinNordiFlex® 30 mg/3 mL Prefilled Pen

    Norditropin NordiFlex 30 mg/3 mL is a multi-dose, disposable, prefilled pen with liquid growth hormone able to deliver doses from 0.1 to 6.0 mg. The dose can be adjusted in increments of 0.1 mg. Your doctor will determine the correct dose for you. Norditropin NordiFlex prefilled pen is designed to be used with NovoFine® disposable needles (sold separately). Norditropin NordiFlex prefilled pen is not recommended for people who are blind or have trouble seeing unless they have the help of a sighted individual trained to use Norditropin NordiFlex.

    Please read these instructions carefully before using this pen

    1 Preparing NorditropinNordiFlex 30 mg/3 mL for Injection

     

    A. Pull off the pen cap and check if the growth hormone solution is clear and colorless by turning the Norditropin NordiFlex upside down once or twice and view the solution through the residual scale window. DO NOT use NorditropinNordiFlex if the growth hormone solution is cloudy or contains particles. Use it only if it is clear and colorless.

    Wash hands well and dry completely.

    Wipe the front rubber stopper on the needle thread with an alcohol swab.

    B. Place a new NovoFine disposable needle onto Norditropin NordiFlex immediately before use. Remove the protective tab from the disposable needle and screw the needle tightly onto Norditropin NordiFlex. Pull off the outer and inner needle caps. Never place a disposable needle on your Norditropin NordiFlex until you are ready to give an injection. Remove the needle immediately after use. If the needle is not removed, some liquid may be expelled from Norditropin NordiFlex.

    2 Performing an Air Shot

    Do an air shot before starting a new NorditropinNordiFlex as follows:

    Small amounts of air may collect in the needle and cartridge. To ensure proper dosing and to avoid injecting air, you must perform an air shot before administering your first injection.

    C. Dial the dosage selector to 0.1 mg. Each line between labeled dosages is 0.1 mg.

     

    D. Hold Norditropin NordiFlex with the needle pointing up, tap the cartridge gently with your finger a few times to make any air bubbles rise to the top of the cartridge.

    E. Still holding Norditropin NordiFlex with the needle up, press the push button all the way in. A drop of liquid should appear at the needle tip. If not, repeat the above steps, no more than 4 times.

    If a drop of liquid still does not appear, call 1-888-NOVO-444 for help.

    3 Setting the Dose

    F. Check that the dose selector is set at 0.0. Dial the number of mg (milligram) that you need to inject. If you dial more than your dose, the dose can be changed up or down by turning the dose selector in either direction. When dialing back, be careful not to press the push button as liquid will come out.

    Use dosage indicator, NOT the clicking sound, as a guide for selecting the dose.

    The numbers on the residual scale can be used to estimate the mg left in the cartridge. DO NOT use these numbers to measure the dose.

    You cannot set a dose higher than the number of mg left in the cartridge. Use a new Norditropin NordiFlex pen to inject the remaining amount of your dose. Be sure to remember the dose already received with the first dose. For example, if your dose is 0.6 mg and you can only set the dose selector to 0.3 mg. You will need to inject an additional 0.3 mg with a new Norditropin NordiFlex pen.

    4 Giving the Injection

    Use the injection technique recommended by your healthcare professional.

    G. This product is for subcutaneous use only. Insert the needle under the skin and press the push button as far as it goes to deliver the dose. To ensure that the full dose is injected keep the needle in the skin for at least 6 seconds after injection with your thumb on the push button. Keep the push button fully pushed in until after the needle has been removed from the skin.

    After the injection, check the dosage indicator window to make sure it shows zero (0.0).

    If zero does not appear, you did not receive the full dose. Call 1-888-NOVO-444 for assistance.

    Note:

    Always press the push button to inject the dose. Turning the dosage selector will not inject the dose.

    5 Removing the NovoFine Disposable Needle

    H. After the injection, remove the needle without recapping and dispose of it in a puncture-resistant container. Used needles should be placed in sharps container (such as red biohazard containers), hard plastic containers (such as detergent bottles), or metal containers (such as an empty coffee can). Such containers should be sealed and disposed of properly.

    It is important that you use a new needle for each injection. Healthcare professionals, relatives and other caregivers should follow general precautionary measures for removal and disposal of needles to reduce the risk of unintended needle stick injuries.

    When the cartridge is empty, dispose of Norditropin NordiFlex without the needle attached.

    6 Maintenance

    Handle Norditropin NordiFlex with care. Protect Norditropin NordiFlex from dust, dirt, and direct sunlight.

    You can clean the outside of Norditropin NordiFlex by wiping it with a soft cloth moistened with water. Do not soak Norditropin NordiFlex in alcohol, wash, or lubricate it.

    7 Important Things to Know

    Norditropin NordiFlex 30 mg/3 mL cannot be used with the NordiFlex PenMate® auto-insertion accessory.
    Store unused Norditropin NordiFlex pens in a refrigerator (2ºC – 8ºC/36ºF – 46ºF). After the initial injection, keep Norditropin NordiFlex 30 mg/3 mL refrigerated and use within 4 weeks.
    Remember to perform an air shot before starting a new Norditropin NordiFlex or before the injection if you dropped or knocked the pen against a hard surface. See diagrams C, D and E.
    If you need to perform more than 4 air shots before the first use of Norditropin NordiFlex to get a droplet of liquid at the needle tip, DO NOT use Norditropin NordiFlex. Call 1-888-NOVO-444 for help.
    Take care not to drop Norditropin NordiFlex  or knock it against a hard surface.
    DO NOT leave Norditropin NordiFlex in a car or other location where it can get too hot or too cold.
    Always have a spare Norditropin NordiFlex disposable pen in order to avoid running out of this product.
    Norditropin NordiFlex is designed to be used with NovoFine disposable needles.
    NEVER place a needle on Norditropin NordiFlex until you are ready to use it. Remove the needle right after use without recapping.
    Dispose of used needles properly, so people will not be harmed.
    Dispose of used Norditropin NordiFlex, without the needle attached.
    To avoid spread of disease, do not let anyone else use your Norditropin NordiFlex, even if you attach a new needle.
    Keep the Norditropin NordiFlex out of the reach of children.
    Novo Nordisk is not responsible for harm due to using the NorditropinNordiFlex with products that are not recommended by Novo Nordisk.

    8 Customer Satisfaction

    Customer service and satisfaction are our top concerns. If you have any questions about Norditropin NordiFlex prefilled pens please call Novo Nordisk Inc. at 1-888-NOVO-444.

    INSTRUCTIONS FOR USE

    Norditropin®FlexPro®

    (somatropin [rDNA origin] injection)

    5 mg/1.5 mL (orange) Prefilled Pen

    Read these instructions before using your Norditropin®FlexPro® pen.

    Norditropin FlexPro contains 5 mg human growth hormone solution and delivers doses from 0.025 mg to 2 mg, in increments of 0.025 mg. Norditropin FlexPro is made to be used with Novo Nordisk® disposable needles. Needles are not included with Norditropin FlexPro.

    Prepare your NorditropinFlexPro pen

    A.

    Pull off the pen cap.
    Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times. If the liquid looks unclear or cloudy, do not use the pen.
    Wash hands well and dry them.
    Wipe the front stopper on the needle thread with an alcohol swab.

    B.

    Take a new disposable needle.
    Tear the paper tab off and screw the needle straight onto the pen.
    Make sure the needle is on tight.
    Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection.

    C.

    Pull off the outer needle cap and inner needle cap and throw them both away.
    If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
    A drop of liquid may appear at the needle tip. This is normal.

    Important:

    Always use a new needle for each injection. This will help prevent contamination.
    Never bend or damage the needle.

    Check the growth hormone flow (airshot)

    Make sure that you receive your full dose by checking the growth hormone flow (performing an airshot) before you select and inject your first dose from a new pen.

    D. Turn the dose selector to select 0.025 mg. This is the smallest amount of medicine for a dose.

    E.

    Hold the pen with the needle pointing up.
    Tap the top of the pen gently a few times to let any air bubbles rise to the top.

    F.

    Press the dose button until the “0″ in the display window lines up with the pointer and a drop of liquid appears at the needle tip.
    If no drop appears, repeat steps D, E and F up to 6 times.
    If no drop appears after these attempts, change the needle and repeat steps D, E and F one more time.
    If a drop of liquid still does not appear, call (1-888-668-6444) for help.

    Important:

    Be careful not to drop NorditropinFlexPro pen or knock it against a hard surface. If this happens you will need to repeat the airshot.
    Always make sure that a drop appears at the needle tip after completing your airshot.

    Select your dose

    Use the dose selector on your NorditropinFlexPro pen to make sure you have the exact dose selected. You can select up to 2 mg per dose.

    G.

    Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer.
    When dialing back, be careful not to press the dose button as liquid will come out.
    To guide you, the dose selector clicks differently when turned forwards, backwards or past the number of mg that is left in the pen.
    When the pen has less than 2 mg, the dose selector stops at the number of mg that is left in the pen.

    How much growth hormone is left in the pen?

    You can use the growth hormone scale to see how much growth hormone is left in the pen.

    You can use the dose selector to see exactly how much growth hormone is left in the pen. If the pen contains less than 2 mg, turn the dose selector until it stops. The figure that lines up with the pointer shows how many mg is left in the pen.

    You cannot set a dose higher than the number of mg left in the pen.
    If there is not enough Norditropin left in the pen to deliver your full dose, use a new Norditropin FlexPro pen to inject the remaining amount of your dose or contact your healthcare provider.
    Be sure to subtract the dose already received. For example, if your dose is 0.6 mg and you can only set the dose selector to 0.3 mg, you should inject another 0.3 mg with a new Norditropin FlexPro pen.

    Important:

    Never use the pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
    Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

    Inject your dose

    Make sure that you receive your full dose by using the injection technique recommended by your healthcare provider. This medicine is injected under your skin (subcutaneous) only.

    H.

    Insert the needle into your skin as your healthcare provider has shown you.
    Press and hold the dose button to inject until the “0″ in the display window lines up with the pointer. As you do this, you may hear or feel a firm click.
    If you remove your finger from the dose button before the “0” is in the display window the full dose has not been delivered. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

    If “0″ does not appear in the display window, you did not receive the full dose. Call 1(-888-668-6444 ) for assistance.

    After the “0” in the display window lines up with the pointer, leave the needle under the skin for at least 6 seconds to make sure that you get your full dose. You can let go of the dose button while you wait.
    Change the injection site using the injection procedure recommended by your healthcare provider.

    Important:

    Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
    Never touch the display window when you inject, as this can block the injection.

    I.

    Remove the needle from your skin. After that, you may see a drop of liquid at the needle tip. This is normal and does not affect the dose you received.
    After the injection, remove the needle right away and put the pen cap back on. If the needle is not removed, some liquid may come out of the Norditropin FlexPro.
    Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider. A special “sharps” container (such as a red biohazard container), a hard plastic container (such as an empty detergent bottle), or a metal container (such as an empty coffee can) should be used. The container should be sealed and disposed of properly.
    Caregivers should be most careful when handling used needles to avoid hurting themselves.

    Care for your NorditropinFlexPro pen

    You must take care of your Norditropin FlexPro pen:

    Do not drop your pen or knock it against hard surfaces. If you do drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (airshot) before you inject.
    Do not try to refill your disposable pen – it is prefilled.
    Do not try to repair your pen or pull it apart.
    Do not expose your pen to dust, dirt or any kind of liquid.
    Do not try to wash, soak or lubricate your pen. You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth. See section “How do I store Norditropin FlexPro?” above for information about how to store your pen.
    Always keep your pen and needles out of reach of others, especially children.
    Never share your needles and pen with anyone.

    Date of Issue: March 2, 2010

    Version: 1

    US Patent Nos. 6,235,004; 6,004,297; 6,582,404; 6,716,198; 6,899,699; 5,849,704; 5,691,169; 5,618,697 and other patents pending.

    Norditropin®, FlexPro®, NorditropinNordiFlex® and NordiFlexPenMate® are registered trademarks of Novo Nordisk Health Care AG.

    Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

    © 2004-2010 Novo Nordisk Health Care AG

    Manufactured by:

    Novo Nordisk A/S

    DK-2880 Bagsvaerd, Denmark

    INSTRUCTIONS FOR USE

    Norditropin®FlexPro®

    (somatropin [rDNA origin] injection)

    10 mg/1.5 mL (blue) Prefilled Pen

    Read these instructions before using your Norditropin®FlexPro® pen.

    Norditropin FlexPro contains 10 mg human growth hormone solution and delivers doses from 0.05 mg to 4 mg, in increments of 0.05 mg. Norditropin FlexPro is made to be used with Novo Nordisk® disposable needles. Needles are not included with Norditropin FlexPro.

    Prepare your NorditropinFlexPro pen

    A.

    Pull off the pen cap.
    Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times. If the liquid looks unclear or cloudy, do not use the pen.
    Wash hands well and dry them.
    Wipe the front stopper on the needle thread with an alcohol swab.

    B.

    Take a new disposable needle.
    Tear the paper tab off and screw the needle straight onto the pen.
    Make sure the needle is on tight.
    Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection.

    C.

    Pull off the outer needle cap and inner needle cap and throw them both away.
    If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
    A drop of liquid may appear at the needle tip. This is normal.

    Important:

    Always use a new needle for each injection. This will help prevent contamination.
    Never bend or damage the needle.

    Check the growth hormone flow (airshot)

    Make sure that you receive your full dose by checking the growth hormone flow (performing an airshot) before you select and inject your first dose from a new pen.

    D. Turn the dose selector to select 0.05 mg. This is the smallest amount of medicine for a dose.

    E.

    Hold the pen with the needle pointing up.
    Tap the top of the pen gently a few times to let any air bubbles rise to the top.

    F.

    Press the dose button until the “0” in the display window lines up with the pointer and a drop of liquid appears at the needle tip.
    If no drop appears, repeat steps D, E, and F up to 6 times.
    If no drop appears after these attempts, change the needle and repeat steps D, E, and F one more time.
    If a drop of liquid still does not appear, call (1-888-668-6444) for help.

    Important:

    Be careful not to drop NorditropinFlexPro pen or knock it against a hard surface. If this happens you will need to repeat the airshot.
    Always make sure that a drop appears at the needle tip after completing your airshot.

    Select your dose

    Use the dose selector on your NorditropinFlexPro pen to make sure you have the exact dose selected. You can select up to 4 mg per dose.

    G.

    Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer.
    When dialing back, be careful not to press the dose button as liquid will come out.
    To guide you, the dose selector clicks differently when turned forwards, backwards or past the number of mg that is left in the pen.
    When the pen has less than 4 mg, the dose selector stops at the number of mg that is left in the pen.

    How much growth hormone is left in the pen?

    You can use the growth hormone scale to see how much growth hormone is left in the pen.

    You can use the dose selector to see exactly how much growth hormone is left in the pen. If the pen contains less than 4 mg, turn the dose selector until it stops.

    The figure that lines up with the pointer shows how many mg is left in the pen.

    You cannot set a dose higher than the number of mg left in the pen.
    If there is not enough Norditropin left in the pen to deliver your full dose, use a new Norditropin FlexPro pen to inject the remaining amount of your dose or contact your healthcare provider.
    Be sure to subtract the dose already received. For example, if your dose is 0.6 mg and you can only set the dose selector to 0.3 mg, you should inject another 0.3 mg with a new Norditropin FlexPro pen.

    Important:

    Never use the pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
    Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

    Inject your dose

    Make sure that you receive your full dose by using the injection technique recommended by your healthcare provider. This medicine is injected under your skin (subcutaneous) only.

    H.

    Insert the needle into your skin as your healthcare provider has shown you.
    Press and hold the dose button to inject until the “0” in the display window lines up with the pointer. As you do this, you may hear or feel a firm click.
    If you remove your finger from the dose button before the “0” is in the display window the full dose has not been delivered. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

    If “0” does not appear in the display window, you did not receive the full dose. Call (1-888-668-6444) for assistance.

    After the “0” in the display window lines up with the pointer, leave the needle under the skin for at least 6 seconds to make sure that you get your full dose. You can let go of the dose button while you wait.
    Change the injection site using the injection procedure recommended by your healthcare provider.

    Important:

    Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
    Never touch the display window when you inject, as this can block the injection.

    I.

    Remove the needle from your skin. After that, you may see a drop of liquid at the needle tip. This is normal and does not affect the dose you received.
    After the injection, remove the needle right away and put the pen cap back on. If the needle is not removed, some liquid may come out of the Norditropin FlexPro.
    Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider. A special “sharps” container (such as a red biohazard container), a hard plastic container (such as an empty detergent bottle), or a metal container (such as an empty coffee can) should be used. The container should be sealed and disposed of properly.
    Caregivers should be most careful when handling used needles to avoid hurting themselves.

    Care for your NorditropinFlexPro pen

    You must take care of your Norditropin FlexPro pen:

    Do not drop your pen or knock it against hard surfaces. If you do drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (airshot) before you inject.
    Do not try to refill your disposable pen – it is prefilled.
    Do not try to repair your pen or pull it apart.
    Do not expose your pen to dust, dirt or any kind of liquid.
    Do not try to wash, soak or lubricate your pen. You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth. See section “How do I store Norditropin FlexPro?” above for information about how to store your pen.
    Always keep your pen and needles out of reach of others, especially children.
    Never share your needles and pen with anyone. 

    Date of Issue: March 2, 2010

    Version: 1

    US Patent Nos. 6,235,004; 6,004,297; 6,582,404; 6,716,198; 6,899,699; 5,849,704; 5,691,169; 5,618,697 and other patents pending.

    Norditropin®, FlexPro®, NorditropinNordiFlex® and NordiFlexPenMate® are registered trademarks of Novo Nordisk Health Care AG.

    Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

    © 2004-2010 Novo Nordisk Health Care AG

    Manufactured by:

    Novo Nordisk A/S

    DK-2880 Bagsvaerd, Denmark

    INSTRUCTIONS FOR USE

    Norditropin®FlexPro®

    (somatropin [rDNA origin] injection)

    15 mg/1.5 mL (green) Prefilled Pen

    Read these instructions before using your Norditropin®FlexPro® pen.

    Norditropin FlexPro contains 15 mg human growth hormone solution and delivers doses from 0.1 mg to 8 mg, in increments of 0.1 mg. Norditropin FlexPro is made to be used with Novo Nordisk® disposable needles. Needles are not included with Norditropin FlexPro.

    Prepare your NorditropinFlexPro pen

    A.

    Pull off the pen cap.
    Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times. If the liquid looks unclear or cloudy, do not use the pen.
    Wash hands well and dry them.
    Wipe the front stopper on the needle thread with an alcohol swab.

    B.

    Take a new disposable needle.
    Tear the paper tab off and screw the needle straight onto the pen.
    Make sure the needle is on tight.
    Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection.

    C.

    Pull off the outer needle cap and inner needle cap and throw them both away.
    If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
    A drop of liquid may appear at the needle tip. This is normal.

    Important:

    Always use a new needle for each injection. This will help prevent contamination.
    Never bend or damage the needle.

    Check the growth hormone flow (airshot)

    Make sure that you receive your full dose by checking the growth hormone flow (performing an airshot) before you select and inject your first dose from a new pen.

    D. Turn the dose selector to select 0.1 mg. This is the smallest amount of medicine for a dose.

    E.

    Hold the pen with the needle pointing up.
    Tap the top of the pen gently a few times to let any air bubbles rise to the top.

    F.

    Press the dose button until the “0” in the display window lines up with the pointer and a drop of liquid appears at the needle tip.
    If no drop appears, repeat steps D, E and F up to 6 times.
    If no drop appears after these attempts, change the needle and repeat steps D, E and F one more time.
    If a drop of liquid still does not appear, call (1-888-668-6444) for help.

    Important:

    Be careful not to drop NorditropinFlexPro pen or knock it against a hard surface. If this happens you will need to repeat the airshot.
    Always make sure that a drop appears at the needle tip after completing your airshot.

    Select your dose

    Use the dose selector on your NorditropinFlexPro pen to make sure you have the exact dose selected. You can select up to 8 mg per dose.

    G.

    Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer.
    When dialing back, be careful not to press the dose button as liquid will come out.
    To guide you, the dose selector clicks differently when turned forwards, backwards or past the number of mg that is left in the pen.
    When the pen has less than 8 mg, the dose selector stops at the number of mg that is left in the pen.

    How much growth hormone is left in the pen?

    You can use the growth hormone scale to see how much growth hormone is left in the pen.

    You can use the dose selector to see exactly how much growth hormone is left in the pen. If the pen contains less than 8 mg, turn the dose selector until it stops.

    The figure that lines up with the pointer shows how many mg is left in the pen.

    You cannot set a dose higher than the number of mg left in the pen.
    If there is not enough Norditropin left in the pen to deliver your full dose, use a new Norditropin FlexPro pen to inject the remaining amount of your dose or contact your healthcare provider.
    Be sure to subtract the dose already received. For example, if your dose is 0.6 mg and you can only set the dose selector to 0.3 mg, you should inject another 0.3 mg with a new Norditropin FlexPro pen.

    Important:

    Never use the pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
    Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

    Inject your dose

    Make sure that you receive your full dose by using the injection technique recommended by your healthcare provider. This medicine is injected under your skin (subcutaneous) only.

    H.

    Insert the needle into your skin as your healthcare provider has shown you.
    Press and hold the dose button to inject until the “0” in the display window lines up with the pointer. As you do this, you may hear or feel a firm click.
    If you remove your finger from the dose button before the “0” is in the display window the full dose has not been delivered. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

    If “0” does not appear in the display window, you did not receive the full dose. Call (1-888-668-6444) for assistance.

    After the “0” in the display window lines up with the pointer, leave the needle under the skin for at least 6 seconds to make sure that you get your full dose. You can let go of the dose button while you wait.
    Change the injection site using the injection procedure recommended by your healthcare provider.

    Important:

    Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
    Never touch the display window when you inject, as this can block the injection.

    I.

    Remove the needle from your skin. After that, you may see a drop of liquid at the needle tip. This is normal and does not affect the dose you received.
    After the injection, remove the needle right away and put the pen cap back on. If the needle is not removed, some liquid may come out of the Norditropin FlexPro.
    Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider. A special “sharps” container (such as a red biohazard container), a hard plastic container (such as an empty detergent bottle), or a metal container (such as an empty coffee can) should be used. The container should be sealed and disposed of properly.
    Caregivers should be most careful when handling used needles to avoid hurting themselves.

    Care for your NorditropinFlexPro pen

    You must take care of your Norditropin FlexPro pen:

    Do not drop your pen or knock it against hard surfaces. If you do drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (airshot) before you inject.
    Do not try to refill your disposable pen – it is prefilled.
    Do not try to repair your pen or pull it apart.
    Do not expose your pen to dust, dirt or any kind of liquid.
    Do not try to wash, soak or lubricate your pen. You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth. See section “How do I store Norditropin FlexPro?” above for information about how to store your pen.
    Always keep your pen and needles out of reach of others, especially children.
    Never share your needles and pen with anyone.

    Date of Issue: March 2, 2010

    Version: 1

    US Patent Nos. 6,235,004; 6,004,297; 6,582,404; 6,716,198; 6,899,699; 5,849,704; 5,691,169; 5,618,697 and other patents pending.

    Norditropin®, FlexPro®, NorditropinNordiFlex® and NordiFlexPenMate® are registered trademarks of Novo Nordisk Health Care AG.

    Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

    © 2004-2010 Novo Nordisk Health Care AG

    Manufactured by:

    Novo Nordisk A/S

    DK-2880 Bagsvaerd, Denmark

    PRINCIPAL DISPLAY PANEL – Norditropin NORDIFLEX 30 MG/3 ML

    Norditropin  NordiFlex®

    Somatropin (rDNA origin) injection

    30 mg/3 mL Prefilled Pen

    1 x 3 mL prefilled disposable pen

    Each 3 mL contains 30 mg somatropin

    CONTAINS ONE

    Norditropin NORDIFLEX® 30 mg/3 mL

    Rx ONLY

    NDC 0169-7703-11

    List: 770311

    Store non-injected/unused pen refrigerated (2ºC-8ºC/36ºF-46ºF). Do not store with needles. After initial injection, keep pen refrigerated. Do not freeze. Use within 4 weeks. Discard unused portion. Avoid direct light. Keep out of the reach and sight of children. For subcutaneous administration only. Please read the enclosed leaflet before use.

    US Patent Nos. 6,235,004; 6,004,297; 5,849,704; 6,582,404 and other patents pending.

    PRINCIPAL DISPLAY PANEL – Norditropin FLEXPRO 5 MG/1.5 ML

    Norditropin®  FlexPro®

    Somatropin (rDNA origin) injection

    5 mg/1.5 mL Prefilled Pen

    1 x 1.5 mL prefilled disposable pen

    Each 1.5 mL contains 5 mg somatropin

    CONTAINS ONE

    Norditropin® FLEXPRO® 5 mg/1.5 mL

    Rx ONLY

    NDC 0169-7704-21

    List: 770421

    PRINCIPAL DISPLAY PANEL – Norditropin FLEXPRO 10 MG/1.5 ML

    Norditropin®  FlexPro®

    Somatropin (rDNA origin) injection

    10 mg/1.5 mL Prefilled Pen

    1 x 1.5 mL prefilled disposable pen

    Each 1.5 mL contains 10 mg somatropin

    CONTAINS ONE

    Norditropin® FLEXPRO® 10 mg/1.5 mL

    Rx ONLY

    NDC 0169-7705-21

    List: 770521

    PRINCIPAL DISPLAY PANEL – Norditropin FLEXPRO 15 MG/1.5 ML

    Norditropin®  FlexPro®

    Somatropin (rDNA origin) injection

    15 mg/1.5 mL Prefilled Pen

    1 x 1.5 mL prefilled disposable pen

    Each 1.5 mL contains 15 mg somatropin

    CONTAINS ONE

    Norditropin® FLEXPRO® 15 mg/1.5 mL

    Rx ONLY

    NDC 0169-7708-21

    List: 770821

    Norditropin 

    somatropin injection, solution

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0169-7704
    Route of Administration SUBCUTANEOUS DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    SOMATROPIN (SOMATROPIN) SOMATROPIN 5 mg  in 1.5 mL
    Inactive Ingredients
    Ingredient Name Strength
    HISTIDINE 1 mg  in 1.5 mL
    HYDROCHLORIC ACID  
    MANNITOL 60 mg  in 1.5 mL
    PHENOL 4.5 mg  in 1.5 mL
    POLOXAMER 188 4.5 mg  in 1.5 mL
    SODIUM HYDROXIDE  
    WATER  
    Packaging
    # Item Code Package Description
    1 NDC:0169-7704-21 1 SYRINGE, PLASTIC in 1 CARTON
    1 1.5 mL in 1 SYRINGE, PLASTIC
    2 NDC:0169-7704-92 1 SYRINGE, PLASTIC in 1 CARTON
    2 1.5 mL in 1 SYRINGE, PLASTIC
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021148 01/03/2005
    Norditropin 

    somatropin injection, solution

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0169-7705
    Route of Administration SUBCUTANEOUS DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    SOMATROPIN (SOMATROPIN) SOMATROPIN 10 mg  in 1.5 mL
    Inactive Ingredients
    Ingredient Name Strength
    HISTIDINE 1 mg  in 1.5 mL
    HYDROCHLORIC ACID  
    MANNITOL 60 mg  in 1.5 mL
    PHENOL 4.5 mg  in 1.5 mL
    POLOXAMER 188 4.5 mg  in 1.5 mL
    SODIUM HYDROXIDE  
    WATER  
    Packaging
    # Item Code Package Description
    1 NDC:0169-7705-21 1 SYRINGE, PLASTIC in 1 CARTON
    1 1.5 mL in 1 SYRINGE, PLASTIC
    2 NDC:0169-7705-92 1 SYRINGE, PLASTIC in 1 CARTON
    2 1.5 mL in 1 SYRINGE, PLASTIC
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021148 01/02/2006
    Norditropin 

    somatropin injection, solution

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0169-7708
    Route of Administration SUBCUTANEOUS DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    SOMATROPIN (SOMATROPIN) SOMATROPIN 15 mg  in 1.5 mL
    Inactive Ingredients
    Ingredient Name Strength
    HISTIDINE 1.7 mg  in 1.5 mL
    HYDROCHLORIC ACID  
    MANNITOL 58 mg  in 1.5 mL
    PHENOL 4.5 mg  in 1.5 mL
    POLOXAMER 188 4.5 mg  in 1.5 mL
    SODIUM HYDROXIDE  
    WATER  
    Packaging
    # Item Code Package Description
    1 NDC:0169-7708-21 1 SYRINGE, PLASTIC in 1 CARTON
    1 1.5 mL in 1 SYRINGE, PLASTIC
    2 NDC:0169-7708-92 1 SYRINGE, PLASTIC in 1 CARTON
    2 1.5 mL in 1 SYRINGE, PLASTIC
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021148 01/03/2005
    Norditropin 

    somatropin injection, solution

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0169-7703
    Route of Administration SUBCUTANEOUS DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    SOMATROPIN (SOMATROPIN) SOMATROPIN 30 mg  in 3 mL
    Inactive Ingredients
    Ingredient Name Strength
    HISTIDINE 3.3 mg  in 3 mL
    POLOXAMER 188 9 mg  in 3 mL
    PHENOL 9 mg  in 3 mL
    MANNITOL 117 mg  in 3 mL
    WATER  
    SODIUM HYDROXIDE  
    HYDROCHLORIC ACID  
    Packaging
    # Item Code Package Description
    1 NDC:0169-7703-11 1 SYRINGE in 1 CARTON
    1 3 mL in 1 SYRINGE
    2 NDC:0169-7703-91 1 SYRINGE in 1 CARTON
    2 3 mL in 1 SYRINGE
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021148 03/30/2009
    Labeler - Novo Nordisk (622920320)
    Establishment
    Name Address ID/FEI Operations
    Novo Nordisk A/S 306711800 MANUFACTURE(0169-7704, 0169-7705, 0169-7708, 0169-7703)

    Revised: 05/2011   Novo Nordisk

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    Norditropin

    Norditropin

    Generic Name: somatropin, e-coli derived (Subcutaneous route, Injection route)

    soe-ma-TROE-pin, E-KOH-lye dee-rived

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    Commonly used brand name(s)

    In the U.S.

    • Accretropin
    • Genotropin
    • Genotropin Miniquick
    • Humatrope
    • Norditropin
    • Norditropin Flexpro
    • Nutropin
    • Nutropin AQ NuSpin 10
    • Nutropin AQ NuSpin 5
    • Nutropin AQ Pen
    • Omnitrope
    • Tev-Tropin

    In Canada

    • Nutropin Aq
    • Saizen

    Available Dosage Forms:

    • Solution
    • Powder for Solution

    Therapeutic Class: Endocrine-Metabolic Agent

    Pharmacologic Class: Somatropin

    Uses For Norditropin

    Somatropin is a man-made version of human growth hormone. Growth hormone is naturally produced by the pituitary gland and is necessary to stimulate growth in children. Man-made growth hormone may be used in adults or children who have certain conditions that prevent normal growth. These conditions include growth hormone deficiency (inability to produce enough growth hormone), chronic kidney disease, idiopathic short stature (unexplained shortness), Noonan syndrome, Turner syndrome, short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years of age.

    This medicine is available only with your doctor’s prescription.

    Before Using Norditropin

    In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

    Allergies

    Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

    Pediatric

    Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of somatropin in children.

    Geriatric

    Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of somatropin in the elderly. However, elderly patients are more sensitive to the effects of somatropin, which may require a dose adjustment in patients receiving somatropin.

    Pregnancy

    Pregnancy Category Explanation
    All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

    Breast Feeding

    There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

    Interactions with Medicines

    Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

    Interactions with Food/Tobacco/Alcohol

    Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

    Other Medical Problems

    The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

    • Brain tumor or
    • Cancer, active or
    • Closed epiphyses (normal bone growth stopped) in children or
    • Diabetic retinopathy (eye condition) or
    • Prader-Willi syndrome (a genetic disorder), if severely overweight or have severe breathing problems or
    • Severe illness after surgery or major medical emergency (e.g., open heart surgery, abdominal surgery, accidental trauma, or respiratory failure)—Should not be used in patients with these conditions.
    • Cancer, history of or
    • Hypopituitarism (pituitary gland produces low hormone levels) or
    • Hypothyroidism (underactive thyroid gland) or
    • Otitis media (ear infection) in children, history of or
    • Scoliosis (abnormally curved spine)—Use with caution. May make these conditions worse.
    • Diabetes, or a family history of—Use with caution. May prevent insulin or other drugs for diabetes from working properly.
    • Turner syndrome—Use with caution. May increase risk of having serious problems (e.g., pancreas, thyroid, or heart and blood vessel problems; ear or hearing disorders; diabetes; increased pressure in the head; and bone problems such as dislocation in the hip bone or scoliosis).

    Proper Use of somatropin, e-coli derived

    This section provides information on the proper use of a number of products that contain somatropin, e-coli derived. It may not be specific to Norditropin. Please read with care.

    This medicine is given as a shot under your skin. Somatropin may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Be sure that you understand exactly how the medicine is prepared and injected.

    This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

    There are many different forms (e.g., vial, cartridge, injection device) available for this medicine. Read all instructions carefully to be sure you know how to use your device.

    Each time you get your medicine, check to be sure you have received the proper device. Talk to your pharmacist if you have questions about the device that you were given.

    You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections.

    Use a new needle, unopened vial, or syringe each time you inject your medicine.

    You might not use all of the medicine in each vial (glass container) or prefilled syringe. Use each vial or syringe only one time. Do not save an open vial or syringe. If the medicine in the vial or syringe has changed color, or if you see particles in it, do not use it.

    Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

    Dosing

    The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

    The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

    • For injection dosage form:
      • For all indications:
        • Adults—Dose is usually based on body weight (depending on the brand of somatropin you are using) and dose must be determined by your doctor. Your doctor will adjust your dose as needed.
        • Children—Dose is based on body weight and must be determined by your doctor. Your doctor will adjust your child’s dose as needed.

    Missed Dose

    This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

    Storage

    Keep out of the reach of children.

    Do not keep outdated medicine or medicine no longer needed.

    Ask your healthcare professional how you should dispose of any medicine you do not use.

    Store this medicine in the refrigerator, away from direct light. Do not freeze or shake.

    Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

    Precautions While Using Norditropin

    If you will be taking this medicine for a long time, it is very important that your doctor check you at regular visits for any problems or unwanted effects that may be caused by this medicine.

    This medicine may cause a serious allergic reaction that requires immediate medical attention. Tell your doctor right away if you have a rash; itching; swelling of the face, tongue, or throat; trouble with breathing; or chest pain after you receive the medicine.

    This medicine may cause a dislocation in the hip bone, especially in patients with growth hormone deficiency or Turner syndrome. Check with your doctor right away if you or your child has a limp or pain in the hip or knee.

    This medicine may affect blood sugar levels. Check with your doctor if you notice a change in the results of your blood or urine sugar tests or if you have any questions.

    This medicine may cause an increased pressure in the head. Check with your doctor immediately if headache, nausea, vomiting, blurred vision, or any other change in vision occurs during treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

    This medicine may cause fluid retention (extra water in the body). Tell your doctor if you have burning, numbness, pain, or tingling in all fingers except the smallest finger; swelling of the hands and feet; or pain, swelling, or stiffness of the muscles. Your doctor may adjust your dose to reduce these side effects.

    Pancreatitis has occurred rarely in some patients receiving somatropin. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

    Before you have any medical tests, tell the medical doctor in charge that you are using this certain brand of somatropin (Humatrope®). The results of some tests may be affected by this medicine.

    Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

    Norditropin Side Effects

    Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

    Check with your doctor immediately if any of the following side effects occur:

    More common

    • Bleeding gums
    • bloating or swelling of the face, arms, hands, ankles, lower legs, or feet
    • burning, numbness, pain, or tingling in all fingers except smallest finger
    • coughing up blood
    • difficulty with breathing or swallowing
    • difficulty with moving
    • dizziness
    • increased menstrual flow or vaginal bleeding
    • muscle pain or stiffness
    • nosebleeds
    • not able to move
    • pain, swelling, or redness in joints
    • prolonged bleeding from cuts
    • rapid weight gain
    • red or black, tarry stools
    • red or dark brown urine
    • tingling of the hands or feet
    • unusual weight gain or loss

    Rare

    • Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
    • blurred vision
    • bone pain
    • change in ability to see colors, especially blue or yellow
    • change in personality
    • changes in vision
    • chills
    • confusion
    • constipation
    • curved spine
    • darkened urine
    • dry mouth
    • fast heartbeat
    • fever
    • flushed, dry skin
    • fracture
    • fruit-like breath odor
    • headache
    • increased hunger
    • increased thirst
    • increased urination
    • indigestion
    • limp pain in the hip or knee
    • loss of appetite
    • loss of consciousness
    • nausea
    • pains in the stomach, side, or abdomen, possibly radiating to the back
    • problems with walking or talking
    • seizures
    • stomachache
    • sweating
    • troubled breathing
    • tumor
    • unusual tiredness or weakness
    • vomiting
    • weakness
    • yellow eyes or skin

    Get emergency help immediately if any of the following symptoms of overdose occur:

    Symptoms of overdose

    • Backache
    • excessive sweating
    • extreme weakness
    • increase in hands and feet size
    • increased volume of pale, diluted urine
    • pain in extremities
    • stop in menstruation

    Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

    More common

    • Large, flat, blue, or purplish patches in the skin
    • unusually warm skin

    Rare

    • Increased growth of skin lesions
    • swelling of the breasts or breast soreness in both females and males

    Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

    Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

    See also: Norditropin side effects (in more detail)

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    Norditropin

    Norditropin

    Generic Name: somatropin (soe ma TROE pin)

    Brand Name: Genotropin, Genotropin Miniquick, Humatrope, Norditropin, Norditropin Cartridge, Norditropin FlexPro Pen, Norditropin Nordiflex Pen, Nutropin, Nutropin AQ, Omnitrope, Saizen, Serostim, Tev-tropin, Zorbtive

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    What is Norditropin (somatropin)?

    Somatropin is a form of human growth hormone. Human growth hormone is important in the body for the growth of bones and muscles.

    Somatropin is used to treat growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth, and other causes. Somatropin is also used to prevent severe weight loss in people with AIDS, or to treat short bowel syndrome.

    Somatropin may also be used for purposes not listed in this medication guide.

    What is the most important information I should know about Norditropin (somatropin)?

    Before you receive somatropin, tell your doctor about all your past and present medical conditions, especially allergies, trauma, surgery, diabetes, cancer, breathing problems, liver or kidney disease, scoliosis, high blood pressure, pancreas disorder, underactive thyroid, or a brain tumor.

    Also tell your doctor about all other medications you use, especially steroids or diabetes medications. Your dosages of these medicines may need to be changed when you start using somatropin. Do not stop using a steroid suddenly or change any of your medication doses without your doctor’s advice.

    If you have Prader-Willi syndrome and are using somatropin, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring.

    Call your doctor at once if you have sudden and severe pain in your upper stomach with nausea and vomiting, fast heartbeat, increased thirst or urination, weight loss, or vision changes and sudden, severe pain behind your eyes.

    What should I discuss with my healthcare provider before using Norditropin (somatropin)?

    Before you receive somatropin, tell your doctor if you have ever had an allergic reaction to a growth hormone medicine, or to drug preservatives such as benzyl alcohol, metacresol or glycerin.

    You should not use this medication if you are allergic to somatropin, or if you have:

    • diabetic retinopathy (a serious eye condition caused by diabetes);

    • cancer; or
    • Prader-Willi syndrome and are also overweight or have sleep apnea or severe respiratory (lung) problems.

    You should also not use somatropin if you have a serious medical condition after having:

    • open heart surgery or stomach surgery;

    • trauma or other medical emergency; or
    • breathing problems (such as lung failure).

    To make sure you can safely take somatropin, tell your doctor if you have any of these other conditions:

    • liver disease;

    • kidney disease (or if you are on dialysis);
    • diabetes;
    • a pituitary gland disorder;
    • scoliosis;
    • high blood pressure (hypertension);
    • a pancreas disorder (especially in children);
    • a history of cancer;
    • carpal tunnel syndrome;
    • underactive thyroid; or
    • a brain tumor or lesion.

    FDA pregnancy category B. Some brands of somatropin are not expected to harm an unborn baby, including Genotropin, Omnitrope, Saizen, Serostim, and Zorbtive.

    FDA pregnancy category C. It is not known whether certain other brands of somatropin will harm an unborn baby, including Humatrope, Norditropin, Nutropin, and Tev-tropin.

    Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

    It is not known whether somatropin passes into breast milk or if it could harm a nursing baby. Do not use somatropin without telling your doctor if you are breast-feeding a baby.

    How should I use Norditropin (somatropin)?

    Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

    Your dose and brand of somatropin, and how often you give it will depend on what you are being treated for. Follow the directions on your prescription label.

    Somatropin is injected into a muscle or under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

    Use a different place on your body each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row. Do not inject this medicine into skin or muscle that is red, sore, infected, or injured.

    Do not shake the medication bottle or you may ruin the medicine. When mixing somatropin with a diluent (liquid), use a gentle swirling motion. Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription.

    Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

    To be sure this medication is helping your condition and not causing harm, your blood and growth progress will need to be tested often. Your eyes may also need to be checked. Visit your doctor regularly.

    If you are being treated for short bowel syndrome, follow the diet plan created for you by your doctor or nutrition counselor to help control your condition. Somatropin is not a cure for short bowel syndrome.

    If you use a form of somatropin that comes in a cartridge for use with an injection pen, use only the pen injection system provided with the somatropin brand you use.

    How you store this medicine will depend on what brand you are using and what diluent you are mixing somatropin with. After mixing somatropin, you may need to use it right away or you may be able to store it for later use. Read and carefully follow the instructions provided with your medicine about proper storage of somatropin before and after it has been mixed. Ask your pharmacist if you have any questions about proper storage of your medication.

    Throw away any somatropin left over after the expiration date on the label has passed.

    What happens if I miss a dose?

    Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

    Call your doctor if you miss more than 3 doses in a row.

    What happens if I overdose?

    Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

    Overdose can cause tremors or shaking, cold sweats, increased hunger, headache, drowsiness, weakness, dizziness, fast heartbeat, and nausea. Long-term overdose may cause excessive growth.

    What should I avoid while using Norditropin (somatropin)?

    If you use Zorbtive to treat short bowel syndrome, avoid drinking fruit juices or soda beverages. Follow the instructions of your doctor or nutrition counselor about what types of liquids you should drink while using Zorbtive.

    Avoid drinking alcohol if you have short bowel syndrome. Alcohol can irritate your stomach and could make your condition worse.

    Norditropin (somatropin) side effects

    If you have Prader-Willi syndrome, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring. Rare cases of serious breathing problems have occurred in patients with Prader-Willi syndrome who use somatropin.

    Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

    Call your doctor at once if you have any of these serious side effects:

    • severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

    • increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss;
    • sudden and severe pain behind your eyes, vision changes;
    • swelling in your head, face, hands, or feet; or
    • numbness or tingling in your wrist, hand, or fingers.

    Less serious side effects may include:

    • headache, feeling tired;

    • redness, soreness, swelling, rash, itching, pain, or bruising where the medicine was injected;
    • pain in your arms or legs, joint stiffness or pain;
    • muscle pain; or
    • cold symptoms such as stuffy nose, sneezing, sore throat.

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    See also: Norditropin side effects (in more detail)

    What other drugs will affect Norditropin (somatropin)?

    Before using somatropin, tell your doctor if you use insulin or take oral (by mouth) medicine to treat diabetes. Somatropin may affect blood sugar levels and you may need to adjust your dose of the diabetes medication. Do not change the dose of your diabetes medication without your doctor’s advice.

    Tell your doctor if you use any type of steroid medicine such as cortisone, dexamethasone, methylprednisolone, prednisone, and others. Steroids can make somatropin less effective and your doses may need to be adjusted. Do not stop using a steroid suddenly. Follow your doctor’s instructions.

    Tell your doctor about all other medications you use, especially cyclosporine (Gengraf, Neoral, Sandimmune), seizure medication, birth control pills, anabolic steroids, or hormone replacement medications for men or women.

    This list is not complete and other drugs may interact with somatropin. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

    Next Page → Side Effects

    More Norditropin resources

    • Side Effects
    • Pregnancy Warnings
    • Drug Interactions
    • Support Group
    • 2 Reviews - Add your own review/rating
    • Norditropin Prescribing Information (FDA)
    • Norditropin MedFacts Consumer Leaflet (Wolters Kluwer)
    • Norditropin Advanced Consumer (Micromedex) – Includes Dosage Information
    • Somatropin Professional Patient Advice (Wolters Kluwer)
    • Genotropin MedFacts Consumer Leaflet (Wolters Kluwer)
    • Genotropin Prescribing Information (FDA)
    • Humatrope Prescribing Information (FDA)
    • Humatrope cartridge MedFacts Consumer Leaflet (Wolters Kluwer)
    • Nutropin Prescribing Information (FDA)
    • Nutropin Subcutaneous, Injection Advanced Consumer (Micromedex) – Includes Dosage Information
    • Nutropin MedFacts Consumer Leaflet (Wolters Kluwer)
    • Nutropin AQ Prescribing Information (FDA)
    • Nutropin AQ MedFacts Consumer Leaflet (Wolters Kluwer)
    • Nutropin Depot Prescribing Information (FDA)
    • Omnitrope Consumer Overview
    • Omnitrope MedFacts Consumer Leaflet (Wolters Kluwer)
    • Omnitrope Prescribing Information (FDA)
    • Saizen MedFacts Consumer Leaflet (Wolters Kluwer)
    • Saizen Prescribing Information (FDA)
    • Serostim Prescribing Information (FDA)
    • Serostim MedFacts Consumer Leaflet (Wolters Kluwer)
    • Tev-Tropin Prescribing Information (FDA)
    • Tev-Tropin MedFacts Consumer Leaflet (Wolters Kluwer)
    • Zorbtive Prescribing Information (FDA)
    • Zorbtive Consumer Overview
    • Zorbtive MedFacts Consumer Leaflet (Wolters Kluwer)

    Compare Norditropin with other medications

    • Adult Human Growth Hormone Deficiency
    • Hypopituitarism
    • Noonan’s Syndrome
    • Pediatric Growth Hormone Deficiency
    • Short Stature for Age
    • Turner’s Syndrome

    Where can I get more information?

    • Your pharmacist can provide more information about somatropin.

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    Norditropin

    Norditropin

    Generic Name: somatropin (rdna origin – refrigerated) (SOE-ma-TROE-pin)

    Brand Name: Examples include Norditropin, Norditropin Nordiflex, and Norditropin FlexPro

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    Norditropin is used for:

    Treating certain children or adults whose bodies do not produce enough growth hormone. It is also used to treat certain children who are not growing normally due to Turner syndrome or Noonan syndrome. It may also be used for other conditions as determined by your doctor.

    Norditropin is a growth hormone. It works by stimulating growth in patients who do not make enough natural growth hormone.

    Do NOT use Norditropin if:

    • you are allergic to any ingredient in Norditropin or to phenol
    • you have active or recurring cancer, a brain tumor, or other unusual growths
    • you have severe breathing problems (eg, respiratory failure) or serious illness caused by complications from surgery or injury
    • you have a certain type of eye problem caused by diabetes (diabetic retinopathy) or if you have had a kidney transplant
    • the patient is a child who has Prader-Willi syndrome and is severely overweight or has severe breathing problems (eg, airway blockage, respiratory infection, sleep apnea)
    • the patient is a child who has epiphyseal closure (bone growth is complete)

    Contact your doctor or health care provider right away if any of these apply to you.

    Before using Norditropin:

    Some medical conditions may interact with Norditropin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

    • if you are pregnant, planning to become pregnant, or are breast-feeding
    • if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
    • if you have allergies to medicines, foods, or other substances
    • if you have a history of kidney problems, lung or breathing problems (eg, airway blockage, sleep apnea), an underactive thyroid, heart problems, ear or hearing problems (eg, repeated ear infections), or endocrine problems (eg, pituitary or adrenal gland problems)
    • if you have a history of diabetes or high blood sugar levels, or if a member of your family has had diabetes
    • if you have a history of leukemia, other types of cancer, or any unusual growths or tumors (especially in the brain)
    • if you have curvature of the spine (scoliosis), Prader-Willi syndrome, or a certain eye problem called papilledema (swelling of the area around your optic nerve)
    • if you are very overweight or have had recent major surgery or injury

    Some MEDICINES MAY INTERACT with Norditropin. Tell your health care provider if you are taking any other medicines, especially any of the following:

    • Corticosteroids (eg, prednisone) or estrogens because they may decrease Norditropin’s effectiveness
    • Anticonvulsants (eg, carbamazepine) or cyclosporine because the risk of their side effects may be increased by Norditropin
    • Insulin or other medicines for diabetes because their effectiveness may be decreased by Norditropin

    This may not be a complete list of all interactions that may occur. Ask your health care provider if Norditropin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

    How to use Norditropin:

    Use Norditropin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

    • An extra patient leaflet is available with Norditropin. Talk to your pharmacist if you have questions about this information.
    • Norditropin is given as an injection under the skin. A health care provider will teach you how to use it. Be sure you understand how to use Norditropin. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
    • Norditropin should be clear and colorless. Do not use Norditropin if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
    • Be sure to rotate your injection site as directed to help avoid thickening or hardening of the skin.
    • Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
    • If you miss a dose of Norditropin, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

    Ask your health care provider any questions you may have about how to use Norditropin.

    Important safety information:

    • Severe and sometimes fatal lung and breathing problems have occurred with use of Norditropin in certain children with Prader-Willi syndrome. These children were usually either very overweight or had severe breathing problems (eg, airway blockage, sleep apnea, lung or airway infection). The risk may be greater in boys. Children with Prader-Willi syndrome should have certain breathing tests before they start Norditropin. They should be monitored for signs of lung or airway infection. They should also have an effective form of weight control. Contact the doctor at once if the patient develops irregular breathing during sleep, new or increased snoring, or symptoms of lung or airway infection (eg, fever, coughing, sore throat, shortness of breath, chest pain or discomfort).
    • Rarely, children using Norditropin have experienced a slipped growth plate in the hip. Contact the doctor right away if the patient develops hip or knee pain or a limp.
    • Pancreas inflammation (pancreatitis) has been reported rarely in patients who take Norditropin. The risk may be greater in children, especially in girls who have Turner syndrome. Contact your doctor right away if you develop stomach or back pain.
    • Diabetes patients – Norditropin may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.
    • Lab tests, including blood sugar levels, thyroid function, and eye exams, may be performed while you use Norditropin. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
    • Use Norditropin with caution in the ELDERLY; they may be more sensitive to its effects.
    • PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Norditropin while you are pregnant. It is not known if Norditropin is found in breast milk. If you are or will be breast-feeding while you use Norditropin, check with your doctor. Discuss any possible risks to your baby.

    Possible side effects of Norditropin:

    All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

    Bone pain; headache; increased sweating; mild flu-like symptoms; mild swelling (eg, of the hands or feet); muscle or joint pain; prickling sensation of the skin; redness or itching at the injection site.

    Seek medical attention right away if any of these SEVERE side effects occur:

    Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); burning, tingling, itching, or numbness in the palm of the hand, fingers, or wrist; change in appearance or size of a mole; chest pain; confusion; ear pain, discharge, or discomfort; fast heartbeat; fever; hearing problems; hip or knee pain; limp; nausea or vomiting; new growth on the skin; one-sided weakness; persistent or severe cough or sore throat; severe or persistent stomach or back pain; severe or persistent swelling of the hands, ankles, or feet; shortness of breath; slurred speech; snoring or irregular breathing during sleep; sudden, severe, or persistent headache or dizziness; symptoms of high blood sugar (eg, increased thirst, hunger, or urination; unusual weakness); thickened or hardened skin at the injection site; trouble breathing; unusual bruising; vision changes.

    This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

    If OVERDOSE is suspected:

    Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include dizziness; excessive thirst or hunger; fainting; fast heartbeat; frequent urination; swelling of the ankles, feet, or hands.

    Proper storage of Norditropin: Store new (unopened) cartridges and prefilled pens in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Protect from light. Do not use Norditropin past the expiration date on the product label.

    For 5 mg per 1.5 mL (orange) and 10 mg per 1.5 mL (blue) strengths: Store used (open) cartridges and prefilled pens in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C), or at room temperature below 77 degrees F (25 degrees C). Do not freeze. Store away from heat, moisture, and light. Throw away any remaining medicine after 4 weeks if stored in the refrigerator or after 3 weeks if stored at room temperature.

    For 15 mg per 1.5 mL (green) and 30 mg per 3 mL (purple) strengths: Store used (open) cartridges and prefilled pens in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Throw away any remaining medicine after 4 weeks.

    Contact your pharmacist if you have any questions about how to properly store Norditropin. Keep Norditropin out of the reach of children and away from pets.

    General information:

    • If you have any questions about Norditropin, please talk with your doctor, pharmacist, or other health care provider.
    • Norditropin is to be used only by the patient for whom it is prescribed. Do not share it with other people.
    • If your symptoms do not improve or if they become worse, check with your doctor.
    • Check with your pharmacist about how to dispose of unused medicine.

    This information is a summary only. It does not contain all information about Norditropin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

    Issue Date: March 6, 2013 Database Edition 13.1.1.003 Copyright © 2013 Wolters Kluwer Health, Inc.

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