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Levitra

Levitra(vardenafil hcl) – Merck

THERAPEUTIC CLASS

Phosphodiesterase type 5 inhibitor

INDICATIONS

Treatment of erectile dysfunction (ED).

ADULT DOSAGE

Adults: Initial: 10mg 1 hr prior to sexual activity. Titrate: May decrease to 5mg or increase to max of 20mg based on response. Max: 1 tab/day. Elderly: ≥65 yrs: Initial: 5mg. Moderate Hepatic Impairment (Child-Pugh B): Initial: 5mg. Max: 10mg. Concomitant Ritonavir: Max: 2.5mg/72 hrs. Concomitant Indinavir/Saquinavir/Atazanavir/Clarithromycin/Ketoconazole 400mg daily/Itraconazole 400mg daily: Max: 2.5mg/24 hrs. Concomitant Ketoconazole 200mg daily/Itraconazole 200mg daily/Erythromycin: Max: 5mg/24 hrs. Concomitant Stable α-blocker: Initial: 5mg; 2.5mg when used with certain CYP3A4 inhibitors.

HOW SUPPLIED

Tab: 2.5mg, 5mg, 10mg, 20mg

CONTRAINDICATIONS

Concomitant nitrates or nitric oxide donors.

WARNINGS/PRECAUTIONS

Avoid when sexual activity is inadvisable due to underlying cardiovascular (CV) status. Increased sensitivity to vasodilation effects with left ventricular outflow obstruction. Decrease in supine BP reported. Avoid with unstable angina, hypotension (resting SBP<90 mmHg), uncontrolled HTN (>170/110 mmHg), recent history of stroke, life-threatening arrhythmia, myocardial infarction (MI) within last 6 months, severe cardiac failure, severe hepatic impairment (Child-Pugh C), end-stage renal disease (ESRD) requiring dialysis, hereditary degenerative retinal disorders including retinitis pigmentosa, congenital QT prolongation. Rare reports of prolonged erections >4 hrs and priapism. Caution with bleeding disorders, peptic ulcers, anatomical deformation of the penis or predisposition to priapism. Rare reports of non-arteritic anterior ischemic optic neuropathy (NAION) with phosphodiesterase type 5 (PDE5) inhibitors. Sudden decrease or loss of hearing accompanied by tinnitus and dizziness reported.

ADVERSE REACTIONS

Headache, flushing, rhinitis, dyspepsia, sinusitis, flu syndrome, dizziness, nausea.

DRUG INTERACTIONS

See Contraindications. Avoid use with Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmics and other agents for ED. Caution with medications known to prolong QT interval. Increased levels with CYP3A4 inhibitors (eg, ritonavir, indinavir, saquinavir, atazanavir, ketoconazole, itraconazole, clarithromycin, erythromycin). Additive hypotensive effect, which may lead to symptomatic hypotension when used with α-blockers. Reduced clearance with CYP3A4/5 and CYP2C9 inhibitors.

PREGNANCY

Category B, not for use in nursing.

MECHANISM OF ACTION

PDE5 inhibitor; increases the amount of cGMP, which causes smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection.

PHARMACOKINETICS

Absorption: Rapid, absolute bioavailability (15%); Tmax=30 min-2 hrs. Distribution: Vd=208L; plasma protein binding (95%). Metabolism: Via CYP3A4, CYP3A5, CYP2C. M1 (major metabolite). Elimination: Feces (91-95%), urine (2-6%); T1/2=4-5 hrs.

ASSESSMENT

Assess for CV disease, left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis), congenital QT prolongation, retinitis pigmentosa, bleeding disorders, active peptic ulceration, anatomical deformation of the penis or conditions that predispose to priapism (eg, sickle cell anemia, multiple myleoma, leukemia), and renal/hepatic impairment. Assess potential underlying causes of ED and for possible drug interactions.

MONITORING

Monitor potential for cardiac risk due to sexual activity, hypotension, color vision changes or other eye adverse events (eg, NAION), hypersensitivity reactions, and hearing impairment. Monitor for adverse events when used in combination with other drugs.

PATIENT COUNSELING

Discuss risks and benefits of therapy. Seek medical assistance if erection persists >4 hrs. Inform that postural hypotension may occur. Advise of potential BP-lowering effect of nitrates, α-blockers and antihypertensive medications, and cardiac risk of sexual activity. Counsel about protective measures necessary to guard against STDs, including HIV; drug does not protect against STDs. D/C and inform doctor if sudden loss of vision or hearing occur. Counsel to take as prescribed.

ADMINISTRATION/STORAGE

Administration: Oral route. Storage: 25°C (77°F); excursions permitted to 15-30°C (59-86°F).


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    Levitra

    Levitra

    Pronunciation Generic Name: vardenafil hydrochloride

    Dosage Form: tablet, film coated

    For ProfessionalsSide EffectsDosageInteractionsMore…

    Indications and Usage for Levitra

    Levitra® is indicated for the treatment of erectile dysfunction.

    Levitra Dosage and Administration

    General Dose Information

    For most patients, the recommended starting dose of Levitra is 10 mg, taken orally, as needed, approximately 60 minutes before sexual activity. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and side effects. The maximum recommended dosing frequency is once per day. Sexual stimulation is required for a response to treatment.

    Use with Food

    Levitra can be taken with or without food.

    Use in Specific Populations

    Geriatrics: A starting dose of 5 mg Levitra should be considered in patients 65 years of age [see Use in Specific Populations (8.5)].

    Hepatic Impairment: For patients with moderate hepatic impairment (Child-Pugh B), a starting dose of 5 mg Levitra is recommended. The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg.

    Do not use Levitra in patients with severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions (5.8), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

    Renal Impairment: Do not use Levitra in patients on renal dialysis [see Warnings and Precautions (5.9), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

    Concomitant Medications

    Nitrates: Concomitant use with nitrates and nitric oxide donors in any form is contraindicated [see Contraindications (4.1)].

    CYP3A4 Inhibitors: The dosage of Levitra may require adjustment in patients receiving potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, atazanavir, and clarithromycin as well as in other patients receiving moderate CYP3A4 inhibitors such as erythromycin [see Drug Interactions (7.2)]. For ritonavir, a single dose of 2.5 mg Levitra should not be exceeded in a 72-hour period. For indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, and clarithromycin, a single dose of 2.5 mg Levitra should not be exceeded in a 24-hour period. For ketoconazole 200 mg daily, itraconazole 200 mg daily, and erythromycin, a single dose of 5 mg Levitra should not be exceeded in a 24-hour period.

    Alpha-Blockers: In those patients who are stable on alpha-blocker therapy, phosphodiesterase type 5 (PDE5) inhibitors should be initiated at the lowest recommended starting dose. Concomitant treatment should be initiated only if the patient is stable on his alpha-blocker therapy. In those patients who are stable on alpha-blocker therapy, Levitra should be initiated at a dose of 5 mg (2.5 mg when used concomitantly with certain CYP3A4 inhibitors). [See Warnings and Precautions (5.6) and Drug Interactions (7.1).]

    Dosage Forms and Strengths

    Levitra is formulated as orange, round, film-coated tablets with “BAYER” cross debossed on one side and “2.5”, “5”, “10” and “20” on the other side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively.

    Contraindications

    4.1 Nitrates

    Administration of Levitra with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated [see Clinical Pharmacology (12.2)]. Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including Levitra, may potentiate the hypotensive effects of nitrates. A suitable time interval following dosing of Levitra for the safe administration of nitrates or nitric oxide donors has not been determined.

    Warnings and Precautions

    The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment.

    Before prescribing Levitra, it is important to note the following:

    5.1 Cardiovascular Effects

    General Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatment for erectile dysfunction, including Levitra, should not be used in men for whom sexual activity is not recommended because of their underlying cardiovascular status.

    There are no controlled clinical data on the safety or efficacy of vardenafil in the following patients; and therefore its use is not recommended until further information is available: unstable angina; hypotension (resting systolic blood pressure of <90 mmHg); uncontrolled hypertension (>170/110 mmHg); recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last 6 months); severe cardiac failure.

    Left Ventricular Outflow Obstruction Patients with left ventricular outflow obstruction, (for example, aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators including PDE5 inhibitors.

    Blood Pressure Effects Levitra has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 7 mmHg systolic and 8 mmHg diastolic) [see Clinical Pharmacology (12.2)]. While this normally would be expected to be of little consequence in most patients, prior to prescribing Levitra, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects.

    Potential for Drug Interactions with Potent or Moderate CYP3A4 Inhibitors

    Concomitant administration with potent CYP3A4 inhibitors (such as ritonavir, indinavir, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Dosage adjustment is necessary when Levitra is administered with certain CYP3A4 inhibitors [see Dosage and Administration (2.4), Drug Interactions (7.2)].

    Long-term safety information is not available on the concomitant administration of vardenafil with HIV protease inhibitors.

    Risk of Priapism

    There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

    Levitra should be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

    Effects on the Eye

    Physicians should advise patients to stop use of all PDE5 inhibitors, including Levitra, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. It is not possible to determine whether these events were related directly to the use of PDE5 inhibitors or to other factors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators such as PDE5 inhibitors [see Adverse Reactions (6.2)].

    Levitra has not been evaluated in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, therefore its use is not recommended until further information is available in those patients.

    Sudden Hearing Loss

    Physicians should advise patients to stop taking all PDE5 inhibitors, including Levitra, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including vardenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)].

    Alpha-Blockers

    Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Levitra, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting) [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)]. Consideration should be given to the following:

    Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors.
    In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended starting dose [see Dosage and Administration (2.4)].
    In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking a PDE5 inhibitor.
    Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs.

    Congenital or Acquired QT Prolongation

    In a study of the effect of Levitra on QT interval in 59 healthy males [see Clinical Pharmacology (12.2)], therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil and the active control moxifloxacin (400 mg) produced similar increases in QTc interval. A postmarketing study evaluating the effect of combining Levitra with another drug of comparable QT effect showed an additive QT effect when compared with either drug alone [see Clinical Pharmacology (12.2)]. These observations should be considered in clinical decisions when prescribing Levitra to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

    Patients taking Class 1A (for example. quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using Levitra.

    Hepatic Impairment

    Dosage adjustment is necessary in patients with moderate hepatic impairment (Child-Pugh B). Do not use Levitra in patients with severe (Child-Pugh C) hepatic impairment. [See Dosage and Administration (2.3) Clinical Pharmacology (12.3)] and Use in Specific Populations (8.6).]

    Renal Impairment

    Do not use Levitra in patients on renal dialysis, as vardenafil has not been evaluated in this population [see Dosage and Administration (2.3) and Use in Specific Populations (8.7)].

    Combination with Other Erectile Dysfunction Therapies

    The safety and efficacy of Levitra used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.

    Effects on Bleeding

    In humans, vardenafil alone in doses up to 20 mg does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Levitra has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore Levitra should be administered to these patients after careful benefit-risk assessment.

    Sexually Transmitted Disease

    The use of Levitra offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered.

    Adverse Reactions

    The following serious adverse reactions with the use of Levitra (vardenafil) are discussed elsewhere in the labeling:

    1.
    Cardiovascular Effects [see Contraindications (4.1) and Warnings and Precautions (5.1)]
    2.
    Priapism [see Warnings and Precautions (5.3)]
    3.
    Effects on Eye [see Warnings and Precautions (5.4)]
    4.
    Sudden Hearing Loss [see Warnings and Precautions (5.5)]
    5.
    QT Prolongation [see Warnings and Precautions (5.7)]

    Clinical Studies Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

    Levitra was administered to over 4430 men (mean age 56, range 18-89 years; 81% White, 6% Black, 2% Asian, 2% Hispanic and 9% Other) during controlled and uncontrolled clinical trials worldwide. Over 2200 patients were treated for 6 months or longer and 880 patients were treated for at least 1 year.

    In placebo-controlled clinical trials, the discontinuation rate due to adverse events was 3.4% for Levitra compared to 1.1% for placebo.

    When Levitra was taken as recommended in placebo-controlled clinical trials, the following adverse reactions were reported (see Table 1).

    Table 1: Adverse Reactions Reported By ≥2% of Patients Treated with Levitra and More Frequent on Drug than Placebo in Fixed and Flexiblea Dose Randomized, Controlled Trials of 5 mg, 10 mg, or 20 mg Vardenafil

    Adverse Reaction Percentage of Patients Reporting Reactions
    Placebo

    N = 1199

    Levitra

    N = 2203

    Headache

    4%

    15%

    Flushing

    1%

    11%

    Rhinitis

    3%

    9%

    Dyspepsia

    1%

    4%

    Accidental Injuryb

    2%

    3%

    Sinusitis

    1%

    3%

    Flu Syndrome

    2%

    3%

    Dizziness

    1%

    2%

    Increased Creatine Kinase

    1%

    2%

    Nausea

    1%

    2%

    Flexible dose studies started all patients at Levitra 10 mg and allowed decrease in dose to 5 mg or increase in dose to 20 mg based on side effects and efficacy.
    All the events listed in the above table were deemed to be adverse drug reactions with the exception of accidental injury.

    Back pain was reported in 2.0% of patients treated with Levitra and 1.7% of patients on placebo.

    Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (headache, flushing, dyspepsia, nausea, and rhinitis) over the 5 mg, 10 mg, and 20 mg doses of Levitra.

    All Vardenafil Studies: Levitra film-coated tablets and vardenafil orally disintegrating tablets have been administered to over 17,000 men (mean age 54.5, range 18–89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year.

    In the placebo-controlled clinical trials for Levitra film-coated tablets and vardenafil orally disintegrating tablets, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo.

    The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of Levitra film-coated tablets and vardenafil orally disintegrating tablets. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug:

    Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain

    Auditory: tinnitus, vertigo

    Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension

    Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases

    Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia

    Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure

    Respiratory: dyspnea, sinus congestion

    Skin and appendages: erythema, rash

    Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis

    Urogenital: increase in erection, priapism

    Postmarketing Experience

    The following adverse reactions have been identified during post approval use of Levitra. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

    Ophthalmologic: Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see Warnings and Precautions (5.4) and Patient Counseling Information (17.7)].

    Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil.

    Neurologic: Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil.

    Otologic: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Patient Counseling Information (17.8)].

    Drug Interactions

    Potential for Pharmacodynamic Interactions with Levitra

    Nitrates: Concomitant use of Levitra and nitrates and nitric oxide donors is contraindicated. The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours after vardenafil were potentiated by a 20 mg dose of Levitra in healthy middle-aged subjects. These effects were not observed when Levitra 20 mg was taken 24 hours before the nitroglycerin (NTG). Potentiation of the hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of Levitra and nitrates is contraindicated [see Contraindications (4.1) and Clinical Pharmacology (12.2).

    Alpha-Blockers: Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Levitra and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with co-administration of vardenafil with terazosin or tamsulosin. [See Dosage and Administration (2.4), Warnings and Precautions (5.6), and Clinical Pharmacology (12.2).]

    Antihypertensives:Levitra may add to the blood pressure lowering effects of antihypertensive agents. In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1.

    Alcohol: Levitra (20 mg) did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight, approximately 40 mL of absolute alcohol in a 70 kg person). Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.

    Effect of Other Drugs on Vardenafil

    In vitro studies Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].

    In vivo studies

    Potent CYP3A4 inhibitors

    Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil AUC and a 4-fold increase in maximum concentration (Cmax) when co-administered with Levitra (5 mg) in healthy volunteers. A 5-mg Levitra dose should not be exceeded in a 24-hour period when used in combination with 200 mg once daily ketoconazole. Since higher doses of ketoconazole (400 mg daily) may result in higher increases in Cmax and AUC, a single 2.5 mg dose of Levitra should not be exceeded in a 24-hour period when used in combination with ketoconazole 400 mg daily. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]

    Indinavir (800 mg t.i.d.) co-administered with Levitra 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax and a 2-fold increase in vardenafil half-life. It is recommended not to exceed a single 2.5 mg Levitra dose in a 24-hour period when used in combination with indinavir. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).]

    Ritonavir (600 mg b.i.d.) co-administered with Levitra 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2.5 mg Levitra dose in a 72-hour period when used in combination with ritonavir. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).].

    Moderate CYP3A4 inhibitors

    Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in Cmax when co-administered with Levitra 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of Levitra in a 24-hour period when used in combination with erythromycin. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]

    Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure.

    Other Drug Interactions No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.

    Cimetidine (400 mg b.i.d.) had no effect on vardenafil bioavailability (AUC) and maximum concentration (Cmax) of vardenafil when co-administered with 20 mg Levitra in healthy volunteers.

    Effects of Vardenafil on Other Drugs

    In vivo studies Nifedipine:Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or Cmax of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of Levitra when taken in combination. In these patients whose hypertension was controlled with nifedipine, Levitra 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.

    Ritonavir and Indinavir: Upon concomitant administration of 5 mg of Levitra with 600 mg BID ritonavir, the Cmax and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of Levitra with 800 mg TID indinavir, the Cmax and AUC of indinavir were reduced by 40% and 30%, respectively.

    Aspirin: Levitra (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by aspirin (two 81 mg tablets).

    Other interactions: Levitra had no effect on the pharmacodynamics of glyburide (glucose and insulin concentrations) and warfarin (prothrombin time or other pharmacodynamic parameters).

    USE IN SPECIFIC POPULATIONS

    Pregnancy

    Pregnancy Category B Levitra is not indicated for use in women. There are no studies of Levitra use in pregnant women. No evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis. This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the maximum recommended human dose (MRHD) of 20 mg.

    In the rat pre-and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day. Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to 1 and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk. The number of living pups born to rats exposed pre- and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre- and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg.

    Nursing Mothers

    Levitra is not indicated for use in women. It is not known if vardenafil is excreted in human breast milk.

    Vardenafil was secreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma. Following a single oral dose of 3 mg/kg, 3.3% of the administered dose was excreted into the milk within 24 hours.

    Pediatric Use

    Levitra is not indicated for use in pediatric patients. Safety and efficacy have not been established in this population.

    Geriatric Use

    Elderly males age 65 years and older have higher vardenafil plasma concentrations than younger males (18 – 45 years), mean Cmax and AUC were 34% and 52% higher, respectively. Phase 3 clinical trials included more than 834 elderly patients, and no differences in safety or effectiveness of Levitra 5, 10, or 20 mg were noted when these elderly patients were compared to younger patients. However, due to increased vardenafil concentrations in the elderly, a starting dose of 5 mg Levitra should be considered in patients ≥65 years of age [see Clinical Pharmacology (12.3)].

    Hepatic Impairment

    Dosage adjustment is necessary in patients with moderate hepatic impairment.

    Do not use Levitra in patients with severe hepatic impairment (Child-Pugh C). Vardenafil has not been evaluated in this patient population.

    A starting dose of 5 mg is recommended in patients with moderate hepatic impairment (Child-Pugh B) and the maximum dose should not exceed 10 mg. In volunteers with moderate hepatic impairment, the Cmax and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. [See Warnings and Precautions (5.8) and Dosage and Administration (2.3).]

    In volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects. No dosage adjustment is necessary in patients with mild hepatic impairment.

    Renal Impairment

    Do not use Levitra in patients on renal dialysis as vardenafil has not been evaluated in such patients.

    No dosage adjustment is necessary in patients with creatinine clearance (CLcr) of 30–80 mL/min. In male volunteers with CLcr = 50-80 ml/min, the pharmacokinetics of vardenafil were similar to those observed in a control group with CLcr >80 mL/min. In male volunteers with CLcr = 30-50 mL/min or CLcr30 mL/min, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with CLcr80 mL/min. [See Dosage and Administration (2.3) and Warnings and Precautions (5.9).]

    Overdosage

    The maximum dose of Levitra for which human data are available is a single 120 mg dose administered to eight healthy male volunteers. The majority of these subjects experienced reversible back pain/myalgia and/or “abnormal vision.”

    In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance because vardenafil is highly bound to plasma proteins and is not significantly eliminated in the urine.

    Levitra Description

    Levitra is administered orally for the treatment of erectile dysfunction. This monohydrochloride salt of vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

    Vardenafil HCl is designated chemically as piperazine, 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f ][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethyl-, monohydrochloride and has the following structural formula:

    Vardenafil HCl is a nearly colorless, solid substance with a molecular weight of 579.1 g/mol and a solubility of 0.11 mg/mL in water.

    Levitra is formulated as orange, round, film-coated tablets with “BAYER” cross debossed on one side and “2.5”, “5”, “10”, and “20” on the other side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively. In addition to the active ingredient, vardenafil HCl, each tablet contains microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide, yellow ferric oxide, and red ferric oxide.

    Levitra – Clinical Pharmacology

    Mechanism of Action

    Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation.

    In vitro studies have shown that vardenafil is a selective inhibitor of PDE5. The inhibitory effect of vardenafil is more selective on PDE5 than for other known phosphodiesterases (15-fold relative to PDE6, 130-fold relative to PDE1, 300-fold relative to PDE11, and 1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10).

    Pharmacodynamics

    Effects on Blood Pressure In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents [see Drug Interactions (7)].

    Effects on Blood Pressure and Heart Rate when Levitra is Combined with Nitrates A study was conducted in which the blood pressure and heart rate response to 0.4 mg nitroglycerin (NTG) sublingually was evaluated in 18 healthy subjects following pretreatment with Levitra 20 mg at various times before NTG administration. Levitra 20 mg caused an additional time-related reduction in blood pressure and increase in heart rate in association with NTG administration. The blood pressure effects were observed when Levitra 20 mg was dosed 1 or 4 hours before NTG and the heart rate effects were observed when 20 mg was dosed 1, 4, or 8 hours before NTG. Additional blood pressure and heart rate changes were not detected when Levitra 20 mg was dosed 24 hours before NTG. (See Figure 1.)

    Because the disease state of patients requiring nitrate therapy is anticipated to increase the likelihood of hypotension, the use of vardenafil by patients on nitrate therapy or on nitric oxide donors is contraindicated [see Contraindications (4.1)].

    Blood Pressure Effects in Patients on Stable Alpha-Blocker Treatment Two clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia (BPH) on stable-dose alpha-blocker treatment for at least four weeks.

    Study 1: This study was designed to evaluate the effect of 5 mg vardenafil compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0.4 mg daily (cohort 1, n=21) and terazosin 5 or 10 mg daily (cohort 2, n=21). The design was a randomized, double blind, cross-over study with four treatments: vardenafil 5 mg or placebo administered simultaneously with the alpha-blocker and vardenafil 5 mg or placebo administered 6 hours after the alpha-blocker. Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing. For blood pressure (BP) results see Table 2. One patient after simultaneous treatment with 5 mg vardenafil and 10 mg terazosin exhibited symptomatic hypotension with standing blood pressure of 80/60 mmHg occurring one hour after administration and subsequent mild dizziness and moderate lightheadedness lasting for 6 hours. For vardenafil and placebo, five and two patients, respectively, experienced a decrease in standing systolic blood pressure (SBP) of 30 mmHg following simultaneous administration of terazosin. Hypotension was not observed when vardenafil 5 mg and terazosin were administered 6 hours apart. Following simultaneous administration of vardenafil 5 mg and tamsulosin, two patients had a standing SBP of 85 mmHg; two and one patient (vardenafil and placebo, respectively) had a decrease in standing SBP of 30 mmHg. When tamsulosin and vardenafil 5 mg were separated by 6 hours, two patients had a standing SBP 85 mmHg and one patient had a decrease in SBP of 30 mmHg. There were no severe adverse events related to hypotension reported during the study. There were no cases of syncope.

    Table 2: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 mg in BPH patients on stable alpha-blocker therapy (Study 1)

    Alpha-Blocker Simultaneous dosing of Vardenafil 5 mg

    and Alpha-Blocker,

    Placebo-Subtracted

    Dosing of Vardenafil 5 mg

    and Alpha-Blocker

    Separated by 6 Hours,

    Placebo-Subtracted

    Terazosin

    5 or 10 mg daily

    Standing SBP

    -3 (-6.7, 0.1)

    -4 (-7.4, -0.5)

    Supine SBP

    -4 (-6.7, -0.5)

    -4 (-7.1, -0.7)

     
    Tamsulosin

    0.4 mg daily

    Standing SBP

    Supine SBP

    -6 (-9.9, -2.1)

    -4 (-7, -0.8)

    -4 (-8.3, -0.5)

    -5 (-7.9, -1.7)

    Blood pressure effects (standing SBP) in normotensive men on stable dose tamsulosin 0.4 mg following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours are shown in Figure 2. Blood pressure effects (standing SBP) in normotensive men on stable dose terazosin (5 or 10 mg) following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours, are shown in Figure 3.

    Figure 2 Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (Study 1)

    Study 2: This study was designed to evaluate the effect of 10 mg vardenafil (stage 1) and 20 mg vardenafil (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=23) on stable therapy with tamsulosin 0.4 mg or 0.8 mg daily for at least four weeks. The design was a randomized, double blind, two-period cross-over study. Vardenafil or placebo was given simultaneously with tamsulosin. Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing. For BP results see Table 3. One patient experienced a decrease from baseline in standing SBP of 30 mmHg following vardenafil 10 mg. There were no other instances of outlier blood pressure values (standing SBP 85 mmHg or decrease from baseline in standing SBP of 30 mmHg). Three patients reported dizziness following vardenafil 20 mg. There were no cases of syncope.

    Table 3: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg in BPH patients on stable alpha-blocker therapy with tamsulosin 0.4 or 0.8 mg daily (Study 2)

    Vardenafil 10 mg

    Placebo-subtracted

    Vardenafil 20 mg

    Placebo-subtracted

    Standing SBP

    -4 (-6.8, -0.3)

    -4 (-6.8, -1.4)

    Supine SBP

    -5 (-8.2, -0.8)

    -4 (-6.3, -1.8)

    Blood pressure effects (standing SBP) in normotensive men on stable dose tamsulosin 0.4 mg following simultaneous administration of vardenafil 20 mg or placebo, or following administration of vardenafil 20 mg or placebo separated by 6 hours are shown in Figure 4.

    Figure 4 Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous administration of vardenafil 10 mg (Stage 1), vardenafil 20 mg (Stage 2), or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (Study 2)

    Blood pressure effects in normotensive men after forced titration with alpha-blockers: Two randomized, double blind, placebo-controlled clinical pharmacology studies with healthy normotensive volunteers (age range, 45-74 years) were performed after forced titration of the alpha-blocker terazosin to 10 mg daily over 14 days (n=29), and after initiation of tamsulosin 0.4 mg daily for five days (n=24). There were no severe adverse events related to hypotension in either study. Symptoms of hypotension were a cause for withdrawal in 2 subjects receiving terazosin and in 4 subjects receiving tamsulosin. Instances of outlier blood pressure values (defined as standing SBP 85 mmHg and/or a decrease from baseline of standing SBP 30 mmHg) were observed in 9/24 subjects receiving tamsulosin and 19/29 receiving terazosin. The incidence of subjects with standing SBP 85 mmHg given vardenafil and terazosin to achieve simultaneous Tmax led to early termination of that arm of the study. In most (7/8) of these subjects, instances of standing SBP 85 mmHg were not associated with symptoms. Among subjects treated with terazosin, outlier values were observed more frequently when vardenafil and terazosin were given to achieve simultaneous Tmax than when dosing was administered to separate Tmax by 6 hours. There were 3 cases of dizziness observed with concomitant administration of terazosin and vardenafil. Seven subjects experienced dizziness mainly occurring with simultaneous Tmax administration of tamsulosin. There were no cases of syncope.

    Table 4: Mean (95% C.I.) maximal change in baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg in healthy volunteers on daily alpha-blocker therapy

    Dosing of Vardenafil and Alpha-Blocker Separated by 6 Hours Simultaneous dosing of Vardenafil and Alpha-Blocker
    Alpha-Blocker Vardenafil

    10 mg

    Placebo-Subtracted

    Vardenafil

    20 mg

    Placebo-Subtracted

    Vardenafil

    10 mg

    Placebo-Subtracted

    Vardenafil

    20 mg

    Placebo-Subtracted

    Terazosin

    10 mg daily

    Standing SBP

    -7 (-10, -3)

    -11 (-14, -7)

    -23 (-31, 16)a

    -14 (-33, 11)a

    Supine SBP

    -5 (-8, -2)

    -7 (-11, -4)

    -7 (-25, 19)a

    -7 (-31, 22)a

     
    Tamsulosin

    0.4 mg daily

    Standing SBP

    -4 (-8, -1)

    -8 (-11, -4)

    -8 (-14, -2)

    -8 (-14, -1)

    Supine SBP

    -4 (-8, 0)

    -7 (-11, -3)

    -5 (-9, -2)

    -3 (-7, 0)

    1.
    Due to the sample size, confidence intervals may not be an accurate measure for these data. These values represent the range for the difference.

    Figure 5 Figure 5: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with terazosin (10 mg) in healthy volunteers

    Figure 6 Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with tamsulosin (0.4 mg) in healthy volunteers

    Effects on Cardiac Electrophysiology The effect of 10 mg and 80 mg vardenafil on QT interval was evaluated in a single-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) crossover study in 59 healthy males (81% White, 12% Black, 7% Hispanic) aged 45-60 years. The QT interval was measured at one hour post dose because this time point approximates the average time of peak vardenafil concentration. The 80 mg dose of Levitra (four times the highest recommended dose) was chosen because this dose yields plasma concentrations covering those observed upon co-administration of a low-dose of Levitra (5 mg) and 600 mg BID of ritonavir. Of the CYP3A4 inhibitors that have been studied, ritonavir causes the most significant drug-drug interaction with vardenafil. Table 5 summarizes the effect on mean uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia and a linear individual correction method) at one hour post-dose. No single correction method is known to be more valid than the other. In this study, the mean increase in heart rate associated with a 10 mg dose of Levitra compared to placebo was 5 beats/minute and with an 80 mg dose of Levitra the mean increase was 6 beats/minute.

    Table 5. Mean QT and QTc changes in msec (90% CI) from baseline relative to placebo at 1 hour post-dose with different methodologies to correct for the effect of heart rate.

    Drug/Dose QT Uncorrected

    (msec)

    Fridericia QT

    Correction

    (msec)

    Individual QT

    Correction

    (msec)

    Vardenafil 10 mg

    -2

    (-4, 0)

    8

    (6, 9)

    4

    (3, 6)

    Vardenafil 80 mg

    -2

    (-4, 0)

    10

    (8, 11)

    6

    (4, 7)

    Moxifloxacina 400 mg

    3

    (1, 5)

    8

    (6, 9)

    7

    (5, 8)

    1.
    Active control (drug known to prolong QT)

    Therapeutic and supratherapeutic doses of vardenafil and the active control moxifloxacin produced similar increases in QTc interval. This study, however, was not designed to make direct statistical comparisons between the drug or the dose levels. The clinical impact of these QTc changes is unknown [see Warnings and Precautions (5)].

    In a separate postmarketing study of 44 healthy volunteers, single doses of 10 mg Levitra resulted in a placebo-subtracted mean change from baseline of QTcF (Fridericia correction) of 5 msec (90% CI: 2,8). Single doses of gatifloxacin 400mg resulted in a placebo-subtracted mean change from baseline QTcF of 4 msec (90% CI: 1,7). When Levitra 10mg and gatifloxacin 400 mg were co-administered, the mean QTcF change from baseline was additive when compared to either drug alone and produced a mean QTcF change of 9 msec from baseline (90% CI: 6,11). The clinical impact of these QT changes is unknown [see Warnings and Precautions (5.7)].

    Effects on Exercise Treadmill Test in Patients with Coronary Artery Disease (CAD): In two independent trials that assessed 10 mg (n=41) and 20 mg (n=39) vardenafil, respectively, vardenafil did not alter the total treadmill exercise time compared to placebo. The patient population included men aged 40-80 years with stable exercise-induced angina documented by at least one of the following: 1) prior history of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), or stenting (not within 6 months); 2) positive coronary angiogram showing at least 60% narrowing of the diameter of at least one major coronary artery; or 3) a positive stress echocardiogram or stress nuclear perfusion study.

    Results of these studies showed that Levitra did not alter the total treadmill exercise time compared to placebo (10 mg Levitra vs. placebo: 433±109 and 426±105 seconds, respectively; 20 mg Levitra vs. placebo: 414±114 and 411±124 seconds, respectively). The total time to angina was not altered by Levitra when compared to placebo (10 mg Levitra vs. placebo: 291±123 and 292±110 seconds; 20 mg Levitra vs. placebo: 354±137 and 347±143 seconds, respectively). The total time to 1 mm or greater ST-segment depression was similar to placebo in both the 10 mg and the 20 mg Levitra groups (10 mg Levitra vs. placebo: 380±108 and 334±108 seconds; 20 mg Levitra vs. placebo: 364±101 and 366±105 seconds, respectively).

    Effects on Eye Single oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green) using the Farnsworth-Munsell 100-hue test and reductions in electroretinogram (ERG) b-wave amplitudes, with peak effects near the time of peak plasma levels. These findings are consistent with the inhibition of PDE6 in rods and cones, which is involved in phototransduction in the retina. The findings were most evident one hour after administration, diminishing but still present 6 hours after administration. In a single dose study in 25 normal males, Levitra 40 mg, twice the maximum daily recommended dose, did not alter visual acuity, intraocular pressure, fundoscopic and slit lamp findings.

    In another double-blind, placebo controlled clinical trial, at least 15 doses of 20 mg vardenafil were administered over 8 weeks versus placebo to 52 males. Thirty-two (32) males (62%) of the patients completed the trial. Retinal function was measured by ERG and FM-100 test 2, 6 and 24 hours after dosing. The trial was designed to detect changes in retinal function that might occur in more than 10% of patients. Vardenafil did not produce clinically significant ERG or FM-100 effects in healthy men compared to placebo. Two patients on vardenafil in the trial reported episodes of transient cyanopsia (objects appear blue).

    Effects on Sperm Motility/Morphology There was no effect on sperm motility or morphology after single 20 mg oral doses of vardenafil in healthy volunteers.

    Pharmacokinetics

    The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. .

    Absorption Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 7.

    Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Maximum observed plasma concentrations after a single 20 mg dose in healthy volunteers are usually reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state. Two food-effect studies were conducted which showed that high-fat meals caused a reduction in Cmax by 18%-50%.

    Distribution The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. Vardenafil and its major circulating metabolite, M1, are highly bound to plasma proteins (about 95% for parent drug and M1). This protein binding is reversible and independent of total drug concentrations.

    Following a single oral dose of 20 mg vardenafil in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing.

    Metabolism Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. M1 is subject to further metabolism. The plasma concentration of M1 is approximately 26% that of the parent compound. This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity.

    Excretion The total body clearance of vardenafil is 56 L/h, and the terminal half-life of vardenafil and its primary metabolite (M1) is approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).

    Pharmacokinetics in Specific Populations

    Pediatrics

    Levitra is not indicated for use in pediatric patients. Vardenafil trials were not conducted in the pediatric population.

    Geriatric

    In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean Cmax and AUC were 34% and 52% higher, respectively, in the elderly males [see Use in Specific Populations (8.5)].

    Hepatic Impairment

    In volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects. In volunteers with moderate hepatic impairment (Child-Pugh B), the Cmax and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment. [See Dosage and Administration (2.3), Warnings and Precautions (5.8), and Use in Specific Populations (8.6).]

    Renal Impairment

    In male volunteers with CLcr = 50–80 mL/min, the pharmacokinetics of vardenafil were similar to those observed in a control group with CLcr >80 mL/min. In male volunteers with CLcr = 30–50 mL/min or CLcr30 mL/min renal impairment groups, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with CLcr80 mL/min). Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis. [See Dosage and Administration (2.3), Warnings and Precautions (5.9), and Use in Specific Populations (8.7).]

    Nonclinical Toxicology

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis Vardenafil was not carcinogenic in rats and mice when administered daily for 24 months. In these studies systemic drug exposures (AUCs) for unbound (free) vardenafil and its major metabolite were approximately 400- and 170-fold for male and female rats, respectively, and 21- and 37-fold for male and female mice, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 20 mg.

    Mutagenesis Vardenafil was not mutagenic as assessed in either the in vitro bacterial Ames assay or the forward mutation assay in Chinese hamster V79 cells. Vardenafil was not clastogenic as assessed in either the in vitro chromosomal aberration test or the in vivo mouse micronucleus test.

    Impairment of Fertility Vardenafil did not impair fertility in male and female rats administered doses up to 100 mg/kg/day for 28 days prior to mating in male, and for 14 days prior to mating and through day 7 of gestation in females. In a corresponding 1-month rat toxicity study, this dose produced an AUC value for unbound vardenafil 200 fold greater than AUC in humans at the MRHD of 20 mg.

    Clinical Studies

    Levitra was evaluated in four major double-blind, randomized, placebo-controlled, fixed-dose, parallel design, multicenter trials in 2431 men aged 20-83 (mean age 57 years; 78% White, 7% Black, 2% Asian, 3% Hispanic and 10% Other/Unknown). The doses of Levitra in these studies were 5 mg, 10 mg, and 20 mg. Two of these trials were conducted in the general erectile dysfunction (ED) population and two in special ED populations (one in patients with diabetes mellitus and one in post-prostatectomy patients). Levitra was dosed without regard to meals on an as needed basis in men with ED, many of whom had multiple other medical conditions. The primary endpoints were assessed at 3 months.

    Primary efficacy assessment in all four major trials was by means of the Erectile Function (EF) Domain score of the validated International Index of Erectile Function (IIEF) Questionnaire and two questions from the Sexual Encounter Profile (SEP) dealing with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3).

    In all four fixed-dose efficacy trials, Levitra showed clinically meaningful and statistically significant improvement in the EF Domain, SEP2, and SEP3 scores compared to placebo. The mean baseline EF Domain score in these trials was 11.8 (scores range from 0-30 where lower scores represent more severe disease). Levitra (5 mg, 10 mg, and 20 mg) was effective in all age categories (45, 45 to 65, and ≥65 years) and was also effective regardless of race (White, Black, Other).

    Trials in a General Erectile Dysfunction Population

    In the major North American fixed-dose trial, 762 patients (mean age 57, range 20-83 years; 79% White, 13% Black, 4% Hispanic, 2% Asian and 2% Other) were evaluated. The mean baseline EF Domain scores were 13, 13, 13, 14 for the Levitra 5 mg, 10 mg, 20 mg and placebo groups, respectively. There was significant improvement (p 0.0001) at 3 months with Levitra (EF Domain scores of 18, 21, 21, for the 5 mg, 10 mg, and 20 mg dose groups, respectively) compared to the placebo group (EF Domain score of 15). The European trial (total N=803) confirmed these results. The improvement in mean score was maintained at all doses at 6 months in the North American trial.

    In the North American trial, Levitra significantly improved the rates of achieving an erection sufficient for penetration (SEP2) at doses of 5 mg, 10 mg, and 20 mg compared to placebo (65%, 75%, and 80%, respectively, compared to a 52% response in the placebo group at 3 months; p 0.0001). The European trial confirmed these results.

    Levitra demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (51% on 5 mg, 64% on 10 mg, and 65% on 20 mg, respectively, compared to 32% on placebo; p 0.0001) at 3 months in the North American trial. The European trial showed comparable efficacy. This improvement in mean score was maintained at all doses at 6 months in the North American trial.

    Trial in Patients with ED and Diabetes Mellitus

    Levitra demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg Levitra), double-blind, placebo-controlled trial of patients with diabetes mellitus (n=439; mean age 57 years, range 33-81; 80% White, 9% Black, 8% Hispanic, and 3% Other).

    Significant improvements in the EF Domain were shown in this study (EF Domain scores of 17 on 10 mg Levitra and 19 on 20 mg Levitra compared to 13 on placebo; p 0.0001).

    Levitra significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (61% on 10 mg and 64% on 20 mg Levitra compared to 36% on placebo; p 0.0001).

    Levitra demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (49% on 10 mg, 54% on 20 mg Levitra compared to 23% on placebo; p 0.0001).

    Trial in Patients with ED after Radical Prostatectomy

    Levitra demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg Levitra), double-blind, placebo-controlled trial in post-prostatectomy patients (n=427, mean age 60, range 44-77 years; 93% White, 5% Black, 2% Other).

    Significant improvements in the EF Domain were shown in this study (EF Domain scores of 15 on 10 mg Levitra and 15 on 20 mg Levitra compared to 9 on placebo; p 0.0001).

    Levitra significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (47% on 10 mg and 48% on 20 mg Levitra compared to 22% on placebo; p 0.0001).

    Levitra demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (37% on 10 mg, 34% on 20 mg Levitra compared to 10% on placebo; p 0.0001).

    How Supplied/Storage and Handling

    Levitra (vardenafil HCl) is formulated as orange, film-coated round tablets with debossed “BAYER” cross on one side and “2.5”, “5”, “10”, and “20” on the other side equivalent to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively.

    Package

    Strength

    NDC Code

    Bottles of 30

    2.5 mg

    0173-0828-13

    5 mg

    0173-0829-13

    10 mg

    0173-0830-13

    20 mg

    0173-0831-13

    Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

    Patient Counseling Information

    “See FDA-approved Patient Labeling (Patient Information)”

    Nitrates

    Physicians should discuss with patients the contraindication of Levitra with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of Levitra with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.

    Cardiovascular

    Physicians should discuss with patients the potential cardiac risk of sexual activity for patients with preexisting cardiovascular risk factors.

    Concomitant Use with Drugs which Lower Blood Pressure

    Physicians should inform their patients that in some patients concomitant use of PDE5 inhibitors, including Levitra, with alpha-blockers can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting). Patients prescribed Levitra who are taking alpha-blockers should be started on the lowest recommended starting dose of Levitra [see Dosage and Administration (2.4) and Drug Interactions (7)]. Patients should be advised of the possible occurrence of symptoms related to postural hypotension and appropriate countermeasures. Patients should be advised to contact the prescribing physician if other anti-hypertensive drugs or new medications that may interact with Levitra are prescribed by another healthcare provider.

    Recommended Administration

    Physicians should discuss with patients the appropriate use of Levitra and its anticipated benefits. It should be explained that sexual stimulation is required for an erection to occur after taking Levitra. Levitra should be taken approximately 60 minutes before sexual activity. Patients should be counseled regarding the dosing of Levitra especially regarding the maximum daily dose. Patients should be advised to contact their healthcare provider for dose modification if they are not satisfied with the quality of their sexual performance with Levitra or in the case of an unwanted effect.

    Priapism

    Physicians should inform patients that there have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for Levitra and this class of compounds. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

    Drug Interactions

    Patients should be advised to contact the prescribing physician if new medications that may interact with Levitra are prescribed by another healthcare provider.

    Vision

    Physicians should advise patients to stop use of all PDE5 inhibitors, including Levitra, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. It is not possible to determine whether these events were related directly to the use of PDE5 inhibitors or to other factors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators such as PDE5 inhibitors [see Adverse Reactions (6.1)].

    Sudden Hearing Loss

    Physicians should advise patients to stop taking PDE5 inhibitors, including Levitra, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including Levitra. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6)].

    Sexually Transmitted Disease

    The use of Levitra offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered.

    Dose Adjustment

    Inform patients that the recommended starting dose of Levitra is 10 mg. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and tolerability. The maximum recommended dosing frequency is one tablet per day.

    FDA-approved patient labeling

    Levitra® (Luh-VEE-Trah)

    (vardenafilHCl) Tablets

    Read the Patient Information about Levitra before you start taking it and again each time you get a refill. There may be new information. You may also find it helpful to share this information with your partner. This leaflet does not take the place of talking with your doctor. You and your doctor should talk about Levitra when you start taking it and at regular checkups. If you do not understand the information, or have questions, talk with your doctor or pharmacist.

    WHAT IMPORTANT INFORMATION SHOULD YOU KNOW ABOUT Levitra?

    Levitra can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. With a sudden drop in blood pressure, you could get dizzy, faint, or have a heart attack or stroke.

    Do not take Levitra if you:

    Take any medicines called “nitrates” (often used to control chest pain, also known as angina).
    Use recreational drugs called “poppers” like amyl nitrate and butyl nitrate.
    (See “Who Should Not Take Levitra?”)

    Tell all your healthcare providers that you take Levitra. If you need emergency medical care for a heart problem, it will be important for your healthcare provider to know when you last took Levitra.

    WHAT IS Levitra?

    Levitra is a prescription medicine taken by mouth for the treatment of erectile dysfunction (ED) in men.

    ED is a condition where the penis does not harden and expand when a man is sexually excited, or when he cannot keep an erection. A man who has trouble getting or keeping an erection should see his doctor for help if the condition bothers him. Levitra may help a man with ED get and keep an erection when he is sexually excited.

    Levitra does not:

    Cure ED
    Increase a man’s sexual desire
    Protect a man or his partner from sexually transmitted diseases, including HIV. Speak to your doctor about ways to guard against sexually transmitted diseases.
    Serve as a male form of birth control.

    Levitra is only for men with ED. Levitra is not for women or children. Levitra must be used only under a doctor’s care.

    HOW DOES Levitra WORK?

    When a man is sexually stimulated, his body’s normal physical response is to increase blood flow to his penis. This results in an erection. Levitra helps increase blood flow to the penis and may help men with ED get and keep an erection satisfactory for sexual activity. Once a man has completed sexual activity, blood flow to his penis decreases, and his erection goes away.

    WHO CAN TAKE Levitra?

    Talk to your doctor to decide if Levitra is right for you.

    Levitra has been shown to be effective in men over the age of 18 years who have erectile dysfunction, including men with diabetes or who have undergone prostatectomy.

    WHO SHOULD NOT TAKE Levitra?

    Do not take Levitra if you:

    Take any medicines called “nitrates” (See “What important information should you know about Levitra?”). Nitrates are commonly used to treat angina. Angina is a symptom of heart disease and can cause pain in your chest, jaw, or down your arm.
    Medicines called nitrates include nitroglycerin that is found in tablets, sprays, ointments, pastes, or patches. Nitrates can also be found in other medicines such as isosorbide dinitrate or isosorbide mononitrate. Some recreational drugs called “poppers” also contain nitrates, such as amyl nitrate and butyl nitrate. Do not use Levitra if you are using these drugs. Ask your doctor or pharmacist if you are not sure if any of your medicines are nitrates.
    Have been told by your healthcare provider to not have sexual activity because of health problems. Sexual activity can put an extra strain on your heart, especially if your heart is already weak from a heart attack or heart disease.

    WHAT SHOULD YOU DISCUSS WITH YOUR DOCTOR BEFORE TAKING Levitra?

    Before taking Levitra, tell your doctor about all your medical problems, including if you:

    1.
    Have heart problems such as angina, heart failure, irregular heartbeats, or have had a heart attack. Ask your doctor if it is safe for you to have sexual activity.
    2.
    Have low blood pressure or have high blood pressure that is not controlled.
    3.
    Have had a stroke.
    4.
    Have had a seizure.
    5.
    Or any family members have a rare heart condition known as prolongation of the QT interval (long QT syndrome).
    6.
    Have liver problems.
    7.
    Have kidney problems and require dialysis.
    8.
    Have retinitis pigmentosa, a rare genetic (runs in families) eye disease
    9.
    Have ever had severe vision loss, or if you have an eye condition called non-arteritic anterior ischemic optic neuropathy (NAION).
    10.
    Have stomach ulcers.
    11.
    Have a bleeding problem.
    12.
    Have a deformed penis shape or Peyronie’s disease.
    13.
    Have had an erection that lasted more than 4 hours.
    14.
    Have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia.
    15.
    Have hearing problems.

    CAN OTHER MEDICATIONS AFFECT Levitra?

    Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Levitra and other medicines may affect each other. Always check with your doctor before starting or stopping any medicines. Especially tell your doctor if you take any of the following:

    Medicines called nitrates (see “What important information should you know about Levitra?”).
    Ketoconazole or itraconazole (such as Nizoral® or Sporanox®).
    Ritonavir (Norvir®) or indinavir sulfate (Crixivan®) saquinavir (Fortavase® or Invirase®) or atazanavir (Reyataz®).
    Erythromycin or clarithromycin.
    Medicines called alpha-blockers. These include Hytrin® (terazosin HCl), Flomax® (tamsulosin HCl), Cardura® (doxazosin mesylate), Minipress® (prazosin HCl) or Uroxatral® (alfuzosin HCl). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients the use of PDE5 inhibitor drugs, including Levitra, with alpha-blockers can lower blood pressure significantly leading to fainting. You should contact the prescribing physician if alpha-blockers or other drugs that lower blood pressure are prescribed by another healthcare provider.
    Medicines that treat abnormal heartbeat. These include quinidine, procainamide, amiodarone and sotalol.
    Other medicines or treatments for ED.

    HOW SHOULD YOU TAKE Levitra

    Take Levitra exactly as your doctor prescribes. Do not take more than one Levitra a day. Doses should be taken at least 24 hours apart. Some men can only take a low dose of Levitra because of medical conditions or medicines they take. Your doctor will prescribe the dose that is right for you.

    If you are older than 65 or have liver problems, your doctor may start you on a lower dose of Levitra.
    If you have prostate problems or high blood pressure, for which you take medicines called alpha-blockers, your doctor may start you on a lower dose of Levitra.
    If you are taking certain other medicines your doctor may prescribe a lower starting dose and limit you to one dose of Levitra in a 72-hour (3 days) period.

    Take 1 Levitra tablet about 1 hour (60 minutes) before sexual activity. Some form of sexual stimulation is needed for an erection to happen with Levitra. Levitra may be taken with or without meals.

    Do not change your dose of Levitra without talking to your doctor. Your doctor may lower your dose or raise your dose, depending on how your body reacts to Levitra.

    Call your doctor or emergency room immediately if you accidentally took more Levitra than prescribed.

    WHAT ARE THE POSSIBLE SIDE EFFECTS OF Levitra?

    The most common side effects with Levitra are headache, flushing, stuffy or runny nose, indigestion, upset stomach, dizziness or back pain. These side effects usually go away after a few hours. Call your doctor if you get a side effect that bothers you or one that will not go away.

    Levitra may uncommonly cause:

    An erection that won’t go away (priapism). If you get an erection that lasts more than 4 hours, get medical help right away. Priapism must be treated as soon as possible or lasting damage can happen to your penis including the inability to have erections.
    Color vision changes, such as seeing a blue tinge to objects or having difficulty telling the difference between the colors blue and green.

    In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including Levitra) reported a sudden decrease or loss of vision in one or both eyes. It is not possible to determine whether these events are related directly to these medicines, to other factors such as high blood pressure or diabetes, or to a combination of these. If you experience sudden decrease or loss of vision, stop taking PDE5 inhibitors, including Levitra, and call a doctor right away.

    Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including Levitra. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking Levitra and contact a doctor right away.

    These are not all the side effects of Levitra. For more information, ask your doctor or pharmacist.

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

    HOW SHOULD Levitra BE STORED?

    Store Levitra at room temperature between 59–86° F (15–30° C).
    Keep Levitra and all medicines out of the reach of children.

    GENERAL INFORMATION ABOUT Levitra

    Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use Levitra for a condition for which it was not prescribed. Do not give Levitra to other people, even if they have the same symptoms that you have. It may harm them.

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

    For more information you can also visit www.Levitra.com, or call 1-866-Levitra.

    WHAT ARE THE INGREDIENTS OF Levitra?

    Active Ingredient: vardenafil hydrochloride

    Inactive Ingredients: microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide, yellow ferric oxide, and red ferric oxide.

    This Patient Information has been approved by the U.S. Food and Drug Administration.

    Products cited in Levitra USPI

    Norvir (ritonavir) is a trademark of Abbott Laboratories

    Crixivan (indinavir sulfate) is a trademark of Merck Co., Inc.

    Invirase or Fortavase (saquinavir mesylate) is a trademark of Roche Laboratories Inc.

    Reyataz (atazanavir sulfate) is a trademark of Bristol-Myers Squibb Company

    Nizoral (ketoconazole) is a trademark of Johnson Johnson

    Sporanox (itraconazole) is a trademark of Johnson Johnson

    Hytrin (terazosin HCl) is a trademark of Abbott Laboratories

    Flomax (tamsulosin HCl) is a trademark of Yamanouchi Pharmaceutical Co., Ltd.

    Cardura (doxazosin mesylate) is a trademark of Pfizer Inc.

    Minipress (prazosin HCl) is a trademark of Pfizer Inc.

    Uroxatral (alfuzosin HCl) is a trademark of Sanofi-Synthelabo

    Manufactured for:

    Bayer HealthCare Pharmaceuticals Inc.

    Wayne, NJ 07470

    Manufactured in Germany

    Distributed by:

    GlaxoSmithKline

    Research Triangle Park

    NC 27709

    Levitra is a registered trademark of Bayer Aktiengesellschaft and is used under license by GlaxoSmithKline.

    Rx Only

    ©2011 Bayer HealthCare Pharmaceuticals Inc. Printed in U.S.A.

    Revision Date: 11/2011

    PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    Levitra 2.5 mg Label

    83491109       NDC 0173-0828-13

    Levitra®

    (VARDENAFIL HCI) TABLETS

    Equivalent to

    2.5 mg vardenafil

    Rx only 30 Tablets

    PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    Levitra 5 mg Label

    83491117      NDC 0173-0829-13

    Levitra®

    (VARDENAFIL HCI) TABLETS

    Equivalent to

    5 mg vardenafil

    Rx only 30 Tablets

    PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    Levitra 10 mg Label

    83491125 NDC 0173-0830-13

    Levitra®

    (VARDENAFIL HCI) TABLETS

    Equivalent to

    10 mg vardenafil

    Rx only 30 Tablets

    PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

    Levitra 20 mg Label

    83491133       NDC 0173-0831-13

    Levitra®

    (VARDENAFIL HCI) TABLETS

    Equivalent to

    20 mg vardenafil

    Rx only 30 Tablets

    Levitra 

    vardenafil hydrochloride tablet, film coated

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0828
    Route of Administration ORAL DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VARDENAFIL HYDROCHLORIDE TRIHYDRATE (VARDENAFIL) VARDENAFIL 2.5 mg
    Inactive Ingredients
    Ingredient Name Strength
    CELLULOSE, MICROCRYSTALLINE  
    CROSPOVIDONE  
    SILICON DIOXIDE  
    MAGNESIUM STEARATE  
    HYPROMELLOSES  
    POLYETHYLENE GLYCOLS  
    TITANIUM DIOXIDE  
    FERRIC OXIDE YELLOW  
    FERRIC OXIDE RED  
    Product Characteristics
    Color ORANGE Score no score
    Shape ROUND Size 6mm
    Flavor Imprint Code BAYER;2;5
    Contains         
    Packaging
    # Item Code Package Description
    1 NDC:0173-0828-13 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021400 08/25/2003
    Levitra 

    vardenafil hydrochloride tablet, film coated

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0829
    Route of Administration ORAL DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VARDENAFIL HYDROCHLORIDE TRIHYDRATE (VARDENAFIL) VARDENAFIL 5 mg
    Inactive Ingredients
    Ingredient Name Strength
    CELLULOSE, MICROCRYSTALLINE  
    CROSPOVIDONE  
    SILICON DIOXIDE  
    MAGNESIUM STEARATE  
    HYPROMELLOSES  
    POLYETHYLENE GLYCOLS  
    TITANIUM DIOXIDE  
    FERRIC OXIDE YELLOW  
    FERRIC OXIDE RED  
    Product Characteristics
    Color ORANGE Score no score
    Shape ROUND Size 6mm
    Flavor Imprint Code BAYER;5
    Contains         
    Packaging
    # Item Code Package Description
    1 NDC:0173-0829-13 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021400 04/23/2003
    Levitra 

    vardenafil hydrochloride tablet, film coated

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0830
    Route of Administration ORAL DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VARDENAFIL HYDROCHLORIDE TRIHYDRATE (VARDENAFIL) VARDENAFIL 10 mg
    Inactive Ingredients
    Ingredient Name Strength
    CELLULOSE, MICROCRYSTALLINE  
    CROSPOVIDONE  
    SILICON DIOXIDE  
    MAGNESIUM STEARATE  
    HYPROMELLOSES  
    POLYETHYLENE GLYCOLS  
    TITANIUM DIOXIDE  
    FERRIC OXIDE YELLOW  
    FERRIC OXIDE RED  
    Product Characteristics
    Color ORANGE Score no score
    Shape ROUND Size 7mm
    Flavor Imprint Code BAYER;10
    Contains         
    Packaging
    # Item Code Package Description
    1 NDC:0173-0830-13 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
    2 NDC:0173-0830-61 1 BLISTER PACK in 1 CARTON
    2 2 TABLET, FILM COATED in 1 BLISTER PACK
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021400 08/25/2003
    Levitra 

    vardenafil hydrochloride tablet, film coated

    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0831
    Route of Administration ORAL DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VARDENAFIL HYDROCHLORIDE TRIHYDRATE (VARDENAFIL) VARDENAFIL 20 mg
    Inactive Ingredients
    Ingredient Name Strength
    CELLULOSE, MICROCRYSTALLINE  
    CROSPOVIDONE  
    SILICON DIOXIDE  
    MAGNESIUM STEARATE  
    HYPROMELLOSES  
    POLYETHYLENE GLYCOLS  
    TITANIUM DIOXIDE  
    FERRIC OXIDE YELLOW  
    FERRIC OXIDE RED  
    Product Characteristics
    Color ORANGE Score no score
    Shape ROUND Size 8mm
    Flavor Imprint Code BAYER;20
    Contains         
    Packaging
    # Item Code Package Description
    1 NDC:0173-0831-13 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
    2 NDC:0173-0831-61 1 BLISTER PACK in 1 CARTON
    2 2 TABLET, FILM COATED in 1 BLISTER PACK
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    NDA NDA021400 08/25/2003
    Labeler - GlaxoSmithKline LLC (167380711)
    Registrant - Bayer HealthCare Pharmaceuticals Inc. (005436809)
    Establishment
    Name Address ID/FEI Operations
    Bayer Pharma AG 341081414 MANUFACTURE(0173-0828, 0173-0829, 0173-0830, 0173-0831)

    Revised: 07/2012   GlaxoSmithKline LLC

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    Levitra

    Levitra

    Pronunciation Generic Name: vardenafil (var-DEN-a-fil)

    Brand Name: Levitra

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    Levitra is used for:

    Treating erectile dysfunction (ED). It may also be used for other conditions as determined by your doctor.

    Levitra is a phosphodiesterase type 5 (PDE5) inhibitor. It works by helping to increase blood flow into the penis during sexual stimulation. This helps you to achieve and maintain an erection.

    Do NOT use Levitra if:

    • you are allergic to any ingredient in Levitra
    • you have been advised by your doctor to avoid sexual activity because of heart problems
    • you have certain heart problems (eg, severe heart failure, angina), low or high blood pressure, severe liver problems or severe kidney problems that require dialysis
    • you have certain hereditary degenerative eye problems (eg, retinitis pigmentosa)
    • you have had a heart attack, stroke, or life-threatening irregular heartbeat within the past 6 months
    • you have a history of a certain type of irregular heartbeat (eg, congenital QT prolongation) or you take certain antiarrhythmic medicines (eg, quinidine, procainamide, amiodarone, sotalol)
    • you are taking a nitrate (eg, isosorbide, nitroglycerin) in any form (eg, capsule, ointment, patch, tablet), or nitroprusside
    • you use certain recreational drugs called “poppers” (eg, amyl nitrate or nitrite, butyl nitrate or nitrite)
    • you take another PDE5 inhibitor (eg, sildenafil, tadalafil) or another medicine that contains vardenafil

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

    Before using Levitra:

    Some medical conditions may interact with Levitra. 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 deformed penis (eg, cavernosal fibrosis, Peyronie disease), blood cell problems (eg, leukemia, multiple myeloma, sickle cell anemia), or any other condition that may increase the risk of a prolonged erection (priapism)
    • if you have a history of a prolonged (more than 4 hours) or painful erection (priapism)
    • if you have a history of certain eye problems (eg, macular degeneration, optic neuropathy, retinitis pigmentosa, sudden vision loss) or hearing problems (eg, ringing in the ears, decreased hearing, hearing loss)
    • if you have a history of liver or kidney problems, dialysis, high or low blood pressure, ulcers, seizures, lung problems (eg, pulmonary veno-occlusive disease), bleeding problems, blood vessel problems, or heart problems (eg, angina, aortic stenosis, heart failure)
    • if you have a history of heart attack, stroke, a certain type of irregular heartbeat (long QT syndrome), or a family history of long QT syndrome

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

    • Alpha-blockers (eg, doxazosin), medicines for high blood pressure, nitrates (eg, isosorbide, nitroglycerin), or nitroprusside because severe low blood pressure with dizziness, lightheadedness, and fainting may occur
    • Certain antiarrhythmics (eg, amiodarone, procainamide, quinidine, sotalol) because the risk of irregular heartbeat may be increased
    • Azole antifungals (eg, itraconazole), HIV protease inhibitors (eg, indinavir, ritonavir), macrolide antibiotics (eg, erythromycin), or telithromycin because they may increase the risk of Levitra’s side effects
    • Rifampin because it may decrease Levitra’s effectiveness

    This may not be a complete list of all interactions that may occur. Ask your health care provider if Levitra 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 Levitra:

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

    • An extra patient leaflet is available with Levitra. Talk to your pharmacist if you have questions about this information.
    • Take Levitra by mouth with or without food.
    • Take Levitra about 1 hour before sexual activity.
    • Do not take Levitra more often than once daily, or as directed by your doctor.
    • Check with your doctor before you eat grapefruit or drink grapefruit juice while you use Levitra.
    • If you miss a dose of Levitra and you still intend to engage in sexual activity, take it as soon as you remember. Continue to take it as directed by your doctor.

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

    Important safety information:

    • Levitra may cause dizziness, drowsiness, fainting, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Levitra with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
    • Levitra may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.
    • Patients with heart problems who take Levitra may be at increased risk for heart-related side effects, including heart attack or stroke. Symptoms of a heart attack may include chest, shoulder, neck, or jaw pain; numbness of an arm or leg; severe dizziness, headache, nausea, stomach pain, or vomiting; fainting; or vision changes. Symptoms of a stroke may include confusion; vision or speech changes; one-sided weakness; or fainting. Contact your doctor or seek medical attention right away if you experience these symptoms.
    • Levitra may rarely cause a prolonged (more than 4 hours) or painful erection. This could happen even when you are not having sex. If this is not treated right away, it could lead to permanent sexual problems such as impotence. Contact your doctor right away if this happens.
    • Levitra does not stop the spread of HIV or other sexually transmitted diseases (STDs) to others through sexual contact. Use barrier methods of birth control (eg, condoms) if you have HIV infection or an STD.
    • Levitra will not prevent pregnancy. If your partner may become pregnant and you wish to avoid pregnancy, be sure to use an effective form of birth control.
    • Levitra may uncommonly cause mild, temporary vision changes (eg, blurred vision, sensitivity to light, blue/green color tint to vision). Contact your doctor if vision changes persist or are severe.
    • Rarely, an eye problem called nonarteritic anterior ischemic optic neuropathy (NAION) has been reported in patients who took Levitra. This may lead to decreased vision or permanent loss of vision in some cases. If you notice a sudden decrease in vision or loss of vision in one or both eyes, contact your doctor right away.
    • Sudden decreases in hearing and loss of hearing have been reported in some patients who have taken Levitra. Sometimes they also noticed ringing in the ears or dizziness. If you notice a sudden decrease or loss of hearing, contact your doctor right away.
    • Do not use other medicines or treatments for ED while you are taking Levitra without first checking with your doctor.
    • Use Levitra with caution in the ELDERLY; they may be more sensitive to its effects.
    • Levitra is not recommended for use in CHILDREN; safety and effectiveness in children have not been confirmed.
    • PREGNANCY and BREAST-FEEDING: Levitra is not approved for use in women. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Levitra while you are pregnant. It is not known if Levitra is found in breast milk. If you are or will be breast-feeding while you use Levitra, check with your doctor. Discuss any possible risks to your baby.

    Possible side effects of Levitra:

    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:

    Dizziness; flushing; headache; heartburn; nausea; stuffy or runny nose; upset stomach.

    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); chest pain; fainting; fast, slow, or irregular heartbeat; memory loss; numbness of an arm or leg; prolonged, painful erection; ringing in the ears; seizures; severe back or muscle pain; severe or persistent dizziness; severe or persistent vision changes; sudden decrease or loss of hearing; sudden decrease or loss of vision in one or both eyes; sudden, severe headache or vomiting.

    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 chest pain; fainting; prolonged erection; severe back or muscle pain; severe dizziness; severe or persistent vision changes.

    Proper storage of Levitra: Store Levitra at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Levitra out of the reach of children and away from pets.

    General information:

    • If you have any questions about Levitra, please talk with your doctor, pharmacist, or other health care provider.
    • Levitra 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 should not be used to decide whether or not to take Levitra or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Levitra. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Levitra. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your healthcare provider for complete information about the risks and benefits of using Levitra.

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

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    Levitra

    Levitra

    Pronunciation Generic Name: vardenafil (Oral route)

    var-DEN-a-fil

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    Commonly used brand name(s)

    In the U.S.

    • Levitra
    • Staxyn

    Available Dosage Forms:

    • Tablet
    • Tablet, Disintegrating

    Therapeutic Class: Erectile Dysfunction Agent

    Pharmacologic Class: Phosphodiesterase Type 5 Inhibitor

    Uses For Levitra

    Vardenafil is used to treat men who have erectile dysfunction (also called sexual impotence). Vardenafil belongs to a group of medicines called phosphodiesterase 5 (PDE5) inhibitors. These medicines prevent an enzyme called phosphodiesterase type-5 from working too quickly. The penis is one of the areas where this enzyme works.

    Erectile dysfunction is a condition where the penis does not harden and expand when a man is sexually excited, or when he cannot keep an erection. When a man is sexually stimulated, his body’s normal response is to increase blood flow to his penis to produce an erection. By controlling the enzyme, vardenafil helps to maintain an erection after the penis is stroked by increasing blood flow to the penis. Without physical action to the penis, such as that occurring during sexual intercourse, vardenafil will not work to cause an erection.

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

    Before Using Levitra

    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

    Vardenafil is not indicated for use in children. Safety and efficacy have not been established.

    Geriatric

    Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of vardenafil in the elderly.

    Pregnancy

    Pregnancy Category Explanation
    All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

    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. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

    Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

    • Cisapride
    • Dronedarone
    • Erythrityl Tetranitrate
    • Fluconazole
    • Isosorbide Dinitrate
    • Isosorbide Mononitrate
    • Mesoridazine
    • Nitroglycerin
    • Pentaerythritol Tetranitrate
    • Pimozide
    • Posaconazole
    • Sparfloxacin
    • Thioridazine

    Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

    • Acecainide
    • Amiodarone
    • Amitriptyline
    • Amoxapine
    • Apomorphine
    • Arsenic Trioxide
    • Asenapine
    • Astemizole
    • Azimilide
    • Azithromycin
    • Boceprevir
    • Bretylium
    • Chloroquine
    • Chlorpromazine
    • Ciprofloxacin
    • Citalopram
    • Clomipramine
    • Clozapine
    • Cobicistat
    • Crizotinib
    • Dasatinib
    • Desipramine
    • Disopyramide
    • Dofetilide
    • Dolasetron
    • Domperidone
    • Fingolimod
    • Flecainide
    • Gatifloxacin
    • Granisetron
    • Halofantrine
    • Haloperidol
    • Ibutilide
    • Iloperidone
    • Imipramine
    • Lapatinib
    • Levofloxacin
    • Lopinavir
    • Lumefantrine
    • Mefloquine
    • Methadone
    • Mifepristone
    • Moricizine
    • Moxifloxacin
    • Nilotinib
    • Norfloxacin
    • Nortriptyline
    • Octreotide
    • Ofloxacin
    • Ondansetron
    • Paliperidone
    • Pazopanib
    • Perflutren Lipid Microsphere
    • Procainamide
    • Prochlorperazine
    • Promethazine
    • Propafenone
    • Protriptyline
    • Quetiapine
    • Quinidine
    • Quinine
    • Ranolazine
    • Salmeterol
    • Saquinavir
    • Sematilide
    • Sodium Phosphate
    • Sodium Phosphate, Dibasic
    • Sodium Phosphate, Monobasic
    • Solifenacin
    • Sorafenib
    • Sotalol
    • Sunitinib
    • Tedisamil
    • Telaprevir
    • Telithromycin
    • Terfenadine
    • Tetrabenazine
    • Toremifene
    • Trazodone
    • Trifluoperazine
    • Trimipramine
    • Vandetanib
    • Vemurafenib
    • Voriconazole
    • Ziprasidone

    Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

    • Alfuzosin
    • Amprenavir
    • Bunazosin
    • Doxazosin
    • Indinavir
    • Itraconazole
    • Phenoxybenzamine
    • Phentolamine
    • Prazosin
    • Tamsulosin
    • Terazosin
    • Trimazosin
    • Urapidil

    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:

    • Abnormal penis, including curved penis and birth defects of the penis—Chance of problems occurring may be increased and this medicine should be used with caution in these patients.
    • Age greater than 50 years or
    • Coronary artery disease or
    • Diabetes or
    • Hyperlipidemia (excess of lipids in the blood) or
    • Hypertension (high blood pressure) or
    • Low cup to disc ratio (eye condition also called “crowded disc”) or
    • Smoking—These conditions may increase risk for a serious eye problem called non-arteritic ischemic optic neuropathy or NAION.
    • Angina (reoccurring chest pain) or
    • Arrhythmia (irregular heartbeat) or
    • Heart attack (within the last 6 months) or
    • Heart failure, severe or
    • Hypertension (high blood pressure), uncontrolled or
    • Hypotension (low blood pressure) or
    • Kidney disease, severe or
    • Liver disease, severe or
    • Retinal disorders (eye problem) or
    • Retinitis pigmentosa (an inherited eye disorder) or
    • Stroke, recent history of—Should not be used in patients with these conditions.
    • Bleeding disorders or
    • Stomach ulcers—Chance of problems occurring may be increased; it is not known if the medicine is safe for use in these patients.
    • Bone marrow cancer or
    • Leukemia (blood related cancer) or
    • Multiple myeloma (blood related cancer) or
    • Sickle-cell anemia (blood disorder)—Vardenafil should be used with caution in these patients as problems with prolonged erection of the penis may occur.
    • Fructose intolerance—The orally disintegrating tablet contains sorbitol, which can make this condition worse.
    • Heart blood flow problems—These conditions may cause you to be more sensitive to vardenafil.
    • Heart disease, underlying—Chance of low blood pressure occurring is greater; vardenafil should be used carefully in these patients.
    • Kidney disease or
    • Liver disease—Chance of problems occurring may be increased. Lower starting doses may be used and doses increased as needed and as tolerated.
    • NAION (serious eye condition) in one or both eyes, history of—May increase your chance of getting NAION again.
    • Phenylketonuria (PKU)—The orally disintegrating tablet contains phenylalanine, which can make this condition worse.
    • QT prolongation (rare heart condition), or history of—Use with caution. May make this condition worse.

    Proper Use of vardenafil

    This section provides information on the proper use of a number of products that contain vardenafil. It may not be specific to Levitra. Please read with care.

    Use vardenafil exactly as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. If too much is used, the chance of side effects or other problems is increased.

    Special patient instructions come with vardenafil. Read the directions carefully before you start using vardenafil and each time you get a refill of your medicine.

    You may take this medicine with or without food.

    This medicine usually begins to work within 60 minutes after taking it. It continues to work for up to 4 hours. Stimulation is required for an erection. If you have any questions about the use and benefits of vardenafil ask your doctor.

    If you are using the disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Place the tablet on your tongue. It should melt quickly. The tablet should be taken without liquids. Do not break, crush, or chew 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 treatment of erectile dysfunction (as needed):
      • For oral dosage form (disintegrating tablets):
        • Adults—10 milligrams (mg) as a single dose, no more than once a day, taken 1 hour before you think sexual activity may occur.
        • Children—Use is not recommended.
      • For oral dosage form (tablets):
        • Adults 65 years of age and older—5 milligrams (mg) as a single dose no more than once a day, 1 hour before sexual intercourse. Your doctor may change your dose if needed.
        • Adults up to 65 years of age—10 mg as a single dose no more than once a day, 1 hour before sexual activity. Your doctor may change your dose if needed.
        • Children—Use is not recommended.

    Storage

    Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

    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.

    Precautions While Using Levitra

    It is important that you tell all of your doctors that you take vardenafil. If you need emergency medical care for a heart problem, it is important that your doctor knows when you last took vardenafil.

    Levitra® also contains vardenafil. If you take too much vardenafil or take it together with these medicines, the chance for side effects will be higher.

    If you experience a prolonged or painful erection for 4 hours or more, contact your doctor immediately. This condition may require prompt medical treatment to prevent serious and permanent damage to your penis.

    This medicine does not protect you against sexually transmitted diseases. Use protective measures and ask your doctor if you have any questions about this.

    It is important to tell your doctor about any heart problems you may have now or may have had in the past. This medicine can cause serious side effects in patients with heart problems.

    Do not use this medicine if you are also using a nitrate medicine, often used to treat angina (chest pain). Nitrate medicines include nitroglycerin, isosorbide, Imdur®, Nitro-Bid®, Nitrostat®, Nitro-Dur®, Transderm Nitro®, Nitrol® Ointment, and Nitrolingual® Spray. Some illegal (“street”) drugs called “poppers” (such as amyl nitrate, butyl nitrate, or nitrite) also contain nitrates.

    Do not drink excessive amounts of alcohol (e.g., 5 glasses of wine or 5 shots of whiskey) when taking vardenafil. When taken in excess, alcohol can increase your chances of getting a headache or getting dizzy, increase your heart rate, or lower your blood pressure.

    If you have sudden loss of vision in one or both eyes, stop using vardenafil and contact your doctor right away.

    Stop using this medicine and check with your doctor right away if you have sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears.

    Do not eat grapefruit or drink grapefruit juice while you are using 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.

    Levitra 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:

    Less common

    • Arm, back, or jaw pain
    • blindness
    • blurred vision
    • chest pain or discomfort
    • chest tightness or heaviness
    • chills
    • cold sweats
    • confusion
    • decreased vision
    • difficult or labored breathing
    • difficulty with swallowing
    • dizziness
    • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
    • eye pain
    • fainting
    • fast, irregular, pounding, or racing heartbeat or pulse
    • headache
    • hives
    • itching
    • nausea
    • nervousness
    • pain or discomfort in the arms, jaw, back, or neck
    • pounding in the ears
    • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
    • shortness of breath
    • skin rash
    • slow or fast heartbeat
    • sweating
    • tearing
    • tightness in the chest
    • unusual tiredness or weakness
    • vomiting
    • wheezing

    Incidence not known

    • Hearing loss

    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

    • Feeling of warmth and redness of the face, neck, arms, and occasionally, upper chest
    • sneezing
    • stuffy nose

    Less common

    • Abnormal ejaculation
    • abdominal or stomach pain
    • abnormal vision
    • acid or sour stomach
    • back pain
    • belching
    • bloody nose
    • body aches or pain
    • burning feeling in the chest or stomach
    • burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
    • changes in color vision
    • changes in vision
    • congestion
    • cough
    • diarrhea
    • difficulty seeing at night
    • difficulty with moving
    • difficulty with swallowing
    • dim vision
    • dry mouth
    • dryness or soreness of the throat
    • excessive muscle tone
    • eye pain
    • face swelling
    • fast heartbeat
    • feeling of constant movement of self or surroundings
    • fever
    • general feeling of discomfort or illness
    • heartburn
    • hoarseness
    • increased redness of the eye
    • increased sensitivity of the eyes to sunlight
    • indigestion
    • itching skin
    • joint pain
    • lack or loss of strength
    • loss of appetite
    • muscle aches and pains
    • muscle cramping
    • muscle stiffness
    • muscle tension or tightness
    • neck pain
    • pain
    • pain or burning in the throat
    • runny nose
    • sensation of spinning
    • shivering
    • sleepiness or unusual drowsiness
    • sleeplessness
    • sore throat
    • sores, ulcers, or white spots on the lips or tongue or inside the mouth
    • stomach discomfort, upset, or pain
    • swollen joints
    • tender, swollen glands in the neck
    • tenderness in the stomach area
    • trouble with sleeping
    • trouble with swallowing
    • unable to sleep
    • voice changes
    • watery eyes

    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: Levitra side effects (in more detail)

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    Levitra

    Levitra

    Pronunciation Generic Name: Vardenafil Hydrochloride
    Class: Phosphodiesterase Type 5 Inhibitors

    VA Class: GU900

    Chemical Name: 1 – [[3 - (3,4 - Dihydro - 5 - methyl - 4 - oxo - 7 - propylimidazo[5,1 - f] – as – triazin – 2 – yl) – 4 – ethoxyphenyl]sulfonyl] – 4 – ethylpiperazine

    Molecular Formula: C23H32N6O4S

    CAS Number: 224785-90-4

    For ProfessionalsSide EffectsDosageInteractionsMore…

    Warning(s)

    Special Alerts:

    [Posted 10/18/2007] FDA informed healthcare professionals of reports of sudden decreases or loss of hearing following the use of PDE5 inhibitors sildenafil (Viagra), tadalafil (Levitra), vardenafil (Cialis) for the treatment of erectile dysfunction, and sildenafil (Revatio) for the treatment of pulmonary arterial hypertension. In some cases, the sudden hearing loss was accompanied by tinnitus and dizziness. Medical follow-up on these reports was often limited which makes it difficult to determine if the loss of hearing was related to the use of one of the drugs, an underlying medical condition or other risk factors for hearing loss, a combination of these factors or other factors. The PRECAUTIONS and ADVERSE REACTIONS sections of the approved product labeling for sildenafil (Viagra), tadalafil, and vardenafil were revised. FDA is working with the manufacturer to revise the labeling for sildenafil (Revatio). For more information visit the FDA website at: , and .

    Introduction

    Vasodilating agent; a selective phosphodiesterase (PDE) inhibitor.1

    Uses for Levitra

    Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

    Erectile Dysfunction

    To facilitate attainment of a sexually functional erection in males with erectile dysfunction (ED, impotence).1

    Levitra Dosage and Administration

    General

    • Dosage must be individualized carefully according to the patient’s tolerance and erectile response.1

    • Sexual stimulation is required for response to therapy.1

    Administration

    Oral Administration

    Administer orally, no more than once daily, without regard to meals.1 3

    Administer approximately 1 hour before anticipated sexual activity.1

    Dosage

    Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

    Available as vardenafil hydrochloride; dosage expressed in terms of vardenafil.1

    Adults

    Erectile Dysfunction
    Oral

    Initially, 10 mg.1 Depending on effectiveness and tolerance, increase dosage to a maximum of 20 mg or decrease to 5 mg. Administer no more frequently than once daily.1

    Prescribing Limits

    Adults

    Erectile Dysfunction
    Oral

    Maximum 20 mg daily.1

    Special Populations

    Hepatic Impairment

    In patients with moderate hepatic impairment (Child-Pugh class B), decrease initial dosage to 5 mg; maximum dosage is 10 mg once daily.1 Not studied in patients with severe hepatic impairment (Child-Pugh class C).1

    Renal Impairment

    Dosage adjustments not required in patients with patients with mild (Clcr of 50–80 mL/minute) to severe (Clcr <30 mL/minute) renal impairment.1 Not studied in patients requiring renal dialysis.1

    Geriatric Patients

    Reduce initial dose to 5 mg given no more frequently than once daily in men ≥65 years of age.1 26

    Cautions for Levitra

    Contraindications

    • Known hypersensitivity to vardenafil or any ingredient in the formulation.1

    • Concomitant use of nitrates, nitrites, or nitric oxide donors, either regularly or intermittently, or α-adrenergic blocking agents.1 28
    • Should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.1 5

    Warnings/Precautions

    Warnings

    Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

    Cardiovascular Effects

    Serious, potentially fatal cardiovascular events reported rarely.1 5 6

    Use not recommended in patients with a recent (within 6 months) MI, stroke, or life-threatening arrhythmia; resting hypotension (<90 mm Hg resting SBP) or hypertension (170/110 mm Hg SBP/DBP); or severe heart failure or unstable angina.1 4 7 8 26

    Possible hypotension; consider whether patients with underlying cardiovascular disease could be affected adversely by vardenafil’s vasodilatory activity.1 Risk of an undesired hypotensive or vasodilatory response is of particular concern in patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis).1 6

    Potentiation of hypotensive effect with organic nitrates may result in life-threatening hypotension and/or hemodynamic compromise.1 Possible significant hypotension when given concurrently with α-adrenergic blocking agents.1 Manufacturers state that concomitant use of nitrates or α-adrenergic blocking agents with vardenafil is contraindicated.1 (See Specific Drugs under Interactions.)

    Possible prolonged QT interval.1 Use not recommended in patients with known prolongation of the QT interval and those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1

    Concomitant Use with Potent CYP3A4 Inhibitors

    Safety not established with long-term use of vardenafil concomitantly with potent CYP3A4 inhibitors (e.g., ritonavir, indinavir, ketoconazole, itraconazole).1 Increased plasma vardenafil concentrations with concomitant use; dosage reduction of vardenafil recommended.1 (See Specific Drugs under Interactions.)

    Priapism

    Possible prolonged erections (>4 hours in duration) and priapism (painful erection >6 hours).1

    May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately.1 Use with caution in patients with conditions that may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).1

    Ocular Effects

    Possible visual disturbances (e.g., abnormal, dim, or blurred vision; changes in color vision [e.g., chromatopsia]).1 4

    Not studied in patients with hereditary degenerative retinal disorders, including those with retinitis pigmentosa.1 Use not recommended until further information is available.1

    Sensitivity Reactions

    Anaphylactic reaction, including laryngeal edema, reported.1

    General Precautions

    Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

    Patient Assessment

    Thorough medical history and physical examination recommended to diagnose erectile dysfunction, determine potential underlying causes, and identify appropriate treatment.1 5

    Review of the patient’s current drug regimens recommended to detect possible drug-induced erectile dysfunction.5

    Hematologic Effects

    No prolongation of bleeding time with vardenafil dosages ≤20 mg.1

    However, not studied in patients with bleeding disorders or active peptic ulcers;1 4 8 therefore, careful risk/benefit assessment is necessary before use in such patients.1 4 8

    GU Effects

    Use with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease).1

    Specific Populations

    Pregnancy

    Category B.1 Not indicated for use in women.1

    Lactation

    Not indicated for use in women.1

    Pediatric Use

    Not indicated for use in neonates or children.1

    Geriatric Use

    Safety and efficacy in males ≥65 years of age similar to that in younger males.1 Increased plasma vardenafil concentrations in men ≥65 years of age compared to that in younger males; therefore consider lower initial dosage.1 (See Geriatric Patients under Dosage and Administration.)

    Hepatic Impairment

    Decreased clearance in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.) Not studied in patients with severe hepatic impairment (Child-Pugh class C), and use of the drug in such patients is not recommended.1 26

    Renal Impairment

    Clearance decreased in patients with moderate (Clcr 30–50 mL/minute) to severe (Clcr <30 mL/minute) renal impairment.1 (See Renal Impairment under Dosage and Administration.) Not studied in patients with end-stage renal disease requiring dialysis.1

    Common Adverse Effects

    Headache,1 2 7 8 flushing, 1 2 7 8 rhinitis,1 2 8 dyspepsia.1 2 7

    Interactions for Levitra

    Metabolized principally by CYP3A4; CYP2C and CYP3A5 appear to play a minor role.1

    Drugs Affecting Hepatic Microsomal Enzymes

    Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma vardenafil concentrations).1

    Specific Drugs

    Drug

    Interaction

    Comments

    α-Adrenergic blocking agents

    Possible symptomatic hypotension 1

    Concurrent use is contraindicated1

    Alcohol

    No potentiation of hypotensive effect reported1

    Antacids (aluminum hydroxide and magnesium hydroxide)

    Pharmacokinetic interaction unlikely1

    Antiarrhythmic agents (amiodarone, procainamide, quinidine, sotalol)

    Possible prolongation of the QTc interval1

    Avoid concomitant use1

    Antihypertensive agents

    Possible additive hypotensive effects

    Antiretroviral agents, HIV protease inhibitors

    Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 29 31 33

    Decreased indinavir and ritonavir concentrations1 29 31 33

    Ritonavir or lopinavir: Do not exceed a single vardenafil dose of 2.5 mg in 72 hours;1 29 no change in ritonavir dosage needed29

    Ritonavir in combination with indinavir, atazanavir, saquinavir, fosamprenavir, or nelfinavir: Do not exceed a vardenafil dosage of 2.5 mg in 72 hours29 33

    Nelfinavir, indinavir, amprenavir, saquinavir, fosamprenavir, or atazanavir: Use initial vardenafil dosage of 2.5 mg and do not exceed a single dose of 2.5 mg in 24 hours1 29 30 31 33

    Monitor closely 29 31 32 33 34

    Antiretroviral agents, nonnucleoside reverse transcriptase inhibitors

    Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)29

    Delavirdine: Use initial vardenafil dosage of 2.5 mg; do not exceed 2.5 mg once in 24 hours29

    Aspirin

    No increase in bleeding time reported1

    Cimetidine

    Pharmacokinetic interaction unlikely1

    Digoxin

    Pharmacokinetic interaction unlikely1

    Erythromycin

    Increased AUC and peak plasma concentrations of vardenafil1

    Reduce initial vardenafil dosage to 5 mg in patients receiving erythromycin1

    Glyburide

    Pharmacokinetic interaction unlikely1

    Inhaled nitrites (e.g., amyl or butyl nitrite)

    Potentiation of hypotensive effect28

    Concomitant use is contraindicated28 (see Cautions)

    Itraconazole

    Possible increased vardenafil concentrations1

    Reduce initial vardenafil dosage to 2.5 mg in patients receiving itraconazole 400 mg daily1

    Reduce initial vardenafil dosage to 5 mg in patients receiving itraconazole 200 mg daily1

    Ketoconazole

    Increased vardenafil concentrations 1

    Reduce initial vardenafil dosage to 2.5 mg in patients in patients receiving ketoconazole 400 mg daily1

    Reduce initial vardenafil dosage to 5 mg in patients receiving ketoconazole 200 mg daily1

    Nifedipine

    Possible additive hypotensive effect1

    Nitrates and nitric acid donors

    Potentiation of vasodilatory effects; potentially life-threatening hypotension and/or hemodynamic compromise can result1

    Concomitant use is contraindicated1 28

    Ranitidine

    Pharmacokinetic interaction unlikely

    Warfarin

    Pharmacokinetic and pharmacodynamic interaction unlikely1

    Levitra Pharmacokinetics

    Absorption

    Bioavailability

    Rapidly absorbed following oral administration; peak concentrations usually attained within 0.5–2 hours.1

    Absolute bioavailability is approximately 15%.1

    Food

    Administration with a high-fat meal reduces the peak plasma concentrations by 18–50%.1 3

    Distribution

    Extent

    Extensively distributed into tissues.1

    Plasma Protein Binding

    Approximately 95% for the drug and major metabolite.1

    Elimination

    Metabolism

    Metabolized in the liver to active metabolite(s) principally via CYP3A4, with minor contributions from CYP3A5 and CYP2C.1

    Elimination Route

    Excreted as metabolites principally in the feces (91–95%) and to a lesser extent in urine (2–6%).1

    Half-life

    Terminal half-life 4–5 hours for drug and major metabolite.1

    Special Populations

    Clearance reduced in men ≥65 years of age, resulting in an increase in AUC and peak plasma concentrations compared with younger males.1

    Clearance reduced in patients with moderate (Clcr of 30–50 mL/minute) or severe (Clcr <30 ml/minute) renal impairment, resulting in an increase in AUC compared with patients with normal renal function.1

    Clearance reduced in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, resulting in an increase in AUC and peak plasma concentrations compared with healthy adults.1

    Stability

    Storage

    Oral

    Tablets

    25°C (may be exposed to 15–30°C).1

    Actions

    • Selective inhibitor of phosphodiesterases (PDEs) with the greatest selectivity for PDE type 5, the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.1

    • Enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP.1 2
    • Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal.1 No effect on erectile function in the absence of sexual stimulation.1
    • Modest peripheral vasodilation accompanied by a small increase in heart rate at usual dosages.1 6 27
    • Although less affinity than sildenafil for PDE type 6 receptor in the retina, some transient visual abnormalities observed.1 27

    Advice to Patients

    Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

    • Importance of informing clinician of risk factors for cardiovascular disease prior to initiating any treatment for erectile dysfunction.1 5

    • Importance of informing clinician of stroke history.1
    • Importance of informing clinician of low or high BP.1
    • Importance of informing clinician of the presence of retinitis pigmentosa.2
    • Importance of informing patients of the potential for life-threatening hypotension and/or hemodynamic compromise with concurrent use of organic nitrates and nitrites (e.g., nitroglycerin, isosorbide dinitrate) or nitric oxide donors (e.g., sodium nitroprusside) in any form, including the recreational use of inhaled nitrites (“poppers”), because of the potential for hypotension and associated dizziness, syncope, or even MI or stroke.1 26
    • Importance of avoiding concurrent use of α-adrenergic blocking agents because of the potential for hypotension, dizziness, or fainting.1
    • Importance of seeking immediate medical attention if an erection persists >4 hours or is painful.1
    • Importance of advising patient that vardenafil does not protect against sexually transmitted diseases (e.g., HIV) and about measures to protect against such transmission.1
    • Importance of contacting a clinician for assessment of therapeutic benefit, the need for possible dosage adjustment, and potential adverse effects.1
    • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
    • Importance of informing patients of other important precautionary information.1 (See Cautions.)

    Preparations

    Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

    Vardenafil Hydrochloride
    Routes

    Dosage Forms

    Strengths

    Brand Names

    Manufacturer

    Oral

    Tablets, film-coated

    2.5 mg (of vardenafil)

    Levitra

    Schering-Plough

    5 mg (of vardenafil)

    Levitra

    Schering-Plough

    10 mg (of vardenafil)

    Levitra

    Schering-Plough

    20 mg (of vardenafil)

    Levitra

    Schering-Plough

    Comparative Pricing

    This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

    Levitra 10MG Tablets (GLAXO SMITH KLINE): 10/$202.99 or 30/$582.97

    Levitra 2.5MG Tablets (SCHERING): 10/$164.00 or 20/$328.00

    Levitra 20MG Tablets (GLAXO SMITH KLINE): 10/$202.99 or 30/$582.97

    Levitra 5MG Tablets (GLAXO SMITH KLINE): 10/$212.99 or 30/$608.97

    Staxyn 10MG Dispersible Tablets (GLAXO SMITH KLINE): 4/$62.99 or 12/$165.96

    Disclaimer

    This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

    The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug’s actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

    AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions November 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

    References

    1. Schering-Plough. Levitra (vardenafil hydrochloride) tablets prescribing information. West Haven, CT; 2004 Oct.

    2. Coleman CI, Carabino JM, Vergara CM. Vardenafil: an oral selective phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction. Formulary. 2003; 38:131-148.

    3. Rajagopalan P, Mazzu A, Xia C et al. Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. J Clin Pharmacol. 2003; 43(3):260-7. [IDIS 495567] [PubMed 12638394]

    4. Brock G, Nehra A, Lipshultz LI et al. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. J Urol. 2003; 170(4 Pt 1):1278-83. [IDIS 504241] [PubMed 14501741]

    5. Jackson G, Betteridge J, Dean J et al. A systematic approach to erectile dysfunction in the cardiovascular patient: a Consensus Statement–update 2002. Int J Clin Pract. 2002; 56(9):663-71. [IDIS 491098] [PubMed 12469980]

    6. Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. Technology and Practice Executive Committee [duplicate publication of Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. ACC/AHA expert consensus document: use of sildenafil (viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999; 33:273-82. [IDIS 426556] [PubMed 9935041]

    7. Hellstrom WJ, Gittelman M, Karlin G et al. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology. 2003; 61(4 Suppl 1):8-14. [PubMed 12657355]

    8. Goldstein I, Young JM, Fischer J et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diabetes Care. 2003; 26(3):777-83. [IDIS 517794] [PubMed 12610037]

    9. National Institutes of Health Office of Medical Applications of Research. Consensus Conference: impotence. JAMA. 1993; 270:83-90. [IDIS 316686] [PubMed 8510302]

    10. Pfizer Inc, New York, NY: Personal communication on sildenafil.

    11. Reviewers’ comments on sildenafil (personal observations).

    12. The Process of Care Consensus Panel. Position paper: the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:59-70.

    13. Palmer BF. Sexual dysfunction in uremia. J Am Soc Nephrol. 1999; 10:1381-8. [PubMed 10361878]

    14. Guay AT, Nankin AR et al. AACE clinical practice guidelines for the evaluation and treatment of male sexual dysfunction. From American Association of Clinical Endocrinologists web site. ()

    15. Whitehead ED, Klyde BJ, Zussman S et al. Treatment alternatives for impotence. Postgrad Med. 1990; 88:139-52. [IDIS 269901] [PubMed 2199954]

    16. Gerber GS, Levine LA. Pharmacological erection program using prostaglandin E1. J Urol. 1991; 146:786-9. [IDIS 287641] [PubMed 1875494]

    17. Porst H. Editorial comments on the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11: 72-3.

    18. Sarramon JP. Editorial comments on the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:73.

    19. Vermeuler A. Editorial comments on the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:74.

    20. Sohn MHH. Editorial comments on the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:72.

    21. Sefetl AD. Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles. Clin Cardiol. 2004; 27(Suppl. 1):I-14-9.

    22. Padma-Nathan H. A new era in the treatment of erectile dysfunction. Am J Cardiol. 1999; 84:18-23N. [PubMed 10404845]

    23. Wespes E, Amar E, Hatzichtistou D et al. Guidelines on reactile dysfunction. Arnhem: European Association of Urology, 2004 Mar. Available at . Accessed 2004 Aug.

    24. Pfizer Inc. Viagra (sildenafil citrate) prescribing information. New York, NY; 2002 Sep.

    25. Lilly ICOS. Cialis (tadalafil) tablets prescribing information. Indianapolis, IN; 2003 Nov.

    26. Schering-Plough, Kenilowrth, NJ. Personal communication.

    27. Crowe SM, Streetman DS. Vardenafil treatment for erectile dysfunction. Ann Pharmacother. 2004; 38:77-85. [IDIS 514325] [PubMed 14742800]

    28. Schering-Plough. Levitra (vardenafil hydrochloride) tablets patient information. From Levitra website: (). Accessed 2005 May16.

    29. Panel on Clinical Practices for Treatment of HIV infection of the Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (Apr 7, 2005). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

    30. Merck & Company Inc. Crixivan (indinavir sulfate) capsules prescribing information. West Point, PA; 2004 May.

    31. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) prescribing information. Princeton, NJ; 2004 Jul.

    32. Roche Pharmaceuticals. Fortovase (saquinavir) soft gelatin capsules prescribing information. Nutley, NJ; 2003 Dec.

    33. GlaxoSmithKline. Lexiva (fosamprenavir calcium) tablets prescribing information. Research Triangle Park, NC; 2004 May.

    34. Roche Laboratories. Invirase (saquinavir mesylate) capsules prescribing information. Nutley, NJ; 2004 Dec.

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    Levitra

    Levitra

    Pronunciation Generic Name: vardenafil (var DEN a fil)

    Brand Name: Levitra, Staxyn

    OverviewSide EffectsInteractionsFor ProfessionalsMore…

    What is vardenafil?

    Vardenafil relaxes muscles and increases blood flow to particular areas of the body.

    Vardenafil is used to treat erectile dysfunction (impotence).

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

    What is the most important information I should know about vardenafil?

    Do not take vardenafil if you are also using a nitrate drug for chest pain or heart problems (such as nitroglycerin). Taking vardenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

    During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of vardenafil.

    Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

    Stop using vardenafil and get emergency medical help if you have sudden vision loss.

    What should I discuss with my healthcare provider before taking vardenafil?

    Do not take vardenafil if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite (“poppers”). Taking vardenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

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

    • heart disease, heart rhythm problems;

    • a recent history (in the past 6 months) of a heart attack, stroke, or congestive heart failure;
    • a personal or family history of “Long QT syndrome”;
    • high or low blood pressure;
    • seizures;
    • liver disease, kidney disease (or if you are on dialysis);
    • a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
    • a bleeding disorder such as hemophilia;
    • a stomach ulcer;
    • hearing or vision problems, history of vision loss;
    • an eye disorder such as retinitis pigmentosa (an inherited condition of the eye);
    • a physical deformity of the penis (such as Peyronie’s disease); or
    • if you have been told you should not have sexual intercourse for health reasons.

    Vardenafil can decrease blood flow to the optic nerve of the eye, causing sudden vision loss. This has occurred in a small number of people taking vardenafil, most of whom also had heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old. It is not clear whether vardenafil is the actual cause of vision loss. Stop using vardenafil and get emergency medical help if you have sudden vision loss.

    FDA pregnancy category B: Although vardenafil is not for use in women, this medication is not expected to be harmful to an unborn baby.

    Although vardenafil is not for use in women, it is not known if vardenafil passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

    Staxyn may contain phenylalanine. Talk to your doctor before using this form of vardenafil if you have phenylketonuria (PKU).

    How should I take vardenafil?

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

    Vardenafil can be taken with or without food.

    Vardenafil is usually taken only when needed, about 60 minutes before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor’s instructions.

    To take the orally disintegrating tablet (Staxyn):

    • Keep the tablet in its blister pack until you are ready to take it. Open the package and peel back the foil from the tablet blister. Do not push a tablet through the foil or you may damage the tablet.

    • Using dry hands, remove the tablet and place it in your mouth. It will begin to dissolve right away.
    • Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.
    • Swallow several times as the tablet dissolves. Do not take Staxyn with liquid.

    Do not take vardenafil more than once a day. Allow 24 hours to pass between doses.

    Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

    Store at room temperature away from moisture and heat.

    What happens if I miss a dose?

    Since vardenafil is used as needed, you are not likely to be on a dosing schedule.

    What happens if I overdose?

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

    Overdose symptoms may include back pain, muscle pain, or vision problems.

    What should I avoid while taking vardenafil?

    Drinking alcohol can increase certain side effects of vardenafil.

    Grapefruit and grapefruit juice may interact with vardenafil and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

    Do not use any other drug to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others), unless your doctor tells you to.

    Vardenafil side effects

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

    During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of vardenafil.

    Stop using vardenafil and call your doctor at once if you have any of these serious side effects:

    • sudden vision loss;

    • ringing in your ears, or sudden hearing loss;
    • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
    • irregular heartbeat;
    • swelling in your hands, ankles, or feet;
    • shortness of breath;
    • vision changes;
    • feeling light-headed, fainting;
    • penis erection that is painful or lasts 4 hours or longer; or
    • seizure (convulsions).

    Less serious side effects may include:

    • warmth or redness in your face, neck, or chest;

    • runny or stuffy nose;
    • headache, dizziness;
    • upset stomach; or
    • back pain.

    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: Levitra side effects (in more detail)

    What other drugs will affect vardenafil?

    Do not take vardenafil with similar medications such as sildenafil (Viagra) or tadalafil (Cialis).

    Before taking vardenafil, tell your doctor about all other medications you use for erectile dysfunction, or if you are using any of the following medications:

    • conivaptan (Vaprisol);

    • imatinib (Gleevec);
    • isoniazid (for treating tuberculosis);
    • an antidepressant such as nefazodone;
    • an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), or telithromycin (Ketek);
    • antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);
    • drugs to treat high blood pressure or a prostate disorder, such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin), tamsulosin (Flomax);
    • heart or blood pressure medication such as diltiazem (Cardizem, Dilacor, Tiazac), nicardipine (Cardene), or verapamil (Calan, Covera, Isoptin, Verelan);
    • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), quinidine (Quin-G), procainamide (Procan, Pronestyl), or sotalol (Betapace); or
    • HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir, Kaletra).

    This list is not complete and other drugs may interact with vardenafil. 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 Levitra resources

    • Side Effects
    • Pregnancy Warnings
    • Drug Images
    • Drug Interactions
    • Support Group
    • 58 Reviews - Add your own review/rating
    • Generic Availability
    • Levitra Advanced Consumer (Micromedex) – Includes Dosage Information
    • Levitra Monograph (AHFS DI)
    • Levitra Consumer Overview
    • Levitra MedFacts Consumer Leaflet (Wolters Kluwer)
    • Levitra Prescribing Information (FDA)
    • Staxyn Prescribing Information (FDA)
    • Staxyn orally disintegrating tablets MedFacts Consumer Leaflet (Wolters Kluwer)
    • Staxyn Consumer Overview

    Compare Levitra with other medications

    • Erectile Dysfunction

    Where can I get more information?

    • Your pharmacist can provide more information about vardenafil.

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