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Pronunciation
(var DEN a fil)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of erectile dysfunction (ED)
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; however, vardenafil is not indicated for use in women. No effects on sperm motility or morphology were observed in healthy males.
Lactation
Excretion in breast milk unknown/not indicated for use in women.
Contraindications
Hypersensitivity to vardenafil or any component of the formulation; concurrent (regular or intermittent) use of organic nitrates in any form (eg, nitroglycerin, isosorbide dinitrate)
Warnings/Precautions
Concerns related to adverse effects:
• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).
• Hearing loss: Sudden decrease or loss of hearing has been reported rarely; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.
• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose.
• Priapism: Has been reported (rarely) with use. Instruct patients to seek immediate medical attention if erection persists >4 hours. Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia).
• Vision loss: Vision loss may occur rarely and be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Risk may be increased with history of vision loss. Other risk factors for NAION include low cup-to-disc ratio (“crowded disc”), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Safety and efficacy were not studied in patients with known degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended.
Disease-related concerns:
• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease).
• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established.
• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/100 mm Hg); unstable angina or angina during intercourse; life-threatening arrhythmias, stroke, or MI within the last 6 months; cardiac failure or coronary artery disease causing unstable angina. Safety and efficacy have not been studied in these patients. Use caution in patients with left ventricular outflow obstruction (eg, aortic stenosis). There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.
• Congenital QT prolongation: Not recommended for use in patients with congenital QT prolongation.
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment (Child-Pugh class B); dosage adjustment is needed. Safety and efficacy have not been studied in patients with severe hepatic impairment (Child-Pugh class C); therefore, use in these patients is not recommended. Per the manufacturer, the oral disintegrating tablet should not be used in patients with moderate-to-severe hepatic impairment.
• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety and efficacy have not been established.
• Renal impairment: Safety and efficacy have not been studied in patients with end-stage renal disease requiring dialysis, therefore, use in these patients is not recommended.
Concurrent drug therapy issues:
• Alpha-blockers: Use with caution in patients taking alpha-blockers; may cause hypotension. Safety of this combination may be affected by other antihypertensives and intravascular volume depletion. Patients should be hemodynamically stable prior to initiating therapy. Initiate vardenafil at the lowest recommended dose.
• Drugs with QT prolongation potential: Use with caution in patients taking medications known to prolong the QT interval. Avoid use in patients taking Class Ia or III antiarrhythmics.
• High potential for interactions: Use film-coated tablet with caution in patients taking strong CYP3A4 inhibitors (see Drug Interactions); dosage reductions may be necessary; consider alternative agents that avoid or lessen the potential for CYP-mediated interactions. Avoid use of the oral disintegrating tablet with moderate-to-strong CYP3A4 inhibitors.
• Nitrates: Concomitant use with all forms of nitrates is contraindicated. If nitrate administration is medically necessary, it is not known when nitrates can be safely administered following the use of vardenafil; the ACC/AHA 2007 guidelines support administration of nitrates only if 24 hours have elapsed.
• Other treatments for erectile dysfunction: Safety and efficacy with other treatments for erectile dysfunction have not been established; concurrent use is not recommended.
Special populations:
• Elderly: Use with caution in the elderly; dosage reduction may be necessary.
Dosage form specific issues:
• Phenylalanine: Some products may contain phenylalanine.
• Sorbitol: Some products may contain sorbitol; do not use in patients with fructose intolerance.
Other warnings/precautions:
• Appropriate use: Potential underlying causes of erectile dysfunction should be evaluated prior to treatment.
Adverse Reactions
>10%:
Cardiovascular: Flushing (8% to 11%)
Central nervous system: Headache (14% to 15%)
2% to 10%:
Central nervous system: Dizziness (2%)
Gastrointestinal: Dyspepsia (3% to 4%), nausea (2%)
Neuromuscular & skeletal: Back pain (2%), CPK increased (2%)
Respiratory: Rhinitis (9%), nasal congestion (3%), sinusitis (3%)
Miscellaneous: Flu-like syndrome (3%)
<2%, postmarketing, and/or case reports: Abdominal pain, abnormal ejaculation, allergic edema, allergic reaction, amnesia (transient global), anaphylactic reaction, angina, angioedema, arthralgia, blurred vision, chest pain, chromatopsia, color vision changes, conjunctivitis, diaphoresis, diarrhea, dim vision, dysethesia, dysphagia, dyspnea, epistaxis, erythema, esophagitis, eye discomfort/pain, facial edema, gastritis, gastroesophageal reflux, GGT increased, glaucoma, hearing decreased, hearing loss, hyper-/hypotension, hypertonia, hypoesthesia, insomnia, intraocular pressure increased, laryngeal edema, liver function tests abnormal, MI, muscle cramps, muscle tone increased, myalgia, myocardial ischemia, neck pain, nonarteritic ischemic optic neuropathy (NAION), ocular hyperemia, pain, palpitation, paresthesia, pharyngitis, photophobia, photosensitivity reaction, postural hypotension, priapism, pruritus, rash, retinal vein occlusion, seizure, sleep disorder, somnolence, syncope, tachycardia, tinnitus, ventricular tachyarrhythmia, vertigo, vision abnormal, vision loss (temporary or permanent), visual acuity reduced, visual field defects, vomiting, watery eyes, weakness, xerostomia
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alpha1-Blockers: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers. Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider therapy modification
Amyl Nitrite: Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite. Risk X: Avoid combination
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Antihypertensives: Phosphodiesterase 5 Inhibitors may enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Boceprevir: May increase the serum concentration of Vardenafil. Management: Limit vardenafil maximum dose to 2.5 mg every 24 hours and monitor closely for symptoms of vardenafil toxicity (including hypotension, visual changes, syncope, and priapism) during treatment with boceprevir. Risk D: Consider therapy modification
Bosentan: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan. Risk C: Monitor therapy
Clarithromycin: May increase the serum concentration of Vardenafil. Management: Recommendations regarding the concomitant use of vardenafil with clarithromycin vary between international labelings and between commercially available vardenafil brand name products (Levitra, Staxyn). Consult appropriate product labelings. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. Consult appropriate product labeling for specific recommendations. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Erythromycin: May increase the serum concentration of Vardenafil. Management: Limit dose of vardenafil film-coated tablets (Levitra) to 5 mg per 24 hours with concomitant use of erythromycin. Concomitant use of vardenafil orally disintegrating tablets (Staxyn) with erythromycin is not recommended. Risk D: Consider therapy modification
Etravirine: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Management: No empiric dosage adjustments are recommended with concomitant therapy; however, dose of the phosphodiesterase inhibitor may need to be altered based on clinical response. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination
Protease Inhibitors: May increase the serum concentration of Vardenafil. Management: Limit vardenafil adult dose to max of 2.5 mg/72 hrs with ritonavir, atazanavir, or darunavir; limit to max adult dose of 2.5 mg/24 hrs with other protease inhibitors. Risk D: Consider therapy modification
Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy
Telaprevir: May increase the serum concentration of Vardenafil. Management: In patients receiving telaprevir, vardenafil dosing should be limited to 2.5 mg per 72-hour period with close monitoring for signs/symptoms of vardenafil toxicity (including hypotension, visual changes, syncope, and priapism). Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: High-fat meals decrease maximum serum concentration 18% to 50%. Serum concentrations/toxicity may be increased with grapefruit juice. Management: Do not take with a high-fat meal. Avoid grapefruit juice.
Storage
Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 25°C (59°F to 86°F). Keep oral disintegrating tablets sealed in blisterpack until ready to use.
Mechanism of Action
Does not directly cause penile erections, but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation and inflow of blood to the corpus cavernosum. Vardenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by vardenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum; at recommended doses, it has no effect in the absence of sexual stimulation.
Pharmacodynamics/Kinetics
Onset of action: ~60 minutes
Absorption: Rapid
Distribution: Vd: 208 L
Protein binding: ~95% (parent drug and metabolite)
Metabolism: Hepatic via CYP3A4 (major), CYP2C and 3A5 (minor); forms metabolite (active)
Bioavailability: ~15%
Film-coated tablet: Elderly (≥65 years): AUC increased by 52%; Hepatic impairment (moderate, Child-Pugh class B): AUC increased by 160%
Oral disintegrating tablet: Elderly (≥65 years): AUC increased by 21% more compared to film-coated tablet. When administered with water, AUC decreases by 29%.
Half-life elimination: Terminal: Vardenafil and metabolite: 3-6 hours
Time to peak, plasma: 0.5-2 hours
Excretion: Feces (~91% to 95% as metabolites); urine (~2% to 6%)
Dosage
Note: Oral disintegrating tablets should not be used interchangeably with film-coated tablets; patients requiring a dose other than 10 mg should use the film-coated tablets.
Oral: Erectile dysfunction:
Adults:
Film-coated tablet (Levitra®): 10 mg 60 minutes prior to sexual activity; dosing range: 5-20 mg; to be given as one single dose and not given more than once daily
Oral disintegrating tablet (Staxyn™): 10 mg 60 minutes prior to sexual activity; maximum: 10 mg/day
Elderly ≥65 years: Initial: 5 mg 60 minutes prior to sexual activity; to be given as one single dose and not given more than once daily
Dosing adjustment with concomitant medications:
Alpha-blocker (dose should be stable at time of vardenafil initiation):
Film-coated tablet (Levitra®): Initial vardenafil dose: 5 mg/24 hours; if an alpha-blocker is added to vardenafil therapy, it should be initiated at the smallest possible dose and titrated carefully.
Oral disintegrating tablet (Staxyn™): Do not use to initiate therapy. Initial therapy should be with film-coated tablets at lower doses. Patients who have previously used film-coated tablets may be switched to oral disintegrating tablets as recommended by healthcare provider.
Film-coated tablet (Levitra®):
Atazanavir: Maximum vardenafil dose: 2.5 mg/24 hours
Clarithromycin: Maximum vardenafil dose: 2.5 mg/24 hours
Darunavir: Maximum vardenafil dose: 2.5 mg/72 hours
Erythromycin: Maximum vardenafil dose: 5 mg/24 hours
Fosamprenavir: Maximum vardenafil dose: 2.5 mg/24 hours
Fosamprenavir/ritonavir: Maximum vardenafil dose: 2.5 mg/72 hours
Indinavir: Maximum vardenafil dose: 2.5 mg/24 hours
Itraconazole:
200 mg/day: Maximum vardenafil dose: 5 mg/24 hours
400 mg/day: Maximum vardenafil dose: 2.5 mg/24 hours
Ketoconazole:
200 mg/day: Maximum vardenafil dose: 5 mg/24 hours
400 mg/day: Maximum vardenafil dose: 2.5 mg/24 hours
Lopinavir/ritonavir: Maximum vardenafil dose: 2.5 mg/72 hours
Nelfinavir: Maximum vardenafil dose: 2.5 mg/24 hours
Ritonavir: Maximum vardenafil dose: 2.5 mg/72 hours
Saquinavir: Maximum vardenafil dose: 2.5 mg/24 hours
Tipranavir: Maximum vardenafil dose: 2.5 mg/72 hours
Oral disintegrating tablet (Staxyn™): Concurrent use not recommended with potent or moderate CYP3A4 inhibitors (atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, saquinavir)
Dosage adjustment in renal impairment: Dose adjustment not needed for mild, moderate, or severe impairment; use not recommended in patients on hemodialysis
Dosage adjustment in hepatic impairment:
Child-Pugh class A: No adjustment required
Child-Pugh class B:
Film-coated tablet (Levitra®): Initial: 5 mg 60 minutes prior to sexual activity (maximum dose: 10 mg); to be given as one single dose and not given more than once daily
Oral disintegrating tablet (Staxyn™): Use not recommended
Child-Pugh class C: Has not been studied; use is not recommended by the manufacturer
Administration: Oral
May be administered with or without food, 60 minutes prior to sexual activity.
Oral disintegrating tablet should not be removed from blister pack until administered. Using dry hands, place immediately on tongue. Tablet will dissolve within seconds; do not take with liquid. Do not crush, split, or chew.
Monitoring Parameters
Monitor for response, adverse reactions, blood pressure, and heart rate.
Dietary Considerations
May take with or without food. Avoid grapefruit juice. Some products may contain phenylalanine. Some products may contain sorbitol; do not use in patients with fructose intolerance.
Patient Education
Use 60 minutes prior to sexual activity. Avoid taking with high-fat meals. This medication does not provide protection against sexually-transmitted diseases, including HIV. You may experience headache, flushing, or blurred vision. Report immediately chest pain, acute head pain, respiratory difficulty, change in vision (seeing a blue tinge to objects or having difficulty telling the difference between the colors blue and green), change in hearing or ringing in the ears, allergic response (eg, chills, fever, respiratory difficulty, rash), genital swelling, or erection lasting >4 hours. Orally disintegrating tablet: Place on tongue; avoid drinking liquids while administering tablet. Do not crush or chew.
Geriatric Considerations
In adults ≥65 years of age, vardenafil plasma concentrations were higher than younger males (mean Cmax was 34% higher), therefore, initial dose should be lower than the usual adult dose. Since the elderly often have concomitant diseases, many of which may be contraindicated with the use of vardenafil, a thorough knowledge of disease and medications must be accessed.
Cardiovascular Considerations
Vardenafil, when used in conjunction with nitrates, may be associated with severe hypotension, myocardial infarction, and possibly death. While there are no clear significant increased cardiovascular events with PDE-5 inhibitors alone, these drugs should be absolutely avoided in conjunction with nitrates and may also induce significant and possibly fatal hypotension in patients with heart failure. Hemodynamic effects of PDE-5 inhibitors alone include a very slight drop in blood pressure without significant changes in heart rate. The most recent guidelines on the use of sildenafil (prototype PDE-5 inhibitor) in patients with cardiovascular disease are outlined in detail (Cheitlin, 1999). The general clinical recommendations are as follows.
Use of PDE-5 inhibitors is contraindicated in patients currently taking nitrate preparations.
Cardiovascular effects of PDE-5 inhibitors may be potentially hazardous in patients with:
• active coronary ischemia (not on nitrates)
• heart failure and with borderline low blood pressure and borderline low volume status
• complicated, multidrug antihypertensive regimens
• potential for drug-drug interactions that may prolong PDE-5 inhibitor half-life (eg, drugs that inhibit cytochrome P450 3A4)
Additional guidelines for the treatment of ED in patients with cardiovascular disease have also been published (Jackson, 2006). These guidelines, referred to as the Princeton II Guidelines, support the use of PDE-5 inhibition only in patients with asymptomatic coronary disease and <3 of the following risk factors: Controlled hypertension, mild stable angina, successful coronary revascularization, previous uncomplicated MI (>6-8 weeks), mild valvular disease, and left ventricular dysfunction (with or without NYHA Class I limitations).
When nitrate administration becomes medically necessary, the ACC/AHA 2004 guidelines on treatment of ST-segment elevation MI and the ACC/AHA 2007 guidelines on treatment of unstable angina/non ST-segment elevation MI supports administration of nitrates only if 24 hours have elapsed after use of sildenafil and 48 hours after use of tadalafil. The appropriate delay for the use of nitrates after vardenafil has not been determined.
Vardenafil is selective for PDE-5 and has limited effect on PDE-3, which controls cardiac contractility.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness; may rarely cause insomnia
Mental Health: Effects on Psychiatric Treatment
May cause flu-like syndrome; consider this when evaluating for potential SSRI discontinuation syndrome; the symptoms are similar. Serum concentration of vardenafil may be increased with concurrent use of fluoxetine, fluvoxamine, and nefazodone; monitor.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Levitra®: 2.5 mg, 5 mg, 10 mg, 20 mg
Tablet, orally disintegrating, oral:
Staxyn™: 10 mg [contains phenylalanine 1.01 mg/tablet; peppermint flavor]
Pricing: U.S. (www.drugstore.com)
Tablet, orally-disintegrating (Staxyn)
10 mg (4): $60.99
Tablets (Levitra)
2.5 mg (10): $164.00
5 mg (10): $163.99
10 mg (10): $202.99
20 mg (10): $202.99
References
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, The Society of Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons,” J Am Coll Cardiol, 2007, 50(7):1-157.
Antman EM, Anbe DT, Armstrong PW, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction),” Circulation, 2004, 110(9):e82-292.
Cheitlin MD, Hutter AM Jr, Brindis RG, et al, “Use of Sildenafil (Viagra®) in Patients With Cardiovascular Disease,” J Am Coll Cardiol, 1999, 33(1):273-82.
Jackson G, Rosen RC, Kloner RA, et al, “The Second Princeton Consensus on Sexual Dysfunction and Cardiac Risk: New Guidelines for Sexual Medicine,” J Sex Med, 2006, 3(1):28-36.
McVary KT, “Clinical Practice. Erectile Dysfunction,” N Engl J Med, 2007, 357(24):2472-81.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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