U.S. Brand Names:
Levitra®
Synonyms:
Vardenafil Hydrochloride
Generic Available:
No
Use:
Treatment of erectile dysfunction
Pregnancy Risk Factor:
B
Pregnancy Implications:
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:
Vardenafil is not indicated for use in women.
Contraindications:
Hypersensitivity to vardenafil or any component of the formulation; concurrent use of organic nitrates (nitroglycerin; scheduled dosing or as needed); concomitant use of alpha blockers
Warnings/Precautions:
There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the patient's cardiovascular status prior to initiating any treatment for erectile dysfunction. Use caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease) and in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia). Patients should be instructed to seek medical attention if erection persists >4 hours.
Not recommended for use in patients with congenital QT prolongation or those taking Class Ia or III antiarrhythmics. Use caution with effective CYP3A4 inhibitors, the elderly, or those with hepatic impairment (Child-Pugh class B); dosage adjustment is needed.
Safety and efficacy have not been studied in patients with the following conditions, therefore, use in these patients is not recommended at this time: Hypotension, uncontrolled hypertension, unstable angina, severe cardiac failure; a life-threatening arrhythmia, myocardial infarction,or stroke within the last 6 months; severe hepatic impairment (Child-Pugh class C); end-stage renal disease requiring dialysis; retinitis pigmentosa or other degenerative retinal disorders. The safety and efficacy of vardenafil with other treatments for erectile dysfunction have not been studied and are not recommended as combination therapy.
Adverse Reactions:
>10%:
Cardiovascular: Flushing (11%)
Central nervous system: Headache (15%)
2% to 10%:
Central nervous system: Dizziness (2%)
Gastrointestinal: Dyspepsia (4%), nausea (2%)
Neuromuscular & skeletal: CPK increased (2%)
Respiratory: Rhinitis (9%), sinusitis (3%)
Miscellaneous: Flu-like syndrome (3%)
<2%: Abdominal pain, abnormal ejaculation, anaphylactic reaction, angina, arthralgia, back pain, blurred vision, chest pain, chromatopsia, color vision changes, conjunctivitis, diaphoresis, diarrhea, dim vision, dysphagia, dyspnea, epistaxis, esophagitis, eye pain, facial edema, gastritis, gastroesophageal reflux, GGT increased, glaucoma, hypertension, hypertonia, hypesthesia, hypotension, insomnia, liver function tests abnormal, MI, myalgia, myocardial ischemia, neck pain, pain, palpitation, paresthesia, pharyngitis, photophobia, photosensitivity reaction, postural hypotension, priapism, pruritus, rash, somnolence, syncope, tachycardia, tinnitus, vertigo, vision abnormal, vomiting, watery eyes, weakness, xerostomia
Overdosage/Toxicology:
Doses of up to 120 mg caused back pain, myalgia, and/or abnormal vision in healthy volunteers. Treatment should be symptomatic and supportive.
Drug Interactions:
Substrate of CYP2C (minor), 3A5 (minor), 3A4 (major)
Alpha-blockers: May lead to significant hypotension in some patients; concomitant use is contraindicated; effect seen with terazosin and tamsulosin.
CYP3A4 inhibitors: May increase the levels/effects of vardenafil. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
Erythromycin: Serum concentrations of vardenafil are increased fourfold when given with erythromycin. Dose of vardenafil should not exceed 5 mg/24 hours.
Indinavir: Serum concentrations of vardenafil are increased 16-fold; half-life is also increased. Dose of vardenafil should not exceed 2.5 mg/24 hours. Serum concentrations of indinavir may be decreased by vardenafil.
Itraconazole: Serum concentrations of vardenafil are increased. Dose of vardenafil should not exceed 5 mg/24 hours when used with itraconazole 200 mg/day or 2.5 mg/24 hours when used with itraconazole 400 mg/day
Ketoconazole: Serum concentrations of vardenafil are increased 10-fold when given with ketoconazole 200 mg/day. Dose of vardenafil should not exceed 5 mg/24 hours when used with ketoconazole 200 mg/day or 2.5 mg/24 hours when used with ketoconazole 400 mg/day
Nitroglycerin (or other nitrates): Concomitant use is contraindicated due to the potential for severe, potentially fatal, hypotensive responses.
Ritonavir: Serum concentrations of vardenafil are increased 49-fold; half-life of vardenafil is prolonged to 26 hours. Dose of vardenafil should not exceed 2.5 mg/72 hours. Serum concentrations of ritonavir may be decreased by vardenafil.
Ethanol/Nutrition/Herb Interactions:
Food: High-fat meals decrease maximum serum concentration 18% to 50%. Serum concentrations/toxicity may be increased with grapefruit juice; avoid concurrent use.
Stability:
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
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:
Absorption: Rapid
Distribution: Vd: 208 L; <0.01% found in semen 1.5 hours after dose
Metabolism: Hepatic via CYP3A4 (major), CYP2C and 3A5 (minor); forms metabolite (active)
Bioavailability: 15%; Elderly (65 years): 52%; Hepatic impairment (Child-Pugh class B): 160%
Half-life elimination: Terminal: Vardenafil and metabolite: 4-5 hours
Time to peak, plasma: 0.5-2 hours
Excretion: Feces (91% to 95% as metabolites); urine (2% to 6%)
Clearance: 56 L/hour
Dosage:
Oral: Adults: Erectile dysfunction: 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
Dosing adjustment with concomitant medications:
Erythromycin: Maximum vardenafil dose: 5 mg/24 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
Ritonavir: Maximum vardenafil dose: 2.5 mg/72 hours
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
Dosage adjustment in renal impairment: Dose adjustment not needed for mild, moderate, or severe impairment; use has not been studied in patients on renal dialysis
Dosage adjustment in hepatic impairment: Child-Pugh class B: 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
Administration:
May be administered with or without food, 60 minutes prior to sexual activity.
Monitoring Parameters:
Monitor for response and adverse reactions.
Dietary Considerations:
May take with or without food
Patient Education:
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy without consulting prescriber. Use exactly as directed 60 minutes prior to sexual activity without regard to meals; avoid taking with high-fat meals or grapefruit juice. Do not combine with other approaches to treating erectile dysfunction without consulting prescriber. Note: This medication does not provide protection against sexually-transmitted diseases, including HIV. You may experience headache, flushing, or blurred vision (use caution when driving at night or in poorly lit environments until response is known). Report immediately chest pain; acute head pain; respiratory difficulty; allergic response (chills, fever, respiratory difficulty, rash); genital swelling; or other adverse reactions.
Anesthesia and Critical Care Concerns/Other Considerations:
Cardiovascular effects of PDE-5 inhibitors may be potentially hazardous in patients with:
active coronary ischemia (not on nitrates)
heart failure and with low blood pressure and low volume status
complicated, multidrug antihypertensive regimens
potential for drug-drug interactions that may prolong PDE-5 inhibitor half-life (eg, drugs that inhibit CYP3A4)
Vardenafil is selective for PDE-5 and has limited effect on PDE3, which controls cardiac contractility.
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 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 (J Am Coll Cardiol, 1999, 33:273-82). 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 low blood pressure and 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)
Vardenafil is selective for PDE-5 and has limited effect on PDE3, 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:
Tablet, as hydrochloride [film-coated]: 2.5 mg, 5 mg, 10 mg, 20 mg
International Brand Names:
Levitra® (AT, BE, BR, CH, CO, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MX, NL, NO, NZ, PL, PT, SE, SI, ZA); Vivanza® (AT, BE, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, NL, NO, PT, SE)
Print this page
Email this page
Twitter
Facebook
YouTube
Email this Page
Print this Page 
![[ Flash player icon ]](http://www.umm.edu/images/flshIcon.png "[ Flash player icon ]")
