Levitra (vardenafil, Bay 38-9456)

Background

According to the National Institutes of Health, erectile dysfunction (ED) affects approximately 15 million to 30 million American men.¹ ED, also called impotence, is the inability to obtain and keep an erection during sexual intercourse. ED may be caused by disease (diabetes, alcoholism, vascular disease), surgical procedures, and medications. ED traditionally has been treated with psychotherapy, surgery, mechanical vacuum devices, and medications. In March 1998, the FDA approved the first oral medication, sildenafil, for the treatment of ED. Levitra, approved by the FDA in August 2003, is the second oral medication for the treatment of ED.

Pharmacology

Penile erection occurs by the relaxation of smooth muscle in the corpus cavernosum. Nitric oxide release at the corpus cavernosum activates cyclic guanosine monophosphate (cGMP), which stimulates smooth muscle relaxation. Degradation of cGMP is regulated by phosphodiesterases. Levitra is a selective inhibitor of cGMP-specific phosphodiesterase type 5; thus it increases the amount of cGMP. Levitra has an onset of action of 1 hour and a duration of up to 1 hour.²

Clinical Trials

Hellstrom and colleagues performed a placebo-controlled, randomized, multicenter, 4-arm, parallel-group, fixeddose study evaluating Levitra for the treatment of men with ED. The trial consisted of a 4-week baseline period with no treatment, followed by a 26- week double-blind treatment phase with Levitra 5, 10, or 20 mg or placebo, and then a 1-week follow-up phase for adverse-event monitoring. Men over the age of 18 with the inability to maintain or achieve an erection sufficient for satisfactory sexual intercourse for longer than 6 months were enrolled. The study utilized erectile function (EF) domain scores on the International Index of Erectile Function (IIEF) questionnaire as the primary efficacy measure.

After 12 weeks, patients on all doses of Levitra showed significant improvement in EF domain scores, versus placebo, and this improvement was maintained at 26 weeks. EF domain scores were significantly higher for the Levitra 10- and 20-mg groups than for the 5-mg group. These EF domain scores were maintained for all groups at week 26, showing the continued superiority of the higher doses.³

Goldstein and colleagues investigated the efficacy and safety of Levitra in males with ED and diabetes mellitus in a multicenter, fixed-dose, double-blind, placebo-controlled trial. This study randomized patients to Levitra 10 or 20 mg or placebo. Most patients reported severe ED and a mean duration of 3.5 years after diagnosis. Most patients enrolled were identified as having type 2 diabetes and poor glycemic control. The study utilized the domain scores and the global assessment question (GAQ) on the IIEF about erection improvement to assess the efficacy of the drug.

After 12 weeks of treatment, patients in the 10- and 20-mg Levitra groups showed a 57% and 72% improvement, respectively, in GAQ results. When EF domain scores were assessed, patients in the 2 treatment groups showed an improved rate of successful penetration and intercourse, compared with placebo. Furthermore, Levitra was able to increase successful intercourse rates for patients at each level of HbA1c and for patients with both type 1 and type 2 diabetes.⁴

Safety

The most common adverse events seen with Levitra were headache, flushing, rhinitis, dyspepsia, sinusitis, flu syndrome, dizziness, increased creatine kinase, and nausea.^2,3 Other less frequent adverse events seen included anaphylaxis, chest pain, myocardial infarction, palpitation, postural hypotension, tachycardia, angina, abdominal pain, myalgia, abnormal or blurred vision, abnormal ejaculation, and priapism.² Contraindications include concurrent therapy with nitrates or alphablockers. Precaution should be advised in patients with cardiovascular complications or low blood pressure. Levitra is also metabolized by CYP450 3A4/5. Therefore, drugs inhibiting these enzymes reduce the clearance of Levitra and should be used with caution.²

Outlook

The recommended dose of Levitra is 10 to 20 mg, and the drug should be taken at least 1 hour prior to expected sexual intercourse. Levitra should not be taken more than once daily.