Tadalafil (Cialis) and Vardenafil (Levitra) Recently Approved Drugs for Erectile Dysfunction

Erectile dysfunction (ED) affects more than 30 million men in the United States, more than 150 million men worldwide, and accounts for half a million visits to health care providers annually (Sharlip, Jarow, & Rajfer, 2003). In August 2003, the FDA approved vardenafil (Levitra^® by Bayer/GlaxoSmithKline), and on November 21, 2003, tadalafil (Cialis^® by Lilly/ICOS) was approved. Both drugs have been available and in widespread use in Europe and Latin America for several months and now join sildenafil (Viagra^® by Pfizer) as oral treatment options for ED in the United States.

Both tadalafil and vardenafil are (like sildenafil) classified as potent and highly selective phosphodiesterase type 5 (PDE5) inhibitors. Inhibition of PDE5 prevents cyclic guanosine monophosphate (cGMP) from being degraded in penile tissue. When the enzyme is inhibited, relaxation of the smooth muscle in the corpus cavernosum occurs and leads to inflow of blood, potentiating erection. Both drugs require sexual stimulation for response (Palacioz, 2003; Thomson Micromedex, 2003).

Tadalafil and vardenafil are indicated for erectile dysfunction of various etiologies. Both drugs were effective in generalized ED clinical studies and also in studies of special populations of men with diabetes and men post nerve-sparing radical prostatectomy. The ages of men in clinical studies ranged from early 20s to early 80s, with average age being mid-50s. There are no published head-to-head studies of either tadalafil or vardenafil with sildenafil. Most studies have compared the drugs to placebo. Many studies excluded sildenafil nonresponders (Abramowicz, 2003; Broda, 2003; Cialis Prescribing Information, 2003). In October 2003, results of a 4-week multicenter, double-blind study of 463 nonresponders to sildenafil were presented at the fall research meeting of the Sexual Medicine Society of North America showing statistical and clinical improvement over baseline in vardenafil users over placebo (Carson et al., 2003).

Tadalafil is available in 10 mg and 20 mg tablets and should be taken orally 30 minutes to 1 hour before sexual activity. Effectiveness may onset in 15 to 30 minutes and can last as long as 36 hours for one dose, facilitating spontaneity. No more than one tablet should be taken in a single 24-hour period. Some clinical trials tested a daily dose of tadalafil (Cialis Prescribing Information, 2003; Porst et al., 2003) (see Patient Education Information).

Vardenafil is available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets. Recommended starting dose for most men is 10 mg taken orally approximately 1 hour before sexual activity. Effectiveness may onset in 30 to 60 minutes and usually lasts approximately 4 to 5 hours (similar to sildenafil). Maximum dosing frequency is once daily (Abramowicz, 2003; Keating & Scott, 2003; Palacioz, 2003) (see Patient Education Information).

Both drugs are well-tolerated and can be taken with or without food, although high-fat meals may delay response time. In mild renal and hepatic impairment, no dose adjustment is required. Dosages may need adjustment in moderate hepatic impairment or in patients receiving potent CYP3A4 inhibitors like ketoconazole, itraconazole, ritonavir, indinivir, and erythromycin (Keating & Scott, 2003; Thomson Micromedex, 2003).

Vardenafil is metabolized for the most part in the liver, primarily by CYP3A4/5 and to a lesser extent by CYP2C. Mean renal clearance of vardenafil was 2.3 L/hour. It has an elimination half-life of 4 to 5 hours and is excreted mostly (91% to 95%) in feces (Keating & Scott, 2003).

Tadalafil is rapidly absorbed following oral administration, and is also primarily metabolized in the liver by the cytochrome P450 (CYP)3A4 isoform. Mean oral clearance is 2.5 L/hour, and mean half-life is 17.5 hours. Approximately two-thirds of the drug is excreted in the feces, with the other third excreted in the urine (Cialis Prescribing Information, 2003).

Neither tadalafil nor vardenafil should be taken with nitrates or nitric oxide donors due to the potential for increased hypotensive effect. Concomitant use with alpha blockers is also contraindicated due to potential for hypotension. Heart attack or stroke within past 6 months, uncontrolled hypertension, significant hypotension, unstable angina, retinitis pigmentosa, severe renal or hepatic impairment are all contraindications for use of PDE5 inhibitors. Blood disorders (leukemia, multiple myeloma, sickle cell anemia). History of allergy or reaction to sildenafil, tadalafil, or vardenafil.

Increased risk for men with severe cardiac disease due to the vasodilatory effects of PDE5 inhibitors. Slightly increased risk of hypotension. Rare reports of prolonged erections (>4 hours) or priapism (painful erections >6 hours) have been reported. Permanent tissue damage can occur if untreated in a timely manner. PDE5 inhibitors cans increase QTc interval. Men at risk for prolonged QT or those taking Class 1A or Class III anti-arrhythmic medications should avoid tadalafil or vardenafil.

Headache Flushing Upset stomach/nausea Stuffy nose Urinary tract infection Visual changes such as mild and temporary changes in blue/green colors or increased sensitivity to light (may not be as likely with tadalafil as with vardenafil or sildenafil) Diarrhea Back pain

(Cialis Prescribing Information, 2003; "FDA Approves," 2003: Palacioz, 2003; Thomson Micromedex, 2003).

Verify that patient does not use any form of nitrates (including recreational drugs). Observe blood pressure reading prior to initiating treatment. Be familiar with drug interactions (drugs that could prolong QT interval, drugs that affect the CYP3A4 pathway, alpha blockers). Discuss with patients possible side effects. Advise patients of rare possibility of prolonged erection/priapism and need to seek immediate treatment if erection lasts longer than 4 hours.

Sildenafil (Viagra) opened the door and set the bar as the first PDE5 inhibitor for oral treatment of erectile dysfunction and has successfully cornered the market for the past 5 years. The addition of two new PDE5 inhibitors is likely to open new doors for treatment of ED. Vardenafil (Levitra) claims more rapid onset, fewer side effects, and better efficacy overall for some men. Tadalafil (Cialis) makes similar claims and offers the additional benefit of a "weekend pill" (24 to 36 hours duration of action for a single dose). And certainly, apomorphine (Uprima^®) for sublingual use, apomorphine nasal spray, and alprostadil gel/cream (Topiglan®/Alprox-TD^®) for topical use are probably not far behind in the race to successfully treat a problem that concerns millions of men and their partners and will continue be a major health issue as baby boomers move into their 50s and 60s.

Urol Nurs. 2004;24(1) © 2004  Society of Urologic Nurses and Associates

Cite this: Tadalafil (Cialis) and Vardenafil (Levitra) Recently Approved Drugs for Erectile Dysfunction - Medscape - Mar 01, 2004.