Tamsulosin

Synopsis

Tadalafil is a reversible phosphodiesterase type 5 (PDE5) inhibitor approved for the treatment of erectile dysfunction (ED). As a class, PDE5 inhibitors (including sildenafil [Viagra] and vardenafil [Levitra]), enhance erectile response to sexual stimulation by increasing penile blood flow. The duration of action of tadalafil is longer than that of sildenafil or vardenafil.

Safety

In general, few side effects occur with tadalafil unless it is taken in conjunction with other drugs. When combined with [[alpha].sub.1]-adrenergic blockers such as doxazosin (Cardura), prazosin (Minipress), and terazosin (Hytrin) but not tamsulosin (Flomax)--tadalafil can cause a significant drop in blood pressure. Similarly, concomitant use of nitrates (including recreational nitrates known as "poppers") with tadalafil also is contraindicated. For life-threatening situations, nitrates may be considered if at least 48 hours have passed since the last dose of tadalafil and if close hemodynamic monitoring is available. Tadalafil will lower blood pressure an additional 4 to 10 mm Hg when used with antihypertensive drugs. Dosage should be limited to 10 mg within a 72-hour period when patients are also taking drugs such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), protease inhibitors, and other drugs that inhibit the CYP3A4 enzyme system. (1)

Patients with cardiovascular diseases have been excluded from studies of tadalafil because so little is known about its safety profile in this population. (1) The current recommendation for patients who experience coital angina after taking a PDE5 inhibitor is to contact emergency services that provide transport to a hospital. (2) Rare reports of priapism have been reported with all of the drugs in this class. (1) Long-term safety has not been established. Because of tadalafil's long duration of action, patients are exposed to its effects for a longer period of time than with sildenafil or vardenafil. (3,4)

Tolerability

The most common dose-related side effects of tadalafil are headache (11 to 15 percent) and dyspepsia (8 to 10 percent). Back pain, beginning 12 to 24 hours after the dose and lasting for up to 48 hours, was reported in 5 to 6 percent of men, as compared with a rate of 3 percent in men receiving placebo. Changes in color vision, which has been reported with sildenafil, has been reported in less than 0.1 percent of patients in clinical trials of tadalafil. (1) Tadalafil differs from sildenafil in its affinity for PDE6 and 11, which may account for fewer reported ocular effects and more reports of back pain with tadalafil than with sildenafil. (3)

Effectiveness

The main outcomes studied in the treatment of ED are achievement of an erection, successful intercourse, and overall satisfaction with sexual function. In five studies evaluating tadalafil in 5-, 10-, and 20-mg doses versus placebo, 321 men were assigned to a 10-mg regimen. In this group, 68 to 77 percent of men reported an erection suitable for insertion, compared with 42 to 55 percent receiving placebo (number needed to treat [NNT]=4 to 4.5). However, slightly fewer men reported successful intercourse (51 to 70 percent, NNT=4 to 5). (1,5) The satisfaction with intercourse was 9.3 out of a maximum score of 15, compared with a score of 7.4 in patients taking placebo, and overall satisfaction was 6.7 out of a possible 10 with tadalafil compared with 5.2 in patients taking placebo. (5) As with the other drugs in this class, overall effectiveness is diminished in patients with diabetes or ED. Tadalafil has not been studied in patients with antidepressant-induced ED. No studies have directly compared tadalafil with sildenafil or vardenafil, but overall success rates have been comparable among the three options.

Price

The cost per dose of tadalafil is comparable to sildenafil or vardenafil and, if sexual activity is desired weekly, the cost is about $39 per month. As a result of its long duration of action, fewer doses of tadalafil may be needed, resulting in a small savings over time.

Simplicity

The usual dose of tadalafil is 10 mg, no more than once per day, taken orally at least 30 to 60 minutes before sexual activity. Its effect may last up to 36 hours. (1,6) The dose can be increased to 20 mg if necessary. Safe dosing of tadalafil includes downward dosage adjustment to 5 mg in patients with moderate to severe renal insufficiency. In patients with mild to moderate hepatic dysfunction, the tadalafil dose should not exceed 10 mg. Tadalafil is not recommended in patients with severe hepatic dysfunction.

Bottom line

Like other PDE5 inhibitors, tadalafil effectively improves the ability of men with erectile dysfunction to achieve an erection and successfully complete intercourse. It is less effective, although still useful, in some men with ED due to diabetes. Its longer duration may require less frequent dosing and may allow the user to take it earlier in the day of planned sexual activity. However, some authorities suggest that, because the sildenafil safety record is more established, it may be preferred over tadalafil. (4)

References

(1.) Package Insert. Cialis. Eli Lilly and Company. Accessed online June 21, 2004, at: http://pi.lilly.com/us/cialis-pi.pdf.

(2.) Debusk RF. Sexual activity in patients with angina. JAMA 2003;290:3129-32.

(3.) Gresser U, Gleiter CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE5 inhibitors sildenafil, vardenafil and tadalafil (review of the literature). Eur J Med Res 2002;8:435-46.

(4.) [No authors listed]. Tadalafil (Cialis) for erectile dysfunction. Med Lett Drug Ther 2003;45:101-2.

(5.) Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins C, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168(4 Pt 1):1332-6.

(6.) Porst H, Padma-Nathan H, Giuliano F, Anglin G, Varanese L, Rosen R. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology 2003;62:121-6.

JOHN A. NOVIASKY, PHARM.D., is clinical pharmacy coordinator, St. Elizabeth Medical Center; Utica, NY, and faculty member, St. Elizabeth Family Medicine Residency Program, Utica.

ASIF MASOOD, M.D., is third-year resident, St. Elizabeth Family Medicine Residency Program, St. Elizabeth Medical Center.

VINCENT LO, M.D., is clinical assistant professor of family medicine, State University of New York, Upstate Medical University, Syracuse, and associate program director, St. Elizabeth Family Medicine Residency Program.

COPYRIGHT 2004 American Academy of Family Physicians
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