Tamsulosin Capsules: A New Drug for BPH
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The alpha blocker class of drugs has become the most useful for the treatment of obstructive symptoms of benign prostatic hyperplasia (BPH). Now, Boehringer-Ingelheim has introduced tamsulosin (Flomax), a new alpha blocker that is selective for alpha-1 receptors subtype that predominate in the prostate and urinary outflow tract, while having minimal effect on alpha receptors in the blood vessels. This selectivity results in relief of obstructive symptoms with minimal effect on blood pressure.
BPH is an age-related condition that affects two-thirds of men over the age of 65 or nearly four million men in this country.
Indications
Tamsulosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia.
Potential Advantages
Tamsulosin is the first subtype-selective alpha-1 adrenergic receptor antagonist. It selectively antagonizes the alpha 1A receptor, which is the predominate alpha adrenoreceptor in the prostate, prostatic urethra, and bladder neck. This selectivity allows tamsulosin to relax the smooth muscles of the urinary tract with no significant effect on blood pressure. In clinical trials, there were generally no clinically significant changes in blood pressure or pulse rate between tamsulosin and placebo in both hypertensive and normotensive patients.1,2 The incidence of side effects normally attributed to non-selective alpha-1 antagonists such as dizziness, headache, and postural hypotension were generally no more common with tamsulosin than with placebo.1 Because of the lack of cardiovascular effects, dose titration is generally not needed for this drug as it is for nonselective alpha blockers.
Clinical trials have shown that tamsulosin produces a significant improvement in maximum urinary flow rate and symptoms scores compared to placebo. The improvement in maximum urinary flow rates was 13-18% (mean, approximately 1.6 mL/sec); improvement in total Boyarsky symptoms scores was about 35% and in AUA scores, 28-49%.1-4 Overall, there are no significant differences between the 0.8 mg and 0.4 mg doses; however, one study did show a greater efficacy with the 0.8 mg dose.3 Two-year follow-up data from European studies were reported at a recent AUA annual meeting. At the 0.4 mg dose, 75% of patients were total Boyarsky symptoms score responders, and about 30% were maximum urinary flow rate responders.5
Potential Disadvantages
Abnormal (retrograde) ejaculation or decreased volume of ejaculation (4.5%) are the most common side effects reported from tamsulosin use.4 In a two-year follow-up trial, 13% of patients discontinued due to adverse events, mainly dizziness and abnormal ejaculation.5 While the incidence of reported signs and symptoms of orthostasis was generally comparable between tamsulosin and placebo, orthostasis (i.e., changes in systolic or diastolic blood pressure, pulse rate, or clinical symptoms upon standing from a supine position) was detected about twice as often in the tamsulosin than in the placebo group.3 Despite the receptor specificity, the potential risk for syncope exists. Cimetidine significantly reduces the clearance of tamsulosin, and these drugs should not be used concomitantly.3 Tamsulosin is extensively metabolized via the cytochrome P450 system. The possibility of interaction with other drugs exists, but this has not been adequately studied to characterize these potential interactions.
Dosing Information
Tamsulosin is supplied in 0.4 mg controlled-release capsules. The recommended dose is 0.4 mg once daily taken about 30 minutes following the same meal each day. Taking the drug on an empty stomach significantly increases the peak concentration of tamsulosin and may increase the potential for side effects. For those who fail to respond to 0.4 mg after 2-4 weeks, the dose can be increased to 0.8 mg once daily. If dosing is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once daily.3
Comments
Tamsulosin is a selective adrenergic alpha 1A receptor subtype antagonist, the type of receptors that predominate in the prostate and urinary outflow tract. It has greater affinity for these receptors than prazosin, doxazosin, or terazosin.6 The selectivity allows the drug to relax the smooth muscles of the prostate, prostatic urethral, and bladder base with minimal effect on vascular smooth muscle tone. The drug is effective and seems to have minimal side effects. There are no published trials between tamsulosin and doxazosin and terazosin. A small trial (n = 40), in abstract form only, reported that tamsulosin 0.2 mg was comparable in efficacy to prazosin 3 mg.7
Clinical Implications
Benign prostatic hyperplasia is a common condition in men over the age of 50. Common symptoms include dysuria, nocturia, urgency, burning, hesitancy, straining, dribbling, and incomplete emptying of the bladder. Treatment includes watchful waiting, surgery, or pharmacotherapy. Pharmacotherapy includes antiandrogens (i.e., finasteride) or alpha-adrenergic blockers. The alpha-adrenergic blockers seem to be the most effective pharmacotherapy.8
While alpha-adrenergic blockers are effective and generally well tolerated, some patients (10-15%) develop significant side effects such as dizziness, headache, syncope, and hypotension.9 The greater receptor selectivity of tamsulosin may offer an alternative for patients who develop significant cardiovascular side effects of less selective agents. The cost of tamsulosin is $1.30 per day for 0.4 mg, which is similar to terazosin (Hytrin), at $1.40/day, more than doxazosin (Cardura) at $1.00/day, and significantly more expensive than prazosin, which is available generically at $0.20/day.
References
1. Chapple CR, et al. Eur Urol 1996;29:155-167.
2. Abrams P, et al. Br J Urol 1995;76:325-336.
3. Flomax Product Information. Boehringer Ingelheim; 1997.
4. Schulman CC, et al. Eur Urol 1996;29:145-154.
5. F-D-C ReportsThe Pink Sheet. April 21, 1997.
6. Wilde MI, et al. Drugs 1996;52:883-898.
7. Hayashida S, et al. (abstract) 23rd Congress of the Societe Internationale d’Urologie. Sept. 18-22, Sidney, Australia.
8. Lepor H, et al. N Engl J Med 1996;335:533-539.
9. Geller J, et al. J Clin Endocrinol Metab 1995;80:745-756.
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