Objective
ALFOTAM is a Sanofi-Synthelabo Inc. trial; the data are available on the Food and Drug Administration Web site. A multicenter, multinational, randomized, placebo-controlled, double-blind, phase III trial, ALFOTAM assessed the efficacy and safety of two dosage levels of alfuzosin Geomatrix (10 mg OD* and 15 mg OD*) vs tamsulosin 0.4 mg and placebo in patients with symptomatic BPH.1
Design
A total of 625 patients were randomized to treatment. A 28-day, single-blind, placebo run-in period was followed by a 3-month, double-blind, double-dummy treatment period during which patients received either alfuzosin 10 mg OD,* tamsulosin 0.4 mg, alfuzosin 15 mg OD* or placebo once a day. Six visits were planned: a screening visit (D-28), an inclusion visit (D0), three intermediate visits (D14, D28 and D58) and an endpoint visit (D84).1
Inclusion/Exclusion Criteria
The study population consisted of men older than 50 years of age with symptomatic BPH diagnosed within three months prior to treatment randomization. Patients had a mean International Prostate Symptom Score (IPSS) ≥13, nocturia ≥2 voids per night, a Qmax of 5 to 12 cc/sec with a voided volume of at least 150 cc, a residual urine volume <350 cc, and at least three months of voiding disturbances. Exclusion criteria included1:
- "bad" compliance during the screening period
- urologic disease other than BPH
- previous prostate surgery
- other invasive procedures for the treatment of BPH
- patients previously unimproved with α-blocker therapy
- those diagnosed with a lower urinary tract infection or a medical condition that would interfere with the efficacy or safety assessment
- patients with a history of orthostatic hypotension or syncope
- patients who received α-blockers within 1 month of study entry
- patients who received androgens, antiandrogens, 5 α-reductase inhibitors, or luteinizing hormone-releasing hormone analogues within 3 months of study entry
Efficacy variables
The primary efficacy endpoints for this study were the mean change from baseline to endpoint in IPSS and mean change from baseline to endpoint in Qmax. Secondary efficacy endpoints included:
- improvement in nocturia
- quality-of-life index
- Urolife scale
- sexual function questionnaire
- Clinical Global Impression
- mean urinary flow rate
- postvoid residual urine measured by transrectal ultrasonography.1
*OD = once daily.
Important Safety Information
Flomax® (tamsulosin HCl) capsules are indicated to treat the signs and symptoms of benign prostatic hyperplasia (BPH). FLOMAX is not indicated to treat hypertension.
FLOMAX is contraindicated in patients who are hypersensitive to tamsulosin HCl or any of its components.
As with other alpha-adrenergic blocking agents, there is a potential risk of syncope. When beginning treatment, or increasing the dose of FLOMAX, patients should be cautioned to avoid driving or performing hazardous tasks where injury could result should syncope occur.
FLOMAX capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g.,ketoconazole).
Rarely (probably less than 1 in 50,000 patients) FLOMAX, like other alpha-1 antagonists, has been associated with priapism. Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition.
Carcinoma of the prostate and BPH cause many of the same symptoms. Patients should be evaluated prior to the start of FLOMAX capsules therapy to rule out the presence of carcinoma of the prostate.
Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha-1 blockers, including FLOMAX capsules. Patients should be advised that if they are considering cataract surgery, to tell their ophthalmologist that they have taken FLOMAX capsules.
In patients with sulfa allergy, allergic reaction to FLOMAX capsules has been rarely reported. If a patient reports a serious or life-threatening sulfa allergy, caution is warranted.
FLOMAX capsules should NOT be used in combination with other alpha-adrenergic blocking agents. Caution is advised when alpha-adrenergic blocking agents, including FLOMAX, are co-administered with PDE 5 inhibitors, as this can potentially cause symptomatic hypotension.
FLOMAX capsules (particularly at a dose higher than 0.4 mg) should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, or in patients known to be CYP2D6 poor metabolizers.
Caution should be exercised with concomitant administration of warfarin and FLOMAX and should be used with caution in combination with cimetidine, particularly at doses higher than 0.4 mg.
The most common side effects are dizziness, abnormal ejaculation, and rhinitis.
Before prescribing FLOMAX, please see the Full Prescribing Information.
1. Center for Drug Evaluation and Research. Food and Drug Administration Web site. Available at: http://www.fda.gov/cder/foi/nda/2003/021287_uroxatral_toc.htm. Accessed July 12, 2006.
