Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia

Abstract

Background: Benign prostatic hyperplasia (BPH) is a common condition in aging men causing lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease progression. Of the different alpha-1 adrenergic receptors (ARs) in the prostate, alpha-1a receptors are known to be central to prostatic smooth-muscle contraction. Recent studies have shown that patients with BPH may also have a predominance of alpha-1d receptors.

Objectives: To evaluate the efficacy and adverse effects of naftopidil, a selective alpha-1d oral alpha-blocking agent for the treatment of LUTS associated with BPH.

Search strategy: Systematic review of trials published January 1950 to January 2009. Sources included MEDLINE and bibliographies of retrieved articles and review articles.

Selection criteria: Eligible trials included: men diagnosed with symptomatic BPH; compared Naftopidil to placebo, control, or combination therapy; evaluated clinically relevant outcomes between randomized groups; had at least 4-weeks follow up; and were published in English language.

Data collection and analysis: Participant demographics and comorbidities, enrollment criteria, outcomes, adverse events, numbers and reasons for dropouts were extracted onto standardized extraction forms by one reviewer. The mean change and per cent improvement from baseline in AUA (American Urological Association Symptom Score) and IPSS (International Prostate Symptom Score) scores and other efficacy outcomes for treatment and control groups were calculated. If feasible, the efficacy outcomes and adverse events data were pooled.

Main results: Eight trials were eligible (N = 744 participants). All trials were conducted in Japan. Study duration ranged from 4 to 17 weeks. The mean age of participants was 68 years; pretreatment mean IPSS = 17.8 and mean peak urine flow (Qmax) = 9.5 mL/s (milliliters/second). No trials compared naftopidil to placebo. In 5 trials (N = 419), naftopidil in doses of 25 to 75 mg/d (milligrams/day) showed a mean IPSS improvement similar to low-dose tamsulosin (0.2 mg/d) (8.4 versus 8.9 points). Compared to a phytotherapy preparation (eviprostat), naftopidil significantly improved total IPSS (-5.9 versus 0.4; P < 0.0002). In one trial, the addition of anticholinergic drugs (oxybutynin or propiverine hydrochloride) to naftopidil did not offer any significant improvement for IPSS or Qmax in comparison to treatment with naftopidil alone. Although IPSS did not significantly differ between high- (75 mg/d) and low-dose (25mg/d) naftopidil, high dose significantly improved Qmax compared to low dose (1.2 mL/s versus 0.2 mL/s). Adverse events reported were few, mild and similar to those seen with 0.2 mg/d tamsulosin.

Authors' conclusions: There are no data from placebo controlled trials regarding the efficacy of naftopidil in men with symptomatic BPH. Limited information suggests that treatment with naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to naftopidil were few and usually mild.