2% 0.3%
Tamsulosin 2.2% 0.5% 0.5% 0.2% 0.3%
Impotencec
Coadministration 5.4% 1.1% 1.8% 0.9% 0.4%
Dutasteride 4.0% 1.1% 1.6% 0.6% 0.3%
Tamsulosin 2.6% 0.8% 1.0% 0.6% 1.1%
Decreased libidod
Coadministration 4.5% 0.9% 0.8% 0.2% 0.0%
Dutasteride 3.1% 0.7% 1.0% 0.2% 0.0%
Tamsulosin 2.0% 0.6% 0.7% 0.2% <0.1%
Breast disorderse
Coadministration 1.1% 1.1% 0.8% 0.9% 0.6%
Dutasteride 0.9% 0.9% 1.2% 0.5% 0.7%
Tamsulosin 0.4% 0.4% 0.4% 0.2% 0.0%
Dizziness
Coadministration 1.1% 0.4% 0.1% <0.1% 0.2%
Dutasteride 0.5% 0.3% 0.1% <0.1% <0.1%
Tamsulosin 0.9% 0.5% 0.4% <0.1% 0.0%
a Coadministration = AVODART 0.5mg once daily plus tamsulosin 0.4mg once daily.
b Includes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure, and premature ejaculation.
c Includes erectile dysfunction and disturbance in sexual arousal.
d Includes libido decreased, libido disorder, loss of libido, sexual dysfunction, and male sexual dysfunction.
e Includes breast enlargement, gynecomastia, breast swelling, breast pain, breast tenderness, nipple pain, and nipple swelling.
Cardiac Failure: In CombAT, after 4years of treatment, the incidence of the composite term cardiac failure in the coadministration group (12/1,610; 0.7%) was higher than in either monotherapy group: dutasteride, 2/1,623 (0.1%) and tamsulosin, 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial eva luating dutasteride in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking dutasteride was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both studies had co-morbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between dutasteride, alone or coadministered with tamsulosin, and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either study.
Additional information regarding adverse reactions in placebo-controlled trials with dutasteride or tamsulosin monotherapy follows:
Dutasteride:
Long-Term Treatment (Up to 4 Years): High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75years with a serum PSA of 2.5ng/mL to 10ng/mL and a negative prostate biopsy within the previous 6months. Subjects were randomized to receive placebo (N=4,126) or 0.5-mg daily doses of dutasteride (N=4,105) for up to 4years. The mean age was 63years and 91% were Caucasian. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving dutasteride (1.0%) compared with men on placebo (0.5%) [see Indications and Usage (1.2), Warnings and Precautions (5.4)]. In a 7-year placebo-controlled clinical trial with another 5 alpha-reductas |
