he dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time-points remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52weeks, with partial recovery at the 24-week follow-up. The clinical significance of dutasteride’s effect on semen characteristics for an individual patient’s fertility is not known.
Tamsulosin: The effects of tamsulosin hydrochloride on sperm counts or sperm function have not been eva luated.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
There have been no clinical trials conducted with JALYN; however, the clinical efficacy and safety of coadministered dutasteride and tamsulosin, which are individual components of JALYN, have been eva luated in a multicenter, randomized, double-blind, parallel group study (the Combination with Alpha-Blocker Therapy, or CombAT, study). Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice.
The most common adverse reactions reported in subjects receiving coadministered dutasteride and tamsulosin were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving coadministration therapy (11%) compared with those receiving dutasteride (2%) or tamsulosin (4%) as monotherapy.
Study withdrawal due to adverse reactions occurred in 6% of subjects receiving coadministered dutasteride and tamsulosin, and in 4% of subjects receiving dutasteride or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to study withdrawal was erectile dysfunction (1% to 1.5%).
In the CombAT study, over 4,800male subjects with BPH were randomly assigned to receive 0.5mg dutasteride, 0.4mg tamsulosin hydrochloride, or coadministration therapy (0.5mg dutasteride and 0.4mg tamsulosin hydrochloride) administered once daily in a 4-year double-blind study. Overall, 1,623subjects received monotherapy with dutasteride; 1,611subjects received monotherapy with tamsulosin; and 1,610subjects received coadministration therapy. The population was aged 49 to 88years (mean age: 66years) and 88% were Caucasian. Table1 summarizes adverse reactions reported in at least 1% of subjects receiving coadminstration therapy and at a higher incidence than subjects receiving either dutasteride or tamsulosin as monotherapy.
Table 1. Adverse Reactions Reported Over a 48-Month Period in ≥1% of Subjects and More Frequently in the Coadministration Therapy Group Than the Dutasteride or Tamsulosin Monotherapy Group (CombAT) by Time of Onset Adverse Reaction Adverse Reaction Time of Onset
Year1 Year2 Year3 Year4
Months0-6 Months7-12
Coadministrationa (n=1,610) (n=1,527) (n=1,428) (n=1,283) (n=1,200)
Dutasteride (n=1,623) (n=1,548) (n=1,464) (n=1,325) (n=1,200)
Tamsulosin (n=1,611) (n=1,545) (n=1,468) (n=1,281) (n=1,112)
Ejaculation disordersb
Coadministration 7.8% 1.6% 1.0% 0.5% <0.1%
Dutasteride 1.0% 0.5% 0.5% 0. |
