ADVERSE REACTIONS
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 evaluated 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 to 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. Over 2 years of treatment, drug-related ejaculation disorders occurred more frequently in subjects receiving coadministration therapy (9%) compared to dutasteride (2%) or tamsulosin (3%) as monotherapy.
- Study withdrawal due to adverse reactions occurred in 5% of subjects receiving coadministered dutasteride and tamsulosin and 3% of subjects receiving dutasteride or tamsulosin as monotherapy. The most common adverse reaction leading to study withdrawal in subjects receiving coadministration therapy was impotence (1%).
In the CombAT study, over 4,800 male subjects with BPH were randomly assigned to receive either 0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride, or coadministration therapy (0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride) administered once daily in a 4-year double-blind study. Adverse reaction information over the first 2 years of treatment is presented below; information for years 2 to 4 is not yet available. During the first 2 years, 1,623 subjects received monotherapy with dutasteride; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received coadministration therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% Caucasian. Table 1 presents clinical adverse reactions considered by the investigator to be possibly drug-related for which the incidence was ≥1% in any treatment group.
Table 1. Adverse Reactions Reported Over a 24-Month Period in ≥1% of Subjects in Any Treatment Group (CombAT) by Time of Onset
| Adverse Reactions |
Adverse Reaction Time of Onset |
| Months 0-6 |
Months 7-12 |
Months 13-18 |
Months 19-24 |
| Coadministration (n)a
|
(n = 1,610) |
(n = 1,524) |
(n = 1,424) |
(n = 1,345) |
| Dutasteride (n) |
(n = 1,623) |
(n = 1,547) |
(n = 1,457) |
(n = 1,378) |
| Tamsulosin (n) |
(n = 1,611) |
(n = 1,542) |
(n = 1,468) |
(n = 1,363) |
| Ejaculation disorders |
|
|
|
|
| Combination |
7.6% |
1.6% |
0.4% |
<0.1% |
| Dutasteride |
1.1% |
0.6% |
0.1% |
0.1% |
| Tamsulosin |
2.2% |
0.5% |
0.4% |
0.1% |
| Impotence |
|
|
|
|
| Combination |
5.5% |
1.2% |
0.8% |
0.3% |
| Dutasteride |
3.9% |
1.2% |
0.6% |
0.7% |
| Tamsulosin |
2.7% |
0.8% |
0.4% |
0.4% |
| Decreased libido |
|
|
|
|
| Combination |
4.5% |
0.9% |
0.4% |
<0.1% |
| Dutasteride |
3.3% |
0.6% |
0.7% |
0.2% |
| Tamsulosin |
1.9% |
0.6% |
0.4% |
0.2% |
| Dizziness |
|
|
|
|
| Combination |
1.1% |
0.4% |
0.2% |
0.0% |
| Dutasteride |
0.4% |
0.2% |
<0.1% |
<0.1% |
| Tamsulosin |
0.9% |
0.5% |
0.3% |
0.1% |
| Breast disordersb
|
|
|
|
|
| Combination |
1.0% |
1.1% |
0.7% |
0.3% |
| Dutasteride |
0.9% |
1.0% |
0.8% |
0.5% |
| Tamsulosin |
0.4% |
0.4% |
0.2% |
0.1% |
|
a Coadministration = Dutasteride 0.5 mg once daily plus tamsulosin hydrochloride 0.4 mg once daily. |
|
b Includes breast tenderness and breast enlargement. |
Cardiac Failure: In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the co-administration group (12/1,610; 0.7%) was higher than in either monotherapy group: AVODART, 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 evaluating AVODART in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking AVODART was 0.6% (26/4,105) compared to 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 AVODART, alone or co-administered 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 controlled trials with dutasteride and tamsulosin monotherapy follows:
Dutasteride: There is no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorders) or breast disorders with increased duration of dutasteride monotherapy (up to 4 years). The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown.
Tamsulosin: According to the tamsulosin prescribing information, in two 13-week treatment trials with tamsulosin monotherapy, treatment-emergent adverse reactions occurring in ≥2% of subjects receiving 0.4 mg tamsulosin hydrochloride and at an incidence higher than in subjects receiving placebo were: infection, asthenia, back pain, chest pain, somnolence, insomnia, rhinitis, pharyngitis, cough increased, sinusitis, and diarrhea.
Signs and Symptoms of Orthostasis: According to the tamsulosin prescribing information, in clinical studies with tamsulosin monotherapy, a positive orthostatic test result was observed in 16% (81/502) of subjects receiving 0.4 mg tamsulosin hydrochloride vs. 11% (54/493) of subjects receiving placebo. Because orthostasis was detected more frequently in the tamsulosin-treated subjects than in placebo recipients, there is a potential risk of syncope [see Warnings and Precaution].
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of the individual components of JALYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to drug exposure.
Dutasteride:
Immune System Disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema.
Tamsulosin:
Immune System Disorders: Hypersensitivity reactions, including rash, urticaria, pruritus, angioedema, and respiratory problems.
Cardiac Disorders: Palpitations.
Skin Disorders: Skin desquamation.
Gastrointestinal Disorders: Constipation, vomiting.
Reproductive System and Breast Disorders: Priapism.
Vascular Disorders: Hypotension.
Ophthalmologic Disorders: During cataract surgery, a variant of small pupil syndrome known as Intraoperative floppy iris syndrome (IFIS) associated with alpha-adrenergic antagonist therapy [see Warnings and Precautions].
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