ADVERSE REACTIONS
Clinical Studies Experience
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 trials of another drug and may not reflect the rates observed in practice.
In a controlled clinical study, 304 patients were treated with Testim® 50 mg or 100 mg or placebo gel for up to 90 days. Two hundred-five (205) patients received Testim 50 mg or 100 mg daily and 99 patients received placebo. Subjects could be counted in both Testim treatment groups if they received both 50 mg and 100 mg at different points in the study and experienced an adverse reaction at both dose levels. Adverse reactions reported by ≥1% of the Testim patients and greater than placebo are listed in Table 1.
Table 1: Incidence of Adverse Reactions (Reported by ≥1% of the
Testim Patients and Greater than Placebo) in the Controlled Clinical
Trial Through 90 Days
|
| Event |
Testim
50 mg
(n=103) |
Testim
100 mg
(n=149) |
Placebo
(n=99) |
| Application Site Reactions |
2% |
4% |
3% |
| Blood Pressure Increased |
1% |
1% |
0% |
| Gynecomastia |
1% |
0% |
0% |
| Headache |
1% |
1% |
0% |
Hematocrit/hemoglobin
Increased |
1% |
2% |
0% |
| Hot Flushes |
1% |
0% |
0% |
| Insomnia |
1% |
0% |
0% |
| Mood Swings |
1% |
0% |
0% |
| Smell Disorder |
1% |
0% |
0% |
Spontaneous Penile
Erection |
1% |
0% |
0% |
| Taste Disorder |
1% |
1% |
0% |
The following adverse reactions occurred in fewer than 1% of patients but were greater in Testim groups compared to the placebo group: activated partial thromboplastin time prolonged, blood creatinine increased, prothrombin time prolonged, appetite increased, sensitive nipples, and acne.
In this clinical trial of Testim, six patients had adverse reactions that led to their discontinuation. These events included: depression with suicidal ideation, urinary tract infection, mood swings and hypertension. No Testim patients discontinued due to skin reaction. In one foreign Phase 3 trial, one subject discontinued due to a skin-related adverse reaction.
In the pivotal U.S. and European Phase 3 trials combined, at the 50 mg dosage strength, the percentage of subjects reporting clinically notable increases in hematocrit or hemoglobin were similar to placebo. However, in the 100 mg dose group, 2.3% and 2.8% of patients had a clinically notable increase in hemoglobin (≥ 19 g/dL) or hematocrit (≥ 58%), respectively, compared to 1.0% and 1.5% of patients in the placebo group, respectively.
In the combined US and European open label extension studies, approximately 140 patients received Testim for at least 6 months. The results from these studies are consistent with those reported for the US controlled clinical trial.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of testosterone gel products. Because the 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.
Secondary Exposure to Testosterone in Children
Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or of the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabrics, such as towels and sheets [see Warnings and Precautions ].
Vascular Disorders
Venous thromboembolism [see Warnings and Precautions]
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