WARNINGS
- Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) have been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Testosterone is not known to produce these adverse effects.
- Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.
- Geriatric patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy. In men receiving testosterone replacement therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility and Laboratory Tests).
- Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
- Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.
- The treatment of hypogonadal men with testosterone esters may potentiate sleep apnea in some patients especially those with risk factors such as obesity or chronic lung diseases.
PRECAUTIONS
Striant® is applied to the upper gum just above the incisor tooth on either side of the mouth. Long-term data on gum safety is available for 117 patients and 51 patients with at least 6 months and 1 year of exposure, respectively. While the available data supports the overall oral safety of Striant®, longer-term data is not currently available and studies continue. Until such longer-term data become available, it is recommended that patients regularly inspect their own gum region where Striant® is applied. Any abnormal finding should be brought promptly to the attention of the patient's physician. In such circumstances, dental consultation may be appropriate.
General
The physician should instruct patients to report any of the following:
- Too frequent or persistent erections of the penis.
- Any nausea, vomiting, changes in skin color, or ankle swelling.
- Breathing disturbances, including those associated with sleep.
Information for Patients
Advise patients to carefully read the attached patient leaflet accompanying each carton of Striant® blister packaged tablets.
Advise patients to regularly inspect the gum region where they apply Striant® and to report any abnormality to their health care professional.
Laboratory Tests
- Hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia) in patients on long-term androgen therapy.
- Liver function, prostate specific antigen (PSA), cholesterol and high-density lipoprotein should be checked periodically.
- Serum total testosterone concentrations may be checked four to twelve weeks after initiating treatment with Striant®. To capture the maximum serum concentration, an early morning sample (just prior to applying the A.M. dose) is recommended. In the infrequent circumstance where the total testosterone concentration in this sample is excessive, therapy with Striant® should be discontinued and an alternative treatment considered.
Drug interactions
Oxyphenbutazone
Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
Insulin
In diabetic patients, the metabolic effects of androgens may decrease blood glucose and therefore, insulin requirements.
Corticosteroids
Concurrent administration of testosterone with ACTH or corticosteroids may enhance edema formation and should be administered cautiously, particularly in patients with cardiac or hepatic disease.
Drug/Laboratory Test Interactions
Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Carcinogenesis, mutagenesis, impairment of fertility
Animal data
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.
Human data
There were rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases.
Striant® has been evaluated in patients for 1 year without reports of cancer related to the product. However, safety in patients beyond 1 year has not been established.
Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.
Geriatric patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy.
In men receiving testosterone replacement therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men.
Pregnancy Category X
(see CONTRAINDICATIONS)
Teratogenic Effects
Striant® is not indicated for women and must not be used in women.
Labor and Delivery
Striant® is not indicated for women and must not be used in women.
Nursing Mothers
Striant® is not indicated for women and must not be used in women.
Pediatric Use
Safety and effectiveness in pediatric male patients below the age of 18 have not yet been established
Geriatric Use
Of the total number of subjects in clinical studies of Striant®, 51 patients (16.5 percent) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, in Study 1, in patients 65 years of age and older, the total testosterone C avg(0-24) value was higher by 12.7% compared to patients less than 65 years of age. In addition, the total T to DHT area-under-the curve ratio was lower in the older population compared to the younger population by 15.6%. These differences may not be clinically significant.
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