There are no controlled clinical trial data with testosterone cypionate injection in the geriatric male (> 65 years of age) to support the efficacy and safety of prolonged use. Impacts to prostate and cardiovascular event rates and patient important outcomes are unknown.
DEPO-TESTOSTERONE should not be used to attempt to enhance athletic performance, or alter body composition. Efficacy and safety of DEPO-TESTOSTERONE use for such purposes have not been established. Patients should be counselled concerning the serious long-term deleterious health issues that are associated with testosterone and anabolic steroid abuse. (See WARNINGS AND PRECAUTIONS; Addiction, Abuse, Misuse and also WARNINGS AND PRECAUTIONS; Dependence)
If testosterone deficiency has not been established, testosterone replacement therapy should not be used for the treatment of sexual dysfunction.
Clinical studies have not established testosterone replacement therapy as a treatment for male infertility.
DEPO-TESTOSTERONE contains benzyl alcohol. The preservative benzyl alcohol has been associated with serious adverse events, including the “gasping syndrome”, and death in pediatric patients. Premature and low-birth weight infants may be more likely to develop toxicity.
Testosterone cypionate should not be used interchangeably with testosterone propionate because of differences in the duration of action.
Addiction, Abuse and Misuse
DEPO-TESTOSTERONE contains testosterone, a Schedule G controlled substance as defined by the Food and Drugs Act.
Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious adverse effects, including psychiatric effects and effects on the cardiovascular system, which may be fatal (see OVERDOSAGE, Chronic overdosage caused by abuse).
If testosterone abuse is suspected, serum testosterone concentrations should be checked to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives.
Carcinogenesis and Mutagenesis
Please see also TOXICOLOGY, Human Data.
Prostatic: Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma (see Special Populations – Geriatrics).
Breast: Patients using long-term testosterone replacement therapy may be at an increased risk for the development of breast cancer.
Hepatic: Prolonged use of high doses of orally active 17-α alkyl-androgens (e.g. methyltestosterone) has been associated with serious hepatic effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular administration of testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas.
Skeletal: Patients with skeletal metastases are at risk of exacerbating hypercalcemia/hypercalciuria with concomitant androgen therapy.
Testosterone may increase blood pressure and should be used with caution in patients with hypertension.
Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease. Diuretic therapy may be required, in addition to discontinuation of the drug.
Some post-market studies suggest increased risk of serious cardiovascular events such as myocardial infarction and stroke associated with testosterone therapy. Patients should be informed of this possible risk when deciding whether to use or to continue to use Depo-Testosterone (testosterone cypionate injection). Before starting testosterone therapy, patients should be assessed for any cardiovascular risk factors (e.g. existing ischaemic heart disease) or prior history of cardiovascular events (e.g. myocardial infarction, stroke, or heart failure). Patients should also be closely monitored for possible serious cardiovascular events while on testosterone therapy. If any of these serious adverse events are suspected, treatment with Depo-Testosterone should be discontinued and appropriate assessment and management initiated.
Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.
Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.
Endocrine and Metabolism
Androgens have been shown to alter glucose tolerance tests. Diabetics should be followed carefully and the insulin or oral hypoglycemic dosage adjusted accordingly (see DRUG INTERACTIONS - Drug-Drug Interactions).
Hypercalciuria/hypercalcemia (caused by malignant tumours) may be exacerbated by androgen treatment. Androgens should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in patients at risk of hypercalciuria/hypercalcemia.
Hypercalcemia may occur in immobilized patients. If this occurs, the drug should be discontinued.
Hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia) in patients on long-term androgen therapy (see Monitoring and Laboratory Tests).
Alkylated derivatives of testosterone such as methandrostenolone, have been reported to decrease the anticoagulant requirement of patients receiving oral anticoagulants (e.g. warfarin). Patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped (see DRUG INTERACTIONS - Drug-Drug Interactions).
Testosterone treatment can cause chorioretinopathy. Chorioretinopathy can lead to visual disturbances.
The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, particularly for those with risk factors such as obesity or chronic lung diseases.
Gynecomastia may frequently develop and occasionally persists in patients being treated for hypogonadism.
Priapism or excessive sexual stimulation may develop.
Oligospermia may occur after prolonged administration or excessive dosage.
Inflammation and pain at the site of intramuscular injection may occur.
Pregnant Women: DEPO-TESTOSTERONE should not be used in pregnant women. Benzyl alcohol can cross the placenta. (see WARNINGS AND PRECAUTIONS, General). Testosterone may cause fetal harm. Testosterone exposure during pregnancy has been reported to be associated with fetal abnormalities. Testosterone is known to cause virilization of the external genitalia of the female fetus when administrated to pregnant women.
Nursing Women: DEPO-TESTOSTERONE should not be used in nursing women.
Pediatrics (< 18 years of age): Androgen therapy should be used cautiously in males with hypogonadism causing delayed puberty. Androgens can accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater risk of compromising final mature height. The effect of androgens on bone maturation should be monitored closely by assessing bone age of the wrist and hand on a regular basis.
Geriatrics (> 65 years of age): There are very limited controlled clinical study data supporting the use of testosterone in the geriatric population and virtually no controlled clinical studies on subjects aged 75 years and over.
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.
Monitoring and Laboratory Tests
Prior to initiating Depo-Testosterone, baseline testosterone levels should be appropriately assessed (see DOSAGE AND ADMINISTRATION, Dosing Considerations). The patients should be monitored (including serum testosterone levels) on a regular basis to ensure adequate response to treatment.
Currently there is no consensus about age specific testosterone levels. The normal serum testosterone level for young eugonadal men is generally accepted to be approximately 10.4 ‑ 34.6 nmol/L (300-1000 ng/dL). However, it should be taken into account that physiological testosterone levels are lower with increasing age. The following laboratory tests, performed routinely, are recommended to ensure that adverse effects possibly caused by or related to testosterone replacement therapy is detected and addressed:
- hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia);
- liver function tests; to detect hepatotoxicity associated with the use of 17-alpha-alkylated androgens;
- prostate specific antigen (PSA) levels, Digital Rectal Examination (DRE), especially if the patient presents with progressive difficulty with urination or a change in voiding habits;
- lipid profile, total cholesterol, LDL, HDL, and triglycerides;
- diabetics should be followed carefully and the insulin or oral hypoglycemic dosage adjusted accordingly (see DRUG INTERACTIONS - Drug-Drug Interactions).