WARNINGS AND PRECAUTIONS
Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer
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•Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.
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•Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications (4),
Adverse
reactions (6.1) and Nonclinical Toxicology].
Potential for Secondary Exposure to Testosterone
Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. 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. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of testosterone gel. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see Dosage and Administration (2.2), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].
Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified.
Polycythemia
Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.
Venous Thromboembolism
There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone gel. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone gel and initiate appropriate workup and management [see Adverse Reactions (6.2)].
Use in Women
Due to lack of controlled evaluations in women and potential virilizing effects, testosterone gel is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.3)].
Potential for Adverse Effects on Spermatogenesis
At large doses of exogenous androgens, including testosterone gel; spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.
Hepatic Adverse Effects
Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has 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 intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone gel is not known to produce these adverse effects.
Edema
Androgens, including testosterone gel, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease [see Adverse Reactions (6.2)].
Gynecomastia
Gynecomastia may develop and may persist in patients being treated with androgens, including testosterone gel, for hypogonadism.
Sleep Apnea
The treatment of hypogonadal men with testosterone products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases [see Adverse Reactions (6.2)].
Lipids
Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.
Hypercalcemia
Androgens, including testosterone gel, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.
Decreased Thyroxine-binding Globulin
Androgens, including testosterone gel, may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Flammability
Alcohol based products including testosterone gel are flammable; therefore patients should be advised to avoid fire, flame or smoking until the testosterone gel has dried.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category X [see Contraindications (4
) ]:
Testosterone gel is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens, such as testosterone, may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Nursing Mothers
Although it is not known how much testosterone transfers into human milk, testosterone gel is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation. [see
Contraindications (4)].
Pediatric Use
Safety and efficacy of testosterone gel in pediatric males less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.
Geriatric Use
There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel to determine whether efficacy in those over 65 years of age differs from younger subjects. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer.
Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.
Renal Impairment
No studies were conducted involving patients with renal impairment.
Hepatic Impairment
No studies were conducted in patients with hepatic impairment.
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