TESTOSTERONE GEL 1% — 25 mg, 50 mg packets; metered-dose pump

Testosterone gel 1% is a topical formulation of the primary male androgen, approved for testosterone replacement therapy in adult men with confirmed hypogonadism. It provides continuous transdermal delivery of testosterone over 24 hours following a single daily application to intact, clean, dry skin of the shoulders, upper arms, and/or abdomen. Approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-hour period .

Mechanism of action: Testosterone and its active metabolite dihydrotestosterone (DHT) are responsible for the normal growth and development of male sex organs and maintenance of secondary sex characteristics. These effects include growth and maturation of prostate, seminal vesicles, penis, scrotum; development of male hair distribution; laryngeal enlargement; vocal cord thickening; alterations in body musculature; and fat distribution . Androgens also promote retention of nitrogen, sodium, potassium, phosphorus, and decrease urinary calcium excretion. They stimulate red blood cell production by enhancing erythropoietin production .

Hypogonadism diagnosis: Male hypogonadism results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations. Symptoms include decreased sexual desire with or without impotence, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics, and osteoporosis . Prior to initiating therapy, diagnosis must be confirmed by measuring morning serum testosterone on at least two separate days with concentrations below the normal range .

Pharmacokinetics: With single daily applications of 50 mg and 100 mg, follow-up measurements confirm that serum testosterone and DHT concentrations are generally maintained within the normal range. Mean steady-state testosterone concentration with 100 mg daily is approximately 612 ng/dL; with 50 mg daily, approximately 365 ng/dL . The skin serves as a reservoir for sustained release. Washing 2 or more hours post-application still maintains testosterone levels within the normal range, but washing earlier lessens levels .

• Men with carcinoma of the breast or known or suspected prostate cancer .
• Women who are pregnant. Testosterone may cause fetal harm .
• Hypersensitivity to testosterone or any component of the formulation .

• Insulin and oral antidiabetics: Androgens may decrease blood glucose and insulin requirements. Monitor diabetic patients closely .
• Oral anticoagulants (warfarin): Changes in anticoagulant activity may occur. More frequent monitoring of INR and prothrombin time is recommended .
• Corticosteroids (ACTH, glucocorticoids): Increased risk of fluid retention. Use with caution in patients with cardiac, renal, or hepatic disease .
• Cyclosporine: Androgens may increase cyclosporine levels; monitor for toxicity .

• Pregnancy: Contraindicated. Testosterone can cause virilization of female fetus. Pregnant women must avoid any exposure .
• Lactation: Not indicated for women; excretion in milk unknown.
• Pediatric use: Safety and efficacy not established in males <18 years. Improper use may affect bone growth .
• Geriatric use: Insufficient long-term safety data to assess potential risks of cardiovascular disease and prostate cancer .
• Hepatic impairment: Use with caution; monitor for edema and liver function .
• Renal impairment: Edema may be a complication; monitor closely .

• Starting dose: 50 mg of testosterone (4 pump actuations, two 25 mg packets, or one 50 mg packet) applied once daily in the morning .
• Dose adjustment: Based on total serum testosterone concentration. Can be adjusted to 50 mg, 75 mg, or 100 mg. Titrate based on serum testosterone measured periodically .
• Application sites: Apply to clean, dry, intact skin of shoulders, upper arms, and/or abdomen. Do NOT apply to genitals, chest, armpits (axillae), knees, or back .
• Administration steps:
  • Tear open packet at dotted line; squeeze entire contents into palm.
  • Apply to application site; allow to dry completely before covering with clothing.
  • Wash hands immediately with soap and water after application .
  • Avoid showering, swimming, or bathing for at least 5 hours after application .
  • Prior to skin-to-skin contact, wash application site thoroughly with soap and water .
• Flammability: Gel is alcohol-based and flammable until dry. Avoid fire, flame, or smoking until gel has dried .
• Storage: Store at room temperature 20°C to 25°C (68°F to 77°F) .

• Symptoms: Exaggerated adverse effects including priapism, edema, polycythemia, and mood changes.
• Management: No specific antidote. Discontinue testosterone gel, provide supportive care, monitor hematocrit and electrolytes. Testosterone is not effectively removed by dialysis .