TESTIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TESTIM (TESTIM).
Testosterone replacement therapy; binds to and activates androgen receptors, modulating gene expression leading to male sexual development and maintenance of secondary sexual characteristics.
| Metabolism | Primarily hepatic via CYP3A4 and other CYPs; metabolites undergo glucuronidation and excretion in urine. |
| Excretion | Testosterone is primarily excreted in urine as glucuronide and sulfate conjugates (approximately 90%), with about 6% excreted in feces via bile. Less than 1% is excreted unchanged. |
| Half-life | Terminal elimination half-life of testosterone from serum is approximately 10-100 minutes after intravenous administration, but after transdermal application of Testim, the apparent half-life is longer (around 1-2 hours) due to continued absorption from the skin depot. The half-life of active metabolites (e.g., dihydrotestosterone) is about 2-3 hours. |
| Protein binding | Approximately 97-99% bound: mainly to sex hormone-binding globulin (SHBG) (about 40-50%) and albumin (about 50-60%), with a small fraction bound to corticosteroid-binding globulin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 1 L/kg, indicating extensive distribution into tissues. Pseudoequilibrium volume of distribution after transdermal application is about 28 L (for a 70 kg individual), suggesting significant partitioning into muscle and fat. |
| Bioavailability | Transdermal gel (Testim 1%): Approximately 10% of the applied dose is systemically absorbed; bioavailability is about 9-14% of the applied amount. Oral testosterone has negligible bioavailability (<1%) due to first-pass metabolism. |
| Onset of Action | Transdermal gel: Serum testosterone levels rise within 30 minutes of application, reaching therapeutic levels within 2-4 hours. Clinical effects (e.g., libido improvement) may be noticed within 1-2 weeks. |
| Duration of Action | Testim 1% gel applied once daily maintains serum testosterone within normal range for 24 hours with consistent daily application. Clinical effects persist throughout treatment duration; discontinuation leads to return of hypogonadal symptoms within weeks. |
Apply 5 g (1 tube) of 1% gel to clean, dry, intact skin of the shoulders, upper arms, or abdomen once daily, preferably in the morning. Dosage may be adjusted to 10 g (2 tubes) depending on clinical response. Apply immediately after opening and avoid bathing or swimming for at least 30 minutes.
| Dosage form | GEL |
| Renal impairment | No specific dose adjustment required for renal impairment. Use caution in severe renal impairment due to potential for reduced clearance of testosterone metabolites. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment (Child-Pugh class A or B), use with caution; start at lowest dose and monitor serum testosterone levels and hepatic function. |
| Pediatric use | Not indicated for use in pediatric patients under 18 years of age. Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment recommended solely based on age. However, elderly patients may be more sensitive to androgenic effects; monitor for prostatic hypertrophy, edema, and sleep apnea. Consider lower initial doses (e.g., 5 g daily) and titrate based on clinical response and serum testosterone levels. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TESTIM (TESTIM).
| Breastfeeding | Excretion into breast milk is unknown; however, testosterone may suppress lactation and cause virilization in the infant. The M/P ratio has not been determined. Breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Testosterone is classified as Pregnancy Category X. Use is contraindicated during pregnancy due to the risk of virilization of the female fetus, including clitoromegaly, labial fusion, and urogenital sinus abnormalities. Risks apply across all trimesters. |
| Fetal Monitoring |
■ FDA Black Box Warning
Testosterone has been associated with increased risk of cardiovascular events (myocardial infarction, stroke) and venous thromboembolism. Use with caution in patients with cardiovascular disease.
| Serious Effects |
Known hypersensitivity to testosterone or any component; history of or suspected prostate cancer; breast cancer; active thrombophlebitis or thromboembolic disorders; severe hepatic or renal impairment; pregnancy or lactation.
| Precautions | Risk of cardiovascular events, venous thromboembolism, erythrocytosis, sleep apnea exacerbation, prostatic hypertrophy, and hepatotoxicity; monitor hematocrit and serum testosterone levels. |
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| Monitor maternal blood pressure, lipid profile, hematocrit/hemoglobin, and liver function tests periodically. Perform pregnancy tests prior to initiation and during therapy if pregnancy is suspected. Assess fetal development via ultrasound if inadvertent exposure occurs. |
| Fertility Effects | Exogenous testosterone can suppress spermatogenesis by inhibiting FSH and LH, leading to reversible infertility in males. In females, adverse effects on ovarian function and fertility may occur due to hormonal imbalance. |