TESTOSTERONE UNDECANOATE
Clinical safety rating: avoid
Corticosteroids may increase edema risk and anticoagulants may have increased effects Can cause polycythemia and increased risk of cardiovascular events.
Testosterone undecanoate is a prodrug of testosterone, which binds to androgen receptors (ARs) in target tissues, leading to activation of androgen-responsive genes that promote male sexual development, maintenance of secondary sexual characteristics, and anabolic effects. It also exerts negative feedback on the hypothalamic-pituitary-gonadal axis, suppressing gonadotropin secretion.
| Metabolism | Testosterone undecanoate is hydrolyzed to testosterone in the body. Testosterone is metabolized via multiple pathways: reduction to 5α-dihydrotestosterone (DHT) by 5α-reductase and to estradiol by aromatase (CYP19A1); conjugation with glucuronic acid via UDP-glucuronosyltransferases (UGTs); and oxidation by cytochrome P450 isoenzymes (e.g., CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6) to various hydroxylated metabolites. |
| Excretion | Renal (5-10% as glucuronide and sulfate conjugates, <1% as unchanged testosterone), Fecal (90% as metabolites via bile). No significant biliary excretion of active drug. |
| Half-life | Terminal elimination half-life: 20.7 days (range 16.5–25.7 days) after intramuscular injection. This prolonged half-life is due to slow release from the oily depot in muscle. With oral administration, half-life is approximately 7–13 hours. |
| Protein binding | 98% bound, primarily to sex hormone-binding globulin (SHBG) (30–40%) and albumin (60–70%). |
| Volume of Distribution | Vd: 1.0–1.2 L/kg. Distributes extensively into tissues including prostate, seminal vesicles, and skeletal muscle; clinical significance: indicates high tissue affinity and slow clearance. |
| Bioavailability | Oral: approximately 3.3% (large first-pass metabolism). Intramuscular (oily solution): 100%. |
| Onset of Action | Intramuscular injection: 7–10 days for significant increase in serum testosterone levels. Oral: 1–2 hours for peak serum concentration. |
| Duration of Action | Intramuscular injection: 8–10 weeks for clinical effect (e.g., normalization of testosterone levels in hypogonadal men). Oral: 24 hours, requiring daily dosing. |
| Action Class | Androgens |
| Brand Substitutes | Testoki 40mg Capsule, Nuvir 40mg Capsule, Andriol 40mg Capsule, Testonova 40mg Capsule, Androsar 40mg Capsule |
1000 mg intramuscularly every 10-14 weeks, followed by a second dose at 6 weeks; maintenance 1000 mg every 10-14 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; insufficient data for severe (GFR <30 mL/min) – use with caution. |
| Liver impairment | Contraindicated in Child-Pugh class C; for Child-Pugh A/B, no specific dose adjustment but monitor for fluid retention and hepatotoxicity. |
| Pediatric use | Not recommended for use in children (<18 years) due to potential premature epiphyseal closure and virilization; no established dosing. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 750 mg IM every 10-14 weeks) due to increased risk of prostatic hypertrophy, edema, and polycythemia; monitor PSA, hematocrit, and cardiovascular status. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Corticosteroids may increase edema risk and anticoagulants may have increased effects Can cause polycythemia and increased risk of cardiovascular events.
| FDA category | Contraindicated |
| Breastfeeding | Excreted in breast milk; may cause virilization in nursing infants. M/P ratio not established. Contraindicated during breastfeeding. |
| Teratogenic Risk | Androgens are contraindicated in pregnancy due to virilization of female fetus; risk is highest during first trimester when genital differentiation occurs. Second and third trimester exposure may cause clitoromegaly, labial fusion, and urogenital sinus abnormalities. Testosterone undecanoate is classified as X in pregnancy. |
■ FDA Black Box Warning
WARNING: PULMONARY OIL MICROEMBOLISM (POEM) AND ANAPHYLAXIS. Serious pulmonary oil microembolism (POEM) reactions, including cough, dyspnea, chest tightness, and throat tightening, have been reported following intramuscular injection of testosterone undecanoate. Anaphylaxis has also been reported. These reactions can occur immediately after injection. Patients should be observed for 30 minutes after each injection in a healthcare setting equipped to manage anaphylaxis. Testosterone undecanoate is not indicated for use in women.
| Serious Effects |
["Breast cancer or known or suspected prostate cancer in men.","Pregnant or breastfeeding women (testosterone may cause fetal harm).","Hypersensitivity to testosterone or any component of the formulation (e.g., castor oil, benzyl benzoate).","Men with a history of venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism) or conditions that increase thromboembolic risk.","Severe hepatic impairment.","Severe renal impairment (not recommended)."]
| Precautions | ["Cardiovascular risk: may increase blood pressure, hematocrit, and risk of venous thromboembolism; use with caution in patients with cardiovascular disease.","Polycythemia: monitor hematocrit; discontinue if levels exceed 54%.","Prostate cancer: use may increase risk; screen for prostate cancer before and during therapy.","Benign prostatic hyperplasia: may worsen symptoms.","Edema: use cautiously in patients with preexisting edema (e.g., heart failure, renal/hepatic disease).","Sleep apnea: may worsen in patients with risk factors.","Lipid profile: may decrease HDL cholesterol.","Hepatic effects: rare reports of hepatic neoplasms with high doses.","Bone growth: premature epiphyseal closure in pediatric patients.","Spermato genesis: may suppress spermatogenesis.","Psychiatric effects: may cause mood changes, aggression, depression.","Hypercalcemia: may occur in immobilized patients or those with metastatic breast cancer.","Injection site reactions: pain, swelling, nodules.","Use in women: contraindicated due to virilizing effects."] |
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| Fetal Monitoring | Monitor maternal blood pressure, lipid profile, hematocrit/hemoglobin, liver function tests, and signs of virilization. In fetus, ultrasound may assess ambiguous genitalia if exposed. |
| Fertility Effects | Exogenous testosterone suppresses endogenous gonadotropins (LH, FSH), leading to oligospermia or azoospermia in males and menstrual irregularities, anovulation in females. Effects are generally reversible upon discontinuation. |