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. |
| Molecular Weight | 456.7 |
| 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 | Androgenic effects may cause virilization of female fetus; avoid use in pregnancy unless clearly needed. |
| 2nd trimester | Continued risk of virilization; avoid use. |
| 3rd trimester | Avoid use; may cause premature closure of epiphyses and virilization. |
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 |
| Placental transfer | Testosterone and its esters cross the placenta; evidence from animal studies and case reports indicates transfer and potential for fetal harm. |
| Breastfeeding |
■ 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 |
Known or suspected carcinoma of the prostateKnown or suspected carcinoma of the male breastWomen who are or may become pregnantHypersensitivity to testosterone undecanoate or any component of the formulation
| 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. |
Loading safety data…
| Testosterone undecanoate is excreted in breast milk in small amounts; potential for adverse effects in nursing infants including virilization. Use during breastfeeding not recommended unless essential. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
| Food/Dietary | High-fat meals may increase absorption if administered with oral formulation, but for injectable, no direct food interaction. However, avoid excessive alcohol intake as it may affect liver function and hormone levels. |
| Clinical Pearls | Testosterone undecanoate is a long-acting injectable formulation requiring careful monitoring of serum testosterone levels and hematocrit due to risk of polycythemia. Administer with caution in patients with sleep apnea, severe heart, liver, or renal disease. Must not be used in men with breast or prostate cancer. Use only in confirmed hypogonadism (symptomatic, with low serum testosterone). The 4 mL injection volume requires deep intramuscular injection in gluteal muscle; risk of pulmonary oil microembolism (POME) rare but serious. Monitor PSA, lipid profile, and liver function regularly. Avoid in men with fertility desire as it suppresses spermatogenesis. |
| Patient Advice | This medication is given as an injection into the muscle by a healthcare provider every 10-14 weeks. · Do not miss appointments; delayed injections can cause return of symptoms. · Report any sudden breathing difficulty, chest pain, or fainting after injection immediately; these may be signs of a serious reaction. · Regular blood tests are required to monitor hormone levels and blood counts. · Avoid high-fat meals on day of injection to reduce risk of post-injection reaction. · Inform your doctor if you have sleep apnea, heart/liver/kidney disease, or diabetes. · This medication can worsen enlarged prostate or prostate cancer; notify doctor if you have difficulty urinating. · Do not use if you are trying to father a child; it reduces sperm count. · Store vials at room temperature away from light and moisture. |