METANDREN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METANDREN (METANDREN).
Androgen receptor agonist; binds to androgen receptors in target tissues, activating gene transcription and promoting protein synthesis, growth of male reproductive organs, and secondary sexual characteristics.
| Metabolism | Hepatic metabolism via CYP3A4, 5α-reductase, and 17β-hydroxysteroid dehydrogenase; excreted in urine. |
| Excretion | Metandren (methyltestosterone) is primarily metabolized in the liver and excreted in the urine as glucuronide and sulfate conjugates. Approximately 90% of a dose is excreted renally, with less than 5% eliminated via feces. Biliary excretion is minimal. |
| Half-life | The terminal elimination half-life of methyltestosterone is approximately 3-4 hours. This short half-life necessitates multiple daily dosing (e.g., 10-50 mg orally 1-3 times daily) to maintain therapeutic androgen levels. However, due to its oral administration and first-pass metabolism, the clinical effect may last longer. |
| Protein binding | Methyltestosterone is extensively bound to serum proteins, primarily sex hormone-binding globulin (SHBG) and albumin, with approximately 97-99% bound. Only the free fraction is pharmacologically active. |
| Volume of Distribution | The volume of distribution (Vd) for methyltestosterone is not well-defined in humans but is estimated to be around 0.5-0.8 L/kg, indicating distribution into total body water. Its Vd suggests moderate tissue penetration, with higher concentrations in prostate, seminal vesicles, and muscle. |
| Bioavailability | Oral: Bioavailability is low and highly variable, ranging from 10% to 50% due to extensive first-pass hepatic metabolism. Buccal administration may achieve higher bioavailability (approximately 30-60%), but this route is not commonly used. Bioavailability via intramuscular injection of methyltestosterone is not applicable as the drug is not administered parenterally. |
| Onset of Action | Oral: Onset of action is typically within 1-2 hours for androgen effects. Buccal administration may have a slightly faster onset due to bypassing first-pass metabolism, but clinical data are limited. Sublingual administration is not standard. |
| Duration of Action | Oral: The duration of action is approximately 4-6 hours. However, the clinical effect (e.g., erythropoiesis stimulation) may persist for days after discontinuation due to slow receptor turnover. Continuous daily dosing is required for sustained androgen effects. |
Oral: 5-25 mg once daily for testosterone replacement therapy in adult males.
| Dosage form | TABLET |
| Renal impairment | No specific dosage adjustments are established for renal impairment; use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment, use with caution and monitor liver function. |
| Pediatric use | Not recommended for use in children due to risk of premature epiphyseal closure and virilization. |
| Geriatric use | Use with caution; monitor for prostatic hypertrophy, fluid retention, and cardiovascular effects. Start at lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METANDREN (METANDREN).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. May cause virilization in female infants and premature growth acceleration. Breastfeeding not recommended. |
| Teratogenic Risk | First trimester: Risk of masculinization of female fetus (clitoral enlargement, labial fusion). Second and third trimesters: Continued risk of female pseudohermaphroditism and potential for premature closure of epiphyseal plates in both sexes. Contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Virilization in female fetuses if used during pregnancy; prolonged use may increase risk of hepatocellular carcinoma.
| Serious Effects |
Pregnancy, lactation, prostate cancer, male breast cancer, severe liver disease, hypercalcemia, hypersensitivity to androgens.
| Precautions | Risk of hepatotoxicity, fluid retention, hypercalcemia, worsening of sleep apnea, and lipid profile changes. Monitor liver function, hematocrit, and serum calcium. Use with caution in patients with renal, hepatic, or cardiac disease. |
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| Pregnancy test prior to initiation. If used inadvertently during pregnancy, perform ultrasound for fetal gender and anatomical assessment. Monitor maternal liver function, lipid profile, and signs of virilization. In newborns, monitor for genital ambiguity (female) or accelerated growth. |
| Fertility Effects | May suppress spermatogenesis via negative feedback on gonadotropins in males. In females, may cause menstrual irregularities and anovulation due to androgenic effects. Effects may be reversible upon discontinuation. |