AVODART
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVODART (AVODART).
Inhibits 5α-reductase types 1 and 2, blocking conversion of testosterone to dihydrotestosterone (DHT), reducing prostate volume and improving urinary symptoms.
| Metabolism | Extensively metabolized in liver via CYP3A4; two major metabolites (dutasteride-glucuronide and hydroxy-dutasteride) are pharmacologically inactive. |
| Excretion | Primarily fecal (approximately 40-50% as metabolites, 15-30% as unchanged drug) and renal (approximately 5-15% as metabolites). Biliary excretion contributes to fecal elimination. Metabolites are excreted in urine and feces; unchanged drug is negligible in urine. |
| Half-life | Terminal elimination half-life is approximately 5 weeks (35 days) for chronic dosing due to extensive tissue binding and slow redistribution. This long half-life allows once-daily dosing and steady-state is reached after 3-6 months. |
| Protein binding | Extensively bound to plasma proteins (approximately 99%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Large volume of distribution (approximately 300-500 L, ~4-7 L/kg) indicating extensive tissue binding and distribution into peripheral compartments, including the prostate. |
| Bioavailability | Bioavailability after oral administration is approximately 60-70% (range 40-80%) under fasting conditions; food does not significantly affect absorption. Absolute bioavailability not determined due to lack of intravenous formulation. |
| Onset of Action | Oral administration: Clinical effect on serum dihydrotestosterone (DHT) reduction occurs within 24 hours; significant improvement in urinary symptoms and prostate volume reduction typically observed after 3-6 months of continuous therapy. |
| Duration of Action | Duration of action persists for several months after discontinuation due to slow elimination. Serum DHT levels remain suppressed for up to 2-3 months after stopping treatment. Clinical effects on prostate volume and symptoms gradually wane over 6-12 months. |
0.5 mg orally once daily.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for renal impairment (including hemodialysis). |
| Liver impairment | No formal studies; use with caution in moderate to severe hepatic impairment (Child-Pugh class B or C) as dutasteride is extensively metabolized by the liver. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dosage adjustment required; monitor for adverse effects such as dizziness or hypotension in elderly patients with comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVODART (AVODART).
| Breastfeeding | Excretion into human milk is unknown. Due to lipophilicity and high protein binding (>99%), transfer likely minimal but not quantified. M/P ratio not established. Contraindicated in breastfeeding due to potential adverse effects on infant development (androgen suppression). |
| Teratogenic Risk | AVODART (dutasteride) is contraindicated in pregnancy. It is a 5-alpha-reductase inhibitor that inhibits dihydrotestosterone synthesis, which is essential for normal male fetal genital development. First trimester exposure poses risk of hypospadias and other urogenital anomalies. Risk extends throughout pregnancy due to continued fetal urogenital development. Second and third trimester exposure risks include ambiguous genitalia in male fetuses. |
■ FDA Black Box Warning
Not approved for use in women or children. Avoid handling crushed or broken capsules if pregnant or planning to become pregnant due to risk of fetal harm (androgen receptor inhibition).
| Serious Effects |
Hypersensitivity to dutasteride or any component; women who are or may become pregnant; children; patients with severe hepatic impairment (Child-Pugh class C).
| Precautions | May increase risk of high-grade prostate cancer (Gleason score 8-10) in men aged ≥50 with elevated PSA and prior negative biopsy. Monitor for urinary retention, hematuria, sexual dysfunction, and depression. Use caution with hepatic impairment. |
| Food/Dietary | No significant food interactions. Take with or without food. Avoid excessive alcohol consumption as it may worsen urinary symptoms. |
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| Fetal Monitoring | Monitor pregnancy status: perform pregnancy test before initiating therapy. If pregnancy occurs, discontinue immediately and refer for fetal ultrasound to assess urogenital development. For accidental exposure during pregnancy, monitor for fetal growth restriction and amniotic fluid index. |
| Fertility Effects | Impairs spermatogenesis: decreases sperm count, sperm motility, and normal morphology. Reversible effects documented after discontinuation. No effect on female fertility. Reduces ejaculate volume. |
| Clinical Pearls | 5-alpha-reductase inhibitor; takes 6-12 months for maximal effect on BPH symptoms; reduces prostate volume by ~20-30%; can cause reversible decrease in serum PSA by ~50% (double PSA value for screening interpretation); contraindicated in women (especially pregnancy) due to risk of fetal genital abnormalities; may increase risk of high-grade prostate cancer (Gabriel et al., PLCO trial); do not use for chemoprevention; monitor for orthostatic hypotension when combined with alpha-blockers. |
| Patient Advice | Take the capsule whole, do not chew or open. · This medication works slowly; you may not see improvement for 6 to 12 months. · Do not donate blood while taking this drug and for 6 months after stopping. · Women who are pregnant or may become pregnant should not handle crushed or broken capsules. · You may experience decreased libido, erectile dysfunction, or ejaculation disorders; these side effects are usually reversible after stopping the drug. · Your PSA levels will be lowered by about 50%; tell your doctor you are taking this drug when having PSA tests. · Report any breast changes (lumps, pain, nipple discharge) or new urinary symptoms. |