Dosing and uses of Avodart (dutasteride)
Adult dosage forms and strengths
capsule
- 0.5mg
Benign Prostatic Hyperplasia
0.5 mg PO qDay
Dosing Modifications
Renal impairment: Dose adjustment not necessary
Hepatic impairment: Dose adjustment not necessary
Pediatric dosage forms and strengths
Safety and efficacy not established
Avodart (dutasteride) adverse (side) effects
Adverse reactions decrease with duration of treatment, except for gynecomastia
1-10%
Impotence
Decreased libido
Ejaculation disorder
Breast disorders
<1%
Dizziness
Frequency not defined
Cardiac failure
Prostate cancer (high grade)
Postmarketing Reports
Immune system disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema
Neoplasms: Male breast cancer
Psychiatric disorders: Depressed mood
Reproductive system and breast disorders: Testicular pain and testicular swelling
Warnings
Contraindications
Hypersensitivity
Women
Children
Cautions
Prior to initiating treatment, rule out other urologic conditions
Pregnant women should avoid handling capsules due to risk of absorption through skin
Obstructive uropathy, liver disease
Patient should not donate blood until 6 months after last dose of dutasteride
Dutasteride lowers serum PSA 40-50%; establish new baseline PSA after 3-6 months of treatment
Monitor for cardiac changes or cardiac failure
5-ARIs and prostate cancer risk
- June 9, 2011: Recent data from 2 large, randomized, controlled trials observed an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer) in trial participants taking 5-alpha reductase inhibitors (5-ARIs)
- The 2 trials are the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial
- The revised prescribing information recommends that prior to initiating therapy with 5-ARIs, appropriate evaluation should be performed to rule out other urologic conditions, including prostate cancer, that might mimic benign prostatic hyperplasia
Pregnancy and lactation
Pregnancy category: X
Lactation: Excretion in milk unknown/contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Avodart (dutasteride)
Mechanism of action
Selective inhibitor of type 1 and type 2 isoforms of 5-alpha-reductase; suppresses serum dihydrotestosterone levels by inhibiting the conversion of testosterone to dihydrotestosterone
Absorption
Bioavailability: 60%
Onset: 1-2 weeks
Peak plasma time: 2-3 hours
Distribution
Protein bound: 99%
Vd: 300-500 L
Metabolism
Hepatic P450 enzyme CYP3A4 & CYP3A5
Metabolites, major: 4'-hydroxydutasteride, 6-hydroxydutasteride (as active as parent), 1,2'-dihydrodutasteride
Elimination
Half-life: 5 weeks (at steady state)
Excretion: Feces (40%), urine (<1%)
