dutasteride (Rx)

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

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 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.

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%)