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Dutasteride

Class: 5-alpha-Reductase Inhibitors
- 5α-reductase Type 1 and 2 Inhibitor
VA Class: HS900
Chemical Name: 5α,17β)-N-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-azaandrost-1-ene-17-carboxamide
Molecular Formula: C27H30F6N2O2
CAS Number: 164656-23-9
Brands: Avodart

Medically reviewed by Drugs.com on Jan 20, 2021. Written by ASHP.

Introduction

Selective inhibitor of steroid 5α-reductase isoenzymes, which are necessary for conversion of testosterone to 5α-dihydrotestosterone (DHT).

Uses for Dutasteride

Benign Prostatic Hyperplasia (BPH)

Treatment of symptomatic BPH to improve symptoms and reduce the risk of acute urinary retention and the need for surgery. Ineffective in patients who do not have evidence of prostatic enlargement.

Used alone or in combination with tamsulosin. Combined therapy with a 5α-reductase inhibitor and an α1-blocker has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression. Men at risk for BPH progression are most likely to benefit from combined therapy.

Steroid 5α-reductase inhibitors may be a useful alternative to surgery in patients with obstructive manifestations who are unwilling to undergo surgical correction of BPH; may aid those who may be at increased risk from, but not necessarily candidates for, prostate surgery. Also may be considered in patients who have symptomatic prostatic enlargement but whose symptoms are not bothersome (i.e., do not interfere with activities of daily living) in order to prevent progression of the disease.

Although drug therapy usually is not as effective as surgical therapy, it may provide adequate symptomatic relief with fewer and less serious adverse effects compared with surgery.

Dutasteride Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.

Swallow capsules whole; do not chew or open. Contact with the capsule contents may irritate oropharyngeal mucosa.

Dosage

Adults

Benign Prostatic Hyperplasia
Oral

0.5 mg once daily, alone or in combination with tamsulosin.

While early symptomatic improvement (e.g., within 3 months) may occur, ≥6 months of therapy may be necessary to determine clinical benefit. Generally, therapy is continued for life.

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment. (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustment not required.

Geriatric Patients

Dosage adjustment not required.

Cautions for Dutasteride

Contraindications

  • Known or suspected pregnancy. (See Fetal/Neonatal Morbidity and also Pregnancy under Cautions.)

  • Use in women of childbearing potential.

  • Use in children.

  • Known hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride, other 5α-reductase inhibitors, or any ingredient in the formulation.

Warnings/Precautions

Fetal/Neonatal Morbidity

May cause fetal harm; teratogenicity demonstrated in animals. Animal studies indicate adverse effects on embryofetal development of male fetuses exposed to the drug during pregnancy (e.g., abnormalities of the external genitalia, decreased prostatic and seminal vesicular weights, distended preputial glands, nipple development).

Because of the potential for absorption through the skin and the subsequent potential risk to a male fetus, pregnant women or women who may become pregnant should not handle the capsules. If contact is made with leaking capsules, wash the affected area immediately with soap and water.

If used during pregnancy or if pregnancy occurs, apprise the pregnant woman of potential fetal hazard to the male fetus.

Seminal drug concentrations not sufficient to warrant the use of condoms to prevent exposure to dutasteride.

Blood Donation

To prevent potential fetal exposure, men receiving the drug should not donate blood during dutasteride therapy and for at least 6 months following discontinuance of the drug.

Patient Assessment

Evaluate candidates for dutasteride therapy for other urologic conditions that might mimic BPH, such as infection, prostate or bladder cancer, stricture disease, uncontrolled diabetes mellitus, neurogenic bladder, or CHF.

Perform digital rectal examinations, as well as other screening tests for prostate cancer (e.g., serum prostate-specific antigen [PSA] concentration), before initiating therapy and periodically thereafter. (See Prostate-specific Antigen under Cautions and also see Specific Drugs and Laboratory Tests under Interactions.)

High-grade Prostate Cancer

5α-Reductase inhibitors may increase risk of development of high-grade prostate cancer.

In 2 placebo-controlled trials evaluating dutasteride (0.5 mg daily for 4 years) or finasteride (5 mg daily for 7 years) for prevention of prostate cancer, overall occurrence of prostate cancer was reduced (due to reduction in lower-grade tumors) but incidence of high-grade tumors (Gleason score 8–10) was increased in men receiving dutasteride or finasteride. Not known whether detection bias (e.g., drug-induced reduction in prostate volume might have aided biopsy detection) or study-related factors influenced results.

Not FDA labeled for prevention of prostate cancer.

Prostate-specific Antigen

Decreases PSA concentrations; may interfere with interpretation of serum PSA determinations. (See Specific Drugs and Laboratory Tests under Interactions.) Concurrent use of tamsulosin does not substantially alter dutasteride’s effect on PSA concentrations.

May decrease serum PSA concentrations in men with prostate cancer; however, clinical benefit has not been demonstrated in patients with prostate cancer treated with dutasteride.

Carefully evaluate any confirmed increase in serum PSA concentration during therapy, even if PSA value is within normal range for men not receiving 5α-reductase inhibitor therapy.

Noncompliance may affect PSA concentrations; consider when evaluating test results.

Breast Neoplasia

Breast cancer reported in 2 patients (1 receiving dutasteride, 1 receiving placebo) in long-term clinical trials. Not known whether a causal relationship exists between long-term dutasteride use and breast neoplasia in men.

Effects on Semen Characteristics

Reductions in sperm count, semen volume, and sperm motility reported; sperm concentration and morphology not altered. Clinical relevance not established.

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and also Contraindications under Cautions.)

Lactation

Not known whether dutasteride is distributed into milk, but the drug is contraindicated in women of childbearing potential.

Pediatric Use

Safety and efficacy not established, but the drug is contraindicated in children.

Geriatric Use

No substantial differences in safety and efficacy relative to younger men, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Not studied in patients with hepatic impairment. Increased exposure to the drug is probable. Use with caution.

Common Adverse Effects

Impotence, decreased libido, ejaculation disorder, breast disorders (tenderness, enlargement).

Interactions for Dutasteride

Metabolized by CYP isoenzymes 3A4 and 3A5 to active metabolites; not metabolized by CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1.

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with inhibitors of CYP3A4 and CYP3A5 (decreased clearance and increased serum concentrations of dutasteride). Use with caution in patients receiving chronic therapy with potent CYP3A4 inhibitors.

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amlodipine

Pharmacokinetic interaction unlikely

Cholestyramine

Pharmacokinetic or pharmacodynamic interaction unlikely

Cimetidine

Possible decreased clearance and increased serum concentrations of dutasteride

Use concomitantly with care

Ciprofloxacin

Possible decreased clearance and increased serum concentrations of dutasteride

Use concomitantly with care

Digoxin

Effect on digoxin pharmacokinetics unlikely

Diltiazem

Decreased clearance and increased serum concentrations of dutasteride

Not considered clinically important

Ketoconazole

Possible decreased clearance and increased serum concentrations of dutasteride

Use concomitantly with care

Ritonavir

Possible decreased clearance and increased serum concentrations of dutasteride

Use concomitantly with care

Tamsulosin

Effect on tamsulosin pharmacokinetics unlikely

Terazosin

Effect on terazosin pharmacokinetics unlikely

Test for PSA

50% decrease in serum PSA concentration within 3–6 months of treatment

No substantial change in ratio of free to total PSA (percentage of free PSA)

Do not interpret decrease in PSA value as a therapeutic effect on prostate cancer

Establish a new baseline PSA 3–6 months after initiation of treatment

For clinical interpretation of isolated PSA values in men receiving dutasteride for ≥3 months, double the reported PSA value for comparison with normal values in men not receiving the drug

No adjustment of reported value of ratio appears to be necessary

Verapamil

Decreased clearance and increased serum concentrations of dutasteride

Not considered clinically important

Warfarin

Effect on warfarin pharmacokinetics or pharmacodynamics unlikely

Dutasteride Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 60%.

Onset

Reduces serum and prostatic 5α-dihydroxytestosterone (DHT) concentrations maximally within 1–2 weeks of initiation of therapy.

Duration

Serum drug concentrations are detectable for up to 4–6 months following discontinuance of therapy.

Food

Decreases peak serum concentrations. Not considered clinically important.

Distribution

Extent

Widely distributed; volume of distribution is 300–500 L.

Distributes into semen.

Plasma Protein Binding

Highly bound to albumin (99%) and α-1 acid glycoprotein (96.6%).

Elimination

Metabolism

Metabolized by CYP3A4 and CYP3A5 to active metabolites.

Elimination Route

Excreted in the feces (45%) and urine (<1%) mainly as metabolites; approximately 55% remained unaccounted.

Half-life

Terminal half-life is approximately 5 weeks at steady state.

Special Populations

In patients with hepatic impairment, pharmacokinetics not studied. Metabolized extensively in the liver, and increased exposure to the drug is probable in hepatic impairment.

In adolescents (<18 years of age), pharmacokinetics not studied.

In patients with renal impairment, pharmacokinetics not studied; however, <0.1% of a dose is excreted in urine in healthy individuals.

In women, pharmacokinetics not studied; use contraindicated.

Effects of race on pharmacokinetics not studied.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Actions

  • Competitive inhibitor of both the type 1 and type 2 isoenzymes of steroid 5α-reductase. These enzymes convert testosterone to DHT.

  • Reduces serum and prostatic DHT concentrations substantially. DHT appears to be the principal androgen responsible for initial development and subsequent enlargement of the prostate gland.

  • Increases serum testosterone (generally remaining within the normal range) and prostatic testosterone concentrations.

Advice to Patients

  • Importance of obtaining and reading patient information on dutasteride before initiation of therapy and with each new prescription refill.

  • Importance of informing patients that dutasteride decreases serum PSA concentrations. Importance of appropriate medical evaluation of any increase in PSA concentration. If a PSA test is performed, importance of patient informing the clinician that he is taking a 5α-reductase inhibitor.

  • Importance of informing patients that the incidence of high-grade prostate cancer was increased in men receiving 5α-reductase inhibitors (including dutasteride) in clinical trials evaluating efficacy of these drugs for prostate cancer prevention.

  • Risk to male fetuses. Importance of advising patients that pregnant women or women who may become pregnant should not handle the drug; if such contact occurs, wash affected area immediately with soap and water and inform clinician. (See Pregnancy under Cautions.)

  • Importance of not donating blood during and for ≥6 months following discontinuance of dutasteride therapy.

  • Advise patients that a decrease in the volume of ejaculate may occur but that this does not appear to interfere with normal sexual function.

  • Advise patients of the small possibility of impotence and decreased libido.

  • Importance of promptly informing clinician of any changes in breasts (e.g., lumps, pain, nipple discharge), since breast changes (enlargement, tenderness, neoplasm) have been reported.

  • Advise patients of possibility of allergic reactions (e.g., rash, pruritus, urticaria, swelling of lips or face).

  • Advise patients that ≥6 months of therapy may be required before improvement in BPH symptoms occurs.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dutasteride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

0.5 mg

Avodart

GlaxoSmithKline

AHFS DI Essentials™. © Copyright 2022, Selected Revisions January 30, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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