5-alpha-reductase inhibitors

1. Finasteride

Generic Name

Finasteride

Drug Class

5-Alpha-Reductase Inhibitor (Type II selective)

ATC Code

G04CB01

Available Formulations

• Oral tablet: 1 mg, 5 mg

Indications

• Benign prostatic hyperplasia (BPH)

• Androgenetic alopecia (male pattern hair loss)

Mechanism of Action

Finasteride selectively inhibits Type II 5-alpha-reductase, the enzyme responsible for converting testosterone into dihydrotestosterone (DHT), a potent androgen that contributes to prostate tissue proliferation and hair follicle miniaturization. Reduction of DHT levels leads to prostate shrinkage and slows the progression of male pattern baldness.

Pharmacokinetics

• Absorption: Rapid oral absorption

• Bioavailability: ~63%

• Time to Peak Plasma Concentration: 1–2 hours

• Distribution: Extensively distributed; ~90% protein bound

• Metabolism: Hepatic (CYP3A4 involved)

• Half-life: ~6 hours (longer in elderly)

• Excretion: Primarily in feces (57%), urine (39%) as metabolites

Dosage and Administration

• BPH: 5 mg orally once daily

• Alopecia: 1 mg orally once daily

• Minimum Duration for Efficacy: 3–6 months

• Discontinuation: Benefits are reversed within 6–12 months after stopping treatment

Contraindications

• Hypersensitivity to finasteride

• Use in women, especially during pregnancy (Pregnancy Category X)

• Not approved for use in children

Warnings and Precautions

• Finasteride suppresses PSA levels; doubling the value is required for accurate prostate cancer screening

• Patients should be monitored for breast enlargement or tenderness, which may indicate malignancy

• Avoid use in hepatic impairment unless clearly necessary

• Tablets should not be handled by pregnant women to avoid transdermal absorption

Adverse Effects

Common:

• Reduced libido

• Erectile dysfunction

• Ejaculatory disorders

Uncommon:

• Breast tenderness and enlargement (gynecomastia)

• Rash, pruritus

• Mood changes or depression

Rare:

• Male breast cancer

• Hypersensitivity reactions

• Infertility (reversible upon discontinuation in most cases)

Drug Interactions

• Finasteride is metabolized by CYP3A4; caution is advised when co-administered with potent CYP3A4 inhibitors (e.g., ketoconazole), although no dosage adjustment is typically required

• No significant interaction with warfarin, digoxin, propranolol, or theophylline

Monitoring Parameters

• Baseline and periodic PSA levels

• Clinical improvement of urinary symptoms

• Signs of depression or adverse sexual effects

Patient Counseling

• Inform patient of the delayed onset of therapeutic benefit

• Warn female caregivers about handling crushed or broken tablets

• Advise that stopping therapy reverses benefits within a few months

• Inform about the potential for persistent sexual side effects in rare cases

Brand Names

• Proscar (5 mg – for BPH)

• Propecia (1 mg – for male pattern hair loss)

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2. Dutasteride

Generic Name

Dutasteride

Drug Class

5-Alpha-Reductase Inhibitor (Dual: Type I and Type II)

ATC Code

G04CB02

Available Formulations

• Oral soft gelatin capsule: 0.5 mg

Indications

• Treatment of symptomatic benign prostatic hyperplasia (BPH)

• Not officially approved for hair loss treatment but studied off-label

Mechanism of Action

Dutasteride inhibits both Type I and Type II isoenzymes of 5-alpha-reductase, resulting in a >90% reduction in circulating dihydrotestosterone (DHT). This leads to significant reduction in prostate size and relief of lower urinary tract symptoms associated with BPH.

Pharmacokinetics

• Absorption: Oral absorption, unaffected by food

• Bioavailability: ~60%

• Time to Peak Plasma Concentration: 2–3 hours

• Distribution: High volume of distribution (300–500 L), >99% protein bound

• Metabolism: Hepatic (CYP3A4 and CYP3A5)

• Half-life: ~5 weeks (accumulates with chronic use)

• Excretion: Mainly via feces (>90%)

Dosage and Administration

• 0.5 mg orally once daily

• May be used in combination with tamsulosin for more effective symptom control in BPH

• Duration for clinical effect: 3–6 months

• Capsules must be swallowed whole

Contraindications

• Hypersensitivity to dutasteride

• Women, especially during pregnancy (Pregnancy Category X)

• Not indicated for pediatric use

Warnings and Precautions

• PSA suppression can mask early detection of prostate cancer; establish baseline and adjust interpretation accordingly

• Possible increased risk of high-grade prostate cancer (FDA boxed warning)

• Avoid contact with leaking capsules, especially by pregnant women

• Use caution in patients with hepatic impairment

Adverse Effects

Common:

• Erectile dysfunction

• Decreased libido

• Ejaculatory disorders

Uncommon:

• Gynecomastia

• Testicular pain

• Mood changes

Rare:

• Depression

• Male breast cancer

• Hypersensitivity reactions

Drug Interactions

• CYP3A4 inhibitors (e.g., ritonavir, verapamil, diltiazem) may increase serum levels

• Co-administration with tamsulosin shows additive efficacy for BPH

• No dose adjustment generally required in renal impairment

Monitoring Parameters

• Serum PSA levels (baseline and during treatment)

• Symptom improvement (e.g., IPSS score in BPH)

• Prostate size and residual urine volume

• Mental health and sexual side effects

Patient Counseling

• May take months before symptoms improve

• Advise that sexual side effects may persist in rare cases

• Capsules must not be chewed or opened

• Warn pregnant women not to handle capsules

Brand Names

• Avodart

• Jalyn (Combination of Dutasteride 0.5 mg + Tamsulosin 0.4 mg)

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Comparison Overview

Characteristic	Finasteride	Dutasteride
Type Inhibited	Type II only	Type I and Type II
DHT Reduction	~70%	>90%
Half-life	~6 hours	~5 weeks
Approved Use	BPH, Hair Loss	BPH
Regulatory Status	FDA, EMA, Global	FDA, EMA, Global
Time to Effect	3–6 months	3–6 months
Off-Label Hair Use	Yes	Yes (not officially)

Global Regulatory Approvals

• Finasteride and Dutasteride are both approved by:

  • U.S. Food and Drug Administration (FDA)

  • European Medicines Agency (EMA)

  • UK Medicines and Healthcare products Regulatory Agency (MHRA)

  • Health Canada

  • Australia’s TGA

  • Japan’s PMDA

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Storage and Handling

• Store at 15–30°C

• Protect from light and moisture

• Finasteride tablets are film-coated; do not crush

• Dutasteride capsules should not be opened or chewed

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Clinical Practice Integration

• Used in monotherapy or combination therapy (with alpha-blockers)

• Particularly indicated for men with moderate-to-severe BPH, prostate >30 mL, or PSA >1.5 ng/mL

• Periodic reevaluation is recommended due to prostate cancer screening implications