Dutasteride capsules for treating benign prostatic hyperplasia in men

Dutasteride is an oral medication primarily used to treat symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. It works alone or in combination with tamsulosin, an alpha-blocker, to improve urinary symptoms, reduce the risk of acute urinary retention, and minimize the need for BPH-related surgery. Dutasteride capsules are not approved for preventing prostate cancer.

Dutasteride capsules (monotherapy): For men with symptomatic benign prostatic hyperplasia to improve symptoms, reduce acute urinary retention risk, and reduce BPH-related surgery risk.

Dutasteride and tamsulosin hydrochloride capsules (combination therapy): For men with symptomatic benign prostatic hyperplasia with enlarged prostate to improve symptoms and manage the condition.

Limitations: Dutasteride-containing products are not approved to prevent prostate cancer.

Dutasteride

Dutasteride is a 5 alpha-reductase inhibitor that blocks both type 1 and type 2 isoforms of the enzyme responsible for converting testosterone into dihydrotestosterone (DHT). DHT is a hormone that contributes to prostate growth. By lowering DHT levels, dutasteride helps shrink the prostate, relieving urinary symptoms associated with BPH. When combined with tamsulosin, which relaxes prostate and bladder neck muscles by blocking alpha1A-adrenergic receptors, the treatment provides improved symptom control.

Monotherapy (Dutasteride capsules):

• Recommended dose: 0.5 mg (one capsule) once daily, swallowed whole.
• May be taken with or without food.
• Do not chew or open capsules to avoid irritation of mouth or throat.

Combination therapy (Dutasteride and tamsulosin hydrochloride capsules):

• One capsule containing 0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride once daily.
• Take approximately 30 minutes after the same meal each day.
• Swallow whole without chewing or opening the capsule.

• Pregnancy: Dutasteride and combination products are contraindicated in females who are or may become pregnant due to risk of fetal harm.
• Patients with a history of clinically significant hypersensitivity reactions (such as serious skin reactions or angioedema) to dutasteride, other 5 alpha-reductase inhibitors, tamsulosin, or any component of the capsule.

Important precautions:

• Dutasteride substantially reduces serum PSA levels by about 50%, potentially masking prostate cancer detection. PSA monitoring should establish a new baseline after 3 months of treatment, and any PSA increase from this baseline warrants evaluation.
• Dutasteride may increase the risk of developing high-grade (Gleason score 8 to 10) prostate cancer.
• Consider other urological conditions possibly causing similar symptoms before starting treatment.
• Women who are or may become pregnant must avoid handling dutasteride capsules due to risk of fetal harm to a male fetus; wash skin immediately if contact occurs.
• Men should not donate blood until at least 6 months after the last dose to prevent exposure of dutasteride to pregnant transfusion recipients.
• Combination therapy with tamsulosin may cause orthostatic hypotension, dizziness, and syncope; patients should be cautioned accordingly.
• Risk of intraoperative floppy iris syndrome during cataract or glaucoma surgery in patients treated with tamsulosin-containing products.
• Priapism (persistent painful erection) is a rare but serious adverse event associated with tamsulosin.
• Combination therapy may show higher incidence of cardiac failure composite events compared with monotherapies, though no causal relationship is established.

Common adverse reactions (≥1%) include:

• Impotence (erectile dysfunction)
• Decreased libido
• Ejaculation disorders (more common with combination therapy)
• Breast disorders (enlargement, tenderness)
• Dizziness (more frequent with combination therapy)

Other reported reactions:

• Hypersensitivity reactions such as rash, urticaria, angioedema, and serious skin reactions.
• Depressed mood.
• Testicular pain and swelling.
• Male breast cancer reported rarely; relationship to dutasteride unknown.

Note:

Dutasteride interactions:

• Metabolized by CYP3A4 and CYP3A5 enzymes; caution when used with potent, chronic CYP3A4 inhibitors (e.g., ritonavir).
• Coadministration with verapamil or diltiazem increases dutasteride exposure but is not clinically significant.
• No significant interaction with warfarin or digoxin.

Tamsulosin interactions (combination therapy):

• Strong CYP3A4 inhibitors (e.g., ketoconazole) significantly increase tamsulosin levels; avoid coadministration.
• Moderate CYP3A4 inhibitors, CYP2D6 inhibitors, or both may increase tamsulosin exposure; use caution.
• Cimetidine increases tamsulosin exposure; use caution.
• Do not use with other alpha-adrenergic antagonists due to increased risk of symptomatic hypotension.
• Caution when combined with phosphodiesterase-5 inhibitors due to risk of symptomatic hypotension.
• Caution advised with concomitant warfarin use; no definitive interaction studies.

Pregnancy:

Dutasteride and dutasteride-containing combination products are contraindicated during pregnancy due to risk of abnormalities in male fetal genitalia. Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT), necessary for normal male genital development. Animal studies have shown feminization of male offspring at doses less than or equivalent to human doses. Women who are or may become pregnant should not handle dutasteride capsules.

Lactation:

Dutasteride is not indicated for use in women. There is no available information on dutasteride presence in human milk or effects on breastfeeding infants.

Single doses of up to 40 mg and daily doses of 5 mg for 6 months have been administered without significant safety concerns. There is no specific antidote for dutasteride overdose. Treatment should be symptomatic and supportive, considering the drug's long half-life.