Dutasteride (Avodart)

1. Health Canada Product Monograph — Dutasteride

• Dutasteride is used alone to treat symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate.
• Dutasteride is used together with the alpha-blocker tamsulosin for moderate to severe symptomatic BPH in men with an enlarged prostate.
• Dutasteride is not approved for the prevention of prostate cancer and should not be used for that purpose.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Dutasteride is for use in men only and must never be taken by women, including women who are or may become pregnant.
• Dutasteride is absorbed through the skin, so pregnant women or women who may become pregnant should never handle dutasteride capsules, especially leaking or damaged ones.
• Pre-clinical data suggest dutasteride may interfere with normal development of the external genital organs of a male fetus if a pregnant woman is exposed, so accidental skin contact should be washed off immediately with soap and water.

• Dutasteride is contraindicated in women, so breastfeeding is not applicable; it is not known whether dutasteride passes into human milk.

• No dose adjustment of dutasteride is needed in older men.
• Dutasteride's half-life lengthens with age, so elimination is slower in men over 70 than in younger men, though clinical studies found no overall difference in safety or effectiveness between older and younger patients.

• Dutasteride is contraindicated in children; BPH is not a childhood condition and safety and effectiveness in children have not been established.

• For monotherapy, the recommended dose of dutasteride is one 0.5 mg capsule taken by mouth once daily.
• For combination therapy with tamsulosin, the recommended dose is one 0.5 mg dutasteride capsule once daily together with one 0.4 mg tamsulosin capsule once daily.
• Dutasteride capsules should be swallowed whole and never chewed or opened, since contact with the contents can irritate the mouth and throat.
• No dose adjustment is needed for renal impairment, since very little dutasteride is eliminated in the urine.
• Caution is advised in patients with liver disease because dutasteride is extensively metabolized and has a long half-life of 3 to 5 weeks; no formal dose adjustment has been established.
• If a dose is missed, the next capsule should simply be taken at the regularly scheduled time; extra capsules should not be taken to make up for a missed dose.
• Improvement in BPH symptoms may be seen after 3 months, but up to 6 months of treatment may be needed to know whether dutasteride is working.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Single daily doses of dutasteride up to 40 mg (80 times the usual dose) have been given for 7 days without significant safety concerns, and doses of 5 mg daily for 6 months produced no additional adverse effects beyond those seen at the normal 0.5 mg dose.
• There is no specific antidote for dutasteride overdose.
• Because dutasteride has a very long half-life, symptomatic and supportive treatment should take this prolonged duration into account.

• Impotence (difficulty achieving or maintaining an erection) may occur.
• Decreased libido (reduced sex drive) may occur.
• Ejaculation disorders, including a reduced amount of semen, may occur.
• Breast enlargement or tenderness may occur.
• Dizziness may occur, particularly when combined with tamsulosin.
• Rare hair loss, mainly on the body, or unusual hair growth (hypertrichosis) has been reported.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Dutasteride may be associated with an increased risk of high-grade (more aggressive) prostate cancer.
• Breast changes such as lumps or nipple discharge should be reported promptly, as breast cancer has been reported rarely in men taking dutasteride.
• Heart failure has been reported more often in men taking dutasteride together with an alpha-blocker such as tamsulosin than with dutasteride alone.
• Serious allergic reactions, including rash, itching, hives, swelling, and severe skin reactions, may occur rarely.
• Testicular pain and swelling have been reported rarely.
• Depressed mood has been reported rarely.
• Sexual side effects such as impotence, decreased libido, and ejaculation problems may persist even after stopping dutasteride.
• Seek urgent medical attention for chest pain, sudden shortness of breath, swelling of the legs, or signs of a severe allergic reaction such as facial swelling or difficulty breathing.

• Use with caution in men with a large residual urine volume or severely reduced urine flow, who may not be good candidates for dutasteride and need close monitoring for urinary obstruction.
• Use with caution in men with liver disease, since dutasteride is extensively metabolized by the liver.
• Use with caution in men with underlying cardiovascular risk factors, since combination therapy with an alpha-blocker has been linked to a higher rate of heart failure.
• Men should have a thorough urological evaluation, including screening for prostate cancer, before starting dutasteride.
• Regular checkups, including digital rectal exams and PSA testing, should continue throughout treatment.
• Men taking dutasteride should not donate blood until at least 6 months after their last dose, to avoid exposing a pregnant transfusion recipient.

• Contraindicated in women.
• Contraindicated in children.
• Contraindicated in patients with known hypersensitivity to dutasteride, other 5-alpha-reductase inhibitors, or any component of the capsule.

• Potent, chronic inhibitors of CYP3A4 such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin may increase dutasteride blood levels, so caution is advised.
• Verapamil and diltiazem have been shown to reduce dutasteride clearance, though the increase in exposure is not considered clinically significant enough to require dose adjustment.
• Dutasteride does not alter the pharmacokinetics of digoxin.
• Dutasteride does not alter the anticoagulant effect of warfarin.
• Concomitant use with the alpha-blockers tamsulosin or terazosin does not affect the pharmacokinetics of either drug.
• Cholestyramine given after a dose of dutasteride does not affect dutasteride absorption.
• No clinically significant adverse interactions were seen when dutasteride was combined with anti-hyperlipidemic drugs, ACE inhibitors, beta-blockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, phosphodiesterase type 5 inhibitors, or quinolone antibiotics.

• Dutasteride can be taken with or without food; its absorption is not affected by meals.
• Chronic consumption of CYP3A4 inhibitors found in food and beverages, such as grapefruit juice, should be avoided or used cautiously with dutasteride since it may raise dutasteride blood levels.

• Dutasteride can be taken at any time of day, with or without food, as long as it is taken consistently once daily.

• Store dutasteride capsules between 15°C and 30°C, out of reach of children, and keep leaking capsules away from women and children.

• Dutasteride shrinks an enlarged prostate over time to improve urinary symptoms, but it can take up to 6 months to see the full benefit.
• Dutasteride lowers PSA levels, so tell any doctor ordering a PSA test that you are taking it.
• Never let a woman who is or might become pregnant handle dutasteride capsules.
• Swallow the capsule whole; do not chew, crush, or open it.
• Continue with your regular prostate cancer screening and checkups while taking dutasteride.