Indications and Usage:
MONOTHERAPY
Dutasteride tablets are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:
● Improve symptoms
● Reduce the risk of acute urinary retention (AUR)
● Reduce the risk of the need for BPH-related surgery.
Pharmacology:
Mechanism of Action:
Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver.
Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor.
Pharmacokinetics:
Absorption: T max is 2 to 3 h; bioavailability is approximately 60%; administration with food decreased C max 10% to 15%.
Distribution: Vd is 300 to 500 L; highly protein bound (99%).
Metabolism: Metabolized by CYP3A4 and CYP3A5.
Elimination: Mainly excreted in feces (approximately 5% as unchanged dutasteride and approximately 40% as metabolites). The half-life is approximately 5 wk.
Adverse Reactions:
CNS: Decreased libido (3%).
Genitourinary: Impotence (5%); breast disorder including breast enlargement and breast tenderness, ejaculation disorder (1%).
Hypersensitivity: Allergic reactions, including angioedema, localized edema, pruritus, rash, serious skin reactions, and urticaria.
Drug Interactions:
CYP3A4 inhibitors (eg, cimetidine, ciprofloxacin, diltiazem, ketoconazole, ritonavir, troleandomycin, verapamil) Plasma concentrations of dutasteride may be elevated, increasing the risk of adverse reactions. Use with caution. However, the change in dutasteride exposure with coadministration of diltiazem or verapamil is not considered clinically important, and no dosage adjustment is recommended.
Food When dutasteride is taken with food, the dutasteride C max is reduced 10% to 15%. This reduction is not considered to be clinically important. Dutasteride may be taken with or without food.
Contraindications:
Pregnancy; women of childbearing potential; children; hypersensitivity to 5-alpha-reductase inhibitors or any component of the product.
Precautions:
● Before taking dutasteride, tell your doctor or pharmacist if you are allergic to it; or to finasteride; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
● Before using this medication, tell your doctor or pharmacist your medical history.
● Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
● Do not donate blood while you are taking this medication and for at least 6 months after you stop taking it. This will prevent the possibility of your blood being given to a pregnant woman. This medication is not usually used in women.
Patient Information:
● Advise patient to read the patient information leaflet before starting dutasteride and with each refill.
● Advise patient that prescribed dose is to be taken once daily without regard to meals, and to try to take the dose at about the same time each day.
● Advise patient that if a dose is missed to take as soon as remembered, but to never take 2 doses the same day.
● Advise patient that drug does not work immediately and that it may take 3 to 6 mo to experience maximum benefit.
● Advise patient to swallow the Tablet whole and to not chew or open the Tablet.
● Advise patient that ejaculate volume may be decreased during treatment, but this decrease does not interfere with normal sexual function.
● Instruct patient to not stop taking dutasteride when symptoms have improved.