Dutasterone (Capsules) Instructions for Use

Marketing Authorization Holder

Pharma-Sintez, JSC (Russia)

Manufactured By

Cyndea Pharma S.L. (Spain)

ATC Code

G04CB02 (Dutasteride)

Active Substance

Dutasteride (Rec.INN WHO registered)

Dosage Form

Dutasterone

Capsules 0.5 mg: 30 or 90 pcs.

Dosage Form, Packaging, and Composition

Capsules soft gelatin, yellow, oblong, opaque; the capsule contents are a yellowish oily liquid.

Excipients: glycerol monocaprylocaprate, type 1 – 349.5 mg, butylated hydroxytoluene (BHT) (E321) – 0.035 mg.

Capsule shell composition gelatin – 156.14 mg, glycerol (glycerin) – 89.2 mg, purified water – 139.84 mg, titanium dioxide (E171) – 1.686 mg, iron oxide yellow dye (E172) – 0.14 mg.
Excipients for lubricating gelatin layers medium-chain triglycerides – q.s., lecithin (soy) (E322) – q.s.

10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (9) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of benign prostatic hyperplasia. 5α-reductase inhibitor

Pharmacotherapeutic Group

Dual 5-alpha-reductase inhibitor

Pharmacological Action

A drug for the treatment of benign prostatic hyperplasia. It suppresses the activity of type 1 and type 2 5α-reductase isoenzymes, which are responsible for the conversion of testosterone to 5α-dihydrotestosterone.

Dihydrotestosterone is the primary androgen responsible for the hyperplasia of the glandular tissue of the prostate.

The maximum effect of dutasteride on reducing dihydrotestosterone concentrations is dose-dependent and is observed 1-2 weeks after the start of treatment.

After 1 and 2 weeks of taking dutasteride at a dose of 0.5 mg/day, the mean serum dihydrotestosterone concentration decreases by 85% and 90%, respectively.

Dutasteride helps reduce the size of the prostate gland, improves urination, and reduces the risk of acute urinary retention and the need for surgical treatment.

Pharmacokinetics

After a single oral dose of 500 mcg, the C_max of dutasteride in serum is reached within 1-3 hours.

With a 2-hour intravenous infusion, the absolute bioavailability is about 60%. The bioavailability of dutasteride is not affected by food intake.

Plasma protein binding is high – more than 99.5%. V_d is 300-500 L.

With daily administration, the serum concentration of dutasteride reaches 65% of C_ss after 1 month and approximately 90% of this level after 3 months.

The C_ss of dutasteride in serum, which is approximately 40 ng/ml, is achieved after 6 months of daily administration of the drug at a dose of 500 mcg.

In semen, as in serum, the C_ss of dutasteride is also reached after 6 months.

After 52 weeks of treatment, the concentrations of dutasteride in semen average 3.4 ng/ml (0.4-14 ng/ml). Approximately 11.5% of dutasteride passes from serum into semen.

In vitro, Dutasteride is metabolized by the CYP3A4 isoenzyme to form two minor monohydroxylated metabolites; however, it is not affected by the CYP2C9, CYP2C19, and CYP2D6 isoenzymes.

After reaching C_ss of dutasteride, unchanged Dutasteride, 3 major metabolites (4'-hydroxydutasteride, 1,2-dihydrodutasteride, and 6-hydroxydutasteride), and 2 minor metabolites are detected in serum by mass spectrometry.

Dutasteride undergoes intensive metabolism. After oral administration of the drug at a dose of 500 mcg/day until steady state is reached, 1-15.4% (average 5.4%) of the administered dose is excreted in the feces unchanged.

The remainder of the dose is excreted as 4 major metabolites, accounting for 39%, 21%, 7%, and 7% respectively, and 6 minor metabolites (each accounting for less than 5%).

Trace amounts of unchanged dutasteride (less than 0.1% of the dose) are excreted in human urine.

When dutasteride is taken at therapeutic doses, its terminal T_1/2 is 3-5 weeks.

Dutasteride is detected in serum (at concentrations greater than 0.1 ng/ml) for up to 4-6 months after discontinuation of its use.

The pharmacokinetics of dutasteride can be described as a first-order absorption process and two parallel elimination processes, one saturable (i.e., concentration-dependent) and one non-saturable (i.e., concentration-independent).

At low serum concentrations (less than 3 ng/ml), Dutasteride is rapidly eliminated by both elimination processes.

After a single dose of 5 mg or less, Dutasteride is rapidly eliminated from the body and has a short T_1/2 of 3-5 days.

At serum concentrations greater than 3 ng/ml, the clearance of dutasteride is lower – 0.35-0.58 L/h, with elimination occurring primarily via a linear non-saturable process with a terminal T_1/2 of 3-5 weeks.

At therapeutic concentrations during daily administration of the drug at a dose of 500 mcg, the slower clearance of dutasteride predominates; the total clearance is linear and concentration-independent.

Indications

Treatment and prevention of the progression of benign prostatic hyperplasia.

ICD codes

Dosage Regimen

Administer one 0.5 mg capsule orally once daily. Swallow the capsule whole; do not chew or crush.

Take the dose at approximately the same time each day, with or without food.

Continue treatment for a minimum of six months to achieve a therapeutic response. Maintain therapy as long as the benefit is sustained.

Forgetfulness of a dose: take the missed dose as soon as remembered, unless it is almost time for the next scheduled dose. Do not double the dose to make up for a forgotten one.

Do not handle crushed or broken capsules. The active substance dutasteride can be absorbed through the skin. In case of contact, wash the area immediately with soap and water.

This regimen applies to adult men, including the elderly. No dosage adjustment is required for renal impairment. Use with caution in patients with significant hepatic impairment.

Adverse Reactions

From the reproductive system erectile dysfunction, change (decrease) in libido, ejaculation disorder, gynecomastia (includes breast tenderness and enlargement).

Allergic reactions rash, pruritus, urticaria, localized edema, angioedema.

From the skin and subcutaneous tissue alopecia (predominantly loss of body hair) or hypertrichosis.

Contraindications

Hypersensitivity to dutasteride and other 5α-reductase inhibitors; contraindicated for use in women and children.

Use in Pregnancy and Lactation

Contraindicated for use in women. Dutasteride is absorbed through the skin, so women should avoid contact with the active substance. In case of such contact, the corresponding area of skin should be washed immediately with soap and water.

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function, because Dutasteride undergoes intensive metabolism in the liver, and its T_1/2 is 3-5 weeks.

Pediatric Use

Contraindicated for use in children. Dutasteride is absorbed through the skin, so children should avoid contact with the active substance. In case of such contact, the corresponding area of skin should be washed immediately with soap and water.

Special Precautions

Should be used with caution in patients with impaired liver function, because Dutasteride undergoes intensive metabolism in the liver, and its T_1/2 is 3-5 weeks.

In patients with benign prostatic hyperplasia, digital rectal examination and other methods of prostate examination should be performed before starting treatment with dutasteride and repeated periodically during treatment to rule out the development of prostate cancer.

Determination of serum PSA concentrations is an important component of the complex of examinations aimed at detecting prostate cancer.

A baseline PSA level of less than 4 ng/ml in patients receiving Dutasteride does not rule out the diagnosis of prostate cancer.

Dutasteride is absorbed through the skin, so women and children should avoid contact with the active substance. In case of such contact, the corresponding area of skin should be washed immediately with soap and water.

Drug Interactions

Since Dutasteride is metabolized by the CYP3A4 isoenzyme, in the presence of CYP3A4 inhibitors, the blood concentrations of dutasteride may increase.

With the simultaneous use of dutasteride with the CYP3A4 inhibitors verapamil and diltiazem, a decrease in clearance is noted.

However, amlodipine, another calcium channel blocker, does not reduce the clearance of dutasteride.

Storage Conditions

Store at 8°C (46°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.