Dutasteride Canon capsules 0.5mg, No. 30

Treatment and prevention of progression of benign prostatic hyperplasia.

For adult men, including elderly patients, the recommended oral dose is 500 mcg 1 time / day. Treatment should be continued for at least 6 months.

Capsules are soft gelatinous, light yellow, oval; the contents of the capsules are oily transparent colorless or slightly colored liquid; slight stratification of the liquid is allowed.

1 caps.

dutasteride 500 mcg

Excipients: glycerin monocaprilocaprate type I 349.465 mg, butylhydroxytoluene - 0.035 mg.

• Hypersensitivity to dutasteride and other 5alpha-reductase inhibitors;

• use in women and children is contraindicated.

pharmachologic effect

An agent for the treatment of benign prostatic hyperplasia. Suppresses the activity of type 1 and type 2 5?-reductase isoenzymes, which are responsible for the conversion of testosterone to 5?-dihydrotestosterone. Dihydrotestosterone is the main androgen responsible for hyperplasia of the glandular tissue of the prostate gland.

The maximum effect of dutasteride on the decrease in the concentration of dihydrotestosterone is dose-dependent and is observed after 1-2 weeks. after starting treatment. After 1 and 2 weeks. taking dutasteride at a dose of 0.5 mg / day, the mean serum dihydrotestosterone concentrations are reduced by 85% and 90%.

Dutasteride helps to shrink the prostate gland, improve urination and reduce the risk of acute urinary retention and the need for surgical treatment.

Pharmacokinetics

After a single dose of 500 mcg, Cmax of dutasteride in serum is achieved within 1-3 hours. With a 2-hour intravenous infusion, the absolute bioavailability is about 60%. The bioavailability of dutasteride is independent of food intake.

Plasma protein binding is high - more than 99.5%. Vd - 300-500 liters.

When taken daily, the serum concentration of dutasteride reaches 65% of the Css after 1 month and approximately 90% of this level after 3 months. The serum Css of dutasteride, approximately 40 ng / ml, is reached after 6 months of daily intake of the drug at a dose of 500 ?g. In semen, as in serum, the Css of dutasteride is also reached after 6 months. After 52 weeks. semen concentrations of dutasteride averaged 3.4 ng / ml (0.4-14 ng / ml). Approximately 11.5% of dutasteride is transferred from serum to semen.

In vitro, dutasteride is metabolized by the CYP3A4 isoenzyme to form two minor monohydroxylated metabolites; however, it is not affected by isoenzymes CYP2C9, CYP2C19 and CYP2D6. After reaching the Css of dutasteride, unchanged dutasteride, 3 major metabolites (4'-hydroxydutasteride, 1,2-dihydrodututasteride, and 6-hydroxydutasteride) and 2 minor metabolites are detected in the serum by mass spectrometry.

Dutasteride is extensively metabolized. After taking the drug orally at a dose of 500 mcg / day until an equilibrium state is reached, 1-15.4% (on average 5.4%) of the dose taken is excreted unchanged in the feces. The rest of the dose is excreted in the form of 4 major metabolites, accounting for 39%, 21%, 7% and 7%, respectively, and 6 minor metabolites (each of which accounts for less than 5%).

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

When taking dutasteride in therapeutic doses, its final T1 / 2 is 3-5 weeks.

Dutasteride is detected in serum (at concentrations of more than 0.1 ng / ml) up to 4-6 months after stopping it.

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 unsaturated (i.e., concentration-independent).

At low serum concentrations (less than 3 ng / ml), dutasteride is rapidly excreted by both elimination processes. After a single dose of 5 mg or less, dutasteride is rapidly excreted from the body and has a short T1 / 2 of 3-5 days.

At serum concentrations of more than 3 ng / ml, the clearance of dutasteride is less - 0.35-0.58 l / h, while excretion is carried out mainly through a linear unsaturated process with a final T1 / 2 of 3-5 weeks. At therapeutic concentrations against the background of daily intake of the drug in a dose of 500 mcg, a slower clearance of dutasteride predominates; overall clearance is linear and concentration-independent.

Side effect

From the reproductive system: erectile dysfunction, change (decrease) in libido, impaired ejaculation, gynecomastia (includes soreness and enlargement of the mammary glands).

Allergic reactions: rash, itching, urticaria, localized edema, angioedema.

On the part of the skin and subcutaneous fat: alopecia (mainly loss of body hair) or hypertrichosis.

Application during pregnancy and lactation

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

Application for violations of liver function

It should be used with caution in patients with impaired liver function. dutasteride undergoes intensive metabolism in the liver, and its T1 / 2 is 3-5 weeks.

Application in children

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

special instructions

It should be used with caution in patients with impaired liver function. dutasteride undergoes intensive metabolism in the liver, and its T1 / 2 is 3-5 weeks.

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

Determination of serum PSA concentrations is an important component of a complex of studies aimed at detecting prostate cancer. A baseline PSA level of less than 4 ng / ml in patients receiving dutasteride does not preclude a diagnosis of prostate cancer.

Dutasteride is absorbed through the skin, therefore women and children should avoid contact with the active substance. In case of such contact, immediately wash the affected skin area with soap and water.

Drug interactions

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

With the simultaneous use of dutasteride with the CYP3A4 inhibitors verapamil and diltiazem, there is a decrease in clearance. However, amlodipine, another calcium channel blocker, does not decrease dutasteride clearance.