Avodart

Avodart is one of those drugs used to treat prostate adenoma. Its active ingredient, dutasteride, has a therapeutic effect on benign prostatic hyperplasia. This drug has its maximum effect one to two weeks after the patient begins taking the drug.

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Indications Avodart

As monotherapy:

Treatment and prevention of progression of benign prostatic hyperplasia by reducing the size of the prostate gland, improving urination, reducing the risk of acute urinary retention and the need for surgical intervention.

As a combination therapy with α1-blockers:

Treatment and prevention of progression of benign prostatic hyperplasia by reducing prostate size, improving urination, and reducing the risk of acute urinary retention and the need for surgical intervention. The combination of dutasteride and the α1-adrenergic blocker tamsulosin has been studied primarily.

Release form

The drug for the treatment of prostate adenoma Avodart is produced in the form of gelatin capsules, which are yellow, oblong, opaque, with the inscription GX CE2 printed in red on one side of each capsule.

Capsules are produced in aluminum blisters. One blister contains ten capsules. There are two forms of Avodart release - three blisters in a pack and nine.

Pharmacodynamics

Avodart is a dual 5a-reductase inhibitor. It is characterized by the suppression of the activity of 5a-reductase isoenzymes of the first and second types, the essence of which is the conversion of testosterone into 5a-dihydrotestosterone (DHT). Dihydrotestosterone is the main androgen responsible for hyperplasia of the glandular tissue of the prostate gland.

The extent to which dutasteride affects how much dihydrotestosterone concentrations decrease depends on the dose of the drug, and is usually observed after one to two weeks of treatment. After a week or two of taking a dose of 0.5 mg per day, serum dihydrotestosterone decreases by 85-90%.

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Pharmacokinetics

A single dose of the drug, equal to half a milligram, causes the maximum concentration of the active substance (dutastride) in the serum, it is achieved one to three hours after taking Avodart.

The percentage of absolute bioavailability of the drug is 60%.

If dutasteride is administered as a single or multiple doses, it will indicate that the volume of distribution is quite large (300 to 500 L). Dutasteride is highly bound to plasma proteins (>99.5%).

If the drug is taken daily for six months at half a milligram, then steady-state concentrations of dutasteride in the serum (Css) can be achieved. They are equal to approximately 40 ng / ml. Within a month, 65% of this level is usually reached, the mark of about 90% is reached after about three months. After fifty-two weeks of treatment, dutasteride will be concentrated in the semen in an amount of an average of 3.4 ng / ml (0.4 - 14 ng / ml). Sperm receives about 11.5% of dutasteride, which is sent there from the serum. The enzyme CYP3A4 of the cytochrome P450 system promotes the metabolism of the active substance, it is this enzyme that converts dutasteride into two monohydroxylated metabolites. It is not affected by the enzymes of this system CYP1A2, CYP2C9, CYP2C19 or CYP2D6. After a period of time, when a steady state concentration of the active substance occurs, the serum contains: unchanged dutasteride itself, 3 major metabolites (4'-hydroxydutasteride, 1,2-dihydrodutasteride and 6-hydroxydutasteride) and 2 minor metabolites.

The metabolism of the active substance of Avodart is characterized by intensity. When taking half a milligram during the day, 1-15.4% (on average 5.4%) of the dose taken is excreted in the feces unchanged. The remaining dose will be reproduced in the form of metabolites.

Trace amounts of the active substance dutasteride (less than 0.1% of the dose) will be excreted unchanged in the urine. When dosed therapeutically, the terminal half-life is three to five weeks. Dutasteride may be detectable in serum even after Avodart has been discontinued for up to six months, usually at concentrations slightly greater than 0.1 ng/mL.

The pharmacokinetics of Avodart, or more precisely its main active substance (dutasteride), is a first-order absorption process and the presence of two parallel elimination processes: one saturable (which depends on concentration) and one non-saturable (which does not depend on concentration). When serum dutasteride concentrations are low (less than 3 ng/mL), both elimination processes rapidly eliminate the active substance. If Avodart is taken once, there is rapid elimination of dutasteride, a process characterized by a short half-life (from three to five days).

When serum concentrations are greater than 3 ng/mL, dutasteride clearance is more pronouncedly slow (0.35–0.58 L/h), and is most often a linear, non-saturable process. When concentrations are therapeutic with a daily dose of 0.5 mg, dutasteride clearance is also slower. Overall, clearance is linear and does not depend on the concentration of the substance.

When Avodart is taken by an older man, there is no need to reduce the dose.

Dosing and administration

Avodart is taken orally, the time of food intake does not matter. The capsule is swallowed whole, without chewing or opening it (the fact is that the composition of the capsule can damage the oral mucosa).

Adult men, including the elderly, are recommended to take the following dose of Avodart: one capsule (0.5 mg dutasteride) once a day.

Avodart acts quite quickly, within a short period of treatment, but doctors recommend taking the drug for at least six months to achieve the maximum therapeutic effect. To cure BPH, Avodart is prescribed as monotherapy, it can also be combined with α1-adrenergic blockers.

For special patient groups:

• in case of kidney dysfunction: if you take a standard dose of 0.5 mg of the drug, then the kidneys will receive less than 0.1% of it. Therefore, in case of kidney dysfunction, patients take a standard dose of the drug, there is no need to reduce it.
• If the patient has impaired liver function, doctors recommend taking Avodart with some caution. There is currently no data on the treatment of this group of patients with Avodart. But dutasteride is characterized by intensive metabolism, the half-life of the drug is three to five weeks, so some caution when used in patients with impaired liver function will not hurt.

Use Avodart during pregnancy

The effects of Avodart and its main active ingredient dutasteride on sperm and on individual patient fertility have not been adequately studied to date.

Taking Avodart is strictly contraindicated for women. This area has also been poorly studied, however, there are suggestions that dutasteride suppresses the level of DCT, as a result of which the development of the genitals in a male fetus may be inhibited. It is also unknown whether dutasteride penetrates into the breast milk of a nursing mother.

Contraindications

Contraindications to taking Avodart are the presence of:

• hypersensitivity to the active substance of the drug (dutasteride), as well as to its other components;
• hypersensitivity to other 5α-reductase inhibitors.

Women and children should not take the drug under any circumstances – it is contraindicated for them.

If the patient has liver failure, Avodart is prescribed with special caution.

Side effects Avodart

Side effects of Avodart and its active ingredient dutasteride include:

• The body's immune system in very rare cases can react with allergic reactions (rash, itching, urticaria, localized swelling), as well as angioedema.
• The reproductive system of the body quite often reacts to the drug with changes in libido, ejaculation disorders, erectile dysfunction, gynecomastia (the presence of pain and enlargement of the mammary glands).
• Taking Avodart may cause alopecia (hair loss on the body) and hypertrichosis on the skin.

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Overdose

When patients were given a dose of 40 mg per day during the studies, which is eighty times the therapeutic dose, no side effects were recorded for a week. Also, no side effects were detected when patients took 5 mg for six months, there were no differences from the recommended dose.

If an overdose of Avodart does occur, symptomatic and supportive treatment is prescribed (there is no antidote for dutasteride).

Storage conditions

Avodart is stored out of the reach of children at a temperature not exceeding thirty degrees Celsius.

Shelf life

Avodart has a shelf life of four years.