Avodart

Avodart is one of those drugs that help treat prostate adenoma. Its active substance - dutasteride - therapeutically affects benign prostatic hyperplasia. The maximum this drug works after a week or two after the patient starts taking the drug. 

[1],

Indications Avodart

As a monotherapy:

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

As a combined therapy with α1-adrenoblockers:

Treatment and prevention of progression of benign prostatic hyperplasia by reducing the size of the prostate, improving urination, reducing the risk of acute urinary retention and the need for surgery. The combination of dutasteride and α1-adrenoblocker tamsulosin was mainly studied.

Release form

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

Issued capsules in aluminum blisters. In one blister - ten capsules. There are two forms of Avodart's release - three blisters in a pack and nine each. 

Pharmacodynamics

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

How much dutasteride affects how much the concentration of dihydrotestosterone decreases depends on the dosage of the drug, usually it is observed after one two weeks after the treatment was started. After a week or two from taking a dose of 0.5 mg per day, dihydrotestosterone in serum is reduced by 85-90%.

[2], [3]

Pharmacokinetics

One dose of the drug, half a milligram, causes the maximum concentration of the active substance (dutasteride) in the serum, it is reached one to three hours after taking Avodart.

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

If dutasteride is taken once or repeatedly, this will indicate that the volume of how it is distributed is large enough (from 300 to 500 liters). Dutasteride has a high degree of binding to plasma proteins (> 99.5%).

If the drug is taken daily for half a year for half a milligram, then it is possible to achieve stable concentrations of serum dutasteride (Css). They are equal to approximately 40 ng / ml. Within a month usually reach 65% of this level, a mark of about 90% is reached after about three months. After fifty-two weeks of treatment, dutasteride will be concentrated in semen at an average of 3.4 ng / ml (0.4-14 ng / ml). Sperm gets close to 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, CYP2S9, CYP2S19 or CYP2D6. After a time when a stable concentration of active substance occurs, the serum contains: unchanged dutasteride itself, 3 large metabolites (4'-hydroxydutasteride, 1,2-dihydrodutasteride and 6-hydroxydutasteride) and 2 small metabolites.

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

Together with the urine, a trace amount of the active substance dutasteride (less than 0.1% of the dose) will be delivered in an unchanged quantity. In case of taking doses of the drug in therapeutic treatment, the final half-life period will be from three to five weeks. Dutasteride can be detected in the serum even after Avodart has stopped taking it for up to six months, in which case it usually stays at a concentration slightly more than 0.1 ng / ml.

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

When serum concentrations reach more than 3 ng / ml, the clearance of dutasteride has a more pronounced slowness (0.35-0.58 l / h), most often a linear unsaturated process is observed. If the concentrations are therapeutic at a daily dose of 0.5 mg, the dutasteride clearance is also slower. In general, the clearance is linear and does not depend on the concentration of the substance.

When Avodart receives an older man, it is not necessary to reduce the dose. 

Dosing and administration

Avodart taken orally, the time of eating does not play a role. Capsules are swallowed whole, do not chew and do not open it (the fact is that the composition of the capsule can damage the oral mucosa).

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

Avodart operates quickly enough during a short period of treatment, but doctors recommend taking the drug for at least six months, to maximize the therapeutic effect. To cure BPH, Avodart is prescribed as monotherapy, and it can also be combined with α1-blockers.

For special patient groups:

•  with violations of the kidneys: if you take a standard dose of 0.5 mg of the drug, the kidneys will account for less than 0.1% of it. Therefore, in case of violations of kidney function, patients take a standard dose of the drug, there is no need to reduce it.
•  if the patient has a disrupted liver function, doctors recommend taking Avodart with some caution. Now there is no data on the treatment of this group of patients with the help of 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 does not interfere. 

Use Avodart during pregnancy

The influence of Avodart and its main active ingredient dutasteride on sperm and individual patient fertility has not been sufficiently studied to date.

Adoption Avodart women categorically contraindicated. This field has also been studied, however, there are suggestions that dutasteride suppresses the level of VCT, as a result of which the development of the genital organs in the fetus-boy can be inhibited. Whether dutasteride penetrates the breast milk of a nursing mother is also not known. 

Contraindications

Contraindications for the admission of Avodart are:

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

Women and children in no case should not take the drug - they are contraindicated.

If the patient has hepatic insufficiency, Avodart is especially cautious. 

Side effects Avodart

Side effects of Avodart and its active substance dutasteride are:

• The immune system of the organism in very rare cases can react with allergic reactions (the presence of rash, itching, hives, localized edema), as well as angioedema.
• The reproductive system of the body often responds to the drug with changes in libido, ejaculation disorders, erectile dysfunction, gynecomastia (the presence of soreness and enlargement of the mammary glands).
• On the skin due to admission Avodart can manifest alopecia (hair on the body fall out), as well as hypertrichosis. 

[4], [5], [6]

Overdose

When patients were prescribed a dose of 40 mg per day during the study, which is eighty times the therapeutic dose, side effects were not recorded for a week. Also, side effects were not detected when taking 5 mg of patients for six months, there were no differences from the recommended dose.

If an overdose of Avodart still occurs, then a symptomatic and supportive treatment is prescribed (there is no antidote for dutasteride).

Storage conditions

Avodart store in a place inaccessible to children, at a temperature not exceeding thirty degrees Celsius.

Shelf life

Shelf life Avodart is four years.