Pharmacodynamics:

Abiraterone is an inhibitor of androgen biosynthesis. In particular, abiraterone selectively inhibits the activity of the enzyme 17α-hydroxylase / C17, 20-lyase (CYP17). This enzyme is necessary for the biosynthesis of androgens in the testes, adrenals, and cells of the tumor of the prostate.

CYP17 catalyzes the transformation of pregnenolone and progesterone by 17α-hydroxylation and breaking of the C17, 20 bonds into testosterone forerunners: dehydroepiandrosterone and androstenedione, separately. The restraint of CYP17 action is additionally joined by an expanded combination of mineralocorticoids in the adrenal organs.

Antiandrogenic treatment, for example, the utilization of luliberin agonists or orchidectomy, debilitates the union of androgens in the balls, however, does not influence the combination of androgens in the adrenal organ and tumor. The utilization of abiraterone together with lylyberyrin agonists (or orchidectomy) brings serum testosterone focuses down to underneath the recognition edge. The convergence of prostate-particular antigen (PSA) fills in as a biomarker in patients with prostate growth.

Pharmacokinetics:

When administered orally, the prodrug of abiraterone acetate is converted to an active metabolite, abiraterone, which has anti-androgenic activity. Joint reception with food increases the absorption of the drug and, therefore, can increase and greatly alter the effect of the drug, so abiraterone should be taken on an empty stomach. The drug binds well to proteins (> 99%) and is metabolized in the liver with the participation of CYP3A4 and SULT2A1 in inactive metabolites. Abiraterone is excreted in feces (~ 88%) and urine (~ 5%). The final half-life is 12 ± 5 hours.

Indications:

In combination with prednisolone for the treatment of metastatic castration-resistant prostate cancer in patients with progression of the disease during or after chemotherapy involving docetaxel

Contraindications: severe liver dysfunction;

– Children and adolescence under 18;

– Hypersensitivity to abiraterone.

Pregnancy and lactation:

The action category for fetus by FDA is N.

Abiraterone is not suitable for use in women. There are no data on the use of the drug in pregnant women. Abiraterone is contraindicated in pregnant women and able to become pregnant with women. It is not known whether the drug or its metabolites are excreted in milk.

To prevent accidental exposure, pregnant women or women of childbearing age should not work with abiraterone without gloves.

It is not known whether abiraterone or its metabolites are present in the sperm. During the treatment, it is necessary to use a condom if a sexual intercourse with a pregnant woman is planned. If the sexual act is planned with a woman of childbearing age, it is necessary to use a condom along with other effective methods of contraception.

Dosing and Administration:

In the combination therapy with prednisone or prednisolone in low doses, the recommended daily dose of abiraterone is 1 g (4 tables of 250 mg) 1 time/day for 1 hour before meals or 2 hours after meals. Abiraterone cannot be taken with food. Within 1 hour after taking the drug, eating is not recommended.

If you miss a regular daily dose of abiraterone or prednisolone the next day, you should take the usual dose of the missed drug.

Side effects:

Most often: peripheral edema, hypokalemia, arterial hypertension and urinary tract infections.

On the part of the liver: hepatotoxicity, accompanied by increased activity of ALT, ACT and total bilirubin (the mechanism of hepatotoxicity development is currently unknown).

Infectious diseases: very often – urinary tract infections.

From the endocrine system: infrequently – insufficiency of adrenal function.

From the side of laboratory indicators: very often – hypokalemia; often hypertriglyceridemia, increased ALT activity.

From the side of the cardiovascular system: very often – arterial hypertension; often – heart failure incl. acute heart failure left ventricular failure, reduced left ventricular ejection fraction, angina pectoris, arrhythmia, atrial fibrillation, tachycardia.

From the osteomuscular system and connective tissue: often – fractures (with the exception of pathological fractures).

From the side of the kidneys and urinary tract: often – hematuria.

Disorders from the gastrointestinal tract: often – dyspepsia.

Common disorders: very often – peripheral edema.

Overdose:

Data on an overdose of abiraterone are limited. There is no specific antidote. In case of an overdose, the drug should be discontinued and general supportive measures should be taken, including arrhythmia control. Liver function should also be monitored.

Special instructions:

Before starting the use of the drug should correct hypokalemia and increase blood pressure. An AD, the concentration of potassium in the blood plasma and the degree of fluid retention should be monitored at least 1 time per month.

Before the treatment with abiraterone, every 2 weeks during the first three months of treatment, and then monthly, the activity of serum transaminases and the concentration of bilirubin should be measured. If during the treatment the patients developed signs of hepatotoxicity (increased ALT activity is 5 times higher than IGN or bilirubin concentration 3 times higher than ULN), therapy should be stopped immediately before the liver function is fully normalized. Repeated therapy in patients with normalized liver function can begin with a reduced dose of 500 mg 1 time/day. If symptoms of hepatotoxicity occur at a dose of 500 mg, abiraterone should be discontinued. With the development of a severe form of hepatotoxicity (ALT activity exceeds HHV 20 times) in any period of therapy, abiraterone should be canceled, re-application in such cases is impossible.

In patients receiving abiraterone, there may be an increase in blood pressure, hypokalemia and fluid retention due to increased concentration, mineralocorticoids in the blood due to inhibition of CYP17. The introduction of SCS simultaneously with abiraterone weakens the stimulating effect of ACTH, which leads to a decrease in the frequency and severity of these adverse reactions.

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