Avodart - instructions for use, analogs, testimonials and release forms (capsules or tablets 500 μg) of a drug for the treatment of benign prostatic hyperplasia or BPH in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Avodart. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Avodart in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Avodart with the presence of existing structural analogues.Use to treat benign prostatic hyperplasia or BPH in men and urination disorders in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Avodart - a drug for the treatment of benign prostatic hyperplasia. Dutasteride (active ingredient of Avodart) is a double 5α-reductase inhibitor. Suppresses the activity of isoenzymes of 5α-reductase 1 and 2 types, which are responsible for the conversion of testosterone to dihydrotestosterone (DHT). Dihydrotestosterone is the main androgen responsible for the hyperplasia of the glandular tissue of the prostate gland.

The maximum effect of dutasteride on decreasing concentrations of DHT is dose-dependent and observed 1-2 weeks after the start of treatment. After 1 and 2 weeks of taking dutasteride at a dose of 500 mcg per day, the mean serum concentrations of dihydrotestosterone decrease by 85% and 90%, respectively.

Composition

Dutasteride + auxiliary substances.

Pharmacokinetics

Bioavailability of dutasteride does not depend on food intake. Has a high degree of binding to plasma proteins (more than 99.5%).With daily intake, the concentration of dutasteride in the serum reaches 65% of the stable level after 1 month and approximately 90% of the stable level after 3 months. Stable serum concentration dutasteride (Css), roughly equal to 40 ng / ml, achieved after 6 months once daily administration of 500 micrograms of the drug. In sperm, as in serum, stable concentrations of dutasteride are also reached after 6 months. After 52 weeks of treatment, the concentrations of dutasteride in the sperm averaged 3.4 ng / ml (0.4 to 14 ng / ml). From serum, about 11.5% of dutasteride enters the semen. Metabolized by the isoenzyme CYP3A4 of the human cytochrome P450 system to form two small monohydroxylated metabolites; however, it does not apply isozymes CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. After reaching Css dutasteride serum using mass spectrometric method detected unchanged dutasteride, 3 major metabolite (4'-gidroksidutasterid, 1,2-digidrodutasterid gidroksidutasterid and 6) and 2 minor metabolite (6,4'-digidroksidutasterid and 15 gidroksidutasterid ). In the human body, dutasteride undergoes intensive metabolism.After ingestion of dutasteride in a daily dose of 500 mcg to achieve Css from 1% to 15.4% (an average of 5.4%) of the accepted dose is excreted through the intestine in unchanged form. The rest is excreted through the intestine in the form of 4 large metabolites, accounting for 39%, 21%, 7% and 7%, respectively, and 6 small metabolites (each accounting for less than 5%). Through the kidney in humans only trace amounts of unchanged dutasteride (less than 0.1% of the dose) are excreted. Dutasteride is found in serum (in concentrations above 0.1 ng / ml) up to 4-6 months after discontinuation.

Pharmacokinetics in specific patient groups

The pharmacokinetics and pharmacodynamics of dutasteride were studied in 36 healthy volunteers aged 24 to 87 years after receiving a single dose (5 mg) of dutasteride. There were no statistically significant differences between different age groups for such pharmacokinetic parameters as AUC and Cmax in blood plasma. There were also no statistically significant differences in the values ​​of the dutasteride half-life between the age groups of men 50-69 years old and over 70 years of age, which include the majority of men with benign prostatic hyperplasia.

Between different age groups, there were no significant differences in the degree of decrease in DHT levels.These results demonstrate that there is no need to reduce the dose of dutasteride depending on the age of the patients.

Indications

• as a monotherapy for the treatment and prevention of the progression of benign prostatic hyperplasia by reducing its size, alleviating symptoms, improving urination, reducing the risk of acute urinary retention, and the need for surgery;
• as a combination therapy with alpha 1-adrenoblockers to treat and prevent the progression of benign prostatic hyperplasia by reducing its size, alleviating symptoms, improving urination, reducing the risk of acute urinary retention, and the need for surgery. The combination of dutasteride and alpha1-adrenoblocker tamsulosin was mainly studied.

Forms of release

Capsules 500 mcg (sometimes mistakenly called pills).

Instructions for use and dosing regimen

The drug can be taken regardless of food intake. Capsules should be swallowed whole, not chewed and not opened, as the contents of the capsule can cause irritation of the mucous membrane of the oropharynx.

Benign prostatic hyperplasia (BPH)

In adult men (including the elderly), the recommended dose of Avodart is 1 capsule (500 μg) once a day.

Although the improvement in the background of the use of the drug occurs rather quickly, treatment should be continued for at least 6 months in order to objectively evaluate the therapeutic effect.

For the treatment of BPH Avodart drug may be designated as a monotherapy or in combination with an alpha 1-blockers (tamsulosin Omnic, cardura, Doxazosin).

When taking 500 μg per day, less than 0.1% of the dose is released through the kidneys, so there is no need to reduce the dose in patients with impaired renal function.

Side effect

• allergic reactions (including rash, itching, hives, localized edema);
• angioedema;
• alopecia (mainly loss of hair on the body);
• hypertrichosis;
• depressive state;
• testicular pain;
• testicular edema;
• erectile disfunction;
• decreased libido;
• violation of ejaculation.

Contraindications

• hypersensitivity to dutasteride and other components of the drug;
• increased sensitivity to other 5α-reductase inhibitors;
• contraindicated in women and children.

Application in pregnancy and lactation

Impact on fertility

The influence of Avodart in a daily dose of 500 μg on the characteristics of semen was studied in healthy volunteers aged 18-52 years. By the 52nd week of treatment, in the group of patients receiving dutasteride, the mean percentages of the total sperm count, sperm volume, and motor activity of spermatozoa were 23%, 26%, and 18%, respectively, compared to baseline in the placebo group. The concentration of spermatozoa and their morphological characteristics did not change.

After 24 weeks of follow-up, the mean percentage change in the total number of spermatozoa in the dutasteride group remained 23% lower compared to baseline. The mean value for all sperm parameters at all time points remained within the norm and did not meet the specified criteria for a clinically significant change (30%), at the 52nd week of treatment in two volunteers in the dutasteride group, the total number of spermatozoa decreased by more than 90% compared with the baseline, with partial recovery at the 24th week of follow-up.

Thus, the clinical significance of the effect of dutasteride on sperm counts and individual patient fertility is unknown.

Pregnancy

Avodart is contraindicated in women. Dutasteride was not studied in women; preclinical data suggest that suppressing the level of DHT can cause inhibition of the development of external genital organs in a male fetus.

Lactation

There is no data on the penetration of dutasteride into breast milk.

Use in children

Avodart is contraindicated in children.

Application in elderly patients

Correction of the dose is not required.

special instructions

Dutasteride is absorbed through the skin, so women and children should avoid contact with damaged capsules. In case of contact with damaged capsules, immediately wash the corresponding skin area with soap and water.

Impaired liver function

Currently, there is no data on the use of Avodart in patients with impaired liver function. Because dutasteride is subject to intensive metabolism, and its half-life is 3-5 weeks, care must be taken when Avodart is treated with patients with impaired liver function.

Heart failure with combined use of dutasteride and tamsulosin

In two 4-year clinical trials, the incidence of heart failure was higher in patients who received a combination of dutasteride and alpha1-adrenoblocker, mostly tamsulosin, than patients who did not receive combination treatment. In these two studies, the incidence of heart failure remained low (less than 1%) with some variability between them. But in general, there were no discrepancies in the frequency of side effects from the cardiovascular system. The causal relationship between the treatment of dutasteride (either as monotherapy or as a combination with alpha 1-adrenergic blocker) and the development of heart failure has not been established.

Effect on the detection of prostate-specific antigen (PSA) and prostate cancer (PCa)

Patients should undergo digital rectal examination, as well as use other methods of prostate examination, before starting treatment with dutasteride, and periodically repeat them during treatment to exclude the development of PCa.

Determination of serum PSA is an important component of screening aimed at detecting PCa. After a 6-month therapy with dutasteride, the average serum PSA level is reduced by approximately 50%. Patients taking dutasteride should be given a new baseline PSA level after 6 months of therapy. In the future, it is recommended to regularly monitor the level of PSA. When interpreting the PSA value of a patient taking dutasteride, the previous PSA value should be used for comparison.

The use of dutasteride does not affect the diagnostic value of PSA as a marker of PCa after the definition of a new baseline PSA level. Any confirmed increase in PSA relative to its lowest value in the treatment with dutasteride may indicate the development of PCa (particularly prostate cancer with a high degree of Gleason differentiation) or non-adherence to dutasteride therapy and should be carefully evaluated even if these PSA levels remain in the limits of normal values ​​for a given age group of patients not taking 5α-reductase inhibitors.

The level of total PSA returns to the initial value within 6 months after the abolition of dutasteride.

The ratio of free PSA to the total remains constant even against the background of dutasteride therapy. If the determination of the percentage of free PSA fraction is additionally used to detect PCa in men receiving dutasteride, correction of this value is not required.

Prostate cancer and high grade tumors

In a 4-year study (REDUCE), placebo and dutasteride were compared in 8,231 volunteers aged 50 to 75 years with a negative biopsy result for PCa and a PSA level of 2.5 ng / ml to 10 ng / ml for a primary examination.

In the course of the study, 6706 patients underwent puncture biopsy of the prostate gland and, based on the results obtained, the degree of malignancy of the Gleason cancer was determined. 1517 patients were diagnosed with PCa during the study. In most cases, both in the dutasteride group and in the placebo group, a highly differentiated prostate cancer was diagnosed (the Gleason score was 5-6). Differences in the number of cases of PCa with an assessment of 7-10 points on the Gleason score in the dutasteride group and placebo group were absent (p = 0.81).

The causal relationship between the intake of dutasteride and the development of PCa of a high degree of gradation has not been established.

Men taking Avodart should regularly undergo examinations to assess the risk of developing PCa, including the level of PSA.

Breast cancer in men

In clinical studies and during post-registration surveillance, breast cancer was reported in men taking Avodart. Patients should be warned that if any changes in the tissues of the mammary glands, such as the appearance of nodules or discharge from the nipples, should immediately be reported to the attending physician.

In clinical studies that evaluated the effect of BPH monotherapy with dutasteride (3,374 patient-years), 2 breast cancers were detected with dutasteride (10 weeks and 11 months) and 1 in the placebo patient. In subsequent clinical trials in which 8231 men aged 50 to 75 years with negative PCa biopsy and PSA levels ranging from 2.5 ng / ml to 10 ng / ml (17489 patient years) who received dutasteride were involved, and patients (5,027 patient-years),who received combined therapy with dutasteride and tamsulosin, there were no cases of breast cancer in any of the comparison groups.

At the moment, it is unclear whether there is a causal relationship between the occurrence of breast cancer in men and the long-term use of dutasteride.

Impact on the ability to drive vehicles and manage mechanisms

Receiving Avodart does not affect the driving of cars or work with mechanisms.

Drug Interactions

Dutasteride is metabolized by the isoenzyme CYP3A4 of the human cytochrome P450 enzyme system. Therefore, in the presence of inhibitors of CYP3A4, the concentrations of dutasteride in the blood can increase.

With the simultaneous use of Avodart with inhibitors of CYP3A4 Verapamil and diltiazem, a decrease in the clearance of dutasteride is noted. At the same time, amlodipine, other calcium channel blockers with simultaneous application with dutasteride do not reduce the clearance of dutasteride. The decrease in clearance of dutasteride and the subsequent increase in its concentration in the blood in the presence of inhibitors of CYP3A4 is not clinically significant due to the wide range of dutasteride safety margins, so there is no need to adjust its dose.

Dutasteride is not metabolized by the following isoenzymes of the human cytochrome P450 system: CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6 or CYP2D6.

Dutasteride does not inhibit the enzymes of the human cytochrome P450 system involved in the metabolism of drugs.

Dutasteride does not displace warfarin, acenocoumarol, fenprocumone, Diazepam and phenytoin from the sites of their binding to plasma proteins, and these drugs, in turn, do not displace dutasteride.

When conducting research on the interaction of Avodart with tamsulosin, terazosin, warfarin, Digoxin and colestyramine, no clinically significant pharmacokinetic or pharmacodynamic interactions were observed in humans.

When dutasteride was used simultaneously with lipid-lowering drugs, ACE inhibitors, beta adrenoblockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, inhibitors of type 5 phosphodiesterase and quinolone antibiotics, no significant undesirable drug interaction was observed.

Analogues of the drug Avodart

Avodart does not have structural analogs for the active substance.

Analogues on the curative effect (agents affecting metabolism in the prostate gland):

• Adenostop;
• Artesine;
• Artesine retard;
• Bioprost;
• Vitanorm;
• Vitaprost;
• Vitaprost forte;
• Glansin;
• Dinindolylmethane;
• Doxazosin;
• Duodart;
• Grain;
• Zooxon;
• Camyrin;
• Cardura Neo;
• Koprivit;
• Kornam;
• Red root plus;
• Myctosin;
• Omnik;
• Omnik Okas;
• Omsulosin;
• Palprostes;
• Penester;
• Permikson;
• Polipressin;
• Prazosin;
• Prostavern Urtika;
• They will prostate;
• Prostamine;
• Prostamol Uno;
• Prostanorm;
• Prostaplant;
• Prostatilen;
• Prosteride;
• Proflosin;
• Samprost;
• Serpens;
• Setegis;
• Sonizine;
• Spem;
• Tadimax;
• Tamsulosin;
• Tanise;
• Terazosin;
• Toviaz;
• Trianol;
• Urocardia;
• Uroprost;
• Urorek;
• Urofin;
• Finasteride;
• Haytrin;
• Cernilton;
• Effect Red root.

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