Urofin - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 90.962 mg, microcrystalline cellulose 30.0 mg, corn pregelatinized starch 15.0 mg, lauryl macrogolglycerides 0.758 mg, sodium carboxymethyl starch (type A) 7.5 mg, magnesium stearate 0.785 mg;

tablet shell: Fall Light Blue 03F20404 (hypromellose (6 cps.) 2.86 mg, titanium dioxide 0.91 mg, indigo carmine (E 132) 0.22 mg, macrogol 6000 0.51 mg).

Description:

Round, biconcave tablets, covered with a film coating of blue color with the marking "F5 "on one side.

Pharmacotherapeutic group:5-alpha reductase inhibitor

ATX: & nbsp

G.04.C.B.01 Finasteride

Pharmacodynamics:

Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of steroid 5-alpha reductase II, an intracellular enzyme that converts testosterone in a more active androgen dihydrotestosterone (DHT). In benign prostatic hyperplasia, its increase depends on the conversion of testosterone to DHT in the prostate gland. Finasteride reduces the concentration of DHT both in the blood and in the tissues of the prostate gland.

Suppression of DHT formation is accompanied by a decrease in the size of the prostate gland, an increase in the maximum rate of urine flow and a decrease in the severity of symptoms associated with prostatic hyperplasia.

Finasteride does not have an affinity for the androgen receptor, has no significant effect on the lipid profile (ie, cholesterol, low-density lipoproteins, high-density lipoproteins, and triglycerides) and bone mineral density.

A single dose of finasteride in a dose of 5 mg leads to a rapid decrease in the concentration of DHT in the serum with a maximum effect achieved after 8 hours.Despite the fact that the concentration of finasteride in the blood plasma undergoes fluctuations for 24 hours, the concentration of DHT remains constant. This means that the concentration of finasteride in the blood plasma is not directly related to the concentration of DHT in the blood plasma.

In patients with DHT, who finasteride in a dose of 5 mg per day was administered for 4 years, there was a decrease in the concentration of DHT in the blood by about 70%, which was associated with a decrease in the volume of the prostate gland by approximately 20%. In addition, approximately 50% decreased the concentration of prostate-specific antigen (PSA) compared to its initial concentration, which suggests a decrease in the growth of prostatic epithelial cells. Reduction in the concentration of DHT and a decrease in the severity of prostatic hyperplasia, accompanied by a decrease in the concentration of PSA, persisted in studies up to 4 years. In these studies, the content of testosterone in the blood increased by approximately 10-20%, remaining within physiological values.

Pharmacokinetics:

Suction

After taking the drug inside finasteride quickly absorbed from the gastrointestinal tract.Bioavailability is about 80% and does not depend on food intake. The maximum concentration is reached approximately 2 hours after administration, the absorption is completed after 6-8 hours.

Distribution

The connection with plasma proteins is about 93%. Plasma clearance - 165 ml / min (70-279 ml / min), the volume of distribution - 76 liters (44-96 liters). With repeated application of finasteride, its accumulation is insignificant. After a daily dose of finasteride of 5 mg, its minimum equilibrium concentration is 8-10 ng / ml, which remains stable over time. Finasteride penetrates the blood-brain barrier. Minor amounts of finasteride are found in the seminal fluid.

Metabolism

Finasteride is metabolized in the liver, has a negligible effect on the cytochrome P450 system. There are two metabolites that have a slight effect of inhibiting 5-alpha reductase.

Excretion

The half-life (T_1/2) on the average is 6 hours (4-12 hours). After ingestion of a dose of finasteride, labeled ¹⁴C, 39% (32-46%) is excreted by the kidneys in the form of metabolites, 57% (51-64%) - through the intestine.

Special patient groups

T_1/2finasteride in patients older than 70 years is 8 hours (6-15 hours).

In patients with impaired renal function (QC 9-55 ml / min) there were no changes in the excretion of finasteride.

These deviations are not clinically significant, so dose adjustments in these patient groups are not required.

Indications:

Treatment and control of the growth of benign prostatic hyperplasia (BPH) in patients with an enlarged prostate gland in order to:

- reducing the size of the enlarged prostate gland, improving the urine flow and reducing the symptoms associated with BPH;

- preventing urological complications (reducing the risk of acute urinary retention) and reducing the risk of need for surgical operations (including transurethral resection of the prostate and prostatectomy).

Contraindications:

- Hypersensitivity to finasteride and other components of the drug;

- pregnancy and women of childbearing age;

- children's age (up to 18 years);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption (due to the presence of lactose monohydrate).

Carefully:

- Violation of the function of the liver;

- patients with a large volume of residual urine and / or significantly reduced urine flow (careful monitoring for obstructive uropathy is necessary).

Pregnancy and lactation:

The drug is not intended for use in women.

Dosing and Administration:

Inside. The tablet should be swallowed whole, not divided and not broken. The recommended dose is 5 mg (1 tablet) per day, regardless of food intake.

Even if improvement is observed within a short period of treatment, the duration of therapy should be at least 6 months to assess its effectiveness.

Liver failure

There is insufficient data on the use of the drug in patients with hepatic insufficiency.

Renal insufficiency

There is no need for correction of the dosing regimen for patients with renal insufficiency of varying severity (with a decrease in QC to 9 ml / min), since pharmacokinetic studies have not revealed a violation of elimination of finasteride. The reception of finasteride in patients on hemodialysis has not been studied.

Elderly patients

The elimination of finasteride from the body in patients older than 70 years is slightly reduced, no correction of the dosing regimen is required.

Side effects:

The most frequent adverse reactions were impotence and decreased libido, which occurred in the early stages of therapy and resolved in most patients with further treatment. Undesirable reactions reported in clinical trials and / or in the postmarketing observation period when taking finasteride 5 mg and / or in smaller doses are presented below. The frequency of their occurrence was classified as follows: very often (≥1 / 10), often (≥1 / 1 (30, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1 / 1000), very rarely (<1/10000), the frequency is unknown (can not be determined from available data).

The frequency of unwanted reactions received during post-marketing surveillance can not be established, as they were obtained in the form of spontaneous communication.

Immune system disorders:

frequency unknown - hypersensitivity reactions, including edema of the lips and face; angioedema, including swelling of the lips, tongue, throat and face.

Disorders of the psyche:

often - decrease libido; the frequency is unknown - depression, decreased libido, continuing after the abolition of treatment.

Heart Disease:

frequency unknown - a feeling of a strong palpitation.

Disorders from the liver and bile ducts:

frequency unknown - an increase in the activity of liver enzymes.

Disturbances from the skin and subcutaneous tissues:

infrequently - rash;

frequency unknown - itching.

Violations of the genitals and mammary glands:

often - impotence;

infrequently - violations of ejaculation, soreness and enlargement of the mammary glands;

frequency unknown - soreness of the testicles, erectile dysfunction, continuing after the withdrawal of treatment; male infertility and / or decreased quality of seminal fluid.

Laboratory and instrumental data:

often - a decrease in the volume of ejaculate.

Additionally, in clinical trials and during post-marketing surveillance, breast cancer in men has been reported (see section Specific silt is indicated).

Therapy of symptoms of prostate disease (MTOPS)

In a comparative study of monotherapy with finasteride 5 mg / day (n = 768), doxazosin 4 or 8 mg / day (n = 756), combined therapy finasteride 5 mg / day + doxazosin 4 or 8 mg / day (n = 786) and placebo (n = 737), the safety and tolerability profile of the combined therapy was generally comparable to that of finasteride and doxazosin in monotherapy.The incidence of ejaculation disorder in patients taking combination therapy was comparable to the sum of the incidence of allergy in monotherapy.

Other data for long-term therapy

In a seven-year, placebo-controlled study, in which 18,882 healthy men were included, 9060 of them had the results of an analysis of a puncture biopsy of the prostate. In 803 patients who took finasteride in a dose of 5 mg / day, prostate cancer was diagnosed (18.4%), and 1147 (24.4%) cases were diagnosed in patients taking placebo.

In the finasteride group, in 280 patients (6.4%) with puncture biopsies, prostate cancer was 7-10 on a scale Gleason compared with 237 (5.1%) patients in the placebo group. An additional analysis of the data indicates that an increase in the incidence of prostate cancer with a high degree of malignancy in the finasteride 5 mg group can be explained by the diagnostic errors associated with the influence of finasteride on the volume of the prostate gland. In general, prostate cancer cases that were identified during the study were classified as intracapsular prostate cancer (clinical stage T1 or T2 in 98%). Clinical significance of data on the Gleason scale 7-10 is unknown.

Laboratory test results

When evaluating the results of laboratory indicators of PSA, one should take into account a decrease in its concentration in patients taking finasteride (see section Special instructions).

Other differences in the levels of standard laboratory indicators between the groups of patients who received finasteride and placebo, was not observed.

Overdose:

Symptoms: when taking a single dose of finasteride to 400 mg and when taking repeated doses of 80 mg per day for three months, there were no clinically significant side effects.

Treatment: there is no specific antidote.

Interaction:

Clinically significant interaction with other drugs has not been identified.

Finasteride, apparently, has no significant effect on the cytochrome P450 system and the metabolism of drugs associated with this system. There were no clinically significant interactions in the combined use of finasteride with propranolol, digoxin, glibenclamide, warfarin, theophylline and phenazone.

Finasteride can be used as a monotherapy or in combination with doxazosin.

Special instructions:

General recommendations

In order to avoid obstructive complications, it is important that patients with a large volume of residual urine and / or with a significant decrease in the urine flow are closely monitored.

There should be an opportunity for an operative intervention.

Before the beginning of therapy it is necessary to exclude diseases. simulating benign hyperplasia prostate cancer - prostate cancer, stricture of the urethra, hypotension of the bladder, violation of its innervation and infectious prostatitis.

It is necessary to stop taking the drug Urophin and immediately consult a doctor if one of the symptoms of angioedema develops: swelling of the face, tongue, or throat; difficulty swallowing; rash / urticaria and difficulty breathing.

Effect on the concentration of PSA and diagnosis of prostate cancer

To date, the clinical advantages of using finasteride in patients with prostate cancer have not been proven. In controlled clinical trials, patients with BPH and elevated PSA concentrations were monitored for PSA and prostate biopsy.It was found that the use of finasteride does not change the frequency of detection of prostate cancer and does not affect the frequency of its occurrence in patients who took finasteride or placebo.

Before starting treatment and periodically during the treatment with finasteride, it is recommended to perform a rectal examination and apply other methods of diagnosing prostate cancer. The determination of serum PSA is also used to detect prostate cancer.

In general, the initial concentration of PSA above 10 ng / ml indicates the need for further examination of the patient and biopsy. When determining the concentration of PSA within 4-10 ng / ml, further examination of the patient is necessary. The concentration of PSA in men with prostate cancer and without this disease can significantly coincide in value, therefore in men with BPH normal values of PSA do not allow to exclude prostate cancer, regardless of the treatment with finasteride. The initial concentration of PSA below 4 ng / ml also does not exclude prostate cancer.

Finasteride causes a decrease in serum PSA concentrations of approximately 50% in patients with BPH, even in the presence of prostate cancer.This fact should be taken into account when assessing the PSA in patients with BPH receiving finasteride treatment, as a decrease in the PSA concentration does not exclude the presence of concomitant prostate cancer.

This decrease can be predicted for any range of values of PSA concentration, although it may differ for specific patients. In patients who took finasteride for 6 months or more, the PSA values should be doubled to be compared with the normal values of this parameter in patients not taking finasteride. This correction preserves the sensitivity and specificity of the PSA analysis and the possibility of detecting prostate cancer.

Any persistent increase in PSA in patients receiving finasteride treatment requires a thorough examination to determine the cause, which may lie in non-compliance with the finasteride regimen.

Finasteride does not significantly reduce the percentage of free PSA (ratio of free PSA to total). This indicator remains constant even under the influence of the reception of finasteride.If the percentage of free PSA is used to diagnose prostate cancer, correction of the values of this indicator is not necessary.

Effect of the drug on laboratory tests

Effect on the concentration of PSA

The concentration of PSA in the blood plasma correlates with the age of the patient and the volume of the prostate gland, and the volume of the prostate gland, in turn, depends on the age of the patient. When

determination of PSA concentration, it should be taken into account that this indicator is reduced in patients taking finasteride. In most patients, a rapid decrease in PSA is observed in the first months of therapy, after which it stabilizes at a new level, which is usually approximately half the value measured before the start of therapy. In connection with this in patients receiving finasteride for 6 or more months, the value of PSA concentration should be doubled to compare it with normal values in men not taking finasteride. For clinical interpretation of the results, see section Special instructions, subsection Effect on the concentration of PSA and diagnosis of prostate cancer.

Breast cancer in men

During the clinical trials and during the post-marketing observation of finasteride 5 mg, the development of breast cancer in men was reported. Patients should be informed to the attending physician of any changes in the area of the mammary glands: compaction, swelling, pain, gynecomastia or discharge from the nipple.

Application in childhood

Finasteride is not indicated for use in children. Safety and effectiveness of use in children are not established.

Liver failure

The effect of hepatic insufficiency on the pharmacokinetics of finasteride is not was investigated.

Influence on development of a fetus of a male

Women of childbearing age and pregnant women should avoid contact with Urophin's shredded and loss-of-integrity tablets, since finasteride may be absorbed and its ability to suppress the conversion of testosterone to DHT may cause impaired development of the genital organs in the male fetus. The tablets of the Urofin preparation are coated with a film sheath and, while maintaining its integrity, contact with the active substance is excluded.

When taking finasteride at a dose of 5 mg per day in patients in small quantities, the active substance in the seminal fluid is determined.It is not known whether seminal fluid finasteride Influence on the male fetus, formed during the fertilization of a woman given a seminal fluid. Women of childbearing age and pregnant women should minimize contact with the semen fluid of the partner taking the drug Urophin.

Effect on the ability to drive transp. cf. and fur:

The adverse effect of the drug on the ability to drive vehicles and work with mechanisms was not reported.

Form release / dosage:

Tablets, film-coated, 5 mg.

Packaging:

For 7 or 10 tablets in PVC / A blistersl or Al/Al.

For 1, 2, 4, 7 or 14 blisters for 7 tablets, according to 1,2, 3, 5, 6 or 10 blisters for 10 tablets with instructions for use in a cardboard bundle.

Storage conditions:Does not require special storage conditions.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002268

Date of registration:04.10.2013

Date of cancellation:2018-10-04

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

INTAS PHARMACEUTICALS, Ltd. India

Representation: & nbspACTAVIS GROUP AO ACTAVIS GROUP AO Iceland

Information update date: & nbsp24.09.2015

Illustrated instructions

Instructions

Urofin (Urofin)