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

Finasteride, a synthetic 4-azasteroid compound, is a specific competitive inhibitor of the 5-alpha reductase type II intracellular enzyme that converts testosterone in a more active androgen - dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), its increase depends on the conversion of testosterone to DHT in the prostate. Finasteride highly effective reduces the concentration of DHT in both plasma and prostate tissue. Suppression of DHT formation is accompanied by a decrease in the size of the prostate gland, an increase in the maximum rate of urination and a decrease in the severity of symptoms associated with prostatic hyperplasia.

Finasteride does not have an affinity for androgen receptors.

According to the results of a clinical trial (PLESS), in which Nazis with moderately or significantly expressed symptoms of BPH and prostatic enlargement, finasteride reduced the incidence of acute urinary retention from 7/100 to 3/100 over a 4-year period, and the frequency of surgical intervention (transurethral resection of the prostate (TURP) or prostatectomy) from 10/100 to 5/100.These changes were also associated with an improvement in the symptomatology of BPH (a 2 point decrease in the quasi-AUA symptom score), a sustained decrease in prostate volume by approximately 20%, and a steady increase in urinary flow rate.

Study MTOPS (Medical Therapy Of Prostate Symptoms) lasting from 4 to 6 years, in which 3,047 men with BPH symptoms were randomized to groups receiving: finasteride in a dose of 5 mg / day; doxazosin in a dose of 4 mg / day or 8 mg / day; a combination of finasteride at a dose of 5 mg / day and doxazosin at a dose of 4 mg / day or 8 mg / day; or placebo.

Treatment resulted in a significant reduction in the risk of clinical progression of BPH, which was 34% (p = 0.002), finestradin supplementation (39%) (p <0.001) and combined therapy (67% (p <0.001) compared with placebo. In most cases, the progression of BPH (274 out of 351) was exacerbated by symptomatic BPH by ≥4 points on the International Prostate Symptom Score (IPSS) scale, and among patients who received finasteride, the risk of worsening of the symptoms assessed by the score decreased by 30% (95% CI: 6-48%), among those receiving doxazosin - by 46% (95% CI: 25-60%), and among those receiving combination therapy - 64% (95% CI: 48-75%) relative to the placebo group. Among patients who received finasteride, the risk of acute urinary retention was reduced by 67% (p = 0.011), in the group receiving doxazosin - by 31% (p = 0.296), and in the group receiving combination therapy - by 79% (p = 0.001) relative to the placebo group. Significant difference from placebo was observed only in the groups of patients who received finasteride and combined therapy.

Pharmacokinetics:

Absorption

The maximum concentration of finasteride in the blood plasma is reached approximately 2 hours after ingestion. Absorption of finasteride from the gastrointestinal tract is completed 6-8 hours after ingestion.

Bioavailability finasterida at ingestion is approximately 80% of the intravenous reference dose and does not depend on the intake of food.

Distribution

The association with plasma proteins is approximately 93%. Plasma clearance is about 165 ml / min, the volume of distribution - 76 liters.

With prolonged therapy, slow accumulation of finasteride is observed in small amounts. With a daily intake of finasteride inside at a dose of 5 mg, its minimum equilibrium concentration in the blood plasma reaches 8-10 ng / ml and over time remains stable.

In patients who received finasteride for 7-10 days, the drug was detected in the cerebrospinal fluid. When taking finasteride at a dose of 5 mg per day, the drug in small amounts is found in seminal fluid.

Metabolism

The half-life (T_1/2) finasteride average is 6 hours.

Excretion

In men after a single oral dose of finasteride, labeled ¹⁴C, 39% of the accepted dose is excreted by the kidneys in the form of metabolites (unchanged finasteride practically not excreted by the kidneys); 57% through the intestine. In this study, 2 metabolites of finasteride, which have a slight inhibitory

action against 5-alpha reductase compared with finasteride. In the elderly, the rate of excretion of finasteride somewhat decreases. With age, the half-life (T_1/2) increases: in men 18-60 years, the average T1/2 is 6 hours, and for men over 70 years - 8 hours. These changes are not of clinical importance, and therefore, a reduction in the dose of the drug in elderly men is not required.

In patients with chronic renal failure (creatinine clearance (CK) from 9 to 55 ml / min), the distribution of the labeled ¹⁴With finasteride with a single dose did not differ from that of healthy volunteers.The connection of finasteride with plasma proteins was also not different in patients with impaired renal function.

With renal insufficiency, a part of the finasteride metabolites, which is normally excreted by the kidneys, is excreted through the intestine. This is manifested by an increase in the amount of finasteride metabolites in the feces with an appropriate decrease in their concentration in the urine. In patients with renal failure who do not need hemodialysis, correction of the dose of finasteride is not required.

Indications:

Treatment of BPH and prevention of urological complications with the aim:

- reduce the risk of acute urinary retention;

- reducing the risk of the need for surgical interventions, including transurethral resection (TUR) of the prostate and prostatectomy.

Treatment to reduce the size of the enlarged prostate gland, improve urination and reduce the symptoms associated with BPH.

In combination with doxazosin to reduce the risk of progression of symptoms associated with BPH.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- age to 18 years;

- pregnancy and use of the drug in women of childbearing age (see p.section "Application during pregnancy and during breast-feeding");

- patients with rare hereditary lactose intolerance, lactase deficiency or impaired glucose-galactose absorption should not take this drug.

Carefully:

- Patients with a large volume of residual urine and / or a significantly reduced rate of urination;

- patients with hepatic insufficiency;

- to the elderly.

Pregnancy and lactation:

The use of PENESTER® is contraindicated in pregnancy and in women of childbearing age. In connection with the ability of inhibitors of 5-alpha reductase type II inhibit the conversion of testosterone to dihydrotestosterone, these agents, including finasteride, when used in pregnant women can cause anomalies in the development of external genitalia in a male fetus. Finasteride not indicated for use in women.

There is no data on the excretion of finasteride with breast milk.

Small amounts of finasteride were found in the sperm of patients who received finasteride in a dose of 5 mg / day. Although clinical data on the effect of finasteride on a male fetus are not available, women of childbearing age should avoid contact with semen from men who take finasteride.

Women of childbearing age and pregnant women should avoid contact with damaged tablets of finasteride, tk. the ability of the drug to inhibit the conversion of testosterone to dihydrotestosterone may cause impaired development of the genital organs in the male fetus.

Dosing and Administration:

Inside, 5 mg once a day, regardless of food intake.

The duration of therapy before evaluating its effectiveness should be at least 6 months, so the course of treatment should be quite long. The drug PENESTER ® can be used in the form of monotherapy, as well as in combination with doxazosin.

Liver failure

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

Renal insufficiency

In patients with various stages of renal failure (with a decrease in CK to 9 ml / min), dose adjustment is not required, since special studies have not demonstrated any changes in the pharmacokinetic profile of finasteride.

Elderly patients

Correction of doses is not required, although pharmacokinetic studies indicate that the excretion of finasteride in patients older than 70 years is somewhat reduced.

Side effects:

Adverse reactions to the drug are divided into system-organ classes in accordance with the classification of the Medical Dictionary on regulatory legal activity (MedDRA). The frequency of adverse reactions was determined according to the following gradation (classification of the World Health Organization): very frequent - more than 1/10, frequent - more than 1/100 to less than 1/10, infrequent - from more than 1/1000 to less than 1/100, rare - from more than 1/10000 to less than 1/1000, very rare - from less than 1/10000, including individual messages, of unknown frequency (the frequency can not be established, as information was obtained from the post-marketing experience of the drug).

Most often, patients experienced impotence and decreased libido, although the incidence of these side effects gradually decreased during treatment.

Immune system disorders: unknown frequency - hypersensitivity reactions, including angioedema (including swelling of the lips, face and larynx).

Disorders of the psyche: frequent - decreased libido; unknown frequency - depression, decreased libido, which persists after discontinuation of therapy.

Heart Disease: an unknown frequency - a feeling of palpitations.

Disorders from the liver and bile ducts: unknown frequency - increased activity of "liver" transaminases.

Disturbances from the skin and subcutaneous tissues: infrequent - rash; unknown frequency - hives, itchy skin.

Violations of the genitals and mammary glands: frequent - erectile dysfunction; infrequent - violation of ejaculation, increase and soreness of the mammary glands; unknown frequency - soreness of testicles, erectile dysfunction, persisting after cessation of therapy; male infertility and / or decreased quality of seminal fluid.

Within the framework of the study MTOPS The use of finasteride in a dose of 5 mg / day was comparedn = 768), doxazosin at a dose of 4 mg / day or 8 mg / day (n = 756), combined therapy with finasteride at a dose of 5 mg / day and doxazosin at a dose of 4 or 8 mg / day (n = 786), and placebo (n = 737). According to the results of this study, the profile of safety and tolerability of combination therapy generally coincided with the profile of its individual components. The frequency of ejaculatory abnormalities in patients receiving combination therapy was comparable to the sum of the frequency of occurrence of this undesirable phenomenon against the background of two types of monotherapy.A 7-year placebo-controlled study was conducted, in which 18,882 healthy men participated. Data available for analysis of puncture biopsy of the prostate gland were obtained for 9 060 subjects, with prostate cancer detected in 803 (18.4%) of men who received finasteride in a dose of 5 mg, and in 1 147 (24.4%) of men receiving a placebo. According to the results of puncture biopsy, prostate cancer with a Grade 7-10 Grade score was diagnosed in 280 (6.4%) of the men in the group receiving finasteride in a dose of 5 mg, while in the placebo group, cancer with this degree of differentiation was diagnosed in 237 (5.1%) patients. The results of additional analysis showed that an increase in the prevalence of low-grade prostate cancer, observed in the group receiving finasteride in a dose of 5 mg, can be explained by a systematic error in evaluating the results associated with the effect of 5 mg finasteride on the volume of the prostate gland. Of the total number of cases of prostate cancer diagnosed in this study, at the time of diagnosis, approximately 98% of cases were attributed to localized cancer (clinical stage T1 or T2).

The clinical significance of data on the tumor process with a degree of differentiation of 7-10 points on the Gleason scale is unknown.

Laboratory indicators

When assessing the results of laboratory studies, it should be borne in mind that in patients receiving finasteride treatment, the content of prostate-specific antigen (PSA) in blood plasma is reduced.

The majority of patients during the first months of therapy experienced a rapid decline in the PSA index with its subsequent stabilization. The initial value of PSA, which is established after the treatment with finasteride, is approximately half of the corresponding index, which was noted before the start of treatment. Thus, in patients treated with finasteride for six months or more, the value of PSA should be doubled compared to the normal values of men who have not been treated.

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

Overdose:

Patients received finasteride once in doses up to 400 mg, and with repeated administration of the drug - in doses up to 80 mg / day for 3 months,no undesirable reactions were observed.

Overdosing of finasteride does not require special treatment.

Interaction:

Clinically significant interaction with other drugs was not revealed.

Finasteride is metabolized predominantly with the participation of isoenzyme CYP3A4 systems of cytochrome P450, without having a significant effect on the function of this system. Although the risk of the influence of finasteride on the pharmacokinetics of other drugs is assessed as not high, there is a possibility that inhibitors or inducers of isoenzyme CYP3A4 systems of cytochrome P450 will affect the plasma concentration of finasteride. Nevertheless, given the available safety data, it seems unlikely that an increase in the concentration of finasteride associated with the concomitant use of such inhibitors will be of clinical importance.

There were no clinically significant interactions in the combined use of finasteride with propranolol, digoxin, glibenclamide, warfarin, theophylline, and phenazone.

Special instructions:

General instructions

To avoid obstructive complications, careful monitoringpatients with a large volume of residual urine and / or significantly difficult urination. Consider the possibility of the need for surgical intervention.

Influence on the content of PSA and diagnosis of prostate cancer

To date, the clinical benefits of using PENESTER® in patients with prostate cancer have not been proven. In controlled clinical trials, patients with BPH and elevated plasma PSA concentrations were monitored for PSA and prostate biopsy results. It was found that the use of finasteride does not appear to change the incidence of prostate cancer detection and does not affect the frequency of its occurrence in patients taking finasteride or placebo.

Before the start of treatment and periodically during the treatment with PENESTER ®, it is recommended to perform a rectal examination and apply other methods of diagnosis of prostate cancer. The determination of PSA in blood plasma 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. In men with BPH, normal values of PSA do not allow excluding prostate cancer, regardless of the treatment with PENESTER®. The initial concentration of PSA below 4 ng / ml also does not exclude prostate cancer.

The drug PENESTER® causes a decrease in the serum PSA concentration by 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 treated with PENESTER ®, as a decrease in the PSA concentration does not exclude the presence of concomitant prostate cancer. This decrease is expected for any range of values of the PSA concentration, although it may differ for specific patients. Analysis of PSA values in more than 3,000 patients in a 4-year, double-blind, placebo-controlled study PLESS confirmed that the 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 receiving treatment with the drug. 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 treated with PENESTER® requires a thorough examination to determine the cause, which may be a failure to adhere to the regimen. The drug PENESTER® does not significantly reduce the percentage of free PSA (ratio of free PSA to total). This indicator remains constant even under the influence of taking the drug. If the percentage of free PSA is used to diagnose prostate cancer, correction of the values of this indicator is not necessary.

Breast cancer in men

During clinical trials, as well as during the postmarketing period in men taking finasteride. cases of breast cancer were noted. Doctors should instruct their patients to immediately report any changes in breast tissue, such as the appearance of seals, pain,gynecomastia or discharge from the nipples.

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 10 or 15 tablets in a blister of PVC / PVDC / Al.

For 3 blisters (10 tablets) or 2 or 6 blisters (15 tablets each) are placed in a cardboard box together with instructions for use.

Storage conditions:

Does not require special storage conditions.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-000133

Date of registration:30.03.2010

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp25.09.2015

Illustrated instructions

Instructions

Penester® (Penester®)