Proscar - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 106.4 mg, corn pregelatinized corn starch 15.0 mg, microcrystalline cellulose 15.0 mg, sodium carboxymethyl starch 7.5 mg, magnesium stearate 0.75 mg, docusate sodium 0.38 mg, iron dye oxide yellow 0.03 mg;

tablet shell: hypromellose 1.15 mg, giprolose 1.15 mg, titanium dioxide E 171 1.04 mg, talc 0.42 mg, indigo carmine lacquer aluminum E 132 0.08 mg.

Description:

Tablets in the form of an apple, blue, covered with a film shell, on one side are engraved with "MSD 72 ", on the other -"PROSCAR".

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 type 5 5-alpha reductase, an 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 gland. PROSCAR® effectively reduces the concentration of DHT in both blood 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 urine flow and a decrease in the severity of symptoms associated with prostatic hyperplasia.

Finasteride does not have an affinity for the androgen receptor. The drug has no significant effect on the lipid profile (ie, total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides) and bone mineral density. Finasteride does not affect the blood levels of cortisol, estradiol, prolactin, thyroid-stimulating hormone and thyroxine in comparison with placebo.

A single dose of finasteride in a dose of 5 mg leads to a rapid decrease in the concentration of DHT in the blood serum with a maximum effect achieved after 8 hours. Despite the fact that the concentration of finasteride in the blood plasma is subject to fluctuations for 24 hours, the DHT concentration 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.

In applying the drug PROSKAR® for 7-10 days in patients referred for prostatectomy decreased DHT concentration in the prostate tissue by about 80% and an increase in the concentration of testosterone in the prostate tissue by 10 times compared with the concentration before treatment.

It was found that long-term (more than 4 years) use of the drug in patients with PROSKAR® DHT and moderately expressed or significantly distinct symptoms of the disease reduced the risk of urological complications (surgery: Transurethral resection of the prostate, or prostatectomy, acute urinary retention requiring catheterization) 51 % and was accompanied by a pronounced and persistent decrease in the volume of the prostate gland, as well as a steady increase in the maximum rate of urine flow and improvement in symptoms (Study PLESS).

Patients taking PROSKAR® for 3 months and achieving reducing prostate volume by about 20%, at termination of treatment the volume of the prostate gland returned to the same size after 3 months.

Thus, treatment with PROSCAR® helps reduce the size of the enlarged prostate gland, increases the flow rate of urine and reduces the symptoms associated with DHT.

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.

The bioavailability of finasteride for oral administration is approximately 80% of the intravenous reference dose and is not dependent on food intake.

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 Proskar ® in a dose of 5 mg per day finasteride is also found in seminal fluid. The content of finasteride in seminal fluid was 50-100 times lower than the dose of finasteride (5 mg), which did not affect the concentration of circulating DHT in adult men.

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 were identified, which have a slight inhibitory effect on 5-alpha reductase compared to finasteride.

In old age The rate of excretion of finasteride is somewhat reduced. With age, the half-life (T_1/2) increases: in men 18-60 years, the average T_1/2is 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 insufficiency (creatinine clearance (CK) from 9 to 55 ml / min.) 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 are on dialysis, correction of the dose of PROSCAR® is not required.

Indications:

Treatment and control of BPH, prevention of urological complications in order to:

- reduce the risk of acute urinary retention;

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

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

In combination with an alpha-adrenoblocker 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 the section "Application in pregnancy and lactation").

PROSCAR® contains lactose, so 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 significantly reduced urine flow should be observed regularly by the doctor for obstructive uropathy.

With caution appoint the drug to patients with hepatic insufficiency and the elderly.

Pregnancy and lactation:

The use of PROSCAR® 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.

PROSCAR® is not indicated for use in women.There is no data on the excretion of finasteride with breast milk.

Dosing and Administration:

PROSKAR® is administered orally, regardless of food intake. The recommended dose is 1 tablet of 5 mg once a day.

PROSCAR® can be used in the form of monotherapy, as well as in combination with an alpha-adrenoblocker doxazosin.

Renal insufficiency

In patients with various stages of renal failure (with a decrease in QC to 9 ml / min.), Dose adjustments are 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:

Side effects identified in clinical trials

In the study PLESS for 4 years, the safety of therapy was evaluated in 1524 patients taking PROSCAR®, compared with 1516 patients taking placebo.

In 74 patients (4.9%) in the group treated with PROSCAR ®, therapy was discontinued due to side effects associated with the drug, compared with 50 patients (3.3%) in the placebo group.57 patients (3.7%) in the group treated with PROSCAR® and 32 patients (2.1%) in the placebo group discontinued treatment due to side effects associated with sexual dysfunction, which were the most frequently identified side effects.

The only clinical adverse events that were considered by the investigators as possible, probably or definitely related to the drug, and the incidence of which, when taking Proskar®, was more than 1% and greater than that with placebo for 4 years, were the phenomena associated with a violation of sexual functions, tenderness of the mammary glands and skin rash.

In the first year of treatment, a violation of sexual function was detected in 8.1% of patients in the group treated with PROSCAR® and 3.7% in the placebo group; decreased libido - in 6.4% and 3.4%; and a violation of ejaculation - 0.8% and 0.1%, respectively. With the use of PROSCAR® during the 2-4 years of the study, the incidence of these side effects in patients taking PROSCAR® was not significantly different from that in patients taking placebo.

The total frequency of side effects during 2-4 years of the study was: violation of sexual function (5.1% in the group of the drug PROSCAR® and 5.1% in the placebo group),decreased libido (2.6% in both groups), ejaculation disorder (0.2% and 0.1%, respectively). Within 1 year, the decrease in ejaculate volume was detected in 3.7% and 0.8% in the PROSCAR® group and placebo, respectively; and within 2-4 years of research, 1.5% and 0.5%, respectively. During 1 year, breast enlargement was also reported (0.5% and 0.1%, respectively), tenderness in the mammary glands (0.4% and 0.1%, respectively) and skin rashes (0.5% and 0 , 2%, respectively). For 2-4 years, the total frequency of these events was: an increase in the mammary glands (1.8% and 1.1% respectively), tenderness in the thoracic glands (0.7% and 0.3% respectively), skin rash (0 , 5% and 0.1% respectively).

In a 7-year, placebo-controlled study that included 18,882 healthy men, puncture biopsy (in 9060 men) showed prostate cancer in 18.4% of patients treated with PROSCAR® and 24.4% of patients , who received a placebo. In 280 men (6.4%) in the group of patients taking PROSCAR® and 237 men (5.1%) in the placebo group, prostate cancer was detected, which was estimated by the results of a puncture biopsy at 7-10 points on the Gleason scale.Additional analysis suggested that the increase in the incidence of high-grade cancer observed in the group of patients taking PROSCAR® may be due to diagnostic errors associated with the effect of the drug on the volume of the prostate gland. In approximately 98% of all diagnosed cases of cancer, the tumor was classified at the time of diagnosis as intracapsular (stage T1 or T2). The clinical significance of the results concerning prostate cancer 7-10 on the Gleason score is unknown in this study.

In the study MTOPS the safety profile and tolerability of therapy in the combined treatment with finasteride at a dose of 5 mg per day and doxazosin 4 mg or 8 mg per day was comparable with the safety and tolerability of each of these agents alone.

During a 4-6-year-old placebo-controlled study MTOPS using an active drug as a control conducted with the participation of 3,047 men, 4 cases of breast cancer in men taking finasteride, and not a single case in men who did not take finasteride. During a 4-year placebo-controlled study PLESS, conducted with the participation of 3,040 men, there were 2 cases of breast cancer in men receiving a placebo, and no cases in men who took finasteride. In the course of a 7-year placebo-controlled study of PCRT (Prostate Cancer Prevention Trial, "Study on the Prevention of Prostate Cancer"), conducted with the participation of 18882 men, was recorded 1 case of breast cancer in a man who took finasteride, and 1 case of breast cancer in a man who received a placebo. Post-registration reports of cases of breast cancer in men who took finasteride. The relationship between the long-term reception of finasteride and the appearance of breast neoplasia in men is not currently established.

Post-registration application experience

In post-marketing practice, the following additional undesirable effects of PROSCAR® and / or finasteride were reported in low doses. Since the reports on these reactions were voluntary, for a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship with the effect of the drug.

From the immune system: hypersensitivity reactions, such as pruritus, hives and angioedema (including swelling of the lips, tongue, throat and face).

From the side of the psyche: depression, decreased libido, which can continue after cessation of treatment.

From the reproductive system and the mammary glands: sexual dysfunction (erectile dysfunction and ejaculatory abnormalities), which can continue after discontinuation of treatment; soreness of testicles; male infertility and / or decreased quality of seminal fluid. It was reported that after the withdrawal of finasteride, the quality of the semen was normalized or improved.

Laboratory indicators

When evaluating the laboratory parameters of the prostate-specific antigen (PSA), one should take into account the decrease in its concentration in patients taking PROSCAR®.

There were no other differences in the levels of standard laboratory parameters between the groups of patients treated with PROSCAR® and placebo.

Overdose:

There is evidence that patients who received PROSCAR® at a dose of up to 400 mg once, as well as in a dose of up to 80 mg per day for 3 months,there was no evidence of any symptoms of an overdose.

Specific recommendations for the treatment of an overdose of PROSCAR® are not available.

Interaction:

Clinically significant interactions of PROSCAR® with other drugs have 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 with the combined use of PROSCAR® with propranolol, digoxin, glibenclamide, warfarin, theophylline, and phenazone.

Despite the absence of special studies of drug interaction, in clinical trials, PROSCAR® was used in conjunction with angiotensin converting enzyme (ACE) inhibitors, paracetamol, acetylsalicylic acid, alpha-adrenoblockers, beta-adrenoblockers, slow calcium channel blockers, nitrates in various dosage forms, diuretics , blockers H₂-gistaminovyh receptors, lipid-lowering agents - inhibitors of HMG-CoA-reductase, non-steroidal anti-inflammatory drugs (NSAIDs),derivatives of quinolone and benzodiazepines without any clinically significant adverse interactions.

Special instructions:

Influence on the content of PSA and diagnosis of prostate cancer

To date, the clinical advantages of using PROSCAR® in patients with prostate cancer have not been proven. In controlled clinical trials, patients with BPH and elevated PSA concentrations monitored the PSA content and the results of prostate biopsy studies. It was found that the use of PROSCAR® apparently does not change the incidence of prostate cancer detection and does not affect its incidence in patients taking PROSCAR® or placebo.

Before starting treatment and periodically during the treatment with PROSAR® it is recommended to perform a rectal examination and apply other methods of diagnosis of 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 coincide to a large extent, therefore in men with BPH normal values of PSA do not allow to exclude prostate cancer, regardless of the treatment with PROSCAR®. The initial concentration of PSA below 4 ng / ml, also does not exclude prostate cancer.

PROSCAR® causes a decrease in 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 content in patients with BPH receiving treatment with the drug PROSKAR ®, as a decrease in the concentration of PSA 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. Analysis of PSA values in more than 3,000 patients in a 4-year, double-blind, placebo-controlled. research PLESS confirmed that those taking PROSCAR®, for 6 months or more,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 finasteride requires a thorough examination to determine the cause, which may be the failure to adhere to the PROSCRAR® regimen.

PROSCAR® 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 PROSCAR®. If the percentage of free PSA is used to diagnose prostate cancer, correction of the values of this indicator is not necessary.

Impact on laboratory performance

The content 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 determining the concentration of PSA, it should be borne in mind that this indicator decreases in patients taking PROSCAR®.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. Therefore, in patients taking PROSCAR® for 6 months or more, the PSA concentration should be doubled to compare it with normal values in men not taking PROSCAR®.

Contact with finasteride is associated with a risk of a teratogenic effect for a male fetus

Pregnant women, as well as women of childbearing age, should avoid contact with the crushed or uncoated tablets of the preparation PROSCAR® because of the possibility of absorption of finasteride, due to the high risk of teratogenic effect on the male fetus (see "APPLICATION WITH PREGNANCY AND IN THE LACTATION PERIOD "). PROSCAR® tablets are film-coated, which prevents contact with the active ingredient, provided that the tablets are not crushed and have not lost their integrity.

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 14 tablets coated with a film sheath in a blister of PVC / PE / PVDC / Al.

1 or 2 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

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:П N013710 / 01-2002

Date of registration:11.04.2008

The owner of the registration certificate:Merck Sharp and Doum B.V.Merck Sharp and Doum B.V. Netherlands

Manufacturer: & nbsp

MERCK SHARP & DOHME, B.V. Netherlands

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp25.09.2015

Illustrated instructions

Instructions

Proscar® (Proscar®)