Proscar tablets: instructions for use, price and reviews

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Finasteride is a selective blocker of type 2 5-alpha reductase , an enzyme that transforms testosterone into dihydrotestosterone . With prostate adenoma, its growth depends on the conversion of testosterone to dihydrotestosterone in prostate cells. Proscar is highly effective in reducing the latter and has no affinity for androgen receptors.

Pharmacokinetics

After taking the drug, 39% of the dose is evacuated in the urine, another 57% in feces. The bioavailability of finasteride is 80%. The highest level in the blood is reached after about 2 hours. Absorption of the drug from the digestive tract is completed 7 hours after use. The half-life is on average 6 hours. Plasma protein binding is 93%. In elderly patients, the rate of elimination of the active substance is slightly reduced. Penetrates the blood-brain barrier.

Proscar 5mg 28 pcs. film-coated tablets

pharmachologic effect

5-alpha reductase inhibitor.

Composition and release form Proscar 5 mg 28 pcs. film-coated tablets

Tablets - 1 tablet:

Active ingredient: finasteride 5.0 mg;
Excipients: lactose monohydrate 106.4 mg, pregelatinized corn starch 15.0 mg, microcrystalline cellulose 15.0 mg, sodium carboxymethyl starch 7.5 mg, magnesium stearate 0.75 mg, sodium docusate 0.38 mg, iron oxide yellow dye (E172) 0.03 mg;
Film shell: hypromellose 1.15 mg, hyprolose (with 0.3% silicon) 1.15 mg, titanium dioxide (E171) 1.04 mg, talc 0.42 mg, indigo carmine dye aluminum varnish (E132) 0.08 mg.

14 tablets per blister made of PVX/PE/PVDC film and aluminum foil.

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

Description of the dosage form

Apple-shaped, blue, film-coated tablets debossed with "MSD 72" on one side and "PROSCAR" on the other.

Directions for use and doses

PROSCAR® is prescribed orally, regardless of meals.

The recommended dose is 1 tablet of 5 mg 1 time per day.

PROSCAR® can be used as monotherapy or in combination with the alpha-blocker doxazosin.

Kidney failure

In patients with various stages of renal failure (with a decrease in CC 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

No dosage adjustment is required, although pharmacokinetic studies indicate that the elimination of finasteride is slightly reduced in patients over 70 years of age.

Pharmacodynamics

Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of type II 5-alpha reductase, an intracellular enzyme that converts testosterone into the more active androgen, dihydrotestosterone (DHT).

In benign prostatic hyperplasia (BPH), its enlargement depends on the conversion of testosterone to DHT in the prostate gland. PROSCAR® highly effectively reduces the concentration of DHT both in the blood and in the prostate tissue. Suppression of DHT formation is accompanied by a decrease in the size of the prostate gland, an increase in the maximum flow rate of urine and a decrease in the severity of symptoms associated with prostatic hyperplasia.

Finasteride has no affinity for the androgen receptor.

The drug does not have a significant effect on the lipid profile (i.e. total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides) and bone mineral density.

Finasteride has no effect on blood levels of cortisol, estradiol, prolactin, thyroid-stimulating hormone and thyroxine compared to placebo.

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

In patients with BPH treated with finasteride 5 mg daily for 4 years, a decrease in blood DHT concentrations of approximately 70% was observed, which was associated with a decrease in prostate volume of approximately 20%. In addition, the concentration of prostate-specific antigen (PSA) decreased by approximately 50% compared to its initial concentration, which suggests a decrease in the growth of prostate epithelial cells.

The decrease in DHT concentration and decrease in the severity of prostatic hyperplasia, accompanied by a decrease in PSA concentration, persisted in studies for up to 4 years. In these studies, testosterone levels in the blood increased by approximately 10-20%, remaining within physiological values.

When using the drug PROSCAR® for 7-10 days in patients referred for prostatectomy, there was a decrease in the concentration of DHT in the prostate tissue by approximately 80% and an increase in the concentration of testosterone in the prostate tissue by 10 times compared to the concentration before treatment.

It has been established that long-term (more than 4 years) use of PROSCAR® in patients with BPH and moderate or severe symptoms of the disease reduces the risk of all urological complications (surgical interventions: transurethral resection of the prostate gland or prostatectomy; acute urinary retention requiring catheterization) by 51 % and was accompanied by a pronounced and persistent decrease in prostate volume, as well as a persistent increase in maximum urinary flow rate and improvement in symptoms (PLESS Study).

In patients taking PROSCAR® for 3 months, the volume of the prostate gland, which decreased by approximately 20%, returned to its previous value within 3 months after stopping treatment.

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

Pharmacokinetics

Absorption

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

The bioavailability of finasteride when administered orally is approximately 80% of the intravenous reference dose and is independent of food intake.

Distribution

The binding to plasma proteins is approximately 93%. Plasma clearance is about 165 ml/min, volume of distribution is 76 l.

With long-term therapy, a slow accumulation of finasteride in small quantities is observed. When finasteride is taken orally daily at a dose of 5 mg, its minimum equilibrium concentration in blood plasma reaches 8-10 ng/ml and remains stable over time.

In patients receiving finasteride for 7-10 days, the drug was detected in the cerebrospinal fluid. When taking PROSCAR® at a dose of 5 mg per day, finasteride was also detected in the 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 elimination half-life (T1/2) of finasteride is on average 6 hours.

Removal

In men, after a single oral dose of 14C-labeled finasteride, 39% of the dose taken is excreted by the kidneys in the form of metabolites (unchanged finasteride is practically not excreted by the kidneys); 57% - through the intestines. This study identified 2 metabolites of finasteride that have negligible 5-alpha reductase inhibitory effects compared to finasteride.

In old age, the rate of elimination of finasteride decreases slightly. With age, the half-life period (T1/2) increases: in men 18-60 years old, the average T1/2 is 6 hours, and in men over 70 years old - 8 hours. These changes are not clinically significant and, therefore, dosage reduction in elderly men is not required.

In patients with chronic renal failure (creatinine clearance (CC) from 9 to 55 ml/min), the distribution of 14C-labeled finasteride when taking a single dose did not differ from that in healthy volunteers. The association of finasteride with plasma proteins also did not differ in patients with impaired renal function.

In case of renal failure, some of the metabolites of finasteride, which are normally excreted by the kidneys, are excreted through the intestines. This is manifested by an increase in the amount of finasteride metabolites in feces with a corresponding decrease in their concentration in urine.

In patients with renal failure on dialysis, no dose adjustment of PROSCAR® is required.

Indications for use Proscar 5 mg 28 pcs. film-coated tablets

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

reducing the risk of acute urinary retention;
reducing the risk of the need for surgical interventions, including transurethral resection of the prostate gland and prostatectomy.

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

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

Contraindications

Hypersensitivity to any of the components of the drug;
Age up to 18 years;
Pregnancy and use of the drug in women of childbearing age.

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

Carefully:

Patients with a large volume of residual urine and/or a significantly reduced urinary flow should be regularly monitored by a physician to identify obstructive uropathy.

The drug is prescribed with caution to patients with liver failure and the elderly.

Application of Proscar 5 mg 28 pcs. film-coated tablets during pregnancy and breastfeeding

The use of PROSCAR® is contraindicated during pregnancy and women of childbearing age. Due to the ability of 5-alpha reductase type II inhibitors to suppress the conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, when used in pregnant women, can cause abnormalities in the development of the external genitalia in the male fetus.

PROSCAR® is not indicated for use in women.

There are no data on the excretion of finasteride into breast milk.

special instructions

Effect on PSA levels and diagnosis of prostate cancer

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

Before starting treatment and periodically during therapy with PROSCAR®, it is recommended to conduct a rectal examination and use other methods for diagnosing prostate cancer.

Serum PSA determination is also used to detect prostate cancer. In general, an initial PSA concentration above 10 ng/ml indicates the need for further examination of the patient and a biopsy. When determining PSA concentrations within 4-10 ng/ml, further examination of the patient is necessary. PSA concentrations in men with and without prostate cancer can be largely the same, so in men with BPH, normal PSA values do not rule out prostate cancer, regardless of treatment with PROSCAR®. An initial PSA concentration 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 must be taken into account when assessing PSA levels in patients with BPH treated with PROSCAR®, since a decrease in PSA concentrations does not exclude the presence of concomitant prostate cancer. This reduction can be expected over any range of PSA concentrations, although it may differ in individual patients. Analysis of PSA values in more than 3000 patients in the 4-year, double-blind, placebo-controlled PLESS study confirmed that in patients taking PROSCAR® for 6 months or more, PSA values should be doubled to compare them with normal values for this indicator in patients not receiving treatment with the drug. This adjustment preserves the sensitivity and specificity of the PSA test and the ability to detect prostate cancer.

Any persistent increase in PSA concentration in patients treated with finasteride requires careful evaluation to determine the cause, which may be non-compliance with PROSCAR®. PROSCAR® does not significantly reduce the percentage of free PSA (the ratio of free PSA to total PSA). 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.

Effect on laboratory parameters

PSA content

Plasma PSA concentrations correlate with patient age and prostate volume, and prostate volume, in turn, depends on patient age. When determining PSA concentration, it should be taken into account that this indicator decreases in patients taking PROSCAR®.

In most patients, a rapid decrease in PSA levels is observed in the first months of therapy, after which it stabilizes at a new level, which is usually approximately half)7 of the value measured before the start of therapy. In this regard, 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®.

Exposure to finasteride is associated with a risk of teratogenicity in the male fetus

Pregnant women, as well as women of childbearing age, should avoid contact with crushed or degraded PROSCAR® tablets due to the possibility of absorption of finasteride due to the high risk of teratogenic effect for the male fetus (see section “USE IN PREGNANCY AND LACTATION” ). 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.

There have been reports of cases of breast cancer in men taking finasteride 5 mg during clinical trials and during the post-marketing period. Doctors should instruct their patients to immediately report any changes in breast tissue, such as swelling, pain, breast enlargement, or nipple discharge.

Mood changes and depression

Mood changes, including depressed mood, depression and, less commonly, suicidal ideation, have been observed in patients taking finasteride 5 mg. Psychiatric symptoms in patients should be monitored, and if they occur, the patient should seek medical advice.

Impact on the ability to drive vehicles and operate machinery

No adverse effects of the drug on the ability to drive vehicles or operate machinery have been reported.

Overdose

There is evidence that patients receiving PROSCAR® at a dose of up to 400 mg once, as well as at a dose of up to 80 mg per day for 3 months, did not experience any symptoms of overdose.

There are no specific recommendations for the treatment of PROSCAR® overdose.

Side effects Proscar 5mg 28 pcs. film-coated tablets

Side effects identified during clinical trials

The PLESS study assessed the safety of 1,524 patients treated with PROSCAR® over a 4-year period, compared with 1,516 patients treated with placebo.

74 patients (4.9%) in the PROSCAR® group discontinued therapy due to drug-related side effects, compared with 50 patients (3.3%) in the placebo group. 57 patients (3.7%) in the PROSCAR® group and 32 patients (2.1%) in the placebo group discontinued treatment due to side effects related to sexual dysfunction, which were the most commonly reported side effects.

The only clinical adverse reactions that were considered by the investigators to be possibly, likely, or definitely related to the drug, and whose incidence with PROSCAR® was greater than 1% and higher than that with placebo during the 4 years of the study, were those related to sexual dysfunction. functions, breast tenderness and skin rash.

In the first year of treatment, sexual dysfunction was detected in 8.1% of patients in the PROSCAR® group and 3.7% in the placebo group; decreased libido - in 6.4% and 3.4%; and ejaculation disorders - 0.8% and 0.1%, respectively. When using PROSCAR® during the 2-4 years of the study, the incidence of the above side effects in patients taking PROSCAR® did not differ significantly from that in patients taking placebo.

Within 1 year, a decrease in ejaculate volume was detected in 3.7% and 0.8% in the PROSCAR and placebo groups, respectively; and during 2-4 years of the study - 1.5% and 0.5%, respectively. Breast enlargement (0.5% and 0.1%, respectively), breast tenderness (0.4% and 0.1%, respectively), and skin rash (0.5% and 0) were also reported at 1 year. .2% respectively). Over the course of 2-4 years, the total incidence of these phenomena was: enlargement of the mammary glands (1.8% and 1.1%, respectively), pain in the mammary glands (0.7% and 0.3%, respectively), skin rash (0 .5% and 0.1% respectively).

In a 7-year placebo-controlled study, which included 18,882 healthy men, according to the results of a needle biopsy (in 9,060 men), prostate cancer was detected in 18.4% of patients receiving PROSCAR®, and in 24.4% of patients who received placebo. 280 men (6.4%) in the PROSCAR® group and 237 men (5.1%) in the placebo group were diagnosed with prostate cancer, which was assessed by needle biopsy as Gleason score 7-10. Additional analysis suggested that the increased incidence of high-grade cancer observed in the group of patients taking PROSCAR® may be due to diagnostic bias associated with the effect of the drug on prostate volume.

In approximately 98% of all cancers diagnosed, the tumor was classified as intracapsular (stage T1 or T2) at diagnosis. The clinical significance of the findings regarding Gleason score 7–10 prostate cancer in this study is unknown.

In the MTOPS study, the safety and tolerability profile of combination treatment with finasteride 5 mg per day and doxazosin 4 mg or 8 mg per day was comparable to the safety and tolerability of each agent alone.

During the 4- to 6-year placebo-controlled MTOPS trial with the active drug as a control in 3047 men, there were 4 cases of breast cancer in men taking finasteride and no cases in men not taking finasteride. During the 4-year, placebo-controlled PLESS study of 3,040 men, there were 2 cases of breast cancer in men receiving placebo and no cases in men taking finasteride. In the 7-year, placebo-controlled Prostate Cancer Prevention Trial, which included 18,882 men, there was 1 case of breast cancer in a man taking finasteride and 1 case of breast cancer in a man taking finasteride. glands in a man receiving a placebo. There have been post-marketing reports of cases of breast cancer in men taking finasteride. The relationship between long-term use of finasteride and the occurrence of breast neoplasia in men has not yet been established.

Post-registration experience of use

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

From the immune system: hypersensitivity reactions such as itching, urticaria and angioedema (including swelling of the lips, tongue, larynx and face).

From the mental side: depression, decreased libido, which may continue after cessation of treatment.

From the reproductive system and mammary glands: sexual dysfunction (erectile dysfunction and ejaculation disorders), which may continue after cessation of treatment; testicular soreness; hematospermia; male infertility and/or decreased quality of seminal fluid. It was reported that after discontinuation of finasteride, the quality of seminal fluid returned to normal or improved.

Laboratory indicators

When assessing laboratory parameters of prostate-specific antigen (PSA), a decrease in its concentration in patients taking PROSCAR® should be taken into account.

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

Drug interactions

No clinically significant interactions of PROSCAR® with other drugs have been identified.

Finasteride does not appear to have a significant effect on the cytochrome P450 system and the metabolism of drugs associated with this system.

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

Despite the lack of specific drug interaction studies, in clinical studies PROSCAR® was used together with angiotensin-converting enzyme (ACE) inhibitors, paracetamol, acetylsalicylic acid, alpha-blockers, beta-blockers, blockers of “slow” calcium channels, nitrates in various dosage forms, diuretics , H2-histamine receptor blockers, lipid-lowering drugs - HMG-CoA reductase inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), quinolone derivatives and benzodiazepines without any clinically significant adverse interactions.

Side effects

The most common adverse events when using the drug were impotence and decreased libido . These disorders occur in the initial stages of treatment and resolve with further therapy in most patients.

Immune disorders: urticaria , itching , angioedema .
Mental disorders: weakened libido, depression .
Circulatory disorders: rapid heartbeat.
Disorders of the hepatobiliary system: increased concentration enzymes .
Skin disorders: rash, itching, urticaria.
Disorders of the mammary glands and reproductive system: erectile dysfunction , enlargement and pain in the mammary glands, impotence , ejaculation , testicular pain, male infertility, decreased sperm quality, decreased ejaculate .
Laboratory data: decreased PSA .

There are reports of breast cancer in men taking Finasteride . You should immediately notify your doctor about changes in the mammary gland (discharge from the nipples, pain, swelling, gynecomastia ).

Proscar®

Side effects identified during clinical trials

The PLESS study assessed the safety of 1,524 patients treated with PROSCAR® over a 4-year period, compared with 1,516 patients treated with placebo.

The total incidence of side effects during 2-4 years of the study was: sexual dysfunction (5.1% in the PROSCAR® drug group and 5.1% in the placebo group), decreased libido (2.6% in both groups), ejaculation disorders (0.2% and 0.1% respectively). Within 1 year, a decrease in ejaculate volume was detected in 3.7% and 0.8% in the PROSCAR® and placebo groups, respectively; and during 2-4 years of study - 1.5% and 0.5%, respectively. Breast enlargement (0.5% and 0.1%, respectively), breast tenderness (0.4% and 0.1%, respectively), and skin rash (0.5% and 0) were also reported at 1 year. .2% respectively). Over the course of 2-4 years, the total incidence of these phenomena was: enlargement of the mammary glands (1.8% and 1.1%, respectively), pain in the mammary glands (0.7% and 0.3%, respectively), skin rash (0 .5% and 0.1% respectively).

Post-registration experience of use

From the immune system:

hypersensitivity reactions such as itching, urticaria and angioedema (including swelling of the lips, tongue, larynx and face).

From the mental side:

depression, decreased libido, which may continue after cessation of treatment.

From the reproductive system and mammary glands:

sexual dysfunction (erectile dysfunction and ejaculation disorders), which may continue after stopping treatment; testicular soreness; male infertility and/or decreased quality of seminal fluid. It was reported that after discontinuation of finasteride, the quality of seminal fluid returned to normal or improved.

Laboratory indicators

When assessing laboratory parameters of prostate-specific antigen (PSA), a decrease in its concentration in patients taking PROSCAR® should be taken into account.

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

Instructions for use (Method and dosage)

The drug is taken regardless of the time of meal.

Proscar, instructions for use

The recommended dosage is 1 tablet of medication once a day. Proscar is approved for use as a monotherapeutic agent or in combination with Doxazosin . The duration of therapy is determined by the doctor individually. To assess the effectiveness, it is necessary to take the medicine for at least 6 months, then treatment is continued.

For elderly patients and for patients with renal insufficiency, dosage adjustment is not required.

special instructions

Before starting therapy with Proscar and regularly during treatment, it is necessary to conduct a rectal examination, as well as research using other methods to detect the occurrence of prostate cancer. PSA testing is also used to detect prostate cancer. If the PSA is above 10 ng/ml, a more extensive examination of the patient is recommended, including a biopsy. It should be remembered that in men with prostate adenoma, PSA concentration does not completely exclude prostate cancer , regardless of Proscar therapy.

Any prolonged increase in PSA in individuals receiving finasteride requires investigation to determine the cause of this phenomenon.

Proscar tab p/pl/o 5mg N28 (Merck Sharp)

In patients with a large volume of residual urine and/or a sharply reduced urine flow, careful monitoring should be carried out for the possible development of obstructive uropathy. Before starting treatment with Proscar and periodically during treatment, a rectal examination should be performed, as well as examination by other methods to detect the presence of prostate cancer. Serum prostate-specific antigen (PSA) testing is increasingly used to detect prostate cancer. In general, if the initial level of prostate-specific antigen is above 10 ng/ml, a more extensive examination of the patient is required, including, if necessary, a biopsy. If the prostate-specific antigen level is between 4 and 10 ng/ml, further examination of the patient is recommended. It must be taken into account that the initial level of prostate-specific antigen below 4 ng/ml does not exclude the possibility of prostate cancer. When assessing the level of prostate-specific antigen, it is necessary to take into account that Proscar reduces its level even in the presence of prostate cancer. Any prolonged increase in the level of prostate-specific antigen in a patient receiving treatment with Proscar should be carefully examined to determine the cause of the increase. No positive clinical effect of Proscar was observed in patients with prostate cancer. In controlled clinical trials in patients with prostate adenoma, Proscar therapy did not lead to a change in the incidence of prostate cancer. Serum levels of prostate-specific antigen correlate with patient age and prostate volume, and prostate volume correlates with patient age. Most patients experience a rapid decline in prostate-specific antigen levels during the first months of treatment, after which levels stabilize at a lower level of approximately half the baseline value. Such a decrease is usually observed at any initial level of prostate-specific antigen, although it can vary significantly in individual patients. In most cases, in patients treated with Proscar for 6 months or more, it is necessary to double the level of prostate-specific antigen to compare with the level of this indicator in untreated patients. In patients with and without prostate cancer, there may be significant overlap in prostate-specific antigen values. Thus, in men with prostate adenoma, a normal level of prostate-specific antigen does not exclude the presence of prostate cancer, regardless of treatment with Proscar.

Analogues of Proscar

Level 4 ATX code matches:
Finast

Penester

Finasteride

Avodart

Zerlon, Alfinal, Penester, Finasteride-OBL, Prosteride, Finast, Urofin, Finasteride-Teva, Finpros.