Composition, form of production and packaging
The tablets covered with a film cover of light yellow color, round, biconcave.
1 tab.
finasteride 5 mg
Excipients: lactose monohydrate, corn starch, povidone K30, sodium carboxymethyl starch (type A), sodium docusate, magnesium stearate.
Composition of the film membrane: hypromellose 2910/5, macrogol 6000, talc, titanium dioxide, simethicone emulsion SE4, iron dye oxide yellow.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
15 pcs. - blisters (4) - packs of cardboard.
15 pcs. - blisters (6) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Finasteride is a synthetic 4-azasteroid compound. It is a specific competitive inhibitor of the 5-alpha reductase type II intracellular enzyme, which converts testosterone into an active androgen-dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), its increase depends on the conversion of testosterone to DHT in the prostate. Finasteride is highly effective in reducing 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) involving patients with mild or severe BPH symptoms and an enlarged prostate, finasteride reduced the incidence of acute urinary retention from 7/100 to 3/100 over a 4-year period, and the frequency of need for 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.
A study of MTOPS (Medical Therapy Of Prostate Symptoms) lasting 4 to 6 years, in which 3,047 men with BPH symptoms were randomized to receive finasteride at 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), doxazosin 39% (p <0.001), and combination therapy 67% (p <0.001) with respect to placebo compared with finasteride. In most cases, the progression of BPH (274 out of 351) was exacerbated by BPP> 4 points on the International Prostate Symptom Score, while among patients receiving finasteride, the risk of worsening of symptom scores decreased by 30%
(95% CI: 6-48%), among those receiving doxazosin - 46% (95% CI: 25-60%), and among those receiving combination therapy - 64% (95% CI: 48 -75%) relative to the placebo group. Among the patients receiving 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 combined therapy - by 79% (p = 0.001 ) relative to the placebo group.
Significant difference from placebo was observed only in the groups of patients receiving finasteride and combination therapy.
PHARMACOKINETICS
Suction
C max finasteride in blood plasma is achieved approximately 2 hours after ingestion. Absorption of finasteride from the digestive 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
Binding to plasma proteins is approximately 93%. Plasma clearance is about 165 ml / min, V d - 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 the drug for 7-10 days, finasteride was found in the cerebrospinal fluid. When taking the drug at a dose of 5 mg / day, finasteride is found in small amounts in seminal fluid.
Metabolism and excretion
T 1/2 finasteride averages 6 hours. In men, after taking a single dose of finasteride labeled with 14C, 39% of the dose is excreted by the kidneys in the form of metabolites (unchanged finasteride is 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.
Pharmacokinetics in special clinical cases
In the elderly, the rate of excretion of finasteride somewhat decreases. With age T 1/2 increases: in men 18-60 years, the average T 1/2 is 6 hours, and in men over 70 years - 8 hours. These changes are not of clinical significance, and therefore, a decrease in the dose of the drug in elderly men is not required.
In patients with chronic renal failure (CK from 9 to 55 ml / min), the distribution of the labeled 14 C finasteride with single dose did not differ from that in healthy volunteers. The binding of finasteride to 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 in order to:
1) reducing the risk of acute urinary retention;
2) reducing the risk of the need for surgical interventions, incl. 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.
DOSING MODE
The drug is taken orally 5 mg 1 time / 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 В® can be used in the form of monotherapy, as well as in combination with doxazosin.
There is insufficient clinical data on the use of the drug in patients with hepatic 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.
Older patients are not required to adjust the dose, although pharmacokinetic studies indicate that the excretion of finasteride in patients older than 70 years is somewhat reduced.
SIDE EFFECT
Adverse reactions are divided into system-organ classes according to the MedDRA classification. The frequency of adverse reactions was determined according to the following gradation (WHO classification): very frequent (> 1/10), frequent (> 1/100 to <1/10), infrequent (> 1/1000 to <1/100), rare (from> 1/10 000 to <1/1000), very rare (from <1/10 000, including individual messages); an unknown frequency (the frequency can not be established, since the information was obtained on the basis of the post-marketing experience of using the drug).
Most often, patients experienced impotence and decreased libido, although the incidence of these side effects gradually decreased during treatment.
On the part of the immune system: an unknown frequency - hypersensitivity reactions, incl. angioedema (including swelling of the lips, face and throat).
Disorders of the psyche: frequent - decreased libido; unknown frequency - depression, decreased libido, which persists after discontinuation of therapy.
From the heart: an unknown frequency - a feeling of palpitations.
On the part of the liver and bile ducts: an unknown frequency - increased activity of "liver" transaminases.
From the skin and subcutaneous tissues: infrequent - rash; unknown frequency - hives, itchy skin.
From 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.
The MTOPS trial compared finasteride at a dose of 5 mg / day (n = 768), doxazosin at a dose of 4 mg / day or 8 mg / day (n = 756), a combination of finasteride 5 mg / day and doxazosin dose 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%) men receiving finasteride at a dose of 5 mg, and in 1 147 (24.4%) men receiving a placebo . According to the results of puncture biopsy, prostate cancer with a Gleason score of 7-10 was diagnosed in 280 (6.4%) of men receiving finasteride at a dose of 5 mg, while in the placebo group, cancer with this degree of differentiation was diagnosed in 237 (5.1%) of patients. The results of additional analysis showed that an increase in the prevalence of low-grade prostate cancer observed in the finasteride group at a dose of 5 mg can be explained by a systematic error in the evaluation of results related to the effect
treatment with finasteride 5 mg per volume of the prostate gland. Of the total number of cases of prostate cancer,
diagnosed in this study, at the time of diagnosis about 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 evaluating 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 relevant indicator before 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 receiving finasteride and placebo were not observed.
CONTRAINDICATIONS
- rare hereditary lactose intolerance, lactase deficiency or impaired glucose / galactose absorption;
- pregnancy and use of the drug in women of childbearing age;
- age up to 18 years;
- Hypersensitivity to any of the components of the drug.
Caution should be given to patients with a large volume of residual urine and / or a significantly reduced rate of urination, patients with hepatic impairment, as well as elderly patients.
PREGNANCY AND LACTATION
The use of the drug Penester В® is contraindicated in pregnancy and in women of childbearing age. In connection with the ability of inhibitors of 5-alpha reductase II type inhibit the conversion of testosterone to dihydrotestosterone, these agents, including. finasteride, when used in pregnant women can cause anomalies in the development of external genital organs in a male fetus. Finasteride is 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 semen of patients receiving finasteride at a dose of 5 mg / day. Although clinical data on the effect of finasteride on the male fetus are not available, women of childbearing age should avoid contact with semen from men taking finasteride.
Women of childbearing age and pregnant women should avoid contact with damaged finasteride tablets,
since 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.
APPLICATION FOR FUNCTIONS OF THE LIVER
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.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should prescribe the drug for violations of liver function.
There is insufficient clinical data on the use of the drug in patients with hepatic insufficiency.
APPLICATION FOR CHILDREN
Contraindicated in childhood to 18 years.
APPLICATION IN ELDERLY PATIENTS
Caution should be given to 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.
SPECIAL INSTRUCTIONS
General instructions
To avoid obstructive complications, it is necessary to carefully monitor patients with a large volume of residual urine and / or a significantly difficult urination.Consider the possibility of the need for surgical intervention.
Influence on the content of PSA and diagnosis of prostate cancer
Until now, the clinical benefits of using Penester В® 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 and does not affect the frequency of its occurrence in patients taking finasteride or placebo.
Before starting treatment and periodically during the treatment with the drug Penester ® , a rectal examination and other methods for diagnosing prostate cancer are recommended. 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 the exclusion of 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 receiving treatment with the drug Penester ® , because a decrease in the concentration of PSA 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 the PSA values ​​in more than 3,000 patients in a 4-year, double-blind, placebo-controlled study PLESS confirmed that in patients taking finasteride for 6 months or more, PSA values ​​should be doubled to be compared with 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 the concentration of PSA in patients receiving treatment with the drug Penester ® , requires careful examination to determine the cause, which may consist in non-compliance with the regimen of taking the drug.
The preparation of 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
In clinical trials, as well as during the postmarketing period, men who received Finasteride had cases of breast cancer. 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.
Impact on the ability to drive vehicles and manage mechanisms
On the adverse effects of the drug on the ability to drive and operate machinery has not been reported.
OVERDOSE
Patients received a single dose of finasteride in doses up to 400 mg, by repeated administration of the drug at doses up to 80 mg / day for 3 months adverse reactions were observed.
An overdose of finasteride does not require special treatment.
DRUG INTERACTION
Clinically significant drug interactions have been identified.
Finasteride is metabolized mainly involving CYP3A4 isoenzyme of cytochrome P450, without exerting a significant influence on the function of the system.Although the risk of finasteride effect on the pharmacokinetics of other drugs is evaluated as low, there is the possibility that inhibitors or inducers of CYP3A4 isoenzyme of cytochrome P450 will affect the plasma concentration of finasteride. Nevertheless, considering the available safety data, it seems unlikely that an increased concentration of finasteride associated with the concomitant use of such inhibitors would be of clinical importance. There were no clinically significant interactions when combined with the use of finasteride propranolol, digoxin, glibenclamide, warfarin, theophylline and phenazone.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children. It does not require any special storage conditions. Shelf life - 3 years.
