Instructions for Penester film-coated tablets 5 mg No. 30
Composition
active ingredient: finasteride;
1 tablet contains finasteride 5 mg;
excipients: lactose monohydrate, corn starch, povidone 30, sodium starch glycolate (type A), docusate sodium, magnesium stearate, hypromellose 2910/5, macrogol 6000, talc, titanium dioxide (E 171), simethicone emulsion SE4, iron oxide yellow (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: yellow, round, biconvex, film-coated tablets, 7.1 mm in diameter.
Pharmacotherapeutic group
Drugs used for benign prostatic hypertrophy. ATC code G04C B01.
Pharmacological properties
Pharmacodynamics.
Finasteride is a specific inhibitor of 5-alpha-reductase type II, an intracellular enzyme that converts testosterone to the more active androgen dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), its enlargement depends on the conversion of testosterone to DHT in prostate tissue. Finasteride is highly effective in reducing both circulating and intraprostatic DHT. Finasteride has no affinity for androgen receptors.
In clinical trials in patients with moderate to severe benign prostatic hyperplasia (BPH), an enlarged prostate on digital rectal examination, and low residual urine volume, finasteride reduced the incidence of acute urinary retention from 7/100 to 3/100 over four years and the need for surgery (transurethral resection of the prostate and prostatectomy) from 10/100 to 5/100. This reduction was accompanied by a 2-point improvement in the QUASI-AUA symptom score (range 0–34), a significant regression of prostate volume by approximately 20%, and a significant increase in urinary flow rate.
The MTOPS (Medical Treatment of Prostatic Symptoms) study was a 4- to 6-year study of 3047 men with symptomatic BPH who were randomized to receive finasteride 5 mg/day, doxazosin 4 or 8 mg/day, a combination of finasteride 5 mg/day and doxazosin 4 or 8 mg/day, or placebo. The primary endpoint was time to clinical progression of BPH (defined as an increase from baseline of 4 or more points on the symptom rating scale, an episode of acute urinary retention, BPH-related renal failure, recurrent urinary tract infection or urosepsis, or urinary incontinence). Compared with placebo, treatment with finasteride, doxazosin, or the combination significantly reduced the risk of clinical progression of BPH by 34% (p = 0.002), 39% (p < 0.001), and 67% (p < 0.001), respectively. The majority of cases (274 of 351) of BPH progression were confirmed by an increase of ≥ 4 points on the symptom rating scale; with treatment, the risk of symptom progression was reduced by 30% (95% confidence interval 6–48%), 46% (95% confidence interval 25–60%), and 64% (95% confidence interval 48–75%), respectively, in the finasteride, doxazosin, and combination groups compared with placebo. Acute urinary retention was observed in 41 of 351 cases of BPH progression; The risk of acute urinary retention was reduced by 67% (p = 0.011), 31% (p = 0.296), and 79% (p = 0.001) in the finasteride, doxazosin, and combination groups, respectively, compared with placebo. Only the finasteride and combination groups were significantly different from the placebo group.
Pharmacokinetics.
In men, after a single oral dose of 14C-labeled finasteride, 39% of the dose was excreted in the urine as metabolites (presumably a small amount of unchanged finasteride was also excreted in the urine). 57% of the dose was excreted in the feces. It has been established that two metabolites of finasteride have a less pronounced inhibitory effect on 5-alpha-reductase. The bioavailability of finasteride when taken orally is approximately 80%. Food intake does not affect the bioavailability of the drug. The maximum concentration of finasteride in the blood plasma is achieved approximately 2 hours after oral administration. Absorption of the drug from the gastrointestinal tract is completed 6-8 hours after its intake. The half-life of finasteride in the blood plasma is on average 6 hours. Plasma protein binding is 93%. Systemic clearance is approximately 165 ml/min, volume of distribution is 76.1 liters.
In patients with chronic renal failure (creatinine clearance from 9 to 55 ml/min), no difference in the rate of elimination of a single dose of finasteride labeled with carbon isotopes 14C was found compared with healthy volunteers. Binding to plasma proteins in these groups of patients was also not different. This is explained by the fact that in patients with renal failure, the proportion of finasteride metabolites that are normally excreted in the urine is excreted in the feces. This is confirmed by an increase in the amount of finasteride metabolites in the feces in these patients with a simultaneous decrease in their concentration in the urine. In connection with the above, for patients with renal failure for whom hemodialysis is not indicated, dose adjustment of finasteride is not required.
There are no data on the pharmacokinetics of the drug in patients with hepatic insufficiency.
Finasteride crosses the blood-brain barrier. Small amounts of finasteride have been detected in seminal fluid.
Indication
Treatment and control of benign prostatic hyperplasia (BPH) in patients with an enlarged prostate gland to:
reduction in size (regression) of the enlarged gland, improvement in urine flow, and reduction of symptoms associated with BPH;
reducing the risk of acute urinary retention and the need for surgical intervention, including transurethral resection of the prostate and prostatectomy.
Contraindication
Hypersensitivity to finasteride or to other components of the drug.
Finasteride is contraindicated for use in women and children.
Pregnancy: use in women when they are or may potentially be pregnant (see section “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
No clinically significant interactions with other drugs have been identified. Finasteride does not have a significant effect on the enzyme system that metabolizes drugs related to cytochrome P450. Although the risk of finasteride affecting the pharmacokinetics of other drugs is assessed as small, it is likely that inhibitors and inducers of cytochrome P450 3A4 will affect the plasma concentration of finasteride. However, given the established safety profile, any increase in finasteride concentrations associated with concomitant use of cytochrome P450 3A4 inhibitors is unlikely to be of clinical significance. Compounds tested in volunteers include propranolol, digoxin, glyburide, warfarin, theophylline, and antipyrine; no clinically significant interactions were found.
Other concomitant therapy: Although no specific interaction studies have been performed, finasteride has been used concomitantly in clinical trials with angiotensin-converting enzyme inhibitors, alpha-blockers, beta-blockers, calcium channel blockers, nitrates, diuretics, H2-receptor antagonists, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and paracetamol, quinolones, and benzodiazepines. No clinically significant adverse interactions have been observed.
Application features
General measures.
Patients with high residual urine volume and/or severely reduced urine flow should be closely monitored for the possible development of obstructive uropathy. Surgical intervention should be considered as an alternative.
Impact on prostate-specific antigen (PSA) and prostate cancer diagnosis.
To date, no clinical benefit has been demonstrated for finasteride treatment in patients with prostate cancer. Patients with benign prostatic hyperplasia and elevated PSA levels have been studied in controlled clinical trials, during which PSA levels were measured several times and prostate biopsy was performed. In these trials, finasteride treatment did not affect the incidence of prostate cancer. The overall incidence of prostate cancer was not significantly different between the finasteride and placebo groups.
Finasteride causes a decrease in serum PSA by approximately 50% in patients with benign prostatic hyperplasia, even in the presence of prostate cancer. This should be taken into account when assessing PSA levels, as this decrease does not exclude concomitant prostate cancer. For correct interpretation, in most patients receiving finasteride for 6 months or more, PSA values should be doubled compared with normal values in untreated individuals. This correction allows maintaining the sensitivity and specificity of PSA determination and maintains its ability to detect prostate cancer.
Any persistent increase in PSA levels in a patient receiving finasteride 5 mg treatment requires careful evaluation to determine the cause, including non-adherence to the finasteride regimen.
Effect of the drug on laboratory data
Impact on PSA levels
Serum PSA levels correlate with patient age and prostate volume, with prostate volume correlating with patient age. When evaluating laboratory PSA values, it is important to consider the fact that PSA levels decline during finasteride treatment. Most patients experience a rapid decline in PSA during the first few months of treatment, after which PSA levels stabilize at a new level that is approximately half of baseline. From this review, typical patients receiving finasteride for 6 months or more should have PSA values that are twice as high as those in untreated individuals.
Finasteride does not significantly reduce the percentage of free PSA (the ratio of free PSA to total). The ratio of free to total PSA remains constant even under the influence of finasteride. When determining the percentage of free PSA, which is used to diagnose prostate cancer, correction of its values is not required.
Breast cancer in men
During clinical trials and in the post-marketing period, breast cancer has been reported in men taking finasteride at a dosage of 5 mg. Physicians should instruct their patients to immediately report any changes in breast tissue, such as swelling, pain, gynecomastia, or nipple discharge.
Mood swings and depression
Mood changes, including depressed mood, depression and, rarely, suicidal ideation, have been reported in patients treated with finasteride 5 mg. Patients should be monitored for psychiatric symptoms and advised to seek medical attention if they occur.
Lactose
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use this medicine.
Liver failure
The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied.
Use during pregnancy or breastfeeding
Use during pregnancy.
Penester® is contraindicated in women.
Finasteride action: risk to the male fetus.
Women of childbearing potential or who are pregnant should avoid contact with crushed or broken finasteride tablets because of the possibility of finasteride passing into the body and the potential risk to a male fetus (see section “Use during pregnancy” above). The tablets are coated, which prevents contact with the active ingredient, provided that the tablets are not crushed or broken.
There is evidence of small amounts of finasteride being excreted in the semen of a patient taking finasteride 5 mg/day. It is not known whether a male fetus may be adversely affected if its mother has been exposed to the semen of a patient taking finasteride. If the patient's sexual partner is or may potentially be pregnant, the patient should be advised to prevent exposure of the female partner to the semen.
Due to the ability of 5-alpha-reductase type II inhibitors to inhibit the conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, may cause abnormalities in the development of the external genitalia in a male fetus.
The tablets of the drug are coated and this prevents contact with the active ingredient, provided that the tablets are not crushed and have not lost their integrity.
Use during breastfeeding.
Penester® is not indicated for use in women. It is not known whether finasteride passes into breast milk.
The ability to influence the reaction speed when driving or working with other mechanisms
The medicine does not affect the ability to drive a car or operate other mechanisms.
Method of administration and doses
The recommended dose is 1 tablet of 5 mg once a day, regardless of meals.
Finasteride can be used as monotherapy or in combination with the alpha-blocker doxazosin.
For patients with renal insufficiency of varying severity (with a decrease in creatinine clearance to 0.9 ml/min), dose adjustment is not required, since pharmacokinetic studies have not revealed any changes in the distribution of finasteride.
There are no data on the use of the drug in patients with impaired liver function.
No dose adjustment is required for elderly patients.
Do not use on children.
Children
Penester® is contraindicated in children.
Safety and efficacy for use in children have not been established.
Overdose
Patients who received finasteride at a dose of up to 400 mg once and at a dose of up to 80 mg per day for 3 months did not experience any adverse effects.
There are no specific recommendations for the treatment of finasteride overdose.
Side effects
The most common adverse reactions are impotence and decreased libido. These adverse reactions occur early in the course of therapy and resolve with continued treatment in most patients.
Adverse reactions reported during clinical trials and/or during post-marketing use are listed in the table below.
The frequency of adverse reactions is defined as: very common (≥1/10), common (≥1/100 - <1/10), uncommon (≥1/1000 - <1/100), rare (≥1/10000 - <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data).
| Organ systems | Frequency of manifestations |
| On the part of the immune system | Not known: hypersensitivity reactions such as angioedema (including swelling of the lips, tongue, throat and face) |
| From the psyche | Common: decreased libido. Not known: decreased libido, which may persist after discontinuation of therapy, depression, anxiety. |
| From the side of the cardiovascular system | Not known: rapid heartbeat. |
| Liver and biliary tract disorders | Not known: increased liver enzymes. |
| Skin and subcutaneous tissue disorders | Uncommon: rash. Not known: pruritus, urticaria. |
| Reproductive system and breast disorders | Common: impotence. Uncommon: ejaculation disorder, breast tenderness and enlargement. Not known: testicular pain, haematomaspermia, sexual dysfunction (erectile dysfunction and ejaculation disorders) which may persist after discontinuation of treatment; male infertility and/or reversible sperm quality disorders (normalisation or improvement of sperm quality has been reported after discontinuation of finasteride). |
| According to research | Common: decreased ejaculate. |
In addition, breast cancer has been reported in men taking finasteride during clinical trials and post-marketing experience (see section 4.4).
Drug treatment of prostate symptoms
The MTOPS trial compared finasteride 5 mg/day (n = 768), doxazosin 4 or 8 mg/day (n = 756), the combination of finasteride 5 mg/day and doxazosin 4 or 8 mg/day (n = 786), and placebo (n = 737). The safety and tolerability profile of the combination therapy was consistent with that of the individual components. The incidence of ejaculation disorders in patients receiving combination therapy was: finasteride 8.3%, doxazosin 5.3%, combination therapy 15%, and placebo 3.9%.
Other long-term study data
In a 7-year placebo-controlled study of 18,882 healthy men, of whom 9,060 had available prostate needle biopsy data, prostate cancer was detected in 803 (18.4%) men taking finasteride and 1,147 (24.4%) men taking placebo. In the finasteride group, 280 (6.4%) men had prostate cancer with Gleason scores of 7–10 detected by needle biopsy, compared with 237 (5.1%) men in the placebo group. Additional analyses suggest that the increased prevalence of high-grade prostate cancer observed in the finasteride group may be explained by the effect of finasteride on prostate volume. Of the total number of prostate cancers diagnosed in this study, approximately 98% of cases were classified as intracapsular (stage T1 or T2) cancer. There is no information on the association between long-term finasteride use and tumors with Gleason scores of 7–10.
Laboratory test data
Serum PSA levels correlate with patient age and prostate volume, with prostate volume correlating with patient age. When evaluating laboratory PSA values, it is important to consider that PSA levels decrease during finasteride treatment (see section 4.4).
Expiration date
3 years.
Storage conditions
Does not require any special storage conditions. Keep out of the reach of children.
Packaging
No. 30 (15x2): 15 tablets in a blister, 2 blisters in a cardboard box.
No. 90 (30x3): 30 tablets in a blister, 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Zentiva, c.s.
Location of the manufacturer and its business address.
At the cable factory 130, Dolní Michalupy, Prague-Dolní Michalupy, 102 00, Czech Republic.
