Finasteride-Teva, 5 mg 30 pcs

Pharmacotherapeutic group: 5-alpha reductase inhibitor

ATCode: G04CB01

Pharmacological properties

Pharmacodynamics

Finasteride, a synthetic 4-azosteroid, 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 increase depends on the conversion of testosterone to DHT in the prostate gland. Finasteride is highly effective in reducing the concentration of DHT in both blood and prostate tissue.

The suppression of DHT formation is accompanied by a decrease in the size of the prostate gland, an increase in the maximum urine flow rate and a decrease in the severity of symptoms associated with prostatic hyperplasia.

Finasteride has no affinity for androgen receptors. The drug has no significant effect on lipid profile (i.e., total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides) and bone mineral density. Finasteride has no effect on plasma levels of cortisol, estradiol, prolactin, thyrotropic hormone and thyroxine compared to placebo.

Single administration of finasteride at a dose of 5 mg leads to a rapid decrease in plasma concentrations of DHT with a maximum effect after 8 hours. Although plasma concentrations of finasteride fluctuate over 24 hours, DHT concentrations remain constant. This means that plasma finasteride concentrations are not directly related to plasma DHT concentrations.

In patients with BPH who took finasteride at a dose of 5 mg daily for 4 years, there was an approximately 70% reduction in plasma DHT concentrations, which was associated with a reduction in prostate volume of approximately 20%. In addition, prostate-specific antigen (PSA) concentrations were reduced by approximately 50% from baseline, suggesting a reduction in prostate epithelial cell growth. The decrease in DHT concentration and the reduction in the severity of prostatic hyperplasia, accompanied by a decrease in PSA concentration, persisted in the studies for up to 4 years. In these studies, plasma testosterone levels increased by approximately 10-20% while remaining within physiological limits.

When finasteride was used for 7-10 days in patients referred for prostatectomy, there was an approximately 80% reduction in prostate tissue DHT concentrations and a 10-fold increase in prostate tissue testosterone concentrations compared to pre-treatment concentrations.

The long-term (more than 4 years) use of finasteride in patients with BPH and moderately severe or significantly severe symptoms of the disease was found to reduce the risk of urologic complications (surgery: transurethral resection of the prostate or prostatectomy; acute urinary retention requiring catheterization) by 51% and was accompanied by a pronounced and sustained reduction in prostate volume, as well as a sustained increase in maximum urine flow rate and improvement in symptoms.

In patients treated with finasteride for 3 months when a decrease in prostate volume of approximately 20% is achieved, the prostate volume returns to its previous size after 3 months if treatment is discontinued.

In summary, treatment with finasteride helps reduce the size of the enlarged prostate, increases the rate of urine flow, and reduces symptoms associated with BPH.

Pharmacokinetics

Absorption. Maximum plasma concentration (C_max) of finasteride is reached 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 165 ml/min, volume of distribution is 76 l.

In long-term therapy there is a slow accumulation of finasteride in small amounts. With daily oral administration of finasteride at a dose of 5 mg, its minimum equilibrium plasma concentration reaches 8-10 ng/ml and remains stable over time.

In patients treated with finasteride for 7-10 days, the drug is detectable in cerebrospinal fluid. When finasteride is taken at a dose of 5 mg per day, the presence of the drug is also noted in seminal fluid. The content of finasteride in seminal fluid was 50 to 100 times less than the finasteride dose (5 mg), which had no effect on circulating DHT concentrations in adult men.

Metabolism. The half-life (T_1/2) of finasteride averages 6 hours.

Extraction. In men, after a single oral dose of ¹⁴C-labeled finasteride, 39% of the dose taken is excreted by the kidneys as metabolites (unchanged finasteride is virtually not excreted by the kidneys); 57% is excreted through the intestine. In this study, 2 metabolites of finasteride were identified that have a negligible inhibitory effect on 5-alpha reductase compared with finasteride.

The excretion rate of finasteride decreases slightly in old age. T_1/2 increases with age: in men 18-60 years old the average T_1/2 is 6 hours and in men over 70 years old it is 8 hours. These changes are not clinically significant and, therefore, there is no need to reduce the dose of the drug in elderly men.

In patients with chronic renal impairment (creatinine clearance (CK) of 9 to 55 mL/min), the distribution of labeled ¹⁴C finasteride at a single dose was not different from that of healthy volunteers. The binding of finasteride to plasma proteins was also not different in patients with impaired renal function.

In renal impairment, part of the metabolites of finasteride that are normally excreted by the kidneys are excreted through the intestine. This is manifested by an increase in the amount of finasteride metabolites in the feces with a corresponding decrease in their concentration in the urine. No dose adjustment is required in patients with renal insufficiency on dialysis.

Indications

Prostatitis, Urinary disorders, Prostate hyperplasia

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

• reducing 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, improve urine flow, and reduce symptoms associated with BPH.
• Combined with doxazosin, an alpha-adrenoblocker, to reduce risk of progression of symptoms associated with BPH.
  

Active ingredient

Finasteride

Composition

1 film-coated tablet contains: active ingredient finasteride 5.0 mg; excipients: Lactose monohydrate (200 mesh) 108.0 mg, pregelatinized starch 5.0 mg, sodium lauryl sulfate 0.5 mg, sodium carboxymethyl starch (type A) 10.0 mg, povidone-K30 2.0 mg, microcrystalline cellulose (PH-102) 18,5 mg, magnesium stearate 1.0 mg, Opadray blue film 03G20795 (hypromellose-6cP (E464) 2.50 mg, titanium dioxide (E171) 0.7944 mg, macrogol-6000 0.40 mg, macrogol-400 0.25 mg, indigocarmine lac aluminum (E132) 0.0556 mg).

How to take, the dosage

The drug Finasteride-Teva is administered orally, regardless of meals.

The recommended dose is 1 tablet of 5 mg once daily.

The drug Finasteride-Teva can be used as monotherapy as well as in combination with the alpha-adrenoblocker doxazosin.

Renal failure

In patients with various stages of renal failure (with a CK decrease up to 9 ml/min), no dose adjustment is required because specific studies have not demonstrated any changes in the pharmacokinetic profile of finasteride.

Elderly patients

Dose adjustment is not required, although pharmacokinetic studies indicate that excretion of finasteride is slightly reduced in patients over age 70.

Interaction

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

Finasteride appears to have no significant effect on the cytochrome P450 system and metabolism of drugs associated with this system.

There have been no clinically significant interactions identified when combining finasteride with propranololol, digoxin, glibenclamide, warfarin, theophylline and phenazone.

. Despite the absence of specific drug interaction studies, finasteride has been used concomitantly with angiotensin-converting enzyme (ACE) inhibitors, paracetamol, acetylsalicylic acid, alpha-adrenoblockers, beta-adrenoblockers, slow calcium channel blockers, nitrates in various dosage forms, diuretics, H<₂-histamine receptor blockers, hypolipidemic agents – HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), quinolone derivatives and benzodiazepines without any clinically significant adverse interactions.

Special Instructions

Impact on PSA and prostate cancer diagnosis

To date, the clinical benefits of Finasteride-Teva in patients with prostate cancer have not been demonstrated. In controlled clinical trials in patients with BPH and elevated PSA concentrations PSA content and results of prostate biopsy studies were monitored. The use of Finasteride-Teva has been found not to alter the detection rate of prostate cancer and has no effect on the prostate cancer rate in patients treated with Finasteride-Teva or placebo.

Preferral rectal examination and other prostate cancer diagnostic methods are recommended before starting treatment and periodically during therapy with Finasteride-Teva. Determination of serum PSA is also used to detect prostate cancer. In general, a baseline PSA concentration above 10 ng/ml indicates the need for further evaluation of the patient and biopsy. When a PSA concentration between 4 and 10 ng/L is determined, further examination of the patient is necessary. PSA concentrations in men with and without prostate cancer may overlap significantly, therefore normal PSA values in men with BPH do not rule out prostate cancer, regardless of treatment with Finasteride-Teva. A baseline PSA concentration below 4 ng/ml also does not rule out prostate cancer.

Finasteride-Teva causes a decrease in serum PSA concentration of approximately 50% in patients with BPH, even in the presence of prostate cancer. This must be considered when assessing PSA in patients with BPH treated with Finasteride-Teva, because a decrease in PSA does not rule out the presence of concomitant prostate cancer. This decline is detectable in any range of PSA values, although this varies from patient to patient. Analysis of PSA values in more than 3,000 patients in a 4-year double-blind, placebo-controlled study confirmed that PSA values should be doubled in those who have taken finasteride for 6 months or longer to compare them to normal values in patients not treated with the drug. This correction preserves the sensitivity and specificity of the PSA test and the ability to detect prostate cancer.

Any sustained increase in PSA concentration in patients treated with finasteride requires careful evaluation to determine the cause, which may be non-compliance with Finasteride-Teva regimen.

Finasteride-Teva does not significantly decrease free PSA percentage (ratio of free to total PSA). This index remains constant even under the influence of Finasteride-Teva. If free PSA percentage is used for prostate cancer diagnosis, correction of the value of this parameter is not necessary.

Impact on laboratory values

PsA concentration

Plasma PSA concentration correlates with patient age and prostate volume, and prostate volume in turn correlates with patient age. When determining PSA concentration, it should be taken into account that this figure is reduced in patients taking Finasteride-Teva. In most patients a rapid decrease in PSA is observed in the first months of therapy, after which there is a stabilization at a new level, which is usually about half of the value measured before the start of therapy. Therefore, in patients taking Finasteride-Teva for 6 months or more the PSA concentration should be doubled in order to compare it to normal values in men not taking Finasteride-Teva.

Contact with finasteride is associated with a risk of teratogenic effects on the male fetus

Pregnant women, as well as women taking finasteride.Pregnant women, as well as women of childbearing age, should avoid contact with crushed or lost value tablets of Finasteride-Teva because of the potential for absorption of finasteride, due to the high risk of teratogenic effects for the male fetus (see section “Use in pregnancy and lactation”). The tablets of Finasteride-Teva are coated with a film, which prevents contact with the active ingredient, provided that the tablets are not crushed and have not lost their integrity.

Breast Cancer in Men

.Because there have been post-registration reports of breast cancer in men who have taken finasteride, the treating physician should immediately report any changes in the patient’s breast, such as: swelling, enlargement of the breasts, discomfort in the breasts, nipple discharge.

Mood changes and depression

Mood changes, including depression and less frequently suicidal ideation, have been observed in patients taking finasteride at a dose of 5 mg. The onset of psychopathological symptoms should be monitored and if so, the patient should be referred to a specialist for consultation.

Effects on driving and operating ability

No adverse effects of the drug on driving and operating ability have been reported.

Synopsis

Capsule-shaped, blue film-coated tablets with “FNT 5” engraved on one side and plain on the other. A cross-section shows the core of the tablet, which is white or almost white.

Contraindications

• High sensitivity to any of the ingredients.
• Age under 18 years.
• Pregnancy and use in women of childbearing age (see section “Use during pregnancy and breast-feeding”).
• Lactose intolerance, lactase deficiency,glucose-galactose malabsorption syndrome.

With caution

Patients with large residual urine volumes and/or significantly decreased urine flow should be monitored regularly by a physician for obstructive uropathy.

Patients with hepatic impairment and the elderly are indicated with caution.

Side effects

adverse reactions identified in clinical trials

The 4-year study evaluated the safety of therapy in 1,524 patients taking finasteride compared with 1,516 patients taking placebo.

In 74 patients (4.9%) in the group taking finasteride, therapy was discontinued due to the occurrence of drug-related adverse reactions, compared to 50 patients (3.3%) in the placebo group. Fifty-seven patients (3.7%) in the finasteride group and 32 patients (2.1%) in the placebo group discontinued therapy because of adverse reactions related to sexual dysfunction, which were the most commonly identified adverse reactions.

The only clinical adverse reactions that were considered by investigators to be possibly, probably, or definitely related to the drug, and whose incidence with finasteride was more than 1% and higher than with placebo during the 4-year study period, were sexual dysfunction, breast soreness, and skin rash.

In the first year of treatment, sexual dysfunction was found in 8.1% of patients in the finasteride group and 3.7% in the placebo group; decreased libido in 6.4% and 3.4%; and ejaculation disorders in 0.8% and 0.1%, respectively. When finasteride was used at years 2-4 of the study, the incidence of the above adverse reactions in patients taking finasteride was not significantly different from that in patients taking placebo.

The cumulative incidence of adverse reactions during years 2-4 of the study was: impaired sexual function (5.1% in the finasteride group and 5.1% in the placebo group), decreased libido (2.6% in both groups), and ejaculation disorder (0.2% and 0.1%, respectively). At 1 year, a decrease in ejaculate volume was found in 3.7% and 0.8% in the finasteride and placebo groups, respectively; and at 2-4 years of the study, 1.5% and 0.5%, respectively. At 1 year, breast enlargement (0.5% and 0.1%, respectively), breast soreness (0.4% and 0.1%, respectively), and skin rash (0.5% and 0.2%, respectively) were also reported. At 2-4 years, the cumulative frequency of these phenomena was: breast enlargement (1.8% and 1.1%, respectively), breast soreness (0.7% and 0.3%, respectively), and skin rash (0.5% and 0.1%, respectively).

In a 7-year placebo-controlled study of 1,882 healthy men, puncture biopsy results (in 9,060 men) showed prostate cancer in 18.4% of patients treated with finasteride and 24.4% of patients treated with placebo. Prostate cancer was detected in 280 men (6.4%) in the group of patients receiving finasteride and 237 men (5.1%) in the placebo group, which was scored 7-10 on the Gleason scale on puncture biopsy results. Additional analysis suggested that the increased rate of high malignancy cancer observed in the group of patients taking finasteride may be due to diagnostic errors associated with the effect of the drug on prostate volume. In approximately 98% of all cases of cancer diagnosed, the tumor was classified at the time of diagnosis as intracapsular (T1 or T2 stage). The clinical significance of results concerning prostate cancer with a Gleason score of 7-10 is unknown in this study.

In the study, the safety and tolerability profile of therapy with combination treatment with finasteride at a dose of 5 mg daily and doxazosin 4 mg or 8 mg daily was comparable to the safety and tolerability of each of these agents alone.

In a 4-6-year placebo-controlled study using the active drug as a control using 3,047 men, there were 4 cases of breast cancer in men taking finasteride and none in men not taking finasteride. In another 4-year placebo-controlled study involving 3,040 men, there were 2 cases of breast cancer in men who received placebo and no cases in men who took finasteride. In a 7-year placebo-controlled study involving 1,882 men, there was 1 case of breast cancer in a man taking finasteride and 1 case of breast cancer in a man receiving a placebo. There have been post-registration reports of breast cancer cases in men taking finasteride. The association between long-term administration of finasteride and the occurrence of breast neoplasia in men has not been established at this time.

Post-registration experience

The following additional adverse reactions of finasteride have been reported in post-registration practice.

The undesirable effects are classified according to their frequency of occurrence: very common (≥ 1/10), common (≥ 1/100, < 1/10), infrequent (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown – the available data are not sufficient to estimate the frequency of side effects.

On the immune system: frequency unknown – hypersensitivity reactions and angioedema (including edema of the lips, tongue, larynx, and face).

Psychiatric disorders:often – decreased libido; frequency unknown – depression, decreased libido persisting after discontinuation of treatment.

Cardiac side: frequency unknown – palpitations.

Hepatic and biliary tract side: frequency unknown – increased concentration of liver enzymes.

Skin: infrequent – rash; frequency unknown – itching, urticaria.

Reproductive system and breast disorders: frequent – erectile dysfunction, decreased ejaculate volume; infrequent – ejaculation disorders, enlarged and painful breasts; frequency unknown – painful testes, erectile dysfunction persisting after stopping treatment, male infertility and/or reduced quality of seminal fluid.

Laboratory measures

When evaluating laboratory measures of PSA, a decrease in its concentration in patients taking finasteride should be taken into account.

There were no other differences in the levels of standard laboratory parameters between the groups of patients receiving finasteride and placebo. There have been reported cases of breast cancer in men in clinical trials and in the post-registration period (see section “Special Precautions”).

Overdose

There is evidence that patients who received finasteride in a dose of up to 400 mg once and in 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 overdose of Finasteride-Teva.

Pregnancy use

The use of Finasteride-Teva is contraindicated in pregnancy and in women of childbearing age. Due to the ability of 5-alpha reductase inhibitors type II to inhibit the conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, when used in pregnant women may cause abnormal development of external genitalia in male fetuses. Finasteride-Teva is not indicated for use in women. There are no data on excretion of finasteride with breast milk.

Similarities

Finast, Penester, Finasteride, Finasteride-Teva, Finasteride-OBL