Finast, 5 mg 30 pcs.

Pharmacodynamics

Finasteride, a synthetic 4-azasteroid compound, 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 both in blood and in prostate tissue.

Suppression of DHT formation is accompanied by decrease in size of prostate gland, increase in maximum urine flow rate and decrease in severity of symptoms associated with prostatic hyperplasia. Finasteride has no affinity to the androgen receptor. The drug has no significant effect on lipid profile (total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL) and triglycerides) and bone mineral density.
Finasteride has no effect on blood levels of cortisol, estradiol, prolactin, thyrotropic hormone and thyroxine compared to placebo.

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

In patients with BPH who were prescribed finasteride at a dose of 5 mg daily for 4 years, there was an approximately 70% reduction in blood DHT concentration, which was associated with a reduction in prostate volume of approximately 20%. In addition, prostate-specific antigen (PSA) concentrations were approximately 50% lower than baseline, suggesting reduced prostate epithelial cell growth. The decrease in DHT concentration and 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, blood 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 DHT concentrations in prostate tissue and a 10-fold increase in testosterone concentrations in prostate tissue compared to pre-treatment concentrations.

Long-term (over 4 years) use of finasteride in patients with BPH and moderately or significantly pronounced symptoms of the disease was found to reduce the risk of all urologic complications (surgical interventions: 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 (PLESS Study).

In patients taking finasteride for 3 months when a reduction of approximately 20% in prostate volume was achieved, the prostate volume returned to its previous size after 3 months when treatment was discontinued.
Thus, treatment with finasteride helps reduce the size of the enlarged prostate, increases urine flow rate, and reduces symptoms associated with BPH.

Pharmacokinetics

Absorption

Maximum plasma concentration 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. Bioavailability is approximately 80% and is independent of food intake.

Distribution

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

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

In patients who received finasteride for 7-10 days, the drug was detected in the cerebrospinal fluid. When finasteride was administered at a dose of 5 mg per day, finasteride was also detected in seminal fluid. The content of finasteride in seminal fluid was 50-100 times less than the finasteride dose taken.

Metabolism

The half-life (T1/2) of finasteride averages 6 hours.

Elimation

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 gut. In this study, 2 metabolites of finasteride were identified that have a slight inhibitory effect on 5-alpha reductase compared to finasteride.

In older age, the excretion rate of finasteride is slightly reduced. The T1/2 increases with age: in men 18-60 years old the average T1/2 is 6 hours and in men over 70 years old it is 8 hours. These changes are not clinically significant and, therefore, no dose reduction is required in elderly men.

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

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

Indications

Treatment and control of pancreatitis, 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 (TURP) 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.

Pharmacological effect

Pharmacodynamics

Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of type II 5-alpha reductase, an intracellular enzyme that converts testosterone into a more active androgen, dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), its enlargement depends on the conversion of testosterone to DHT in the prostate gland. Finasteride is highly effective in reducing the concentration of DHT in both the 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 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 (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides) and bone mineral density.
Finasteride has no effect on the 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 maximum effect achieved after 8 hours. Although the plasma concentration of finasteride fluctuates over a 24-hour period, the concentration of DHT 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 BPH treated with finasteride 5 mg daily for 4 years, there was an approximately 70% decrease in blood DHT concentrations, which was associated with an approximately 20% decrease in prostate volume. 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 finasteride was used for 7–10 days in patients referred for prostatectomy, there was an approximately 80% decrease in prostate tissue DHT concentrations and a 10-fold increase in prostate tissue testosterone concentrations compared with pretreatment concentrations.

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

In patients who took finasteride for 3 months and achieved a reduction in prostate volume of approximately 20%, when treatment was stopped, the prostate volume returned to its previous size after 3 months.
Thus, treatment with finasteride helps to reduce the size of an enlarged prostate gland, increases the flow rate of urine and reduces 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. Bioavailability is about 80% and does not depend on 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 finasteride at a dose of 5 mg per day, finasteride is also found in the seminal fluid. The content of finasteride in seminal fluid was 50-100 times less than the dose of finasteride taken.

Metabolism

The half-life (T1/2) of finasteride averages 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, 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, part of the metabolites of finasteride, which is normally excreted by the kidneys, is 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 finasteride is required.

Special instructions

Effect on PSA levels and diagnosis of prostate cancer

To date, the clinical benefits of finasteride 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 finasteride did not appear to change the incidence of prostate cancer detection and did not affect the incidence of prostate cancer in patients treated with finasteride or placebo.

Before starting treatment and periodically during finasteride therapy, it is recommended to perform 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 may be largely the same, so in men with BPH, normal PSA values ​​do not rule out prostate cancer, regardless of finasteride treatment. An initial PSA concentration below 4 ng/ml also does not exclude prostate cancer.

Finasteride causes a decrease in serum PSA concentrations of 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 receiving finasteride, 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.

An analysis of PSA values ​​in more than 3,000 patients in the 4-year, double-blind, placebo-controlled PLESS study confirmed that in those taking finasteride for 6 months or more, PSA values ​​should be doubled to compare with normal values ​​in patients not receiving finasteride. 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 finasteride.
Finasteride 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 the drug. 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 concentration correlates 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 finasteride. 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 the value measured before the start of therapy. In this regard, in patients taking finasteride for 6 months or more, the PSA concentration should be doubled to compare it with normal values ​​in men not taking the drug.

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 damaged Finast® tablets due to the possibility of absorption of finasteride, due to the high risk of teratogenic effect for the male fetus (see section “Use during pregnancy and breastfeeding”). Finast® tablets are film-coated, which prevents contact with the active ingredient, provided that the tablets are not crushed and have not lost their integrity.

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

Active ingredient

Finasteride

Composition

Each film-coated tablet contains:

Active ingredient:

Finasteride 5 mg

Excipients:

Lactose 86.75 mg

Microcrystalline cellulose (Ultra 102) 12 mg

Sodium carboxymethyl starch (type A) 6 mg

Pregelatinized corn starch 12 mg

Docusate sodium 2.5 mg

Magnesium stearate 0.75 mg

Shell:

Hypromellose (15 cps) 2.4 mg

Propylene glycol 0.4 mg

Titanium dioxide 0.8 mg

Talc 0.4 mg

Pregnancy

The use of Finast® is contraindicated in women with preserved reproductive potential and during pregnancy.

Type II 5-alpha reductase inhibitors, including finasteride, when used in pregnant women, can cause abnormalities in the development of the external genitalia in the male fetus.

The drug is not indicated for use in women. There is no data on the excretion of finasteride in breast milk.

Contraindications

Hypersensitivity to finasteride and/or other components of the drug; children under 18 years of age; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; pregnancy and use of the drug in women with preserved reproductive potential.

Patients with a large volume of residual urine and/or a significantly reduced urine outflow should be regularly monitored by a physician to identify obstructive uropathy; the drug should be prescribed with caution to patients with liver failure and the elderly.

Side Effects

Side effects identified during clinical trials

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

Seventy-four patients (4.9%) in the finasteride 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 finasteride 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 considered by the investigators to be possibly, probably, or definitely drug-related and with an incidence greater than 1% with finasteride and greater than placebo during the 4-year study period were those related to sexual function, breast tenderness, and skin rash. In the first year of treatment, sexual dysfunction was detected 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 – 0.8% and 0.1%, respectively. When using the drug in years 2-4 of the study, the incidence of the above side effects in patients taking finasteride did not differ significantly from that in patients taking placebo.

The total incidence of side effects during 2-4 years of the study was: impaired sexual function (5.1% in the drug group and 5.1% in the placebo group), decreased libido (2.6% in both groups), impaired ejaculation (0.2% and 0.1%, respectively). Within 1 year, a decrease in ejaculate volume was detected in 3.7% and 0.8% in the drug group and placebo group, respectively; and during 2-4 years of the study – 1.5% and 0.5%, respectively. Breast enlargement was also reported at 1 year (0.5% and
0.1%, respectively), tenderness in the mammary glands (0.4% and 0.1%, respectively) and skin rash (0.5% and 0.2%, 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 that included 18,882 healthy men, needle biopsies (9,060 men) identified prostate cancer in 18.4% of patients receiving finasteride and in 24.4% of patients receiving placebo. 280 men (6.4%) in the finasteride group and 237 men (5.1%) in the placebo group had 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 finasteride group may be due to diagnostic bias associated with the drug’s effect 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 for 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. During the 7-year, placebo-controlled Prostate Cancer Prevention Trial, a study involving 18,882 men, there was 1 case of breast cancer in a man taking finasteride and 1 case of breast cancer in a man receiving 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-marketing experience of application

The following additional adverse effects of finasteride at low doses have been reported in post-marketing experience. 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; 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), the 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 finasteride and placebo groups.

Interaction

No clinically significant interactions of finasteride with other drugs were found.

Finasteride has no effect on cytochome P450, an enzyme system that ensures drug metabolism.

Concomitant food intake reduces the rate of absorption of finasteride, however, food does not affect the overall bioavailability.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children!

Shelf life

2 years.

Manufacturer

Dr. Reddy’s Laboratories Ltd, India