Finasteride genepharm

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FINASTERIDE GENE PHARM (FINASTERIDE GENE PHARM)

Composition:

Active substance: finasteride;

1 tablet contains 5 mg of finasteride;

Excipients: lactose monohydrate; pregelatinized corn starch; sodium starch glycolate (type A); iron oxide yellow; sodium lauryl sulfate; microcrystalline cellulose; colloidal anhydrous silicon dioxide; magnesium stearate; purified water;

Tablet coating: hydroxypropylcellulose; hypromellose; titanium dioxide (E 171); indigo carmine (E 132); sunset yellow FCF (E 110); quinoline yellow (E 104).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: light blue, round, biconvex tablets with a nominal diameter of 6.5 mm.

Pharmacotherapeutic group. Inhibitors of testosterone 5-α-reductase. ATC code G04CB01.

Pharmacological properties.

Pharmacodynamics.

Finasteride is a specific inhibitor of type II 5-alpha-reductase, an intracellular enzyme that converts testosterone into the more potent androgen dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), prostate enlargement is dependent upon the conversion of testosterone to DHT within prostate tissue. Finasteride effectively reduces both circulating and intraprostatic DHT levels. Finasteride has no affinity for androgen receptors.

In clinical studies involving patients with moderate to severe symptoms of benign prostatic hyperplasia (BPH), enlarged prostate on digital rectal examination, and low post-void residual volume, Finasteride GeneFARM reduced the incidence of acute urinary retention from 7 per 100 to 3 per 100 over four years and the need for surgical intervention (transurethral resection of the prostate and prostatectomy) from 10 per 100 to 5 per 100. This reduction was accompanied by an improvement of approximately 2 points on the AUA symptom score scale (range 0–34), a significant regression of prostate volume by approximately 20%, and a significant increase in urinary flow rate.

The MTOPS (Medical Therapy of Prostatic Symptoms) study was a 4–6-year trial involving 3047 men with symptomatic BPH who were randomized to receive finasteride 5 mg/day, doxazosin 4 or 8 mg/day, combination therapy with 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 of ≥4 points from baseline on symptom score scale, episode of acute urinary retention, BPH-related renal insufficiency, 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 progression events (274 out of 351) were confirmed by an increase of ≥4 points on the symptom score scale; under 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%) in the finasteride, doxazosin, and combination groups, respectively, compared to placebo. Acute urinary retention occurred in 41 out of 351 cases of BPH progression; under treatment, 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 to placebo. Only the finasteride and combination therapy groups showed a statistically significant difference compared to the placebo group.

Pharmacokinetics.

In men, after a single oral dose of radiolabeled carbon-14 finasteride, 39% of the administered dose was excreted in the urine as metabolites (a negligible amount of unchanged finasteride was likely also excreted in urine). 57% of the administered dose was eliminated in feces. Studies have also shown that two metabolites of finasteride exhibit weaker inhibitory activity against 5-alpha-reductase. The bioavailability of finasteride after oral administration is approximately 80%. Food intake does not affect the bioavailability of the drug. Maximum plasma concentration of finasteride is reached approximately 2 hours after oral administration. Absorption of the drug from the gastrointestinal tract is completed within 6–8 hours after administration. The mean elimination half-life of finasteride in plasma is approximately 6 hours. Plasma protein binding is 93%. Systemic clearance is approximately 165 ml/min, and volume of distribution is 76.1 liters.

In elderly patients, the elimination rate of finasteride is slightly reduced. In men over 70 years of age, the elimination half-life of finasteride is approximately 8 hours, compared to 6 hours in individuals aged 18 to 60 years. However, this does not necessitate dose reduction in elderly patients.

In patients with chronic renal impairment (creatinine clearance from 9 to 55 ml/min), no differences were observed in the elimination rate of a single dose of radiolabeled carbon-14 finasteride compared to healthy volunteers. Plasma protein binding in these patient groups was also unchanged. This is explained by the fact that in patients with renal impairment, the fraction of finasteride metabolites normally excreted in urine is instead eliminated in feces. This is confirmed by increased levels of finasteride metabolites in feces and concomitantly decreased concentrations in urine in these patients. Therefore, dose adjustment of Finasteride GeneFARM is not required in patients with renal impairment who are not undergoing hemodialysis.

Pharmacokinetic data in patients with hepatic impairment are not available.

Finasteride crosses the blood-brain barrier. A small amount of finasteride has been detected in semen.

Clinical characteristics.

Indications.

Finasteride Jenepharm is indicated for the treatment and control of benign prostatic hyperplasia (BPH) in patients with an enlarged prostate gland, with the following objectives:

• reduction in size (regression) of the enlarged gland, improvement of urinary flow, and reduction of symptoms associated with BPH;
• reduction in the risk of acute urinary retention and the need for surgical intervention, including transurethral resection of the prostate and prostatectomy.

Contraindications.

Hypersensitivity to finasteride or to any component of this medicinal product.

Finasteride Jenepharm is not indicated for use in women and children.

Pregnancy: should not be used in women who are or may potentially be pregnant (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction.

No clinically significant interactions with other drugs have been identified. Finasteride Jenepharm has no notable effect on the enzyme system metabolizing drugs related to cytochrome P450 3A4. Although the risk that finasteride affects the pharmacokinetics of other medicinal products is considered low, there is a possibility that inhibitors and inducers of cytochrome P450 3A4 may influence plasma concentrations of finasteride. However, considering the established safety profile, any increase in finasteride concentration due to concomitant use of such inhibitors is unlikely to be of clinical significance. Compounds tested in clinical studies involving patients include propranolol, digoxin, glyburide, warfarin, theophylline, and antipyrine; no clinically significant interactions were observed.

Concomitant therapy. Although no specific interaction studies have been conducted, finasteride has been used concomitantly in clinical studies 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 were observed.

Special precautions for use.

General precautions

Careful monitoring for possible development of obstructive uropathy is necessary in patients with large residual urine volume and/or markedly reduced urinary flow. Surgical intervention should be considered as an alternative option.

Effect on prostate-specific antigen (PSA) and diagnosis of prostate cancer

To date, a beneficial clinical effect of finasteride treatment on patients with prostate cancer has not been demonstrated. Patients with benign prostatic hyperplasia (BPH) and elevated PSA levels were monitored in controlled clinical studies with multiple PSA measurements and prostate biopsies. In these studies, treatment with finasteride did not affect the frequency of detection of prostate cancer. The overall incidence of prostate cancer was not significantly different between patients receiving finasteride and those receiving placebo.

Before initiating treatment and periodically during treatment with Finasteride GenePharm, patients should be examined by digital rectal examination and other methods to rule out prostate cancer. Serum PSA measurement is also used in the detection of prostate cancer. In general, if baseline PSA level exceeds 10 ng/mL (Hybritech), thorough evaluation of the patient, including biopsy if necessary, should be performed. A PSA level between 4–10 ng/mL warrants further investigation. There is considerable overlap in PSA levels between men with and without prostate cancer. Therefore, in men with benign prostatic hyperplasia, normal PSA values do not exclude the presence of prostate cancer, regardless of treatment with Finasteride GenePharm. A baseline PSA level below 4 ng/mL does not exclude the presence of prostate cancer.

Finasteride GenePharm causes a reduction in serum PSA levels by approximately 50% in patients with benign prostatic hyperplasia, even in the presence of prostate cancer. This decrease in serum PSA levels in patients with benign prostatic hyperplasia receiving Finasteride GenePharm must be taken into account when interpreting PSA values, as this reduction does not exclude concomitant prostate cancer. This reduction is predictable across the entire range of PSA values, although it may vary among individual patients.

For correct interpretation, in most patients receiving Finasteride GenePharm for 6 months or longer, PSA values should be doubled compared to normal values in individuals not receiving treatment. This adjustment maintains the sensitivity and specificity of PSA testing and preserves its ability to detect prostate cancer.

Any persistent increase in PSA levels in a patient receiving finasteride 5 mg requires thorough evaluation to determine the cause, including non-adherence to the Finasteride GenePharm treatment regimen.

Effect of the drug on laboratory parameters

Effect on PSA levels

Serum PSA levels correlate with patient age and prostate volume, and prostate volume correlates with age. When evaluating laboratory PSA parameters, it should be noted that PSA levels decrease during treatment with Finasteride GenePharm. In most patients, a rapid decline in PSA occurs during the first few months of treatment, after which PSA stabilizes at a new level approximately half of the baseline value. Post-treatment baseline PSA levels are approximately half of pre-treatment levels. Therefore, in typical patients receiving Finasteride GenePharm for 6 months or longer, PSA values should be doubled compared to normal values in untreated individuals.

Finasteride GenePharm does not significantly alter the percentage of free PSA (ratio of free to total PSA). The ratio of free to total PSA remains constant even under the influence of Finasteride GenePharm. When using the percentage of free PSA for the diagnosis of prostate cancer, correction of its value is not required.

Breast cancer in men

Cases of male breast cancer have been reported during clinical trials and in the post-marketing period in men taking finasteride 5 mg. Physicians should inform patients about the need to report immediately any changes in breast tissue (such as swelling, pain, gynecomastia, or nipple discharge).

Mood changes and depression

Cases of mood changes, including depressive mood, depression, and, less frequently, suicidal ideation, have been reported in patients receiving finasteride 5 mg. Patients should be monitored for the development of psychiatric symptoms, and if such symptoms occur, they should be advised to seek medical help.

Lactose

The drug contains lactose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take Finasteride GenePharm.

Hepatic impairment

The effect of hepatic impairment on the pharmacokinetics of finasteride has not been studied.

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially sodium-free.

The drug contains the colouring agent "Yellow West FCF", which may cause allergic reactions.

Use during pregnancy or breastfeeding

Use during pregnancy

Finasteride GenePharm is contraindicated in pregnant women.

Effect of finasteride – risk to male fetus

Women who are or may potentially become pregnant should avoid contact with crushed or damaged Finasteride GenePharm tablets due to the potential for finasteride absorption and subsequent risk to a male fetus (see section "Use during pregnancy"). Finasteride GenePharm tablets are coated, which prevents contact with the active ingredient as long as the tablets are intact and not crushed.

Available data indicate that small amounts of finasteride may be excreted in semen of patients taking finasteride 5 mg daily. It is unknown whether exposure of a pregnant woman to semen from a finasteride-treated patient could adversely affect a male fetus. If a patient's sexual partner is or may potentially be pregnant, the patient should be advised to avoid exposing his partner to semen.

Because type II 5-alpha-reductase inhibitors can inhibit the conversion of testosterone to dihydrotestosterone, these agents, including finasteride, may cause abnormalities in the development of external genitalia in a male fetus.

Use during breastfeeding

Finasteride GenePharm is not indicated for use in women. It is unknown whether finasteride is excreted in human breast milk.

Ability to influence reaction speed when driving or operating machinery

Does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

The recommended dose is – 1 tablet of 5 mg once daily, taken during or regardless of meals.

Finasteride Jenepharm may be used as monotherapy or in combination with the alpha-blocker doxazosin (see section "Pharmacological Properties").

The duration of treatment is determined individually by a physician. Although symptomatic improvement may be observed earlier, at least six months of continuous treatment are required to properly assess therapeutic efficacy, after which treatment should be continued. The risk of acute urinary retention decreases within four months after completion of treatment.

For patients with renal impairment of varying severity (creatinine clearance as low as 9 mL/min), dosage adjustment is not required, as pharmacokinetic studies have shown no changes in finasteride distribution.

There are no data on the use of the drug in patients with hepatic impairment.

Dosage adjustment is not required for elderly patients.

Do not use in children.

Children

Finasteride Jenepharm is contraindicated in children.

The safety and efficacy of the drug in children have not been established.

Overdose

In patients who received Finasteride Jenepharm at single doses up to 400 mg and at doses up to 80 mg daily for 3 months, no adverse effects were observed.

There are no specific recommendations for the treatment of overdose with Finasteride Jenepharm.

Adverse reactions.

The most common adverse reactions are impotence and decreased libido. These adverse reactions occur at the beginning of the treatment course and resolve with continued therapy in most patients.

Adverse reactions reported during clinical trials and/or post-marketing use are listed below in the table.

The frequency of adverse reactions is defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), unknown (cannot be estimated from available data).

In addition, during clinical studies and in post-marketing use, cases of breast cancer in men taking finasteride have been reported (see section "Special warnings and precautions for use").

Medical Therapy of Prostatic Symptoms (MTOPS)

In the MTOPS study, finasteride 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), combination therapy with finasteride 5 mg/day and doxazosin 4 or 8 mg/day (n=786), and placebo (n=737) were compared. The safety and tolerability profile of combination therapy was consistent with the profiles of the individual components. The incidence of ejaculation disorders in patients receiving combination therapy was: finasteride – 8.3%, doxazosin – 5.3%, combination therapy – 15%, placebo – 3.9%.

Other long-term study data

In a seven-year placebo-controlled study involving 18,882 healthy men, needle biopsy data of the prostate gland were available for analysis in 9,060 subjects. Prostate cancer was detected in 803 (18.4%) men receiving Finasteride GenePharm and in 1,147 (24.4%) men receiving placebo. In the Finasteride GenePharm treatment group, 280 (6.4%) men had Gleason score 7–10 prostate cancer identified by needle biopsy, compared to 237 (5.1%) men in the placebo group. Additional analyses suggest that the increased incidence of high-grade prostate cancer observed in the Finasteride GenePharm group may be explained by the effect of Finasteride GenePharm on prostate volume. Of the total number of prostate cancer cases diagnosed in this study, approximately 98% were classified as intracapsular (Stage T1 or T2) cancer. Information on the relationship between long-term use of Finasteride GenePharm and tumors with Gleason scores 7–10 is lacking.

Laboratory findings

Serum PSA levels correlate with patient age and prostate volume, with prostate volume itself correlating with patient age. When evaluating laboratory PSA results, it should be noted that PSA levels decrease during treatment with Finasteride GenePharm (see section "Special warnings and precautions for use").

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 film-coated tablets in a blister pack.

3 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

GenePharm S.A., Greece.

Manufacturer's address and place of business.

18th km Marathona Avenue, Pallini Attiki, 15351, Greece.