Finagen

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FINAGEN (FINAGEN)

Composition:

Active substance: finasteride;

1 tablet contains 5 mg of finasteride;

Excipients: lactose monohydrate; microcrystalline cellulose; sodium starch glycolate (type A); pregelatinized starch; sodium lauryl sulfate; magnesium stearate; tablet coating: Opadry 20A50535 blue (hydroxypropylcellulose, hypromellose, titanium dioxide (E 171), talc, indigo carmine aluminum lake (E 132), iron oxide yellow (E 172)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex tablets with beveled edges, coated with a blue film coating, imprinted with "E" on one side and "61" on the other.

Pharmacotherapeutic group.

Agents used in benign prostatic hyperplasia.

ATC code G04C B01.

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 on 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 BPH symptoms, enlarged prostate on digital rectal examination, and low residual urine volume, finasteride 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 associated with a 2-point improvement on the symptom score scale QUASI-AUA (range 0–34), 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 daily, doxazosin 4 or 8 mg daily, combination of finasteride 5 mg daily and doxazosin 4 or 8 mg daily, or placebo. The primary endpoint was time to clinical progression of BPH (defined as an increase of ≥4 points from baseline on the symptom score scale, acute urinary retention, BPH-related renal failure, recurrent urinary tract infection or urosepsis, or urinary incontinence). Compared with placebo, treatment with finasteride, doxazosin, or combination therapy significantly reduced the risk of clinical progression of BPH by 34% (p=0.002), 39% (p<0.001), and 67% (p<0.001), respectively. Most cases (274 of 351) of BPH progression 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 (CI) 6–48%), 46% (95% CI 25–60%), and 64% (95% CI 48–75%) in the finasteride, doxazosin, and combination groups, respectively, compared to placebo. Acute urinary retention occurred in 41 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 significant difference compared to the placebo group.

Pharmacokinetics.

In men, after a single oral dose of carbon-14C-labeled finasteride, 39% of the administered dose was excreted in the urine as metabolites (a small 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 oral bioavailability of finasteride 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. Drug absorption from the gastrointestinal tract is complete within 6–8 hours after administration. The mean plasma half-life of finasteride is approximately 6 hours. Plasma protein binding is 93%. Systemic clearance is approximately 165 mL/min, and volume of distribution is 76.1 L.

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

In patients with chronic renal impairment (creatinine clearance from 9 to 55 mL/min), no differences in the elimination rate of a single dose of carbon-14C-labeled finasteride were observed 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 concomitant reduction in their concentration in urine in these patients. Therefore, dose adjustment of Finagen is not required in patients with renal impairment who are not candidates for hemodialysis.

Data on the pharmacokinetics of the drug in patients with hepatic impairment are not available.

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

Clinical characteristics.

Indications.

Treatment and control of benign prostatic hyperplasia (BPH) in patients with enlarged prostate gland in order to:

• reduce the size (regress) of the enlarged gland, improve urinary flow, and reduce symptoms associated with BPH;
• reduce the risk of developing 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 medication.

Finagen is not indicated for use in women and children.

Pregnancy: for information on use of the drug in pregnant women or women who may potentially be pregnant, see section "Use during pregnancy or breastfeeding".

Interaction with other medicinal products and other forms of interaction.

No clinically significant interaction of Finagen with other drugs has been observed. Finasteride does not significantly affect the enzyme system metabolizing drugs associated with 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 the plasma concentration of finasteride. However, considering the established safety profile, any increase in finasteride concentration due to concomitant use of such inhibitors is unlikely to have clinical significance. Compounds tested in clinical studies involving patients include propranolol, digoxin, glyburide, warfarin, theophylline, and antipyrine; no clinically significant interactions were observed.

Other concomitant therapy. Although specific interaction studies have not 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 acetylsalicylic acid 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 decreased 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 in patients with prostate cancer has not been proven. Patients with benign prostatic hyperplasia (BPH) and elevated PSA levels were followed in controlled clinical trials with multiple PSA measurements and prostate biopsies. In these studies, finasteride treatment did not affect the detection rate of prostate cancer. The overall incidence of prostate cancer was not significantly different between patients receiving finasteride and those receiving placebo.

Prior to initiating treatment and periodically during treatment with Finagen, patients should be evaluated by digital rectal examination and other appropriate methods for the presence of prostate cancer. Serum PSA measurement is also used in the detection of prostate cancer. In general, a baseline PSA level above 10 ng/mL (Hybritech) warrants thorough evaluation, including, if necessary, prostate biopsy. A PSA level between 4–10 ng/mL warrants further patient evaluation. 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 finasteride treatment. A baseline PSA level below 4 ng/mL does not exclude the presence of prostate cancer.

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

For correct interpretation, in most patients receiving Finagen for 6 months or longer, PSA values should be doubled when 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 level in a patient receiving finasteride 5 mg requires thorough investigation to determine the cause, including non-adherence to the Finagen 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 patient age. When evaluating laboratory PSA parameters, it is important to consider that PSA levels decrease during treatment with Finagen. 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 the baseline value. Post-treatment baseline PSA levels are approximately half of pre-treatment levels. Therefore, in typical patients receiving Finagen for 6 months or longer, PSA values should be doubled compared to normal values in untreated individuals.

Finagen 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 Finagen. When using the percentage of free PSA for prostate cancer diagnosis, 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 necessity to promptly report any changes in breast tissue (such as swelling, pain, gynecomastia, or nipple discharge).

Mood changes and depression

Cases of mood changes, including depressed mood, depression, and rarely suicidal ideation, have been reported in patients receiving finasteride 5 mg. Patients should be monitored for the emergence of psychiatric symptoms, and medical advice should be sought if such symptoms occur.

Lactose

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

Hepatic impairment

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

Use during pregnancy or breastfeeding.

Pregnancy

Finagen 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 Finagen tablets due to the possibility of finasteride absorption and the potential risk to a male fetus (see section "Use during pregnancy or breastfeeding"). Finagen 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 patient treated with finasteride may adversely affect a male fetus. If a patient's sexual partner is or may potentially be pregnant, the patient is advised to avoid exposing her to his semen.

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

Breastfeeding period

Finagen 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.

Finagen does not affect the ability to drive a vehicle or operate machinery.

Method of Administration and Dosage

The recommended dose is 1 tablet of 5 mg once daily, independent of food intake.

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

The duration of treatment should be determined individually by the physician. Although symptomatic improvement may occur earlier, at least six months of treatment are required to assess therapeutic efficacy, after which treatment should be continued. The risk of acute urinary retention decreases for up to four months after discontinuation of therapy.

No dose adjustment is required for patients with renal impairment of any degree of severity (including creatinine clearance as low as 9 mL/min), as pharmacokinetic studies have shown no changes in finasteride disposition.

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

No dose adjustment is necessary for elderly patients.

Not intended for use in children.

Children

Finagen is contraindicated in children.

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

Overdose

In patients who received finasteride at doses up to 400 mg as a single dose or 80 mg daily for 3 months, no adverse effects were observed.

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

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), frequency not known (cannot be estimated from the available data).

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

Medical treatment of prostate-related symptoms

In the MTOPS study, finasteride 5 mg once daily (n=768), doxazosin 4 or 8 mg once daily (n=756), combination therapy with finasteride 5 mg once daily and doxazosin 4 or 8 mg once daily (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 as follows: 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 and in 1,147 (24.4%) men receiving placebo. In the finasteride 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 observed increased incidence of high-grade prostate cancer in the finasteride group can be explained by the effect of finasteride on prostate volume. Of all 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 and tumors with Gleason scores 7–10 is lacking.

Laboratory test data

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 taken into account that PSA levels decrease during treatment with finasteride (see section "Special precautions").

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging.

10 tablets per blister pack, 1 or 3 blister packs per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Aurobindo Pharma Limited - Unit III, India.

Manufacturer's address and site of operations.

Survey No. 313, 314 – Blocks I, II, III, IV, Bachupally, Bachupally Mandal, Medchal-Malkajgiri District, Telangana State, 500090, India.