Prostan

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROSAN (PROSAN)

Composition:

Active substance: finasteride;

1 tablet contains 5 mg of finasteride;

Excipients: lactose monohydrate, potato starch, povidone 25, sodium croscarmellose, magnesium stearate, microcrystalline cellulose, hypromellose (hydroxypropylmethylcellulose), propylene glycol, titanium dioxide (E 171), polysorbate 80, talc, polyethylene glycol 6000 (macrogol 6000), colorant Ponceau 4R (E 124).

Pharmaceutical form. Coated tablets.

Main physicochemical properties: round, coated tablets of reddish-pink color, with convex upper and lower surfaces; when examined under a magnifying glass, the cross-section reveals a core surrounded by a single continuous layer.

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). Enlargement of the prostate in benign prostatic hyperplasia (BPH) is dependent on the conversion of testosterone to DHT in prostate tissue. Finasteride effectively reduces both circulating and intraprostatic DHT levels. Finasteride has no affinity for androgen receptors.

In patients with moderate to severe symptoms of BPH, enlarged prostate and low residual urine volume, the drug reduces the frequency of acute urinary retention and the need for surgical intervention (transurethral resection of the prostate and prostatectomy). This is accompanied by an improvement of 2 points on the symptom score scale QUASI-AUA (range 0–34), significant regression of prostate volume, and increased urinary flow rate.

Studies have demonstrated that, compared to placebo, treatment with finasteride, doxazosin, or their combination significantly reduces the risk of clinical progression of BPH. The risk of developing acute urinary retention is lower in groups receiving finasteride, doxazosin, or their combination compared to placebo.

Pharmacokinetics.

In men, after a single oral dose of carbon-14C-labeled finasteride, 39% of the administered dose was excreted in urine as metabolites (a negligible amount of unchanged finasteride was likely also excreted in urine), and 57% of the 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 completed within 6–8 hours after administration. The mean plasma elimination 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 liters.

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 necessitate a dose reduction in elderly patients.

In patients with chronic renal insufficiency (creatinine clearance ranging 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 insufficiency, the fraction of finasteride metabolites normally excreted in urine is instead eliminated via feces. This is confirmed by increased levels of finasteride metabolites in feces and concomitant reduction in their urinary concentration. Therefore, dose adjustment is not required for patients with renal insufficiency who are not undergoing hemodialysis.

Pharmacokinetic data in patients with hepatic insufficiency 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 BPH in patients with enlarged prostate gland aimed at:

• reducing the size (regression) of the enlarged gland, improving urine flow, and alleviating 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.

Contraindications.

Hypersensitivity to finasteride or to any component of this medication.

Prostan is not indicated for use in women and children.

Pregnancy: use 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 interactions with other drugs have been identified. Finasteride has no substantial effect on the enzyme system metabolizing drugs related to cytochrome P450. 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 finasteride plasma concentrations. However, given the established safety profile, any increase in finasteride concentration due to concomitant use of cytochrome P450 3A4 inhibitors is unlikely to have clinical significance. Compounds tested in humans include propranolol, digoxin, glyburide, warfarin, theophylline, and antipyrine; no clinically relevant interactions were found.

Special precautions.

General precautions

Careful monitoring of patients with a large residual urine volume and/or significantly reduced urine flow is necessary due to the possible development of obstructive uropathy.

Effect of the drug 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 monitored during controlled clinical trials with multiple PSA measurements and prostate biopsies. In these studies, finasteride treatment did not affect the frequency of prostate cancer detection. The overall incidence of prostate cancer was not significantly different between patients treated with finasteride and those receiving placebo.

Before starting treatment and periodically during therapy, patients should be examined by digital rectal examination and other methods to rule out prostate cancer. Serum PSA measurement is also used to detect prostate cancer. Generally, if baseline PSA level exceeds 10 ng/mL (Hybritech), a thorough evaluation of the patient should be performed, including, if necessary, prostate biopsy. A PSA level between 4 and 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 prostate cancer, regardless of treatment with the drug. A baseline PSA level below 4 ng/mL does not exclude the presence of prostate cancer.

Finasteride reduces serum PSA levels by approximately 50% in patients with benign prostatic hyperplasia, even in the presence of prostate cancer. This reduction must be taken into account when interpreting PSA levels, as it does not exclude concomitant prostate cancer. The reduction is expected across the entire range of PSA values, although levels may vary in individual patients. In most patients treated with the drug for 6 months or longer, PSA values should be doubled compared to normal values in individuals not taking the drug. This adjustment maintains the sensitivity and specificity of PSA testing and allows for detection of prostate cancer.

Any persistent increase in PSA levels in patients taking finasteride 5 mg requires thorough evaluation to determine the cause, including non-compliance with the prescribed dosing 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 should be taken into account that PSA levels decrease during treatment with the drug. Most patients experience a rapid decline in PSA during the first months of treatment, after which PSA stabilizes at a new level approximately half the baseline value. Therefore, in patients taking the drug for 6 months or longer, PSA values should be doubled compared to normal values in individuals not taking the drug.

Finasteride does not significantly alter the percentage of free PSA (ratio of free PSA to total PSA). The ratio of free to total PSA remains constant even under the influence of the drug. When determining the percentage of free PSA used in the diagnosis of prostate cancer, correction of its values 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 instruct their patients to immediately report any changes in breast tissue, including lumps, pain, gynecomastia, or nipple discharge.

Lactose

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

Hepatic impairment

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

Use during pregnancy or breastfeeding.

Pregnancy.

Prostan is contraindicated in pregnant women.

Women who are or may become pregnant should avoid contact with crushed or damaged Prostan tablets.

There is evidence of excretion of small amounts of finasteride in semen of patients taking finasteride 5 mg daily. It is unknown whether exposure to semen from a finasteride-treated patient could adversely affect a male fetus carried by the patient's sexual partner. If a patient's sexual partner is pregnant or potentially pregnant, the patient should be advised to avoid exposing her to his semen.

Because 5-alpha-reductase type II inhibitors, including finasteride, can inhibit the conversion of testosterone to DHT, they may cause abnormalities in the development of external genitalia in male fetuses.

Prostan tablets are coated, which prevents contact with the active ingredient as long as the tablets are not crushed or damaged.

Breastfeeding period.

Prostan is not indicated for use in women. It is unknown whether finasteride is excreted in human milk.

Ability to influence reaction speed when driving or operating machinery.

Does not affect the ability to drive vehicles or operate machinery.

Method of Administration and Dosage.

The recommended dose is – 1 tablet of 5 mg once daily. It should be taken regardless of food intake.

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

The duration of treatment is determined individually by a physician. Although improvement in the patient's condition may be observed earlier, the drug should be taken for at least 6 months to properly evaluate its effectiveness, after which treatment should be continued.

Dosage adjustment is not required for elderly patients or for patients with renal insufficiency of varying severity (including creatinine clearance reduced to 9 ml/min).

There are no data regarding the use of the drug in patients with impaired liver function.

Do not use in children.

Children.

Prostan is contraindicated in children.

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

Overdose.

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

There are no specific recommendations for the treatment of finasteride overdose.

Adverse Reactions

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

Immune system disorders.

Hypersensitivity reactions, including pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face).

Psychiatric disorders.

Decreased libido, which may persist after discontinuation of therapy, depression.

Cardiac disorders.

Tachycardia.

Hepatobiliary disorders.

Elevated liver enzymes.

Skin and subcutaneous tissue disorders.

Rash, pruritus, urticaria.

Reproductive system and breast disorders.

Impotence, ejaculation disorders, breast tenderness and enlargement, testicular pain, erectile dysfunction which may persist after discontinuation of treatment; male infertility and/or reversible abnormalities in semen quality (improvement or normalization of semen quality has been reported after discontinuation of finasteride).

Investigations.

Decreased ejaculate volume.

In addition, cases of male breast cancer have been reported in men taking finasteride during clinical trials and post-marketing use. Any changes in breast tissue, including lumps, pain, gynecomastia, or nipple discharge, should be reported to a physician immediately.

When comparing the safety profiles of monotherapy with finasteride (5 mg/day) and doxazosin (4 or 8 mg/day) versus combination therapy with finasteride (5 mg/day) and doxazosin (4 or 8 mg/day) versus placebo, the safety and tolerability profile of combination therapy was consistent with the safety profiles of the individual components. The incidence of ejaculation disorders in patients receiving combination therapy was comparable to the sum of the incidences observed with the two monotherapies.

There is no information on the association between long-term use of finasteride and tumors (with Gleason scores 7–10).

Laboratory test findings.

When evaluating laboratory data for PSA, it should be noted that PSA levels decrease in patients taking finasteride. In most patients, a rapid decline in PSA occurs during the first few months of therapy, after which PSA levels stabilize at a new baseline. The baseline level after treatment is approximately half the pre-treatment value. Therefore, in most patients who have been taking finasteride for 6 months or longer, the PSA value should be doubled when comparing to normal reference ranges in untreated men.

In standard laboratory tests, no other differences were observed between patients receiving finasteride and those receiving placebo.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30°C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 1 or 3 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "Tekhnolog".

Manufacturer's address and place of business.

8 Stara Prorizhna Street, Uman, Cherkasy region, 20300, Ukraine.