4.1. Therapeutic indications

Finasteride is indicated for the treatment and control of benign prostatic hyperplasia (BPH) in patients with an enlarged prostate to:

− cause regression of the enlarged prostate, improve urinary flow and improve the symptoms associated with BPH

− reduce the incidence of acute urinary retention and the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy.

4.2. Posology and method of administration

Posology

The recommended adult dose is one 5 mg tablet daily, with or without food.

Finasteride can be administered alone or in combination with the alpha-blocker doxazosin (see section 5.1).

Although early improvement in symptoms may be seen, treatment for at least six months may be necessary to assess whether a beneficial response has been achieved. Thereafter, treatment should be continued long term. The risk of acute urinary retention is reduced within four months of treatment.

Dosage in the elderly

Dosage adjustments are not necessary although pharmacokinetic studies have shown that the elimination rate of finasteride is slightly decreased in patients over the age of 70.

Dosage in hepatic insufficiency

The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied (see section 4.4).

Dosage in renal insufficiency

No adjustment in dosage is required in patients with varying degrees of renal insufficiency (creatinine clearances as low as 9 mL/min), as pharmacokinetic studies did not indicate any change in the disposition of finasteride.

Paediatric population

Finasteride is contraindicated in children.

Method of administration

Finasteride is for oral use only.

4.3. Contraindications

Finasteride is not indicated for use in women or children.

Finasteride is contraindicated in the following:

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy - Use in women when they are or may potentially be pregnant. (see section 4.6 “Exposure to finasteride - risk to male fetus”).

4.4. Special warnings and precautions for use

General

• Patients with large residual urine and/or severely diminished urinary flow should be carefully monitored for obstruction uropathy.

• Consultation of an urologist should be considered in patients treated with finasteride.

• Obstruction due to trilobular growth pattern of the prostate should be excluded before starting treatment with finasteride.

• To avoid obstructive complications it is important that patients with large residual urine and/or heavily decreased urinary flow are carefully controlled.

• The possibility of surgery should be an option.

Women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets because of the possibility of absorption of finasteride and the subsequent potential risk to a male foetus. Finasteride tablets have a film coating which prevents contact with the active ingredient provided that the tablets have not been broken or crushed (see sections 4.6 and 6.6).

Effects on prostate-specific antigen (PSA) and prostate cancer detection

No clinical benefit has yet been demonstrated in patients with prostate cancer treated with finasteride. Patients with BPH and elevated PSA were monitored in controlled clinical studies with serial PSAs and prostate biopsies. In these BPH studies, finasteride did not appear to alter the rate of prostate cancer detection and the overall incidence of prostate cancer was not significantly different in patients treated with finasteride or placebo.

Digital rectal examination, as well as other evaluations for prostate cancer, should be performed on patients with BPH prior to initiating therapy with finasteride and periodically thereafter. Serum PSA is also used for prostate cancer detection. Generally a baseline PSA >10 ng/mL (Hybritech) prompts further evaluation and consideration of biopsy; for PSA levels between 4 and 10 ng/mL, further evaluation is advisable. There is considerable overlap in PSA levels among men with and without prostate cancer. Therefore, in men with BPH, PSA values within the normal reference range do not rule out prostate cancer regardless of treatment with finasteride. A baseline PSA <4 ng/mL does not exclude prostate cancer.

Finasteride causes a decrease in serum PSA concentrations by approximately 50% in patients with BPH, even in the presence of prostate cancer. This decrease in serum PSA levels in patients with BPH treated with finasteride should be considered when evaluating PSA data and does not rule out concomitant prostate cancer. This decrease is predictable over the entire range of PSA values, although it may vary in individual patients. In patients treated with finasteride for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men. This adjustment preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect prostate cancer.

Any sustained increase in PSA levels of patients treated with finasteride should be carefully evaluated, including consideration of non-compliance to therapy with finasteride.

Percent free PSA (free to total PSA ratio) is not significantly decreased by finasteride and remains constant even under the influence of finasteride. When percent free PSA is used as an aid in the detection of prostate cancer, no adjustment to its value is necessary.

Drug/laboratory test interactions

Effect on levels of PSA

Serum PSA concentration is correlated with patient age and prostatic volume, and prostatic volume is correlated with patient age. When PSA laboratory determinations are evaluated, consideration should be given to the fact that PSA levels decrease in patients treated with finasteride. In most patients, a rapid decrease in PSA is seen within the first months of therapy, after which time PSA levels stabilize to a new baseline. The post-treatment baseline approximates half of the pre-treatment value. Therefore, in typical patients treated with finasteride for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men. For clinical interpretation, see section 4.4 “Effects on prostate-specific antigen (PSA) and prostate cancer detection”.

Percent free PSA (free to total PSA ratio) is not significantly decreased by finasteride. The ratio of free to total PSA remains constant even under the influence of finasteride. When percent free PSA is used as an aid in the detection of prostate cancer, no adjustment to its value is necessary.

Breast cancer in men

Breast cancer has been reported in men taking finasteride 5 mg during clinical trials and the post-marketing period. Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps, pain, gynaecomastia or nipple discharge.

Mood alterations and depression

Mood alterations including depressed mood, depression and, less frequently, suicidal ideation have been reported in patients treated with finasteride 5 mg. Patients should be monitored for psychiatric symptoms and if these occur, the patient should be advised to seek medical advice.

Pediatric population

Finasteride is not indicated for use in children.

Safety and effectiveness in children have not been established.

Lactose

The tablet contains lactose monohydrate. Patients with any of the following genetic deficiencies should not take this medicine: galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

Hepatic insufficiency

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

4.5. Interaction with other medicinal products and other forms of interaction

No drug interactions of clinical importance have been identified. Finasteride is metabolized primarily via, but does not appear to affect significantly, the cytochrome P450 3A4 system. Although the risk for finasteride to affect the pharmacokinetics of other medicinal products is estimated to be small, it is probable that inhibitors and inducers of cytochrome P450 3A4 will affect the plasma concentration of finasteride. However, based on established safety margins, any increase due to concomitant use of such inhibitors is unlikely to be of clinical significance. Compounds which have been tested in man have included propranolol, digoxin, glibenclamide, warfarin, theophylline, and phenazone and no clinically meaningful interactions were found.

4.6. Fertility, pregnancy and lactation

Pregnancy

Finasteride is contraindicated for use in women when they are or may potentially be pregnant (see section 4.3).

Because of the ability of Type II 5 α-reductase inhibitors to inhibit conversion of testosterone to dihydrotestosterone, these medicinal products, including finasteride, may cause abnormalities of the external genitalia of a male foetus when administered to a pregnant woman.

In animal developmental studies, dose-dependent development of hypospadias were observed in the male offspring of pregnant rats given finasteride at doses ranging from 100 μg/kg/day to 100 mg/kg/day, at an incidence of 3.6% to 100%. Additionally, pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, transient nipple development and decreased anogenital distance, when given finasteride at doses below the recommended human dose. The critical period during which these effects can be induced has been defined in rats as days 16-17 of gestation.

The changes described above are expected pharmacological effects of Type II 5 α-reductase inhibitors. Many of the changes, such as hypospadias, observed in male rats exposed in utero to finasteride are similar to those reported in male infants with a genetic deficiency of Type II 5 α-reductase. It is for these reasons that finasteride is contraindicated in women who are or may potentially be pregnant.

No effects were seen in female offspring exposed in utero to any dose of finasteride.

Exposure to finasteride - risk to male foetus

Women should not handle crushed or broken tablets of finasteride when they are or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male foetus (see pregnancy). Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.

Small amounts of finasteride have been recovered from the semen in subjects receiving finasteride 5 mg/day. It is not known whether a male foetus may be adversely affected if his mother is exposed to the semen of a patient being treated with finasteride. When the patient's sexual partner is or may potentially be pregnant, the patient is recommended to minimise exposure of his partner to semen.

Breast-feeding

Finasteride is not indicated for use in women.

It is not known whether finasteride is excreted in human milk.

4.7. Effects on ability to drive and use machines

There are no data to suggest that finasteride affects the ability to drive or use machines.

4.8. Undesirable effects

The most frequent adverse reactions are impotence and decreased libido. These adverse reactions occur early in the course of therapy and resolve with continued treatment in the majority of patients.

The adverse reactions reported during clinical trials and/or post-marketing use with finasteride and/or finasteride at lower doses are listed in the table below.

Frequency of adverse reactions is determined as follows:

Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), not known (cannot be estimated from the available data).

The frequency of adverse reactions reported during post-marketing use cannot be determined as they are derived from spontaneous reports.

System Organ Class

Frequency: adverse reaction

Immune system disorders

Not known: hypersensitivity reactions such as angioedema (including swelling of the lips, tongue, throat and face)

Psychiatric disorders

Common: decreased libido

Not known: decreased libido that may continue after discontinuation of treatment, depression, anxiety, suicidal ideation

Cardiac disorders

Not known: palpitation

Hepatobiliary disorders

Not known: increased hepatic enzymes

Skin and subcutaneous tissue disorders

Uncommon: rash

Not known: pruritus, urticaria

Reproductive system and breast disorders

Common: impotence

Uncommon: ejaculation disorder, breast tenderness, breast enlargement

Not known: testicular pain, haematospermia, sexual dysfunction (erectile dysfunction and ejaculation disorder) that continue after discontinuation of treatment; male infertility and/or poor seminal quality. Normalization or improvement of seminal quality has been reported after discontinuation of finasteride.

Investigations

Common: decreased volume of ejaculate

In addition, the following has been reported in clinical trials and post-marketing use: male breast cancer (see section 4.4).

Medical Therapy of Prostatic Symptoms (MTOPS)

The MTOPS study compared finasteride 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), combination therapy of finasteride 5 mg/day and doxazosin 4 or 8 mg/day (n=786), and placebo (n=737). In this study, the safety and tolerability profile of the combination therapy was generally consistent with the profiles of the individual components. The incidence of ejaculation disorder in patients receiving combination therapy was comparable to the sum of incidences of this adverse experience of the two monotherapies..

Other Long-Term Data

In a 7-year placebo-controlled trial that enrolled 18,882 healthy men, of whom 9060 had prostate needle biopsy data available for analysis, prostate cancer was detected in 803 (18.4%) men receiving finasteride and 1147 (24.4%) men receiving placebo. A greater number of high grade tumours (Gleason scores of 7-10) were detected on needle biopsy in patients in the finasteride group, 280 (6.4%) vs 237 (5.1%) men in the placebo group.

Additional analyses suggest that the increase in the prevalence of high-grade prostate cancer observed in the finasteride group may be explained by a detection bias due to the effect of finasteride on prostate volume. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (stage T1 or T2). The relationship between long-term use of finasteride and tumours with Gleason scores of 7-10 is unknown.

Laboratory Test Findings

Serum PSA concentration is correlated with patient age and prostatic volume, and prostatic volume is correlated with patient age. When PSA laboratory determinations are evaluated, consideration should be given to the fact that PSA levels are decreased in patients treated with finasteride (see section 4.4). In most patients, a rapid decrease in PSA is seen within the first months of therapy, after which time PSA levels stabilise to a new baseline. The post-treatment baseline approximates half of the pre-treatment value. Therefore, in typical patients treated with finasteride for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men.

For clinical interpretation see section 4.4 'Effects on prostate-specific antigen (PSA) and prostate cancer detection'.

No other difference was observed in patients treated with placebo or finasteride in standard laboratory tests.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/ risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Patients have received single doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for up to three months without any adverse effects.

No specific treatment of overdosage with finasteride is recommended.