Selective 5-alpha reductase inhibitors.

Finasteride

Each tablet contains 5 mg of finasteride.

Blue-coloured, apple-shaped, film-coated tablets marked 'Proscar' on one side and 'MSD 72' on the other.

'Proscar' 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.

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

'Proscar' can be administered alone or in combination with the alpha-blocker doxazosin.

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.

No dosage adjustment is required in the elderly or in patients with varying degrees of renal insufficiency (creatinine clearances as low as 9 ml/min).

There are no data available in patients with hepatic insufficiency.

'Proscar' is contra-indicated in children.

Not applicable.

Hypersensitivity to any component of this product; women who are or may potentially be pregnant; children.

General

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

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

No clinical benefit has yet been demonstrated in patients with prostate cancer treated with 'Proscar'.

Digital rectal examination, as well as other evaluations for prostate cancer, should be carried out on patients with BPH prior to initiating therapy with 'Proscar' and periodically thereafter. Generally, when PSA assays are performed 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 'Proscar'. A baseline PSA <4 ng/ml does not exclude prostate cancer.

'Proscar' 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 'Proscar' 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 'Proscar' 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 'Proscar'.

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

Excipients

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Obstructive uropathy. Exclude prostate cancer; evaluate prior to and during therapy. Females may absorb drug from semen or handling tablets; risk in pregnancy.

No clinically important drug interactions have been identified. 'Proscar' does not appear to significantly affect the cytochrome P450linked drug metabolising enzyme system. Compounds which have been tested in man include propranolol, digoxin, glibenclamide, warfarin, theophylline, and antipyrine and no clinically meaningful interactions were found.

Other concomitant therapy: Although specific interaction studies were not performed in clinical studies, 'Proscar' was used concomitantly with ACE inhibitors, alpha-blockers, beta-blockers, calcium channel blockers, cardiac nitrates, diuretics, H₂ antagonists, HMG-CoA reductase inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin and paracetamol, quinolones and benzodiazepines without evidence of clinically significant adverse interactions.

'Proscar' is well tolerated. In controlled clinical studies where patients received 5 mg of finasteride over periods of up to four years, the following adverse reactions were considered possibly, probably or definitely drug-related and occurred with a frequency greater than placebo and greater than or equal to 1%: impotence, decreased libido, ejaculation disorder, decreased volume of ejaculate; breast enlargement, breast tenderness and rash. There was no evidence of increased adverse experiences with increased duration of treatment with 'Proscar' and the incidence of new drug-related sexual adverse experiences decreased with duration of treatment.

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 events without regard to drug relationship were: finasteride 8.3%, doxazosin 5.3%, combination 15.0%, placebo 3.9%.

Other long-term data

In a 7 year placebo-controlled trial that enrolled 18,882 healthy men, of 9060 had prostate needle biopsy data available for analysis, prostate cancer was detected in 803 (18.4%) men receiving 'Proscar' and 1147 (24.4%) men receiving placebo. In the 'Proscar' group, 280 (6.4%) of men had prostate cancer with Gleason scores of 7-10 detected on needle biopsy vs 237 (5.1%). 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 'Proscar' and tumours with Gleason scores of 7-10 is unknown.

Post Marketing Experience

The following additional adverse experiences have been reported in post-marketing experience:

− hypersensitivity reactions, including pruritus, urticaria and swelling of the lips and face

− testicular pain.

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 generally decrease in patients treated with 'Proscar'. 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 'Proscar' for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men.

For clinical interpretation see 'Special warnings and precautions for use', Effects on prostate-specific antigen (PSA) and prostate cancer detection.

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

Merck Sharp & Dohme Limited

(POM)

31 August 2010