Finasteride 5mg Film-Coated Tablets

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Finasteride 5 mg film coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 5 mg of finasteride.

Excipients:

Each tablet contains 1.667 mg docusate sodium.

Each tablet contains 97.583 mg lactose monohydrate.

For a full list of excipients, see Section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Light blue, biconvex film-coated tablets.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Finasteride 5 mg film coated tablets are 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

In adults

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

Finasteride 5 mg film coated tablets can be administered alone or in combination with the alpha-blocker doxazosin (see section 5.1 ‘Pharmacodynamic properties’).

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.

In the elderly

No dosage adjustment is required in the elderly.

In patients with renal insufficiency

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

In patients with hepatic insufficiency

There are no data available in patients with hepatic insufficiency.

In children

Finasteride 5 mg film coated tablets are contra-indicated in children.

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 4.6 Pregnancy and lactation, Exposure to finasteride - risk to male fetus).

4.4 Special warnings and precautions for use

General

Patients with large residual urine volume and / or severely decreased urinary flow should be carefully monitored for obstructive uropathy. The possibility of surgery should be an option.

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 5 mg film coated tablets. Patients with BPH and elevated serum prostate specific antigen (PSA) were monitored in controlled clinical studies with serial PSAs and prostate biopsies. In these BPH studies, finasteride 5 mg 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 5 mg or placebo.

Digital rectal examination, as well as other evaluations for prostate cancer, should be carried out on patients with BPH prior to initiating therapy with finasteride 5 mg film coated tablets and periodically thereafter. Serum PSA is also used for prostate cancer detection. Generally, when PSA assays are performed, a baseline PSA >10ng/ml (Hybritech) prompts further evaluation and consideration of biopsy; for PSA levels between 4 and 10ng/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 5 mg film coated tablets. A baseline PSA <4ng/ml does not exclude prostate cancer.

Finasteride cause 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 5 mg film coated tablets should be considered when evaluating PSA data and does not rule out concomitant prostate cancer. This decrease is predictable over the entire range of the PSA values, although it may vary in individual patients. Analysis of PSA data from over 3000 patients in the 4-year, doubleblind, placebo-controlled finasteride Long-Term Efficacy and Safety Study (PLESS) confirmed that in typical patients treated with finasteride 5 mg 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 5mg should be carefully evaluated, including consideration of non-compliance to therapy with Finasteride 5 mg film coated tablets.

Percent free PSA (free to total PSA ratio) is not significantly decreased by Finasteride 5 mg film coated tablets and remains constant even under the influence of Finasteride 5 mg film coated tablets. When percent free PSA is used as an aid in the detection of prostate cancer, no adjustment 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 5 mg. 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 5 mg for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men. For clinical interpretation, see 4.4 Special warnings and precautions for use, Effects on PSA and prostate cancer detection.

Breast cancer in men

Breast cancer has been reported in men taking finasteride 5 mg during clinical trials and in 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.

Paediatric 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 drug: galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

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 clinically important drug interactions have been identified. Finasteride 5 mg film coated tablets do not appear to significantly affect the cytochrome P450 3A4 system. Although the risk for finasteride to affect the pharmacokinetics of other drugs 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 include propranolol, digoxin, glibenclamide, warfarin, theophylline, phenazone and no clinically meaningful interactions were found.

Other Concomitant therapy:

Although specific interaction studies were not performed in clinical studies, Finasteride 5 mg film coated tablets were used concomitantly with ACE inhibitors, alpha-blockers, beta-blockers, calcium channel blockers, cardiac nitrates, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAID's), quinolones and benzodiazepines without evidence of clinically significant adverse interactions.

4.6 Fertility, pregnancy and lactation

Pregnancy

Finasteride 5 mg film coated tablets are contra-indicated in women who are or may potentially be pregnant. (See 4.3 Contraindications).

Because of the ability of type II 5 alpha-reductase inhibitors to inhibit conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, may cause abnormalities of the external genitalia of a male fetus when administered to a pregnant woman.

In animal developmental studies, hypospadias were observed in the male offspring of pregnant rats given finasteride at doses ranging from 100 p g/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 5 alpha-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 5 alpha reductase. It is for these reasons that Finasteride 5 mg film coated tablets are contra-indicated 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 fetus

Crushed or broken Finasteride 5 mg film coated tablet tablets should not be handled by women who are or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus (see 4.6 Pregnancy and lactation 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 film coated tablets/day. It is not known whether a male fetus may be adversely affected if his mother is exposed to the semen of a patient being treated with finasteride. Therefore, when the sexual partner of a patient is or may potentially be pregnant, the patient should either avoid exposure of his partner to semen (e.g. by use of a condom) or discontinue Finasteride 5 mg film coated tablets.

Breast-feeding

Finasteride 5 mg film coated tablets are 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

Finasteride 5 mg film coated tablets are 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 Finasteride 5 mg film coated tablets and the incidence of new drug-related sexual adverse experiences decreased with duration of treatment.

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 5mg 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	Unknown: hypersensitivity reactions: angioedema (including swelling of the lips, tongue, throat and face)
Psychiatric disorders	Common: decreased libido Unknown: depression, decreased libido that continued after discontinuation of treatment
Cardiac disorders	Unknown: palpitation
Hepatobiliary disorders	Unknown: increased hepatic enzymes
Skin and subcutaneous tissue disorders	Uncommon: rash Unknown: pruritus, urticaria

Reproductive system and breast disorders

Common: impotence Uncommon: ejaculation disorder, breast tenderness, breast enlargement Unknown: testicular pain, erectile dysfunction that continued after discontinuation of treatment; male infertility

and/or poor seminal quality

Investigations

Common: decreased volume of ejaculate

In addition, the following has been reported in clinical trials and postmarketing use: male breast cancer (see 4.4 Special warnings and precautions for use).

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%. The incidence of ejaculation disorder in patients receiving combination therapy was comparable to the sum of incidences of this adverse experience for 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. In the finasteride group, 280 (6.4%) of men had prostate cancer with Gleason scores of 7-10 detected on needle biopsy 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 5 mg group may be explained by a detection bias due to the effect of finasteride 5 mg on prostate volume. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (stage T1 or T2) at diagnosis. The relationship between long-term use of finasteride and tumours with Gleason scores of 7-10 is unknown.

Post Marketing Experience

The following additional adverse experiences have been reported in postmarketing experience:

- hypersensitivity reactions, including pruritus, urticaria and swelling of the lips and face testicular pain.

Laboratory test findings

When PSA laboratory determinations are evaluated, consideration should be given to the fact that PSA levels generally decrease in patients treated with Finasteride 5 mg film coated tablets (see section 4.4 Special warnings and precautions for use

For clinical interpretation see section 4.4 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 Finasteride 5 mg film coated tablets 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: www.mhra.gov.uk/yellowcard.

System Organ Class	Frequency	MedDRA Term
Infections and infestations	Uncommon	Sepsis (immunosuppression), cellulitis at injection site
Infections and infestations	Not known	Pneumonia, liver abscess
Immune system	Not known	Anaphylaxis, allergic oedema
Neoplesms benign, malignant and	Uncommon	Lentigo
Blood and lymphatic system	Common	Anaemia, megaloblastosis, leucopenia, thrombocytop enia
Metabolism and nutrition	Common	Anorexia, hyperuricaemia
Nervdus system disorders	Common	At high doses cerebellar or cerebral influence with deterioration of the level of consciousness, dysarthria, nystagmus
	Uncommon	hHeadache, peripheral neuropathy and paraplegia at intrathecal administration
	Not known	Dizziness, neuritis, neural toxicity
Eye disorders	Common	Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis, conjunctivitis (may occur with rash)
Cardiac disorders	Uncommon	Pericarditis
Cardiac disorders	Very rare	Arrhythmia
Vascular	Not known	Thrombophlebitis
Respiratory, thoracic and	Uncommon	Shortness of breath, sore throat
Gartsointestinal disorders	Common	Dysphagia, abdominal pain, nausea, vomiting, diarrhoea, oral / anal inflammation or ulceration
	Uncommon	Esophagitis, esophageal ulceration, pneumatosis cystoides intestinalis, necrotising colitis, peritonitis
	Not known	Pancreatitis, gastrointestinal necrosis
Hepatobiliary disorders	Common	Reversible effects on the liver with increased enzyme levels
Hepatobiliary disorders	Not known	Hepatic dysfunction, jaundice
Skin and subcutaneous tissue disorders	Common	Reversible undesirable effects to the skin, such as erythema, bullous dermatitis, urticaria, vasculitis, alopecia
	Uncommon	Skin ulceration, pruritus, burning pain of palms and soles
	Very rare	Neutrophilic eccrine hidradenitis
	Not known	Freckling, rash

Musculoskeletal and	Uncommon	Myalgia, arthralgia
Renal and urinary	Common	Renal dysfunction, urinary retention
General disorders and administrat ion site conditions	Common	Fever, thrombophlebitis at the injection site
General disorders and administrat ion site conditions	Not known	Chest pain and injection site reaction (pain and inflammation at the subcutaneous injection sites)
Investigati ons	Not known	Reduced reticulocytes, cellular changes in the morphology of bone marrow and peripheral smears

Cytarabine (Ara-C) Syndrome: (Immunoallergic effect):

Fever, malaise, myalgia, occasional chest pain, exanthema, conjuctivitis and nausea may occur 6-12 h after start of therapy. Corticosteroids may be considered as prophylaxis and therapy. If they are effective, therapy with cytarabine may be continued.

After Intrathecal use

Nervous system disorders

The risk of CNS toxicity increases if the cytarabine treatment - given as high dose i.v. or intrathecally - is combined with another CNS toxic treatment such as radiation therapy, high dose or intrathecal methotrexate or when given intrathecally in short intervals or in doses above 30 mg/m²

Necrotising leukencephalopathy, bone marrow depression, myelopathy resulting in para- or quadriplegia, paralysis and other isolated neurotoxicities have been reported.

Eye disorders Blindness.

Gastrointestinal disorders

Nausea, vomiting.

General disorders and administration site conditions

Headache, fever and/or other symptoms of an arachnoiditis.

Adverse effects due to high dose cytarabine treatment, other than those seen with conventional doses include:

Infections and infestations:

Sepsis, liver abscess

Hematological toxicity

Seen as profound pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.

Nervous system disorders

After treatment with high doses of cytarabine, symptoms of cerebral or cerebellar influence like personality changes, affected alertness, dysarthria, ataxia, tremor, nystagmus, headache, confusion, somnolence, dizziness, coma, convulsions, peripheral motor and sensory neuropathies appear in 8-37 % of treated patients. The incidence in elderly (>55 years) may be even higher. Other predisposing factors are impaired liver and renal function, previous CNS treatment (e.g., radiotherapy) and alcohol abuse. CNS disturbances are in the most cases reversible.

The risk of CNS toxicity increases if the cytarabine treatment - given as high dose i.v.- combined with another CNS toxic treatment such as radiation therapy or high dose.

Corneal and conjunctival toxicity:

Reversible lesion of corneal and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops.

Respiratory, thoracic and mediastinal disorders

Clinical signs as present in pulmonary oedema/ARDS (adult respiratory distress syndrome) may develop, particularly in high-dose therapy. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26 % in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.

A diffuse interstitial pneumonitis without clear cause that may have been related to cytarabine was reported in patients treated with experimental intermediate doses of cytarabine (1g/m²) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, VP-16).

A syndrome of sudden respiratory distress, rapidly progressing to pulmonary oedema and a radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia; fatal outcome has been reported.

Gastrointestinal disorders:

Gastrointestinal necrosis, necrotizing colitis, gastrointestinal ulceration (including pneumatosis cystoides intestinalis leading to peritonitis). Especially in treatment with high doses of cytarabine, more severe reactions may appear in addition to common symptoms. Intestinal perforation or necrosis with ileus and peritonitis have been reported.

Hepatobiliary disorders:

Liver damage with increased hyperbilirubinemia hepatomegaly, Budd-Chiari-syndrome (hepatic venous thrombosis) and pancreatitis have been observed after high-dose therapy.

Skin and subcutaneous tissue disorders:

Skin rash leading to desquamation, alopecia.

Respiratory, thoracic and mediastinal disorders:

Clinical signs as present in pulmonary oedema/ARDS may develop, particularly in high-dose therapy. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26 % in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.

Others:

Following cytarabine therapy, cardiomyopathy with subsequent death and rhabdomyolysis have been reported. One case of anaphylaxis that resulted in cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of cytarabine.

The gastro-intestinal undesirable effects are reduced if cytarabine is administered as infusion. Local glucocorticoides are recommended as prophylaxis of haemorrhagic conjunctivitis.

Amenorrhoea and azoospermia (sec section 4.6)

Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body, may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.

A Cytarabine syndrome has been described. It is characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6 - 12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.

Cases of pancreatitis have been observed with the induction of cytarabine.

Reporting of suspected adverse reactions

4.9 Overdose

No specific treatment of overdosage with Finasteride 5 mg film coated tablets are recommended. Patients have received single doses of Finasteride 5 mg film coated tablets up to 400 mg and multiple doses of Finasteride 5 mg film coated tablets up to 80 mg/day for up to three months without any adverse effects.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Finasteride is a competitive inhibitor of human Type II 5 a-reductase, an intracellular enzyme which metabolises testosterone into the more potent androgen, dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), enlargement of the prostate gland is dependent upon the conversion of testosterone to DHT within the prostate. Finasteride 5 mg film coated tablets are highly effective in reducing circulating and intraprostatic DHT. Finasteride has no affinity for the androgen receptor.

In clinical studies of patients with moderate to severe symptoms of BPH, an enlarged prostate on digital rectal examination and low residual urinary volumes, Finasteride 5 mg film coated tablets reduced the incidence of acute retention of urine from 7/100 to 3/100 over four years and the need for surgery (TURP or prostatectomy) from 10/100 to 5/100. These reductions were associated with a 2-point improvement in QUASI-AUA symptom score (range 0-34), a sustained regression in prostate volume of approximately 20% and a sustained increase in urinary flow rate.

Medical therapy of prostatic symptoms

The Medical Therapy of Prostatic Symptoms (MTOPS) Trial was a 4- to 6-year study in 3047 men with symptomatic BPH who were randomised to receive finasteride 5 mg/day, doxazosin 4 or 8 mg/day*, the combination of 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 a >4 point confirmed increase from baseline in symptom score, acute urinary retention,

BPH-related renal insufficiency, recurrent urinary tract infections or urosepsis, or incontinence. Compared to placebo, treatment with finasteride, doxazosin, or combination therapy resulted in a significant reduction in 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 the events (274 out of 351) that constituted BPH progression were confirmed >4 point increases in symptom score; the risk of symptom score progression was reduced by 30 (95% CI 6 to 48%), 46 (95% CI 25 to 60%), and 64% (95% CI 48 to 75%) in the finasteride, doxazosin, and combination groups, respectively, compared to placebo. Acute urinary retention accounted for 41 of the 351 events of BPH progression; the risk of developing 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 were significantly different from placebo

* Titrated from 1 mg to 4 or 8 mg as tolerated over a 3-week period

5.2 Pharmacokinetic properties

After an oral dose of ¹⁴C-finasteride in man, 39% of the dose was excreted in the urine in the form of metabolites (virtually no unchanged drug was excreted in the urine), and 57% of total dose was excreted in the faeces. Two metabolites have been identified which possess only a small fraction of the 5 alpha-reductase activity of finasteride.

The oral bioavailability of finasteride is approximately 80%, relative to an intravenous reference dose, and is unaffected by food. Maximum plasma concentrations are reached approximately two hours after dosing and the absorption is complete within 6-8 hours. Protein binding is approximately 93%. Plasma clearance and the volume of distribution are approximately 165 ml/min and 76 1, respectively.

In the elderly, the elimination rate of finasteride is somewhat decreased. Halflife is prolonged from a mean half-life of approximately 6 hours in men aged 18-60 years to 8 hours in men aged more than 70 years. This is of no clinical significance and does not warrant a reduction in dosage.

In patients with chronic renal impairment, whose creatinine clearance ranged

from 9-55 ml/min, the disposition of a single dose of ¹⁴C-finasteride was not different from that in healthy volunteers. Protein binding also did not differ in patients with renal impairment. A portion of the metabolites which normally is excreted renally was excreted in the faeces. It therefore appears that faecal excretion increases commensurate to the decrease in urinary excretion of metabolites. Dosage adjustment in non-dialysed patients with renal impairment is not necessary.

There are no data available in patients with hepatic insufficiency.

Finasteride has been found to cross the blood-brain barrier. Small amounts of finasteride have been recovered in the seminal fluid of treated patients.

5.3 Preclinical safety data

No further information provided.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core

Cellulose, Microcrystalline Docusate sodium Lactose monohydrate Magnesium stearate Pregelatinised maize starch Sodium starch glycolate Povidone

Coating

Indigo carmine (E132) Titanium dioxide (E171) Hypromellose Hydroxypropylcellulose Purified talc

6.2 Incompatibilities

None reported.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

6.5 Nature and contents of container

PVC/Aluminium blisters packs of 10, 14, 15, 20, 28, 30, 50, 56, 98, 100, 300 tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Women should not handle crushed or broken Finasteride 5 mg film coated tablets when they are or may potentially be pregnant (see 'Contraindications', 'Pregnancy and Lactation', Exposure to finasteride - risk to male foetus).

7 MARKETING AUTHORISATION HOLDER

Generics [UK] Ltd t/a Mylan

Station Close

Potters Bar

Herts

EN6 1TL

8 MARKETING AUTHORISATION NUMBER(S)

PL 04569/0721

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/04/2007

10 DATE OF REVISION OF THE TEXT

07/10/2015