Finasteride 1 Mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Finasteride 1 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1 mg of finasteride.
Excipients:
Each tablet contains 112 mg of lactose monohydrate (see section 4.4).
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated Tablets.
Brown, round film-coated tablets, debossed “FNT1” on one side and plain on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Finasteride is indicated for the treatment of men with male pattern hair loss (androgenetic alopecia) to increase hair growth and prevent further hair loss.
Finasteride is not indicated for use in women or children.
4.2 Posology and method of administration
The recommended dosage is one 1 mg tablet daily. Finasteride may be taken with or without food.
There is no evidence that an increase in dosage will result in increased efficacy.
Efficacy and duration of treatment should continuously be assessed by the treating physician. Generally, three to six months of once daily treatment are required before evidence of stabilisation of hair loss can be expected. Continuous use is recommended to sustain benefit. If treatment is stopped, the beneficial effects begin to reverse by six months and return to baseline by 9 to 12 months.
No dosage adjustment is required in patients with renal insufficiency.
No data are available on the concomitant use of Finasteride and topical minoxidil in male pattern hair loss.
4.3 Contraindications
Finasteride is contra-indicated in women (see 4.6 ‘Pregnancy and lactation’ and 5.1 ‘Pharmacodynamic properties’) and in patients with hypersensitivity to finasteride or any excipients of this product.
Finasteride is not indicated for use in women or children.
Finasteride should not be taken by men who are taking finasteride 5 mg or any other 5 a-reductase inhibitor for benign prostatic hyperplasia or any other condition.
4.4 Special warnings and precautions for use
In clinical studies with finasteride in men 18-41 years of age, the mean value of serum prostate-specific antigen (PSA) decreased from 0.7 ng/ml at baseline to 0.5 ng/ml at month 12. Doubling the PSA level in men taking finasteride should be considered before evaluating this test result.
Long-term data on fertility in humans are lacking, and specific studies in subfertile men have not been conducted. The male patients who were planning to father a child were initially excluded from clinical trials. Although animal studies did not show relevant negative effects on fertility, spontaneous reports of infertility and/or poor seminal quality were received post-marketing. In some of these reports, patients had other risk factors that might have contributed to infertility. Normalisation or improvement of seminal quality has been reported after discontinuation of finasteride.
Hepatic insufficiency
The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied.
Breast cancer has been reported in men taking finasteride 1 mg during the postmarketing period. Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps, pain, gynaecomastia or nipple discharge.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Paediatric Population
Finasteride should not be used in children. There are no data demonstrating efficacy or safety of finasteride in children under the age of 18.
4.5 Interaction with other medicinal products and other forms of interaction
Finasteride is metabolised via (but does not appear to 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.
Although specific interaction studies were not performed, in clinical studies finasteride doses of 1 mg or more were used concomitantly with ACE inhibitors, paracetamol, alpha blockers, benzodiazepines, beta blockers, calcium-channel blockers, cardiac nitrates, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, prostaglandin synthetase inhibitors (NSAIDs), and quinolones, without evidence of clinically significant adverse interactions.
4.6 Fertility, pregnancy and lactation
Pregnancy
Finasteride is contraindicated for use in women due to the risk in pregnancy.
Because of the ability of finasteride (type II 5a-reductase inhibitors) to inhibit conversion of testosterone to dihydrotestosterone (DHT) in some tissues, these drugs, including finasteride, may cause abnormalities of the external genitalia of a male foetus when administered to a pregnant woman (see 6.6 Instructions for use/handling).
Exposure to finasteride: risk to male foetus
A small amount of finasteride, less than 0.001% of the 1 mg dose per ejaculation,- has been detected in the seminal fluid of men taking Finasteride. Studies in Rhesus monkeys have indicated that this amount is unlikely to constitute a risk to the developing male foetus (see Section 5.3).
During continual collection of adverse experiences, post-marketing reports of exposure to finasteride during pregnancy via semen of men taking 1 mg or higher doses have been received for eight live male births, and one retrospectively-reported case concerned an infant with simple hypospadias. Causality cannot be assessed on the basis of this single retrospective report and hypospadias is a relatively common congenital anomaly with an incidence ranging from 0.8 to 8 per 1000 live male births. In addition, a further nine live male births occurred during clinical trials following exposure to finasteride via semen during pregnancy, and no congenital anomalies have been reported.
Crushed or broken tablets of Finasteride should not be handled by women 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. Finasteride tablets are coated to prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed.
Breast-feeding
Finasteride is contra-indicated for use in lactation. It is not known whether it 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
Side effects, which usually have been mild, generally have not required discontinuation of therapy.
Finasteride for male pattern hair loss has been evaluated for safety in clinical studies involving more than 3,200 men. In three 12-month, placebo-controlled, double-blind, multicentre studies of comparable design, the overall safety profiles of Finasteride and placebo were similar. Discontinuation of therapy due to any clinical adverse experience occurred in 1.7% of 945 men treated with Finasteride and 2.1% of 934 men treated with placebo. By the fifth year of treatment with Finasteride, the proportion of patients reporting each of the above side effects decreased to <0.3%.
Finasteride has also been studied for prostate cancer risk reduction at 5 times the dosage recommended for male pattern hair loss. 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 5 mg and 1147 (24.4%) men receiving placebo. In the finasteride 5 mg group, 280 (6.4%) men had prostate cancer with Gleason scores of 7-10 detected on needle biopsy vs. 237 (5.1%) men in placebo group. 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 5 mg and tumours with Gleason scores of 7-10 is unknown.
Tabulated list of adverse reactions
The adverse reactions during clinical trials and/or post-marketing use are listed in the table below. Frequency of adverse reactions is determined as follows: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <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 reactions |
|
Immune system disorders |
Not known |
Hypersensitivity reactions, including rash, pruritus, urticaria and angioedema (including swelling of the lips, tongue, throat and face) |
|
Cardiac disorders |
Not known |
Palpitation |
|
Psychiatric disorders |
Uncommon* Uncommon |
Decreased libido Depressed moodf. |
|
Hepatobiliary disorders |
Not known |
Increased hepatic enzymes |
|
Reproductive system and breast disorders |
Uncommon* |
Erectile dysfunction, ejaculation disorder (including decreased volume of ejaculate) |
|
Not known |
Breast tenderness and enlargement, testicular pain, infertility** |
* Incidences presented as difference from placebo in clinical studies at Month 12. f This adverse reaction was identified through post-marketing surveillance but the incidence in randomized controlled Phase III clinical trials (Protocols 087, 089, and 092) was not different between finasteride and placebo.
** see section 4.4 Special warnings and precautions for use.
Drug-related sexual undesirable effects were more common in the finasteride 1mg-treated men than the placebo-treated men, with frequencies during the first 12 months of 3.8% vs 2.1%, respectively. The incidence of these effects decreased to 0.6% in finasteride 1mg-treated men over the following four years. Approximately 1% of men in each treatment group discontinued due to drug-related sexual adverse experiences in the first 12 months, and the incidence declined thereafter.
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.
4.9 Overdose
In clinical studies, single doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for three months (n=71) did not result in dose-related undesirable effects.
No specific treatment of overdosage with Finasteride is recommended.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Finasteride is a competitive and specific inhibitor of type II 5a-reductase. Finasteride has no affinity for the androgen receptor and has no androgenic, anti-androgenic, oestrogenic, anti-oestrogenic, or progestational effects. Inhibition of this enzyme blocks the peripheral conversion of testosterone to the androgen DHT, resulting in significant decreases in serum and tissue DHT concentrations. Finasteride produces a rapid reduction in serum DHT concentration, reaching significant suppression within 24 hours of dosing.
Hair follicles contain type II 5a-reductase. In men with male pattern hair loss, the balding scalp contains miniaturised hair follicles and increased amounts of DHT. Administration of finasteride decreases scalp and serum DHT concentrations in these men. Men with a genetic deficiency of type II 5a-reductase do not suffer from male pattern hair loss. Finasteride inhibits a process responsible for miniaturisation of the scalp hair follicles, which can lead to reversal of the balding process.
Studies in men
Clinical studies were conducted in 1879 men aged 18 to 41 with mild to moderate, but not complete, vertex hair loss and/or frontal/mid-area hair loss. In the two studies in men with vertex hair loss (n=1553), 290 men completed 5 years of treatment with Finasteride vs. 16 patients on placebo. In these two studies, efficacy was assessed by the following methods: (i) hair count in a representative 5.1cm2 area of scalp, (ii) patient self assessment questionnaire, (iii) investigator assessment using a seven point scale, and (iv) photographic assessment of standardised paired photographs by a blinded expert panel of dermatologists using a seven point scale.
In these 5- year studies men treated with Finasteride improved compared to both baseline and placebo beginning as early as 3 months, as determined by both the patient and investigator assessments of efficacy. With regard to hair count, the primary endpoint in these studies, increases compared to baseline were demonstrated starting at 6 months (the earliest time point assessed) through to the end of the study. In men treated with Finasteride these increases were greatest at 2 years and gradually declined thereafter to the end of 5 years; whereas hair loss in the placebo group progressively worsened compared to baseline over the entire 5 year period. In Finasteride treated patients, a mean increase from baseline of 88 hairs [p <0.01; 95% CI (77.9, 97.80; n=433] in the representative 5.1 cm area was observed at 2 years and an increase from baseline of 38 hairs [p <0.01; 95% CI (20.8, 55.6); n=219]was observed at 5 years, compared with a decrease from baseline of 50 hairs [p <0.01; 95% CI (80.5, -20.6);n=47] at 2 years and a decrease from baseline of 239 hairs [p <0.01; 95% CI (-304.4, -173.4); n=15] at 5 years in patients who received placebo. Standardised photographic assessment of efficacy demonstrated that 48% of men treated with finasteride for 5 years were rated as improved, and an additional 42% were rated as unchanged. This is in comparison to 25% of men treated with placebo for 5 years who were rated as improved or unchanged. These data demonstrate that treatment with Finasteride for 5 years resulted in a stabilisation of the hair loss that occurred in men treated with placebo.
An additional 48-week, placebo-controlled study designed to assess the effect of Finasteride on the phases of the hair-growth cycle (growing phase [anagen] and resting phase [telogen]) in vertex baldness enrolled 212 men with androgenetic alopecia. At baseline and 48 weeks, total, anagen and telogen hair counts were obtained in a 1-cm2 target area of the scalp. Treatment with Finasteride led to improvements in anagen hair counts, while men in the placebo group lost anagen hair. At 48 weeks, men treated with Finasteride showed net increases in total and anagen hair counts of 17 hairs and 27 hairs, respectively, compared to placebo. This increase in anagen hair count, compared to total hair count, led to a net improvement in the anagen-to-telogen ratio of 47% at 48 weeks for men treated with Finasteride, compared to placebo. These data provide direct evidence that treatment with Finasteride promotes the conversion of hair follicles into the actively growing phase.
Studies in women
Lack of efficacy was demonstrated in post-menopausal women with androgenetic alopecia who were treated with Finasteride in a 12 month, placebo-controlled study (n=137). These women did not show any improvement in hair count, patient self-assessment, investigator assessment, or ratings based on standardised photographs, compared with the placebo group.
5.2 Pharmacokinetic properties
Absorption
Relative to an intravenous reference dose, the oral bioavailability of finasteride is approximately 80%. The bioavailability is not affected by food. Maximum finasteride plasma concentrations are reached approximately two hours after dosing and the absorption is complete after six to eight hours.
Distribution
Protein binding is approximately 93%. The volume of distribution of finasteride is approximately 76 litres.
At steady state following dosing with 1 mg/day, maximum finasteride plasma concentration averaged 9.2 ng/ml and was reached 1 to 2 hours postdose; AUC (0-24 hr) was 53 ng^hr/ml.
Finasteride has been recovered in the cerebrospinal fluid (CSF), but the drug does not appear to concentrate preferentially to the CSF. A small amount of finasteride has also been detected in the seminal fluid of subjects receiving the drug.
Biotransformation
Finasteride is metabolised primarily via the cytochrome P450 3A4 enzyme subfamily. Following an oral dose of 14C-fmasteride in man, two metabolites of the drug were identified that possess only a small fraction of the 5a-reductase inhibitory activity of finasteride.
Elimination
Following 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.
Plasma clearance is approximately 165 ml/min.
The elimination rate of finasteride decreases somewhat with age. Mean terminal halflife is approximately 5-6 hours in men 18-60 years of age and 8 hours in men more than 70 years of age. These findings are of no clinical significance and hence, a reduction in dosage in the elderly is not warranted.
Characteristics in Patients
No adjustment in dosage is necessary in non-dialysed patients with renal impairment.
5.3 Preclinical safety data
In general, the findings in laboratory animal studies with oral finasteride were related to the pharmacological effects of 5a-reductase inhibition.
Intravenous administration of finasteride to pregnant rhesus monkeys at doses as high as 800 ng/day during the entire period of embryonic and foetal development resulted in no abnormalites in male foetuses. This represents at least 750 times the highest estimated exposure of pregnant women to finasteride from semen. In confirmation of the relevance of the Rhesus model for human foetal development, oral administration of finasteride 2 mg/kg/day (100 times the recommended human dose or approximately 12 million times the highest estimated exposure to finasteride from semen) to pregnant monkeys resulted in external genital abnormalities in male foetuses. No other abnormalities were observed in male foetuses and no finasteride-related abnormalities were observed in female foetuses at any dose.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Core
Lactose monohydrate (200 mesh) Starch, pregelatinised Sodium laurilsulfate Sodium starch glycolate (Type A) Povidone (K30)
Cellulose, microcrystalline Magnesium stearate
Coating
Hypromellose 6 cP (E464) Titanium dioxide (E171) Macrogol 6000 Macrogol 400 Iron oxide red (E172)
Iron oxide yellow (E172)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in the original package.
6.5 Nature and contents of container
Transparent PVC/PVdC-aluminium blisters.
Blister packs of 7, 28, 30, 50 (Hospital Packs), 84, 98 and 100 Film-coated Tablets Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
TEVA UK Ltd
Brampton Road, Hampden Park Eastbourne, BN22 9AG England
8 MARKETING AUTHORISATION NUMBER(S)
PL 00289/0825
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10/08/2009
10 DATE OF REVISION OF THE TEXT
29/09/2015