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 film-coated tablet contains 1 mg of finasteride.
Excipient with known effect: Each film-coated tablet contains 87.49mg of lactose monohydrate.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet (tablet)
Red, round, biconvex film-coated tablets, with a 6.5 mm nominal diameter and embossed with ‘BL1’ on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Finasteride 1 mg is indicated for treatment of the first stage of the hair loss (androgenetic alopecia) in males. Finasteride 1 mg stabilizes the process of the androgenetic alopecia in the 18-41 year old males. Its effectiveness in bitemporary recession nor in the loss of hair has not been determined.
4.2 Posology and method of administration
Posology
The recommended dosage is one 1 mg tablet daily. The tablet should be swallowed whole and must not be divided or crushed (See section 6.6). The film-coated tablets can either be taken on an empty stomach or with a meal.
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.
Dosage in renal insufficiency
No dosage adjustment is required in patients with renal insufficiency.
Dosage in hepatic insufficiency
There are no data available in patients with hepatic insufficiency
No data are available on the concomitant use of finasteride and topical minoxidil in male pattern hair loss.
Method of administration
For oral use
4.3 Contraindications
Hypersensitivity to active substance(s) or to any of the excipients listed in section 6.1
Contraindicated in women: see sections 4.6 and 5.1.
This medicine is not indicated for use in women or children and adolescents.
4.4 Special warnings and precautions for use
This medicine must not be used in children. There are no data demonstrating efficacy or safety of finasteride in children under the age of 18.
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.
This decrease in serum PSA concentrations needs to be considered, if during treatment with Finasteride Tablets 1mg, a patient requires a PSA assay. In this case doubling the PSA value should be considered before making a comparison with the results from untreated men.
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.
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 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.
Important information regarding the ingredients of this medicine
This medicine contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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 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 have included propranolol, digoxin, glibenclamide, warfarin, theophylline, and phenazone and no clinically meaningful interactions were found.
Due to lacking data for the concomitant use of finasteride and topical minoxidil in male pattern hair loss the combination is not recommended.
4.6 Fertility, pregnancy and lactation
Pregnancy
This medicine is contra-indicated for use in women when they are or may potentially be pregnant (see section 4.3)
Because of the ability of 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 section 6.6).
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. 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 (e. g. by using condoms).
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.
Lactation
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 this medicine 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.
In these studies, the following drug-related adverse experiences were reported in >1% of men treated with finasteride decreased libido (Finasteride, 1.8% vs. placebo, 1.3%) and erectile dysfunction (1.3%, 0.7%). In addition, decreased volume of ejaculate was reported in 0.8% of men treated with finasteride and 0.4% of men treated with placebo. Resolution of these side effects occurred in men who discontinued therapy with finasteride and in many who continued therapy. The effect of finasteride on ejaculate volume was measured in a separate study and was not different from that seen 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.
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.
|
Immune system disorders: |
Not known: Hypersensitivity reactions, such as rash, pruritus, urticaria and angioedema including swelling of the lips, tongue, throat and face. |
|
Cardiac disorders: |
Not known: Palpitation |
|
Psychiatric disorders: |
Uncommon*: Decreased libido. Uncommon: Depressed mood |
|
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**. **See section 4.4. |
* 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.
Drug-related sexual undesirable effects were more common in the finasteride 1 mg-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 1 mg-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.
In addition, the following have been reported in post-marketing use: persistence of sexual dysfunction (decreased libido, erectile dysfunction and ejaculation disorder) after discontinuation of treatment with finasteride; male breast cancer (see section 4.4).
Reporting of suspected adverse reactions
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www. mhra. gov. uk/yellowcard. By
reporting side effects you can help provide more information on the safety of this medicine.
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
Pharmacotherapeutic group: Other dermatologicals ATC code: D11AX10
Finasteride is a 4-azasteroid, which inhibits human Type 2 5a-reductase (present within the hair follicles) with greater than 100-fold selectivity over human Type 1 5a-reductase, and blocks the peripheral conversion of testosterone to the androgen dihydrotestosterone (DHT). In men with male pattern hair loss, the balding scalp contains miniaturized hair follicles and increased amounts of DHT. Finasteride inhibits a process responsible for miniaturization of the scalp hair follicles, which can lead to reversal of the balding process.
Studies in men:
The efficacy of Finasteride 1 mg was demonstrated in three studies in 1879 men 18 to 41 years of age with mild to moderate, but not complete, vertex hair loss and frontal/mid-area hair loss. In these studies, hair growth was assessed using four separate measures including hair count, ratings of photographs of the head by an expert panel of dermatologists, investigator assessment, and patient self-assessment.
In the two studies in men with vertex hair loss, treatment with Finasteride 1 mg was continued for 5 years, during which time patients improved compared
to both baseline and placebo beginning at 3 to 6 months. While hair improvement measures compared to baseline in men treated with Finasteride 1 mg were generally greatest at 2 years and gradually declined thereafter (e.g., hair count in a representative 5.1 cm2 area was increased 88 hairs from baseline at 2 years and 38 hairs from baseline at 5 years), hair loss in the placebo group progressively worsened compared to baseline (decrease of 50 hairs at 2 years and 239 hairs at 5 years). Thus, although improvement compared to baseline in men treated with Finasteride 1 mg did not increase further after 2 years, the difference between treatment groups continued to increase throughout the 5 years of the studies. Treatment with Finasteride 1 mg for 5 years resulted in stabilization of hair loss in 90% of men based on photographic assessment and in 93% based on investigator assessment. In addition, increased hair growth was observed in 65% of men treated with Finasteride 1 mg based on hair counts, in 48% based on photographic assessment, and in 77% based on investigator assessment. In contrast, in the placebo group, gradual hair loss over time was observed in 100% of men based on hair counts, in 75% based on photographic assessment, and in 38% based on investigator assessment. In addition, patient self-assessment demonstrated significant increases in hair density, decreases in hair loss, and improvement in appearance of hair after treatment over 5 years with Finasteride 1 mg (see Table below).
|
Percent of Patients Improved as Assessed by Each of the 4 Measures | |||||||
|
Year 1t |
Year 2tt |
Year 5tt | |||||
|
Finasteride 1 mg |
placebo |
Finasteride 1 mg |
placebo |
Finasteride 1 mg |
placeb o | ||
|
Hair Count |
(N=679 ) 86 |
(N=672) 42 |
(N=433 ) 83 |
(N=47) 28 |
(N=219) 65 |
(N=15) 0 | |
|
Global Photographic Assessment |
(N=720 ) 48 |
(N=709) 7 |
(N=508 ) 66 |
(N=55) 7 |
(N=2 79) 48 |
(N=16) 6 | |
|
Investigator Assessment |
(N=748 ) 65 |
(N=747) 37 |
(N=535 ) 80 |
(N=60) 47 |
(N=2 71) 77 |
(N=13) 15 | |
|
Patient SelfAssessment: Satisfaction with |
(N=750 ) |
(N=747) 22 |
(N=535 ) |
(N=60) 25 |
(N=284) 63 |
(N=15) 20 | |
39
51
In a 12-month study, in men with frontal/mid-area hair loss, hair counts were obtained in a representative 1 cm area (approximately 1/5 the size of the area sampled in the vertex studies). Hair counts, adjusted to a 5.1 cm area, increased by 49 hairs (5%) compared to baseline and by 59 hairs (6%) compared to placebo. This study also demonstrated significant improvements in patient self-assessment, investigator assessment, and ratings of photographs of the head by an expert panel of dermatologists.
Two studies of 12 and 24 weeks duration showed that a dose 5-fold the recommended dose (finasteride 5 mg daily) produced a median decrease in ejaculate volume of approximately 0.5 mL (-25%) compared with placebo. This decrease was reversible after discontinuation of treatment. In a study of 48 weeks of duration, finasteride 1 mg daily produced a median decrease in ejaculate volume of 0.3 mL (-11%) compared with a 0.2 mL (-8%) decrease for placebo. No effect was observed on sperm count, motility or morphology. Longer-term data are not available. It has not been feasible to undertake clinical studies which directly elucidate possible negative effects on fertility. However, such effects are judged as very unlikely (see also 5.3 Preclinical safety data).
Studies in women
Lack of efficacy was demonstrated in post-menopausal women with androgenetic alopecia who were treated with finasteride 1 mg for tablets 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 standardized 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-finasteride 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 half-life 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
Mutagenicity/carcinogenity
Studies on genotoxicity and carcinogenicity have not revealed any hazards for humans.
Reproduction disturbing effect including fertility
The effects on embryonal and fetal development have been studied in rats, rabbits and rhesus monkeys. In rats treated with 5-5,000 times the clinical dose, a dose-related occurrence of hypospadias has been observed in male fetuses. In rhesus monkeys, treatment with oral doses of 2 mg/kg/day has also resulted in external genital abnormalities. Intravenous doses of up to 800 ng/day in rhesus monkeys have not shown any effects in male fetuses. This represents at least 750 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day (see 5.2 Pharmacokinetic properties). In the rabbit study the foetuses were not exposed to finasteride during the period critical for genital development.
Neither ejaculation volume, sperm count nor fertility were affected in the rabbit after treatment with 80 mg/kg/day, a dose that in other studies is shown to have pronounced weight lowering effect of accessory sexual glands. In rats treated for 6 and 12 weeks with 80 mg/kg/day (approx. 500 times the clinical exposure) no effect on fertility was observed. After 24-30 weeks treatment some reduced fertility and pronounced weight reduction of prostate and seminal vesicle were seen. All changes were reversible within a 6-week period. The reduced fertility has been shown to be due to impaired seminal plug formation, an effect that has no relevance to man. The development of the newborns and their reproduction capacity at the age of sexual maturation were without remark. After insemination of female rats with epididymis sperms from rats treated for 36 weeks with 80 mg/kg/day no effect was seen on a number of fertility parameters.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients Tablet core
Lactose monohydrate Maize starch pregelatinised Docusate sodium Iron oxide yellow (E172) Sodium starch glycollate Microcrystalline cellulose Colloidal anhydrous silica Magnesium stearate Film-coating Opadry Pink consists of:
Hypromellose Hydoxypropyl cellulose Talc
Titanium dioxide (E171) Iron oxide red (E172)
Iron oxide yellow (E172)
6.2 Incompatibilities
None
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
White PVC/PE/PVDC/Al and/or Al/Al blister packs of 7, 28, 30, 84 or 98 tablets .Not all pack sizes may be marketed.
Special precautions for disposal
6.6
Crushed or broken tablets of finasteride should not be handled by women when they are or may potentially be pregnant (see section 4.6).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Bristol Laboratories Limited,
Unit 3, Canalside,
Northbridge Road, Berkhamsted,
Herts, HP4 1EG, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 17907/0497
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/09/2015
10 DATE OF REVISION OF THE TEXT
01/09/2015