Finasteride 1mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Finasteride 1mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1mg of finasteride.
Excipient(s):
Each tablet also contains 44mg of lactose.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet
Light brown, round biconvex film-coated tablet debossed with “FIN” on one side and “1” on reverse.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Early stages of androgenetic alopecia in men, Finasteride 1mg Film-coated Tablets stabilizes the process of androgenetic alopecia in men 18-41 years of age. Efficacy in bitemporal recession and end-stage hair loss has not been established.
4.2 Posology and method of administration
Route of administration: oral use.
Men: 1mg once daily with or without food for 3-6 months before any noticeable difference is evident. There is no evidence that higher doses of finasteride result in increased efficacy.
Efficacy and duration should be continuously assessed by the treating physician. Generally, continued treatment for 3-6 months is required before stabilisation of hair loss can be expected. Continued treatment is advised to
sustain benefit. If treatment is stopped, the beneficial effects begin to reverse after about 6 months, and return to baseline after 9-12months.
No data are available on the concomitant use of Finasteride with topical minoxidil for the treatment of male hair loss.
Dosage in the elderly. No dosage adjustment is required in the elderly (see section 5.2).
Dosage in renal insufficiency. Dosage adjustments are not necessary (see section 5.2)
Dosage in hepatic insufficiency. There are no data available for the use of finasteride in patients with hepatic insufficiency (see section 4.4 and 5.2).
Children: This medicine should not be administered to children (see section 4.3).
Finasteride 1 mg Film-coated Tablets is contraindicated in children (see section 4.3)
4.3 Contraindications
Contra-indicated in women: see 4.6 Pregnancy and lactation and 5.1 Pharmacodynamic properties.
Hypersensitivity to finasteride or to any of the excipients.
4.4 Special warnings and precautions for use
Finasteride should 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. 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.
Breast Cancer has been reported in men taking finasteride 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, gynecomastia or nipple discharge.
The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied.
This product contains lactose, so patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine (see section 2 and 6.1).
4.5 Interaction with other medicinal products and other forms of interaction
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 include propranolol, digoxin, glibenclamide, warfarin, theophylline, and antipyrine and no clinically significant interactions were found.
Other concomitant therapy. Although specific interaction studies were not performed in clinical trials, a product containing finasteride was used concomitantly with ACE inhibitors, acetaminophen, acetylsalicylic acid, alpha-blockers, beta-blockers, calcium channel blockers, cardiac nitrates, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, non-steroidal antiinflammatory drugs, quinolones and benzodiazepines without evidence of clinically significant adverse interactions.
4.6 Pregnancy and lactation
Pregnancy:
Finasteride is contraindicated for use in women due to the risk in pregnancy. Because of the ability of finasteride to inhibit conversion of testosterone to dihydrotestosterone (DHT) finasteride may cause abnormalities of the external genitalia of a male fetus when administered to a pregnant woman (see 6.6 Instructions for use/handling).
Small amounts of finasteride have been recovered from the semen in treated subjects. 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 patient’s sexual partner is or may become pregnant, the patient should either avoid exposure of his partner to semen (e.g. by use of a condom) or discontinue treatment with finasteride.
Exposure to finasteride - risk to male fetus
Women who are or may become pregnant should not handle crushed or broken Finasteride 1 mg tablets because of the possibility of absorption of finasteride and the risk to a male fetus (see above and section 6.6).
Lactation
Finasteride 1mg tablets are not indicated for use in women. It is not known whether it is excreted in human milk.
4.7 Effects on ability to drive and use machines
Finasteride has a negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
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.
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Immune system disorders: |
Not known: Hypersensitivity reactions, including rash, pruritus, urticaria and swelling of the lips and face. |
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Cardiac disorder: |
Not known: Palpitation |
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Psychiatric: |
Uncommon*: Decreased libido. |
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Hepatobiliary disorders: |
Not known: Increased hepatic enzymes. |
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Reproductive system and breast disorders |
Uncommon*: Erectile dysfunction, ejaculation disorder (including decreased volume of ejaculate). |
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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.
Drug-related sexual undesirable effects were more common in the finasteride-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-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.
Persistence of erectile dysfunction after discontinuation of treatment with Finasteride has been reported in post-marketing use.
In addition, the following have been reported in postmarketing use: persistence of erectile dysfunction after discontinuation of treatment with finasteride; male breast Cancer (see section 4.4 Special warnings and precautions for use).
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 dermatological preparations
ATC code: D11AX10
Finasteride is a synthetic 4-azasteroid and is chemically similar to testosterone and acts as a competitive and specific inhibitor of steroid 5a-reductase type II, an intracellular enzyme that converts testosterone into the more potent androgen 5a-dihydrotestosterone (DHT). Finasteride has no affinity for the androgen receptor and has no androgenic, anti-androgenic, oestrogenic, antioestrogenic, 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 5 a-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.
Clinical studies in men with mild to moderate, but not complete, vertex hair loss and/or frontal/mid-area hair loss demonstrated that: treatment with finasteride for 5yr reduced androgenetic alopecia compared to both baseline and placebo as early as 3 months, and promoted hair growth at 6 months (the earliest time point assessed); maximal efficacy was observed after treatment for 2 years. Therefore, finasteride stabilised hair loss compared with placebo treatment in men with androgenetic alopecia. An additional placebo-controlled study over a 48-week period found that finasteride promoted the conversion of hair follicles into the actively growing hair phase.
A study conducted in post-menopausal women with androgenetic alopecia showed that finasteride was ineffective compared with placebo over a 12-month period.
5.2 Pharmacokinetic properties
Bioavailability:
The oral bioavailability of finasteride is approximately 80% and is not affected by food. Maximum finasteride plasma concentrations are reached approximately 2 hours after dosing and the absorption is complete after 6 to 8 hours.
Distribution:
Protein binding is approximately 93%. The volume of distribution is approximately 76 liters (44-96 l). 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 x hr/ml.
Finasteride has been recovered in the cerebrospinal fluid (CSF), but the drug does not appear to concentrate preferentially to the CSF. A very small amount of finasteride has also been detected in the seminal fluid of subjects receiving finasteride. Studies in rhesus monkeys showed that this amount is not considered to constitute a risk to the developing male fetus (see 4.6 Pregnancy and lactation, and 5.3 Preclinical safety data).
Biotransformation:
Finasteride is metabolized primarily via but does not affect the cytochrome P450 3A4 system. Following an oral dose of 14C-finasteride in man, two metabolites of finasteride 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, approximately 39% (3246%) of the dose was excreted in the urine in the form of metabolites. Virtually no unchanged drug was excreted in the urine and 57% (51-64%) of total dose was excreted in the feces.
Plasma clearance is approximately 165 ml/min (70-279 ml/min).
The elimination rate of finasteride decreases somewhat with age. Mean terminal plasma half-life is approximately 5-6 hours (3-14 hours) (in men more than 70 years of age 8 hours (6-15 hours)). These findings are of no clinical significance and hence, a reduction in dosage in the elderly is not warranted.
Hepatic insufficiency:
The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied.
Renal insufficiency:
In patients with chronic renal impairment, with creatinine clearances ranging from 9-55 ml/min, area under the curve, maximum plasma concentrations, half-life, and protein binding of unchanged finasteride after a single dose of 14C-finasteride were similar to values obtained in healthy volunteers.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of general toxicity, genotoxicity and carcinogenicity.
Reproduction toxicity studies:
Dose-dependent development of hypospadias was observed in the male offspring of pregnant rats given finasteride at doses ranging from 100 pg/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-5a-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-5a-reductase.
Intravenous administration of finasteride to pregnant rhesus monkeys at doses as high as >800 ng/day during the entire period of embryonic and fetal development resulted in no abnormalities in male fetuses. 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 fetal development, oral administration of finasteride 2mg/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 fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:
Lactose monohydrate Cellulose, Microcrystalline (E460)
Pregelatinised Maize Starch Sodium Starch Glycolate (Type A)
Docusate Sodium Magnesium Stearate (E470b)
Tablet coating:
Red and yellow iron oxides (E172)
Hypromellose (E464)
Titanium dioxide (E171) Macrogol
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
No special requirements.
6.5 Nature and contents of container
Aluminium foil/PVC/PE/PVdC blisters in cartons of 14, 28 or 98 tablets.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
Crushed or broken tablets of Finasteride 1mg Film-coated Tablets should not be handled by women when they are or may potentially be pregnant because of the possibility of absorption of finasteride and subsequent potential risk to a male fetus (see 4.6 Pregnancy and lactation).
Finasteride tablets have a film coating which prevents contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.
7 MARKETING AUTHORISATION HOLDER
Dr. Reddy’s Laboratories (UK) Ltd,
6 Riverview Road,
Beverley,
HU17 OLD, UK
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MARKETING AUTHORISATION NUMBER(S)
PL 08553/0251
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/07/2009
DATE OF REVISION OF THE TEXT
11/07/2010
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