Terbinafine Hydrochloride 1% Cream
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
TERBINAFINE HYDROCHLORIDE 1 % cream
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
10 mg terbinafine hydrochloride (equivalent to 8.89 mg terbinafine)
Excipients with known effect:
1g of cream contains:
40 mg cetyl alcohol 40 mg cetostearyl alcohol
For full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Cream.
White or almost white cream, with slight almond odour.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Fungal infections of the skin caused by Trichophyton (e.g. T. Rubrum, T.Mentagrophytes, T. Verrucosum, T. Violaceum), Microsporum canis and Epidermophyton floccosum.
Yeast infections of the skin, principally those caused by the genus Candida (eg. C. albicans).
Pityriasis (tinea) versicolor due to Pityrosporum orbiculare (also known as
Malassezia furfur).
4.2 Posology and method of administration
Terbinafine cream can be applied once or twice daily.
Cleanse and dry the affected areas thoroughly before application of Terbinafine cream. Apply the cream to the affected skin and surrounding area in a thin layer and rub in lightly. In the case of intertriginous infections (submammary, interdigital, intergluteal, inguinal) the application may be covered with a gauze strip, especially at night.
Duration and frequency of treatment
The likely durations of treatment are as follows:
Tinea corporis, cruris: 1 to 2 weeks Tinea pedis: 1 week Cutaneous candidiasis: 2 weeks Pityriasis versicolor: 2 weeks
Relief of clinical symptoms usually occurs within a few days. Irregular use or premature discontinuation of treatment carries the risk of recurrence. If there are no signs of improvement after two weeks, the diagnosis should be verified.
Dosing in special populations:
Paediatric population
The experience with topical terbinafine cream in children is still limited and its use cannot therefore be recommended.
Elderly patients
There is no evidence to suggest that elderly patients require different dosages or experience side-effects different to those of younger patients.
Method of administration For cutaneous use.
4.3 Contraindications
Known hypersensitivity to the active substance or any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Terbinafine cream is for external use only. Contact with the eyes should be avoided. May be irritating to the eyes. If it gets into the eyes accidentally, the eyes should be washed with plenty of water and the patient should consult a doctor or ophthalmologist if necessary.
Terbinafine cream contains cetyl alcohol and stearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis).
4.5 Interaction with other medicinal products and other forms of interaction
There are no known drug interactions with Terbinafine cream.
4.6 Fertility, pregnancy and lactation Fertility
Foetal toxicity and fertility studies in animals suggest no adverse effects.
Pregnancy
There is no clinical experience with Terbinafine cream in pregnant women, therefore, unless the potential benefits outweigh any potential risks, Terbinafine cream should not be administered during pregnancy.
Breastfeeding
Terbinafine is excreted in breast milk and therefore mothers should not receive Terbinafine cream whilst breast-feeding. Infants should also not be allowed to come into contact with any treated skin, including the breast.
4.7 Effects on ability to drive and use machines
Terbinafine cream has no influence on the ability to drive and use machines.
4.8 Undesirable effects
Local symptoms such as pruritus, skin exfoliation, application site pain, application site irritation, pigmentation disorder, skin burning sensation, erythema and scab may occur at the site of application.
These minor symptoms must be distinguished from hypersensitivity reactions such as widespread pruritis, rash, bullous eruptions and hives which are reported in sporadic cases but require discontinuation.
In case of accidental contact with the eyes terbinafine hydrochloride may be irritating to the eyes.
In rare cases, the underlying fungal infection may be aggravated.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: 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), or not known (can not to be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Immune system disorders
Not known: Hypersensitivity
Eye disorders
Rare: Eye irritation
Skin and subcutaneous tissue disorders
Common: Skin exfoliation, pruritus
Uncommon: Skin lesion, scab, skin disorder, pigmentation disorder, erythema,
skin burning sensation
Rare: Dry skin, dermatitis contact, eczema
Not known: Rash
General disorders and administration site conditions
Uncommon: Pain,application site pain,irritation
Rare: condition aggravated
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 website www.mhra.gov .uk/yellowcard.
4.9 Overdose
The low systemic absorption of topical terbinafine cream renders overdosage extremely unlikely. Accidental ingestion of the contents of one 30g tube of Terbinafine Cream, which contains 300mg terbinafine hydrochloride, is comparable to one Terbinafine 250mg tablet (adult oral unit dose).
However, should a larger amount of Terbinafine Cream be inadvertently ingested, adverse effects similar to those observed with an overdosage of Terbinafine tablets are to be expected. These include headache, nausea, epigastric pain and dizziness.
If accidentally ingested, the recommended treatment of overdosage consists of eliminating the drug, primarily by the administration of activated charcoal, and giving symptomatic supportive therapy, if needed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antifungal for topical use ATC code: D01A E15
Terbinafine is an antimycotic with a broad-spectrum of anti-fungal activity belonging to the allylamine group. At low concentrations terbinafine is fungicidal against dermatophytes, moulds and certain dimorphic fungi. The activity against yeasts, e.g. Candida species is fungicidal or fungistatic depending on the species.
Terbinafine interferes specifically with fungal sterol biosynthesis at an early step. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane. The enzyme squalene epoxidase is not linked to the cytochrome P450 system.
5.2 Pharmacokinetic properties
Less than 5% of the dose is absorbed after topical application; systemic exposure is therefore very slight.
5.3 Preclinical safety data
In long-term studies (up to 1 year) in rats and dogs no marked toxic effects were seen in either species up to oral doses of about 100 mg/kg a day. At high oral doses, the liver and possibly also the kidneys were identified as potential target organs.
In a two-year oral carcinogenicity study in mice, no neoplastic or other abnormal findings attributable to treatment were made up to doses of 130 (males) and 156 (females) mg/kg a day. In a two-year oral carcinogenicity study in rats at the highest dose level, 69 mg/kg a day, an increased incidence of liver tumours was observed in males. The changes, which may be associated with peroxisome proliferation, have been shown to be species-specific since they were not seen in the carcinogenicity study in mice or in other studies in mice, dogs or monkeys.
During the studies of high dose oral terbinafine in monkeys, refractile irregularities were observed in the retina at the higher doses (non-toxic effect level was 50 mg/kg). These irregularities were associated with the presence of a terbinafine metabolite in ocular tissue and disappeared after drug discontinuation. They were not associated with histological changes.
A standard battery of in vitro and in vivo genotoxicity tests revealed no evidence of a mutagenic or clastogenic potential for the drug.
No adverse effects on fertility or other reproduction parameters were observed in studies in rats or rabbits.
6
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium hydroxide Benzyl alcohol Sorbitan stearate Cetyl palmitate Cetyl alcohol Cetostearyl alcohol Polysorbate 60 Isopropyl myristate Water purified.
6.2 Incompatibilities
None known.
6.3 Shelf life
4 years
6.4 Special precautions for storage
Store in original package.
6.5 Nature and contents of container
Aluminium tube closed by polyethylene cap. The tubes are containing 7.5 g, 15 g or 30 g cream.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Niche Generics Limited
1 The Cam Centre Wilbury Way, Hitchin Hertfordshire SG4 OTW United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 19611/0085
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30/03/2007
10 DATE OF REVISION OF THE TEXT
06/08/2014