INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
TERBICIL TABLET

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

TERBICIL TABLET

COMPOSITION:
Each tablet contains terbinafine hydrochloride equivalent to 250 mg terbinafine base.

PHARMACOLOGICAL CLASSIFICATION:
A 20.2.2. Antimicrobial (Chemotherapeutic) agents. Fungicides.

PHARMACOLOGICAL ACTION:
Pharmacodynamics:
Terbinafine is an allylamine which has a broad spectrum of antifungal activity. At low concentrations terbinafine is fungicidal against dermatophytes, moulds and certain fungi. The activity 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. When given orally, the medicine concentrates in skin at levels associated with fungicidal activity.
Pharmacokinetics:
A single oral dose of 250 mg terbinafine results in mean peak plasma concentrations of 0,97 mg/mL within 2 hours after administration. The absorption half-life is 0,8 hours and the distribution half-life is 4,6 hours.
Terbinafine binds strongly to plasma proteins. It rapidly diffuses through the dermis and concentrates in the lipophilic stratum corneum.
Terbinafine is also secreted in sebum, thus achieving high concentrations in hair follicles, hair and sebum rich skins. There is also evidence that terbinafine is distributed into the nail plate within the first few weeks of commencing therapy. Biotransformation results in metabolites with no antifungal activity, which are excreted predominantly in the urine. The elimination half-life is 17 hours.
There is no evidence of accumulation.
No age-dependent changes in pharmacokinetics have been observed but the elimination rate may be reduced in patients with renal or hepatic impairment, resulting in higher blood levels of terbinafine.
The bioavailability of terbinafine is unaffected by food.

INDICATIONS:
Fungal infections of the skin caused by Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum canis and Epidermophyton floccosum.
TERBICIL is indicated in the treatment of:

•	ringworm (tinea corporis, tinea cruris and tinea pedis) where oral therapy is considered appropriate due to the site, severity or extent of the infection.
•	onychomycosis.

CONTRA-INDICATIONS:

•	Hypersensitivity to terbinafine hydrochloride or any of the excipients.
•	Impaired liver function.
•	Pregnancy and lactation, as safety has not been demonstrated.

INTERACTIONS:
The plasma clearance of TERBICIL may be accelerated by medicines which induce metabolism (such as rifampicin) and may be inhibited by drugs which inhibit cytochrome P450 (such as cimetidine). Where co-administration of such agents is necessary, the dosage of TERBICIL may need to be adjusted accordingly.
It has been reported that TERBICIL inhibits the CYP2D6-mediated metabolism. This in vitro finding may be of clinical relevance for patients receiving compounds predominantly metabolised by this enzyme, such as tricyclic antidepressants (TCA’s), beta- blockers, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is) Type B. Other studies undertaken in vitro and in healthy volunteers suggest that TERBICIL shows negligible potential to inhibit or induce the clearance of drugs that are metabolised via other cytochrome P450 enzymes (e.g. cyclosporin, tolbutamine, terfenadine, triazolam, oral contraceptives). However, some cases of menstrual disturbance (breakthrough bleeding and irregular cycle) have been reported in patients taking TERBICIL concomitantly with oral contraceptives.

PREGNANCY AND LACTATION:
There is no clinical experience with TERBICIL in pregnant women.
Terbinafine is excreted in breast milk and therefore mothers should not receive treatment with TERBICIL whilst breast-feeding.

DOSAGE AND DIRECTIONS FOR USE:
The duration of treatment varies according to the indication and the severity of the infection.
250 mg once daily.
Skin infections:
Likely durations of treatment are as follows:
Tinea pedis (interdigital, plantar/moccasin type): 2 to 6 weeks
Tinea corporis: 4 weeks
Tinea cruris: 2 to 4 weeks
Onychomycosis: The duration of treatment for most patients is between 6 weeks and 3 months. Treatment periods of less than 3 months can be anticipated in patients with fingernail infection, toenail infection other than of the big toe, or patients of younger age. In the treatment of toenail infections, 3 months is usually sufficient although a few patients may require treatment of 6 months or longer. Poor nail outgrowth during the first weeks of treatment may enable identification of those patients in whom longer therapy is required.
Complete resolution of the signs and symptoms of infection may not occur until several weeks after mycological cure.
Children:
As data is still limited, its use is not recommended.
Elderly:
There is no evidence to suggest that elderly patients require different dosages or experience side-effects different to those of younger patients. The possibility of impairment of liver or kidney function should be considered in this age group.
Impaired renal function:
Patients with impaired renal function (creatinine clearance less than 50 mL/minute or serum creatinine of more than 300 mmol/L) should receive half the normal dose.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Gastro-intestinal disorders:
Frequent: Dyspepsia, fullness, loss of appetite, nausea, mild abdominal pain, diarrhoea.
Less frequent: Taste loss and taste disturbance have been reported in approximately 0,6% of patients treated with TERBICIL.
This usually resolves slowly on medicine discontinuation.
Nervous System disorders:
Frequent: Headache.
Less frequent: Psychiatric disturbances such as depression and anxiety.
Paraesthesia, hypoaesthesia, dizziness, vertigo, malaise and fatigue.
Skin and subcutaneous tissue disorders:
Frequent: Rash, urticaria.
Less frequent: Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity and angioneurotic oedema, psoriasis.
If progressive skin rash occurs, treatment with TERBICIL should be discontinued.
Hepato-biliary disorders:
Less frequent: Jaundice, cholestasis and hepatitis.
If hepatic dysfunction develops, treatment with TERBICIL should be discontinued (SEE ALSO PRECAUTIONS FOR USE)
Haematological disorders:
Less frequent: Neutropenia, thrombocytopenia and agranulocytosis.
Musculo-skeletal disorders:
Less frequent: Arthralgia and myalgia.
These may occur as part of a hypersensitivity reaction in association with allergic skin reactions.

Special Precautions:
Rarely, cases of cholestasis and hepatitis have been reported, these usually occur within two months of starting treatment.

If a patient presents with signs or symptoms suggestive of liver dysfunction such as pruritus, unexplained persistent nausea, anorexia or tiredness, or jaundice, vomiting, fatigue, abdominal pain or dark urine, or pale stools, hepatic origin should be verified and TERBICIL should be discontinued. Single dose pharmacokinetic studies in patients with pre-existing liver disease have shown that the clearance of TERBICIL may be reduced by about 50%. The therapeutic use of TERBICIL in patients with chronic or active liver disease has not been studied in prospective clinical trials, and therefore cannot be recommended.

TERBICIL should be used with caution in patients with psoriasis, as very rare cases of exacerbation of psoriasis have been reported.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
A few cases of overdose (up to 5 g) have been reported, giving rise to headache, nausea, epigastric pain and dizziness. The recommended treatment of overdosage consists in eliminating the drug, primarily by the administration of activated charcoal, and giving symptomatic supportive therapy if needed.

IDENTIFICATION:
White to off-white, round, scored, biconvex tablets with “250”on one side and a breakline on the other side.

PRESENTATION:

1.	Blister packs made up of transparent PVdC coated PVC/Aluminium of pack size 14.
2.	White, opaque high density polyethylene containers sealed with a white, opaque polypropylene lid of pack size 14.

STORAGE CONDITIONS:
Store below 25°C in tightly closed containers.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
TERBICIL: A38/20.2.2/0484

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive , Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
23 August 2005

574984/050311
UNIPRINT - POS

New addition to this site: January 2006
Source: Pharmaceutical Industry
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