COMPOSITION
Each tablet contains
Terbinafine 250mg
PHARMACODYNAMICS
Terbinafine
inhibits ergosterol
synthesis by inhibiting squalene epoxidase, an enzyme that is part of
the fungal cell membrane synthesis pathway. Because terbinafine
prevents conversion of squalene to lanosterol, ergosterol cannot be synthesized. This is thought to change
cell membrane permeability, causing fungal cell lysis.
PHARMACOKINETICS
Terbinafine is an ally amine
which has a broad spectrum of antifungal activity. At low concentrations of
0.97 mcg/ml within 2 hours of administration. The absorption half life is 0.8
hrs and the distribution half-life is 4-6 hours. The bioavailability of
terbinafine is moderately affected by food, but not sufficiently to require
dosing adjustments.
Terbinafine binds strongly to
plasma proteins (99%). It rapidly diffuses through the dermis and concentrates
in the lipophyllic stratum corneum. Terbinafine is also secreted in sebum, thus
achieving high concentrations in hair follicles, hair and sebum-rich skin.
There is also evidence that terbinafine is distributed into the nail plate in
the first few weeks after commencing therapy.
INDICATIONS
Fungal infection of the skin,
hair and nails caused by dermatophytes such as trichophyton (e.g. T.rubum,
T.mentagrophytes, T.verrucosum, T.tonsurans, T.violaceum), microsporum canis
and Epidermophyton floccosum.
Oral Terbinafine is indicated
in the treatment of ringworm (tinea corporis, tinea pedis, tinea cruris and tinea
capitis) and the yeast infection of the skin caused by genus candida (candida
albicans) where oral therapy is considered appropriate owing to the site,
severity or extent of the infection, Onychomycosis (fungal infection of nail) caused by
dermatophyte fungi.
DOSAGE AND ADMINISTRATION
The duration of the treatment
varies according to the indication and the severity of the infection.
Children
No data are available in
children under two years of age (usually < 12kg.)
Children weighing
<20kg/62.5mg once daily.
Children weighing 20-40kg/125
mg once daily.
Children weighing
>40kg/250mg once daily.
Adults
250 mg once daily.
Skin infections
Likely duration of treatment:
Tinea pedis (interdigital,
plantar/moccasin type) 2 to 6 weeks.
Tinea corporis, cruris: 2 to 4
weeks.
Cutaneous candidiasis: 2 to 4
weeks.
Complete resolution of signs
and symptoms infection may not occur until several weeks after mycological
cure.
Hair and scalp infections
Likely duration of treatment.
Tinea capitis: 4 weeks.
Tinea capitis occurs primarily
in children.
Onychomychosis
for most patients the duration
for successful treatment is between 6 weeks and 3 months.
Less than 3 months can be
anticipated for the treatment of fingernail infections or moderate infections
of toenails.
In the remaining case 3 months
of therapy is usually sufficient, although some patients, particularly those
with nail infection of the big toes, may require treatment for 6 months or
longer. Poor nails outgrowth, as observed during the first weeks of therapy may
enable identification of those patients in whom treatment longer than 3 months
indicated.
In fungal nail infections the
optimal clinical effect is seen some months after mycological cure and
cessation of treatment. This is related to the period required for outgrowth of
healthy nail tissue.
CONTRAINDICATIONS
Hypersensitivity to
terbinafine.
PRECAUTIONS
Patients with pre-existing,
stable chronic liver dysfunction or impaired renal function (creatinine
clearance less than 50 ml/min or serum creatinine of more than 300 μmol/L
should be received half of the normal dose.
PREGNANCY AND LACTATION
Foetal toxicity and fertility
studies in animals suggest no adverse effects. Since clinical experience in
pregnant women is very limited, terbinafine should not be used during pregnancy
unless potential benefits outweigh any potential risks. Terbinafine is excreted
in the breast milk; therefore mothers receiving oral treatment with terbinafine
should not breast-feed. If treatment si topical, the small amounts absorbed
through the skin are unlikely to affect the infant.
DRUG
INTERACTIONS
According to results studies
undertaken in vitro and in healthy volunteers, terbinafine shows negligible
potentials for inhibiting or inducing the clearance of drugs that are
metabolized via the cytochrome P450 system (e.g. cyclosporine, tolbutamide, or
oral contraceptives). Nevertheless cautious use of terbinafine is advised in
women on oral contraceptives since a few cases of menstrual disorders have been
reported in patients taking this drug combination. On other hand the plasma
clearance of terbinafine may be accelerated by drugs which induced metabolism
(such as rifampicin) and may be inhibited by drugs which inhibit cytochrome
P450 (such as cimetidine). When co-administration of such agents is necessary,
the dosge of terbinafine may need to adjusted accordingly.
SIDE EFFECTS
In general terbinafine is well
tolerated. Side effects are mild to moderate and transient. The most common are
gastrointestinal symptoms (feeling of fullness, loss of appetite, nausea, mild
abdominal pain, diarrhea) or non serious form of skin reactions (rash,
urticaria).
Isolated cases of serious skin
reaction (e.g. Stevens Johnson Syndrome, toxic epidermal necrolysis) have been
reported. If progressive skin rash occurs, terbinafine treatment should be
discontinued.
Rarely, terbinafine may cause
taste disturbances, including taste loss, which recover within several weeks
after discontinuation of drug.
Isolated cases of significant
hepatobiliary dysfunction have been reported.
Although a casual relationship
to the drug has not been established treatment with terbinafine should be
discontinued if hepatobiliary dysfunction develops. Isolated cases of
neutropenia have been reported.
