INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
MICROCIDAL®-125 TABLETS
MICROCIDAL®-500 TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

MICROCIDAL^®-125 TABLETS
MICROCIDAL^®-500 TABLETS

COMPOSITION:
Each tablet contains 125 mg or 500 mg of griseofulvin.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.7 Antifungal antibiotics.

PHARMACOLOGICAL ACTION:
Griseofulvin is fungistatic in vitro for various species of the dermatophytes Microsporum, Epidermophyton and Trichophyton. The drug has no effect on bacteria or on other fungi.
A prominent morphologic manifestation of the action of griseofulvin is the production of multinucleate cells as the drug inhibits fungal mitosis. Griseofulvin causes disruption of the mitotic spindle by interacting with polymerized microtubules. Although the effects of the drug are thus similar to those of colchicine and the vinca alkaloids, its binding sites on the microtubular protein are distinct. There is evidence that griseofulvin binds to a microtubule-associated protein in addition to its binding to tubulin.
Although failure of ringworm lesions to improve is not rare, isolates from these patients usually are still susceptible to griseofulvin in vitro.
The oral administration of a 0,5 g to 1 g dose of griseofulvin produces peak plasma concentrations of approximately 1 microgram/mL in about 4 hours. Blood levels are quite variable.
Griseofulvin has a half-life in plasma of about 1 day, and approximately 50% of the oral dose can be detected in the urine within 5 days, mostly in the form of metabolites. The primary metabolite is 6-methylgriseofulvin. Barbiturates decrease the absorption of griseofulvin from the gastrointestinal tract.
The drug is deposited in keratin precursor cells. The antibiotic present in such cells when they differentiate is tightly bound to, and persists in, keratin and makes this substance resistant to fungal invasion. For this reason, the new growth of hair or nails is the first to become free of disease. As the fungus-containing keratin is shed, it is replaced by normal tissue. Griseofulvin is detectable in the stratum corneum of the skin within 4 to 8 hours of oral administration. Sweat and transepidermal fluid loss play an important role in the transfer of the drug in the stratum corneum. Only a very small fraction of a dose of the drug is present in body fluids and tissues.

INDICATIONS:
Mycotic diseases of the skin, hair and nails due to Microsporum, Trichophyton, or Epidermophyton respond to griseofulvin therapy.
It must be stressed that, since other fungal diseases are not affected by the medicine, careful mycological study with identification of the responsible organism is the only basis on which therapy can be selected accurately.
Also infections of the hair (tinea capitis) caused by M. canis, M audouini, T. schoenleini, and T. verrucosum; “ringworm”of the glabrous skin; tinea cruris and tinea corporis caused by M. canis, T. rubrum, T. verrucosum and E. floccosum; and tinea of the hands (T. rubrum, T. mentagrophytes) and beard (Trichophyton species) are readily treatable with griseofulvin.
Griseofulvin also is highly effective in “athlete’s foot”or epidermophytosis involving the skin and nails, the vesicular form of which is most commonly due to T. mentagrophytes and the hyperkeratotic type to T. rubrum. Trichophyton rubrum and T. mentagrophytes infections may require higher-than-conventional doses.

CONTRA-INDICATIONS:
Porphyria. It may precipitate an acute attack.
Liver failure.
Pregnancy. Griseofulvin crosses the placenta and it has been shown to be embryo toxic and teratogenic in rats.
Hypersensitivity to griseofulvin.

WARNINGS:
Men receiving griseofulvin should not father children within six months of treatment. The warning is based on data from in vitro studies using mammalian cells which demonstrated aneuploidy. Griseofulvin may impair the ability to drive or operate machinery and has been reported to enhance the effects of alcohol. Use with extreme caution in patients with systemic lupus erythematosus, as griseofulvin may precipitate or aggravate it.

DOSAGE AND DIRECTIONS FOR USE:
Adults:        500 mg to 1g per 24 hours. Doses of 1,5 g to 2,0 g per 24 hours may be used for short periods in severe or extensive infections.
Children:        10 mg/kg per 24 hours.
Take with or after meals, especially fatty meals, in order to minimise possible gastrointestinal irritation and to increase absorption.
Best results are obtained when the daily dose is divided and given at 6-hour intervals. Treatment must be continued until infected tissue is replaced by normal hair, skin or nails, which requires 2-6 months for skin and hair infections, 6 to 9 months for fingernails, and at least a year for toenails.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects are usually mild and transient. They consist of headache, skin rashes, dryness of the mouth, an altered sensation of taste, and gastrointestinal disturbances.
Angioderma, erythema multiform, toxic epidermal necrolysis, proteinuria, leucopenia and other blood dyscrasias, candidiasis, paraesthesia, photosensitisation, and severe headache have been reported occasionally. Depression, confusion, dizziness, insomnia, and fatigue have also been reported.
Reports of hepatotoxicity have been attributed to griseofulvin. Oral thrush, granulocytopenia or leucopenia and peripheral neuritis can also occur less frequently.
Drug Interactions:
Phenobarbitone has been reported to decrease the gastrointestinal absorption of griseofulvin. Griseofulvin may increase the rate of metabolism and diminish the side effects of some drugs such as coumarin anticoagulants and oral contraceptives. Use of an alternate or additional means of contraception if taking oestrogen-containing oral contraceptives concurrently with griseofulvin and for one month after stopping griseofulvin therapy is advisable. Griseofulvin has also been reported to reduce the plasma concentrations of salicylate in patients taking aspirin.
Since griseofulvin is derived from a species of Penicillum, it is theoretically possible that patients intolerant to penicillins or penicillamine may be intolerant of griseofulvin also. However, cross-sensitivity between griseofulvin and penicillins or penicillamine has not been clinically substantiated. In addition penicillin-sensitive patients have received griseofulvin without difficulty.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
The symptoms of overdosage are those stated under side-effects above and in these cases the dosage should be reduced or the medicine discontinued. Treatment is supportive and symptomatic.

IDENTIFICATION:

125 mg:	A white, flat, bevelled edge tablet, bisected on the one side and engraved with the Lennon logo on the other side.
500 mg:	A white, biconvex tablet, engraved with the Lennon logo.

PRESENTATION:

125 mg :	Plastic containers of 100 tablets.
500 mg :	Plastic containers of 30 or 100 tablets.

STORAGE INSTRUCTIONS:
Store in airtight, well-closed containers below 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
125 mg - K/20.1.7/218
500 mg - K/20.1.7/219

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharmacare Limited
7 Fairclough Road
Korsten
PORT ELIZABETH
6020

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
September 1977.
        D236
                        A & S PRINTERS

Updated on this site: November 2002        Source: Community Pharmacy
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