WARNINGS
Prophylactic Usage: Safety and efficacy of prophylactic use of this drug have not been established.
Chronic feeding of griseofulvin, at levels ranging from 0.5-2.5% of the diet, resulted in the development of liver tumors in several strains of mice, particularly in males. Smaller particle sizes result in an enhanced effect. Lower oral dosage levels have not been tested. Subcutaneous administration of relatively small doses of griseofulvin once a week during the first three weeks of life has also been reported to induce hepatomata in mice. Although studies in other animal species have not yielded evidence of tumorigenicity, these studies were not of adequate design to form a basis for conclusions in this regard.
In subacute toxicity studies, orally administered griseofulvin produced hepatocellar necrosis in mice, but this has not been seen in other species. Disturbances in porphyrin metabolism have been reported in griseofulvin-treated laboratory animals. Griseofulvin has been reported to have a colchicine-like effect on mitosis and cocarcinogenicity with methylcholanthrene in cutaneous tumor induction in laboratory animals.
Reports of animal studies in the Soviet literature state that a griseofulvin preparation was found to be embryotoxic and teratogenic on oral administration to pregnant Wistar rats. Rat reproduction studies done in the United States and Great Britain were inconclusive in this regard. Pups with abnormalities have been reported in the litters of a few bitches treated with griseofulvin. Because the potential for adverse effects on the human fetus cannot be ruled out, additional contraceptive precautions should be taken during treatment with griseofulvin and for a month after termination of treatment. GRIFULVIN V should not be prescribed to women intending to become pregnant within one month following cessation of therapy.
Suppression of spermatogenesis has been reported to occur in rats but investigation in man failed to confirm this. Griseofulvin interferes with chromosomal distribution during cell division, causing aneuploidy in plant and mammalian cells. These effects have been demonstrated in vitro at concentrations that may be achieved in the serum with the recommended therapeutic dosage.
Since griseofulvin has demonstrated harmful effects in vitro on the genotype in bacteria, plants, and fungi, males should wait at least six months after completing griseofulvin therapy before fathering a child.
PRECAUTIONS
Patients on prolonged therapy with any potent medication should be under close observation. Periodic monitoring of organ system function, including renal, hepatic and hemopoietic, should be done.
Since griseofulvin is derived from species of penicillin, the possibility of cross sensitivity with penicillin exists; however, known penicillin-sensitive patients have been treated without difficulty.
Since a photosensitivity reaction is occasionally associated with griseofulvin therapy, patients should be warned to avoid exposure to intense natural or artificial sunlight. Should a photosensitivity reaction occur, lupus erythematosus may be aggravated. Drug Interactions: Patients on warfarin-type anticoagulant therapy may require dosage adjustment of the anticoagulant during and after griseofulvin therapy. Concomitant use of barbiturates usually depresses griseofulvin activity and may necessitate raising the dosage.
The concomitant administration of griseofulvin has been reported to reduce the efficacy of oral contraceptives and to increase the incidence of breakthrough bleeding.
|
