Ultramicrosize Griseofulvin 165 mg Tablet, 30-count — NDC 73308-435-30 (Billing 73308-0435-30)

WARNINGS Prophylactic Usage: Safety and efficacy of griseofulvin for prophylaxis of fungal infections have not been established. Since griseofulvin has demonstrated harmful effects in vitro on the genotype in bacteria, plants, and fungi, males should wait at least 6 months after completing griseofulvin therapy before fathering a child. Females should avoid risk of pregnancy while receiving griseofulvin therapy.

Animal Toxicology : 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 3 weeks of life has also been reported to induce hepatomata in mice. Thyroid tumors, mostly adenomas but some carcinomas, have been reported in male rats receiving griseofulvin at levels of 2.0%, 1.0%, and 0.2% of the diet, and in female rats receiving the two higher dose levels. 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 hepatocellular 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.

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. Usage in Pregnancy: Griseofulvin should not be prescribed to pregnant patients or to women contemplating pregnancy (see CONTRAINDICATIONS ).

Animal Reproduction Studies: It has been reported in the literature that griseofulvin was found to be embryotoxic and teratogenic on oral administration to pregnant rats. Pups with abnormalities have been reported in the litters of a few bitches treated with griseofulvin. Suppression of spermatogenesis has been reported to occur in rats, but investigation in man failed to confirm this.

ADVERSE REACTIONS When adverse reactions occur, they are most commonly of the hypersensitivity type, such as skin rashes and urticaria, and rarely, angioneurotic edema and epidermal necrolysis (Lyell’s syndrome), and may necessitate withdrawal of therapy and appropriate countermeasures. Paresthesias of the hands and feet have been reported rarely after extended therapy. Other side effects reported occasionally are oral thrush, nausea, vomiting, epigastric distress, diarrhea, headache, fatigue, dizziness, insomnia, mental confusion, and impairment of performance of routine activities.

Proteinuria, nephrosis, leukopenia, hepatic toxicity, GI bleeding, and menstrual irregularities have been reported rarely. Administration of the drug should be discontinued if granulocytopenia occurs. When rare, serious reactions occur with griseofulvin, they are usually associated with high dosages, long periods of therapy, or both.

PRECAUTIONS Patients on prolonged therapy with any potent medication should be under close observation. Periodic monitoring of organ system function, including renal, hepatic, and hematopoietic, should be done. Since griseofulvin is derived from species of Penicillium , 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. Lupus erythematosus or lupus-like syndromes, or exacerbation of existing lupus, have been reported in patients receiving griseofulvin. Drug Interactions: Griseofulvin decreases the activity of warfarin-type anticoagulants so that patients receiving these drugs concomitantly may require dosage adjustment of the anticoagulant during and after griseofulvin therapy.

Barbiturates usually depress griseofulvin activity, and concomitant administration may require a dosage adjustment of the antifungal agent. The effects of alcohol may be potentiated by griseofulvin, producing such effects as tachycardia and flush. Griseofulvin may potentiate an increase in hepatic enzymes that metabolize estrogens at an increased rate, including the estrogen component of oral contraceptives, thereby causing possible decreased contraceptive effects and menstrual irregularities.