Phenobarbital Griseofulvin

Riegelman S, Rowland M, Epstein WL. Griseofulvin-phenobarbital interaction in man JAMA 1970213(3) 426-31. 

Jamali F, Axelson JE. Griseofulvin-phenobarbital interaction a formulation-dependent phenomenon. JP/iarw Sci (1978) 67, 466-70. 

Griseofulvin is usually well tolerated. Headache is common with initiation of therapy. Hepatotoxicity (especially in patients with acute intermittent porphyria), dermatitis, and gastrointestinal distress also occur. Griseofulvin increases warfarin metabolism, and griseofulvin metabolism is increased by phenobarbital. 

These are prepared by rapid solidification of the fused melt of two components that show complete liquid miscibility but negligible solid-solid solubility. Thermodynamically, such a system is an intimately blended physical mixture of its two crystalline components. Thus, the X-ray diffraction pattern of a eutectic constitutes an additive composite of the two components. A phase diagram of a two-component system is shown in Fig. 1. Examples of this type include phenacetin-phenobarbital, chloramphenicol-urea, griseofulvin-sucdnic acid, paracetamol-urea, and the dispersions of giiseofulvin and tolbutamide in polyethylene glycol-(PEG-2000).[ ... 

The concomitant use of phenobarbital reduces griseofulvin concentrations, an effect that has been attributed to induction of Uver enzjmes by phenobarbital (53). 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Doses of griseofulvin are 15-20 mg/kg/d for 6 to 8 weeks in children with the microsized form. More frequent side effects are minor headaches, gastrointestinal reactions and cutaneous eruptions. The major drug interactions have been noted with phenobarbital, anticoagulants and oral contraceptives. 

The antifungal effects of griseofulvin can be reduced or even abolished by phenobarbital. 

Two epileptic children taking phenobarbital 40 mg daily did not respond to long-term treatment for tinea eapitis with griseofulvin 125 mg three times daily until the barbiturate was withdrawn. ... 

Five other patients (3 also taking phenytoin) similarly did not respond to griseofulvin while taking phenolwbital. Two studies, in a total of 14 healthy subjects, found that phenobarbital 30 mg three times daily reduced the serum levels of oral griseofulvin by about one-third, and the absorption was reduced from 58.1% without phenobarbital to 40.6% in the presence of phenobarbital. ... 

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