GRISEOFULVIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Binds to microtubular protein tubulin, disrupting mitotic spindle formation and inhibiting fungal cell mitosis. Also interferes with fungal nucleic acid synthesis and cell wall deposition.
| Metabolism | Hepatic metabolism via CYP450 enzymes (primarily CYP3A4); induces CYP3A4 activity. |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine; metabolites excreted in urine (approximately 50%) and feces (approximately 36%) within 24 hours. |
| Half-life | Terminal elimination half-life is 9 to 24 hours; clinically, it allows once or twice daily dosing. |
| Protein binding | Highly protein bound: approximately 97% bound; mainly to albumin. |
| Volume of Distribution | Apparent Vd: approximately 1.5 L/kg; indicates extensive tissue distribution, particularly into skin, hair, and nails. |
| Bioavailability | Oral bioavailability: variable, approximately 25% to 70% (enhanced by high-fat meal). |
| Onset of Action | Time to clinical effect: 48 to 72 hours after oral administration for dermatophytosis; detectable in stratum corneum within 48 hours. |
| Duration of Action | Duration: 2 to 4 weeks after discontinuation; persists in keratin until replaced. |
| Molecular Weight | 352.76 |
500 mg orally once daily or 250 mg orally twice daily; microsize formulation: 500-1000 mg orally once daily; ultramicrosize formulation: 330-375 mg orally once daily. Administer with fatty meal to enhance absorption.
| Dosage form | TABLET |
| Renal impairment | No specific guideline; consider dose reduction in severe renal impairment (CrCl < 30 mL/min) due to risk of toxicity, though not formally established. Use with caution. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution and consider reduced dosing; no specific dose recommendations available. |
| Pediatric use | Children > 2 years: 10-20 mg/kg/day orally (microsize) in single or divided doses; maximum 500 mg/day. For ultramicrosize: 5-10 mg/kg/day; maximum 375 mg/day. |
| Geriatric use | No specific dose adjustment; use with caution due to potential for renal impairment and increased risk of adverse effects. Monitor renal function and consider lower end of dosing range. |
| 1st trimester | Contraindicated due to teratogenic effects in animal studies; associated with fetal abnormalities including conjoined twins. |
| 2nd trimester | Contraindicated; potential fetal harm, including skeletal and central nervous system defects. |
| 3rd trimester | Contraindicated; risk of fetal toxicity and adverse effects on fetal development. |
Clinical note
Warfarin metabolism is decreased increasing INR Can cause photosensitivity and lupus-like syndrome.
| Placental transfer | Crosses placenta in animal studies; human data limited but presumed to cross. |
| Breastfeeding | Excreted into human milk; potential for adverse effects in nursing infant, including hepatotoxicity and bone marrow suppression. Use only if clearly needed with monitoring. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Headache Diarrhea Rash Indigestion Abnormal liver enzyme Itching Taste change Nausea Abdominal pain Flatulence |
| Serious Effects |
PregnancyPorphyriaHepatocellular failureHypersensitivity to griseofulvin
| Precautions | Hepatotoxicity (monitor hepatic function), Photosensitivity reactions, Lupus-like syndrome or exacerbation of systemic lupus erythematosus, Neuropsychiatric effects (confusion, dizziness, blurred vision), Potential for cross-sensitivity with penicillins |
| Food/Dietary | High-fat meals significantly increase absorption; take with whole milk, ice cream, or fatty foods. Avoid alcohol due to disulfiram-like reaction (flushing, headache, nausea). |
Loading safety data…
| Lactation Rating |
| L4 |
| Teratogenic Risk | Contraindicated in pregnant women due to known teratogenicity in animal studies. First trimester: Highest risk of fetal malformations (e.g., conjoined twins, skeletal defects). Second and third trimesters: Potential for fetal harm, but data limited; avoid use. |
| Fetal Monitoring | Monitor liver function tests (LFTs) and complete blood count (CBC) periodically in pregnant or postpartum women. Fetal ultrasound to assess for anomalies if inadvertent exposure occurs during first trimester. |
| Fertility Effects | May impair spermatogenesis in males (reversible upon discontinuation). No significant impact on female fertility reported in animal studies; human data limited. |
| Clinical Pearls | Griseofulvin is fungistatic and requires prolonged therapy; it is ineffective for Candida or superficial yeast infections. It is teratogenic and contraindicated in pregnancy. Monitor for hepatotoxicity and blood dyscrasias. Avoid concurrent use with warfarin (decreases anticoagulant effect) and oral contraceptives (reduces efficacy). Ultraviolet light exposure may cause photosensitivity. |
| Patient Advice | Take with a high-fat meal to increase absorption. · Complete the full course, even if symptoms improve. · Avoid alcohol during treatment (risk of disulfiram-like reaction). · Use effective contraception during and for 1 month after therapy. · Report signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain) or blood abnormalities (fever, sore throat, easy bruising). · Limit sun exposure and use sunscreen; photosensitivity may occur. |