GRISEOFULVIN

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Warfarin metabolism is decreased increasing INR Can cause photosensitivity and lupus-like syndrome.

Breastfeeding	Excreted in human milk; M/P ratio not established. Potential for adverse effects in nursing infant (e.g., hepatotoxicity, gastrointestinal symptoms). Use caution; alternative agents preferred.
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

Warnings & precautions

■ FDA Black Box Warning

No FDA boxed warning.

Side Effect Profile

Common Effects	Headache Diarrhea Rash Indigestion Abnormal liver enzyme Itching Taste change Nausea Abdominal pain Flatulence
Serious Effects

Absolute Contraindications

["Hypersensitivity to griseofulvin or any component","Porphyria","Hepatocellular disease","Pregnancy (category C)","Concomitant use with barbiturates (decreased absorption)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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