GRIS-PEG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GRIS-PEG (GRIS-PEG).
Griseofulvin binds to and disrupts microtubule function by interfering with the polymerization of tubulin, thereby inhibiting fungal cell mitosis and nucleic acid synthesis.
| Metabolism | Primarily metabolized in the liver via demethylation and glucuronidation, involving CYP450 enzymes (particularly CYP1A2). |
| Excretion | Primarily renal (as glucuronide conjugates): ~80%; fecal/biliary: ~10-15%; unchanged drug <1%. |
| Half-life | Terminal elimination half-life 14-24 hours. With continuous therapy, time to steady-state is ~3-5 days. |
| Protein binding | ~80% bound to plasma albumin (primarily) and other proteins. |
| Volume of Distribution | Vd ~1-2 L/kg, indicating extensive tissue distribution; concentrates in skin, hair, nails, and adipose tissue. |
| Bioavailability | Oral (ultramicrosize formulation): bioavailability ~75-90% (enhanced by high-fat meal). |
| Onset of Action | Oral: detectable serum levels within 2-3 hours; clinical antifungal effect begins after ~48-72 hours (requires incorporation into keratin). |
| Duration of Action | Therapeutic levels persist in keratin for weeks after discontinuation; tinea capitis treatment requires 6-8 weeks; tinea corporis 2-6 weeks. |
For tinea capitis and other dermatophyte infections: 500 mg oral daily as a single dose or in divided doses. For more severe infections, up to 1 g daily in divided doses.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines available. Use with caution in patients with severe renal impairment. |
| Liver impairment | Contraindicated in patients with hepatic failure. No specific Child-Pugh based modifications reported; avoid use in significant hepatic impairment. |
| Pediatric use | Children >2 years: 10-20 mg/kg/day orally in divided doses; maximum 500 mg/day for tinea capitis. For tinea pedis, 5-10 mg/kg/day. |
| Geriatric use | No specific adjustments recommended; monitor renal function and potential for adverse effects in elderly due to age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GRIS-PEG (GRIS-PEG).
| Breastfeeding | Griseofulvin is excreted in human milk; M/P ratio not established. Potential for hepatic toxicity in nursing infants. Contraindicated in breastfeeding due to risk of hepatocellular carcinoma in animal studies. |
| Teratogenic Risk | First trimester: Animal studies show teratogenic effects (cleft palate, skeletal abnormalities) at high doses. Second trimester: Risk of hepatic tumors in neonates reported in some animal models. Third trimester: No specific human data; potential for hepatotoxicity. FDA Pregnancy Category C. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to griseofulvin or any component.","Porphyria (may exacerbate).","Severe liver disease.","Pregnancy (Category C) and lactation."]
| Precautions | ["Hepatotoxicity: Monitor liver function tests.","Photosensitivity: Avoid prolonged sun exposure.","Potential for drug interactions with warfarin, oral contraceptives, and cyclosporine."] |
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| Fetal Monitoring |
| Monitor liver function tests (ALT, AST, ALP, bilirubin) monthly. Assess fetal growth and amniotic fluid volume via ultrasound every 4-6 weeks during pregnancy. Monitor for signs of hepatotoxicity in mother. |
| Fertility Effects | Animal studies indicate griseofulvin may impair spermatogenesis and reduce fertility in males. Effects on female fertility not well studied; potential for menstrual irregularities. |