GRISACTIN ULTRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GRISACTIN ULTRA (GRISACTIN ULTRA).
Griseofulvin binds to tubulin and disrupts microtubule function, inhibiting fungal cell division and nucleic acid synthesis.
| Metabolism | Metabolized in the liver via glucuronidation; induces cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C9, CYP2C19). |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine; approximately 30-50% of a dose is eliminated in feces as metabolites, with minor biliary excretion. |
| Half-life | Terminal elimination half-life ranges from 6.5 to 9 hours (mean ~7.5 hours) in patients with normal hepatic function; prolonged in hepatic impairment. |
| Protein binding | Extensively bound (>99%) mainly to serum albumin; also binds to corticosteroid-binding globulin. |
| Volume of Distribution | Apparent volume of distribution (Vd) is approximately 1.5 to 2 L/kg, indicating extensive tissue distribution and lipid solubility. |
| Bioavailability | Oral bioavailability is variable due to poor aqueous solubility; micronized formulation (GRISACTIN ULTRA) yields improved absorption, with estimates of 25-70% (mean ~50%); absorption enhanced by fatty meal. |
| Onset of Action | Clinical effect (decrease in pruritus) typically seen within 24 hours after oral administration; measurable griseofulvin in plasma within 30 minutes, peak at 4 hours. |
| Duration of Action | Duration of therapeutic effect: approximately 12 to 24 hours after a single oral dose; requires continuous daily dosing for fungistatic effect; treatment duration for tinea infections is 4-6 weeks for skin, up to 12 months for nails. |
| Molecular Weight | 352.77 |
500 mg orally once daily or 250 mg orally twice daily; for severe infections, 500 mg twice daily or 250 mg three times daily. Maximum daily dose: 1 g. Administer with or after meals.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment for GFR ≥50 mL/min. For GFR 10-49 mL/min: decrease dose by 50% (e.g., 250 mg daily). For GFR <10 mL/min: administer 125 mg daily. Hemodialysis: no supplemental dose needed. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% (e.g., 250 mg daily). Child-Pugh C: contraindicated or avoid use. |
| Pediatric use | Children >2 years: 10-15 mg/kg orally once daily or divided twice daily (maximum 750 mg/day). Weight-based: 5-7.5 mg/kg every 12 hours. Administer with meals. |
| Geriatric use | Start at lower end of dosing range (250 mg daily) due to age-related renal decline; monitor renal function and adjust per creatinine clearance. |
| 1st trimester | Contraindicated due to teratogenic effects (craniofacial defects, CNS abnormalities). |
| 2nd trimester | Contraindicated due to risk of fetal harm (hydantoin syndrome). |
| 3rd trimester | Contraindicated due to risk of fetal hydantoin syndrome and neonatal hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for GRISACTIN ULTRA (GRISACTIN ULTRA).
| Placental transfer | Crosses placenta; documented in human studies with measurable fetal serum levels. |
| Breastfeeding | Griseofulvin is excreted into breast milk; avoid breastfeeding due to potential toxicity and carcinogenicity in infants. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to griseofulvinPorphyriaHepatic failurePregnancy
| Precautions | Hepatotoxicity risk; monitor liver function., May exacerbate systemic lupus erythematosus., Can cause photosensitivity reactions., Potential for cross-sensitivity with penicillins; use with caution in penicillin-allergic patients., May interact with warfarin, oral contraceptives, and alcohol. |
| Food/Dietary | Take with high-fat meals to increase absorption. Avoid alcohol due to risk of disulfiram-like reaction. |
| Clinical Pearls |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | Category X. Contraindicated in pregnancy. Associated with fetal abnormalities including conjoined twins, CNS defects, and spontaneous abortion. Risk is highest during first trimester; use during second and third trimesters may cause fetal hepatotoxicity and growth restriction. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, GGT, bilirubin) and CBC with differential at baseline and monthly. Monitor renal function and urinalysis. Fetal ultrasound for anomalies if inadvertent exposure. Assess for signs of hepatotoxicity in mother and infant. |
| Fertility Effects | Griseofulvin impairs spermatogenesis and may cause transient infertility in males. In females, it may disrupt menstrual cycles and decrease fertility. Effects are reversible upon discontinuation. |
| GRISACTIN ULTRA (griseofulvin ultramicrosize) is used for dermatophyte infections. Administer with fatty meals to enhance absorption. Avoid in patients with porphyria or hepatocellular disease. Monitor for potential drug interactions with warfarin (reduced anticoagulant effect) and oral contraceptives (reduced efficacy). |
| Patient Advice | Take with fatty foods like whole milk or peanut butter for best absorption. · Complete full course of therapy even if symptoms improve. · Avoid alcohol as it may cause a disulfiram-like reaction. · May cause photosensitivity; use sunscreen and avoid prolonged sun exposure. · Report signs of liver toxicity: jaundice, dark urine, abdominal pain. |