GRISEOFULVIN, ULTRAMICROSIZE
Clinical safety rating: avoid
Warfarin metabolism is decreased increasing INR Can cause photosensitivity and lupus-like syndrome.
Binds to tubulin, disrupting microtubule function and inhibiting fungal cell mitosis; deposited in keratin precursor cells, making keratin resistant to fungal invasion.
| Metabolism | Hepatic metabolism via CYP450 (demethylation and conjugation); metabolites are inactive. |
| Excretion | Renal (<1% unchanged); fecal (36% as metabolites); tissue deposition may persist for weeks. |
| Half-life | 9-24 hours (mean 15 hours); prolonged in liver disease. |
| Protein binding | 84% bound to albumin. |
| Volume of Distribution | 1.5-2 L/kg; indicates extensive tissue distribution, especially skin, hair, nails, and liver. |
| Bioavailability | Ultramicrosize formulation: approximately 95% absorbed (compared to 25-70% for microsize). |
| Onset of Action | 48-72 hours for serum levels to reach therapeutic range; clinical improvement in tinea infections typically seen within 2-4 weeks. |
| Duration of Action | Therapeutic effect persists for weeks after cessation due to deposition in keratin precursor cells. |
| Molecular Weight | 352.77 |
250-375 mg orally once daily or 500-750 mg orally once daily for severe infections.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | Contraindicated in severe hepatic disease. For Child-Pugh A or B, use with caution and monitor liver function; no specific dose adjustment established. |
| Pediatric use | 10-20 mg/kg/day orally as a single dose or divided twice daily; maximum 750 mg/day. |
| Geriatric use | Use with caution due to potential age-related hepatic impairment; no specific dose adjustment recommended, but monitor for adverse effects. |
| 1st trimester | Contraindicated due to teratogenic effects in animal studies and case reports of conjoined twins in humans. |
| 2nd trimester | Contraindicated; avoid use unless no alternative, as fetal risk cannot be excluded. |
| 3rd trimester | Contraindicated; avoid use near term due to potential neonatal adverse effects. |
Clinical note
Warfarin metabolism is decreased increasing INR Can cause photosensitivity and lupus-like syndrome.
| FDA category | Contraindicated |
| Placental transfer | Grifulvin V crosses the placenta; concentrations in fetal blood have been reported. |
| Breastfeeding | Grifulvin V (ultramicrosize) is excreted into breast milk in small amounts. Because of the potential for adverse effects in the nursing infant, especially gastrointestinal disturbances and sensitization, use during breastfeeding is not recommended. However, if used, monitor infant for diarrhea, rash, and milk rejection. |
■ FDA Black Box Warning
No black box warning.
| Common Effects | Application site reactions burning irritation itching and redness Skin peeling Headache Diarrhea Rash Indigestion Abnormal liver enzyme Itching Taste change Nausea Abdominal pain Flatulence |
| Serious Effects |
PregnancyPorphyriaHepatic failureHypersensitivity to griseofulvin
| Precautions | Hepatotoxicity (monitor liver function), Hypersensitivity reactions, Lupus-like syndrome exacerbation, Photosensitivity, Carcinogenic in animal studies (avoid prolonged use), Monitor blood dyscrasias (rare) |
| Food/Dietary | High-fat meals enhance absorption. Grapefruit and grapefruit juice may increase serum levels; avoid concurrent use. Alcohol can cause disulfiram-like reaction (avoid). |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | GRISEOFULVIN, ULTRAMICROSIZE is contraindicated in pregnancy. First trimester: known teratogen with increased risk of fetal malformations including conjoined twins and central nervous system defects. Second and third trimesters: avoid; potential for fetal toxicity based on animal studies. No human data available. |
| Fetal Monitoring | Monitor hepatic function tests (AST, ALT, bilirubin) and complete blood count periodically during therapy. Assess for signs of hypersensitivity reactions. Fetal monitoring via ultrasound if inadvertent exposure during pregnancy. |
| Fertility Effects | Animal studies show reduced spermatogenesis and testicular degeneration in males; reversible after discontinuation. No human studies on fertility effects. May impair fertility in both sexes. |
| Clinical Pearls | Grifulvin V (ultramicrosize) is first-line for tinea capitis, especially Microsporum canis. Note that ultramicrosize griseofulvin is 50% more bioavailable than microsize; 250 mg ultramicrosize = 500 mg microsize. Avoid in porphyria and hepatocellular disease. Duration: ≥6 weeks for tinea capitis; may need up to 4 months for tinea pedis or onychomycosis. Enhanced absorption with fatty meal. Monitor CBC, LFTs, and renal function. Contraindicated in pregnancy (pregnancy category D). |
| Patient Advice | Take with a full glass of water and a fatty meal (e.g., whole milk, ice cream, peanut butter) to improve absorption. · Complete the full course of therapy even if symptoms improve; minimum 6 weeks for scalp infections, may be longer for toenail infections. · Do not take if you have liver disease, porphyria, or are pregnant or planning pregnancy; use effective contraception. · Avoid alcohol during treatment as it may cause a disulfiram-like reaction (flushing, headache, nausea). · Report any signs of liver injury: yellowing skin/eyes, dark urine, abdominal pain, or unusual fatigue. · May increase sensitivity to sunlight; wear sunscreen and protective clothing. · Swallow tablets whole; do not crush or chew. |