FULVICIN P/G 330
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FULVICIN P/G 330 (FULVICIN P/G 330).
Fulvicin P/G 330 contains griseofulvin, which inhibits fungal cell mitosis by disrupting the microtubule function, binding to tubulin and preventing assembly of spindle fibers during metaphase.
| Metabolism | Primarily metabolized in the liver via CYP3A4 and other isoforms; undergoes O-demethylation and glucuronidation. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine. Biliary/fecal excretion of metabolites: ~36% in feces, ~13% in urine. |
| Half-life | Terminal half-life approximately 9-22 hours in adults, with a mean of ~13 hours. Clinical context: steady-state achieved in 2-3 days; may guide dosing interval. |
| Protein binding | Approximately 80-85% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent Vd approximately 1-2 L/kg; indicates extensive tissue distribution, particularly to skin, hair, nails, and keratin. |
| Bioavailability | Oral bioavailability approximately 30-40% (microsize); FULVICIN P/G 330 (ultramicrosize) has enhanced absorption with bioavailability ~50-60%. |
| Onset of Action | Oral: detectable serum levels in 2-4 hours; antifungal effect onset variable; significant clinical improvement may take weeks. |
| Duration of Action | Therapeutic levels sustained for 24 hours; clinical duration requires prolonged therapy (weeks to months) due to keratin affinity. |
| Molecular Weight | 352.77 |
330 mg orally once daily with fatty meal to enhance absorption.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; drug is primarily hepatically metabolized. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C); caution in moderate impairment (Child-Pugh class B) with dose reduction to 165 mg once daily. |
| Pediatric use | For children weighing <50 kg: 10-20 mg/kg/day (max 750 mg/day) orally in single or divided doses with fatty meal. |
| Geriatric use | No specific dose adjustment in elderly; monitor for potential increased risk of adverse effects due to age-related hepatic dysfunction. |
| 1st trimester | Griseofulvin is contraindicated in the first trimester due to teratogenic effects observed in animal studies and reports of conjoined twins in humans. |
| 2nd trimester | Avoid use unless benefit outweighs risk; limited human data but potential fetal harm. |
| 3rd trimester | Avoid use near term; griseofulvin may increase risks to the fetus. |
Clinical note
Comprehensive clinical and safety monograph for FULVICIN P/G 330 (FULVICIN P/G 330).
| Placental transfer | Griseofulvin crosses the placenta in humans; fetal levels may reach therapeutic concentrations. |
| Breastfeeding | Griseofulvin is excreted into human milk. The manufacturer recommends discontinuing nursing or the drug due to potential for adverse effects in the infant, including gastrointestinal disturbances and skin rashes. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Pregnancy (especially first trimester)PorphyriaSevere liver diseaseHypersensitivity to griseofulvin
| Precautions | Hepatotoxicity: Monitor liver function tests; discontinue if signs of liver injury occur, Carcinogenicity: Associated with hepatocellular carcinoma in animal studies, Use in pregnancy: Contraindicated (Category C in older classification; avoid due to teratogenicity in animals), Lupus erythematosus: May exacerbate or precipitate systemic lupus erythematosus, Photosensitivity: Caution with exposure to sunlight, Leukopenia and granulocytopenia: Monitor blood counts with prolonged therapy, Cross-allergenicity with penicillins: Possible in patients with penicillin allergy |
| Food/Dietary | High-fat meals significantly increase absorption; take with meals containing at least 20-30g of fat. Avoid alcohol during therapy and for 48 hours after discontinuation due to risk of disulfiram-like reaction. No other significant food interactions. |
Loading safety data…
| Lactation Rating |
| L4 (Probably Hazardous) - limited data suggest significant risk to infant. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Data limited; animal studies show fetal abnormalities (skeletal malformations, cleft palate) at high doses. Second and third trimesters: Potential fetal harm; avoid use unless benefit outweighs risk. Embryotoxic effects reported in multiple species. |
| Fetal Monitoring | Monitor liver function tests (LFTs) before and during therapy. Assess renal function. In pregnant patients, consider serial ultrasounds to monitor fetal growth if exposure occurs. Watch for maternal gastrointestinal adverse effects. |
| Fertility Effects | Animal studies show reduced fertility and impaired spermatogenesis in males. In females, ovarian suppression and anovulation observed. Reversible upon discontinuation. Clinical significance in humans not fully established. |
| Clinical Pearls | Fulvicin P/G 330 is a micronized formulation of griseofulvin, a fungistatic antibiotic used for dermatophyte infections. Administer with a fatty meal to enhance absorption (bioavailability increases up to 4-5 times). Monitor liver function tests and complete blood counts in prolonged therapy. Avoid in porphyria and hepatocellular failure. May potentiate warfarin effect; reduce warfarin dose. Also decreases efficacy of oral contraceptives; advise alternative contraception. Drug interactions include barbiturates (decreased griseofulvin absorption) and alcohol (disulfiram-like reaction). |
| Patient Advice | Take with a fatty meal (e.g., whole milk, ice cream, or fatty fish) to improve absorption. · Complete the full course of treatment even if symptoms improve, typically 2-8 weeks depending on infection site. · Avoid alcohol during treatment and for 48 hours after stopping to prevent disulfiram-like reaction (flushing, nausea, headache). · Inform your doctor if you are taking oral contraceptives; griseofulvin may reduce their effectiveness. · Report any signs of liver toxicity: yellowing of skin/eyes, dark urine, severe fatigue, or abdominal pain. · Do not take if you have a history of porphyria or severe liver disease. · Use sunscreen and protective clothing; griseofulvin may cause photosensitivity. · If you are pregnant or planning to become pregnant, discuss with your healthcare provider; griseofulvin is contraindicated in pregnancy. |