GRIFULVIN V
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GRIFULVIN V (GRIFULVIN V).
Binds to microtubule-associated proteins and disrupts fungal mitotic spindle formation, thereby inhibiting fungal cell division. It also interferes with fungal nucleic acid synthesis.
| Metabolism | Primarily hepatic metabolism via demethylation and conjugation. Main metabolite is 6-demethylgriseofulvin. CYP450 enzymes involved, but specific isozymes not well characterized. |
| Excretion | Renal (1% unchanged), fecal (33% as metabolites), biliary (minor). Extensive hepatic metabolism; <1% excreted unchanged in urine. |
| Half-life | Terminal half-life: 9–24 hours. Clinical context: Steady-state achieved in 2–5 days; prolonged in hepatic impairment. |
| Protein binding | 97% bound to albumin; minor binding to α1-acid glycoprotein. |
| Volume of Distribution | Vd: 1.5–2.0 L/kg. Clinical meaning: Extensive tissue distribution, high concentration in skin, hair, nails, fat, and liver. |
| Bioavailability | Oral: 40–70% (ultramicrosize formulation, GRIFULVIN V). Enhanced by fatty meal; absorption variable. |
| Onset of Action | Oral: Clinical improvement in tinea infections typically within 48–72 hours; detectable in stratum corneum within 4–8 hours. |
| Duration of Action | Oral: Duration correlates with residence time in keratin; therapeutic levels persist in skin for 2–4 weeks after discontinuation. Treatment durations: tinea capitis 4–6 weeks, tinea pedis 4–8 weeks. |
| Molecular Weight | 352.77 |
500 mg orally once daily (non-microsize formulation) or 250 mg twice daily; typical duration is 4-8 weeks for tinea capitis, 2-6 weeks for tinea corporis, 4-6 weeks for tinea pedis.
| Dosage form | SUSPENSION |
| Renal impairment | No specific guidelines; use with caution in renal impairment. For CrCl <50 mL/min, consider dose reduction or alternative therapy. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose recommendation. |
| Pediatric use | Children ≥2 years: 10-20 mg/kg/day orally in divided doses (max 500 mg) for microsize; for ultramicrosize, 5-10 mg/kg/day (max 250 mg). |
| Geriatric use | No specific dose adjustment; use lowest effective dose due to potential renal decline and increased risk of adverse effects. |
| 1st trimester | Contraindicated due to evidence of embryotoxicity and teratogenicity in animal studies; use only if clearly needed and no safer alternative. |
| 2nd trimester | Safety not established; avoid use unless potential benefit justifies potential risk to fetus. |
| 3rd trimester | Safety not established; avoid use near term due to potential for bleeding in newborn. |
Clinical note
Comprehensive clinical and safety monograph for GRIFULVIN V (GRIFULVIN V).
| Placental transfer | Griseofulvin crosses the placenta in animal studies; human data limited but presumed to cross. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for adverse effects in nursing infant (e.g., diarrhea, rash); manufacturer recommends discontinue nursing or drug due to potential tumorigenicity. |
■ FDA Black Box Warning
Hepatotoxicity: Grifulvin V may cause severe liver injury, including hepatitis and hepatic failure. Use is contraindicated in patients with hepatic disease or a history of liver problems. Monitor liver function tests periodically.
| Serious Effects |
Hypersensitivity to griseofulvin or any componentPorphyriaHepatic failurePregnancy (especially first trimester; category C)
| Precautions | Hepatotoxicity: Monitor liver function tests; discontinue if signs of liver injury occur., Carcinogenicity: Associated with hepatomas and thyroid tumors in animal studies; clinical significance unknown., Photosensitivity: Avoid excessive sunlight or UV exposure due to increased risk of skin reactions., Lupus-like syndrome: May exacerbate systemic lupus erythematosus or induce lupus-like symptoms., Porphyria: Can precipitate acute attacks in patients with porphyria; contraindicated in these patients., Renal impairment: Use with caution; may require dose adjustment., Drug interactions: May decrease efficacy of oral contraceptives; reduce warfarin effect; potentiate alcohol effects. |
| Food/Dietary |
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| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | Grifulvin V (griseofulvin) is contraindicated in pregnancy (FDA Category X). Teratogenic effects include conjoined twins, CNS abnormalities, and skeletal malformations in animal studies. In humans, first trimester exposure is associated with a significant risk of spontaneous abortion and major congenital defects; second and third trimester risks include intrauterine growth restriction and fetal toxicity. |
| Fetal Monitoring | If accidental exposure occurs during pregnancy, perform detailed fetal anatomy ultrasound and monitor fetal growth throughout gestation. In pregnant patients, obtain serial liver function tests (LFTs) and complete blood counts (CBC) due to griseofulvin hepatotoxicity and bone marrow effects. Monitor for signs of fetal distress via nonstress testing in third trimester. |
| Fertility Effects | In males, griseofulvin may cause temporary oligospermia and reduce sperm motility; spermatogenesis typically recovers after discontinuation. In females, no direct impairment of fertility, but in animal studies, high doses caused hormonal disruption. Fertility may be indirectly affected by underlying dermatophyte infection. |
| Ingestion with a high-fat meal (e.g., whole milk, eggs, avocado) significantly increases absorption of griseofulvin. Avoid low-fat meals. May cause disulfiram-like reaction with alcohol (flushing, headache, nausea, vomiting). |
| Clinical Pearls | GRIFULVIN V (griseofulvin, microsize) is a fungistatic agent used for dermatophyte infections. It is effective against Microsporum, Trichophyton, and Epidermophyton species but not against Candida or Pityriasis versicolor. Absorption is enhanced when taken with a high-fat meal. It is hepatically metabolized and induces CYP450 enzymes, potentially reducing efficacy of oral contraceptives, warfarin, and other drugs. Tinea capitis often requires 6-8 weeks of therapy; adjunctive selenium sulfide shampoo reduces spore shedding. Monitor hepatic function monthly. Contraindicated in porphyria, severe liver disease, and pregnancy (Pregnancy Category X). |
| Patient Advice | Take this medication with a meal or a glass of milk to increase absorption; avoid low-fat meals. · Complete the full course of treatment, even if symptoms improve; treatment may last several months for nail infections. · This medication can make you sensitive to sunlight; use sunscreen and avoid prolonged sun exposure. · Do not drink alcohol during treatment due to risk of disulfiram-like reaction (flushing, headache, nausea). · Inform your doctor if you are or plan to become pregnant; this drug can cause fetal harm. · Tell your doctor about all medications you take, especially oral contraceptives, blood thinners, or barbiturates. · Griseofulvin may decrease the effectiveness of oral contraceptives; use a backup method of birth control. · Report any signs of liver problems: yellowing of eyes/skin, dark urine, severe stomach pain, or persistent nausea. |