FULVICIN-U/F
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FULVICIN-U/F (FULVICIN-U/F).
Inhibition of fungal cell mitosis by binding to microtubules, disrupting spindle formation and nuclear division.
| Metabolism | Hepatic oxidation via CYP450 enzymes (primarily CYP3A4), producing inactive metabolites. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine; metabolites excreted in bile and feces. |
| Half-life | Terminal half-life approximately 9.5 hours; may be prolonged in liver disease. |
| Protein binding | Approximately 97% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Apparent volume of distribution is 0.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 35-70% due to variable absorption from the gastrointestinal tract (enhanced with high-fat meals). |
| Onset of Action | Onset of action is slow; clinical improvement in dermatophyte infections typically seen after 2-3 weeks of oral therapy. |
| Duration of Action | Duration of action is prolonged; drug persists in skin, hair, and nails for up to 2 weeks after cessation, aiding in eradication of fungi. |
| Molecular Weight | 352.77 |
125 mg orally once daily with a high-fat meal for 7 days, then 125 mg every other day for 7 days (total 13 doses).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; pharmacokinetics not significantly affected. |
| Liver impairment | Contraindicated in Child-Pugh class C; for class A or B, use with caution and monitor liver function; no specific dose reduction guidelines. |
| Pediatric use | Not recommended for use in children due to lack of safety and efficacy data. |
| Geriatric use | No specific dose adjustment; use with caution due to potential age-related renal and hepatic decline; monitor for adverse effects. |
| 1st trimester | Griseofulvin is teratogenic in animals; avoid use during first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited data; potential for hepatotoxicity and fetal effects; use only if clearly needed. |
| 3rd trimester | Contraindicated near term due to risk of fetal harm; avoid use. |
Clinical note
Comprehensive clinical and safety monograph for FULVICIN-U/F (FULVICIN-U/F).
| Placental transfer | Griseofulvin crosses the placenta; fetal concentrations reach maternal levels. |
| Breastfeeding | Griseofulvin is excreted into breast milk in small amounts; potential for adverse effects in nursing infants (e.g., diarrhea, rash). Avoid breastfeeding during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
PorphyriaHepatic failureHypersensitivity to griseofulvinPregnancy (especially third trimester)
| Precautions | Hepatotoxicity (monitor liver function); photosensitivity (avoid prolonged sun exposure); caution in alcoholics or liver disease; possible exacerbation of porphyria; lupus-like syndrome; hypersensitivity reactions. |
| Food/Dietary | Administration with fatty foods (e.g., whole milk, ice cream, fatty meats) significantly increases absorption. Avoid alcohol due to potential disulfiram-like reaction (flushing, tachycardia). Grapefruit juice may increase drug levels; consider avoiding. |
Loading safety data…
| L3 (Moderately Safe) - but avoid due to potential infant effects. |
| Teratogenic Risk | Pregnancy Category X. Griseofulvin is contraindicated in pregnant women and women who may become pregnant. Animal studies have demonstrated teratogenic and embryotoxic effects (e.g., skeletal abnormalities, cleft palate) in multiple species. There is no adequate human data; therefore, fetal risk cannot be excluded. Use during the first trimester carries the highest risk. Effective contraception should be used during and for 1 month after therapy. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, alkaline phosphatase) periodically due to potential hepatotoxicity. Monitor renal function (BUN, creatinine) if renal impairment suspected. Assess for hypersensitivity reactions (rash, urticaria). In pregnant patients (if inadvertently exposed), perform a fetal ultrasound to assess for structural anomalies. |
| Fertility Effects | Griseofulvin has been shown to cause testicular atrophy and reduced spermatogenesis in animal studies. In humans, impaired fertility has been reported, particularly with long-term use. It may also interfere with oral contraceptive efficacy via enzyme induction (CYP3A4). Patients planning pregnancy should discontinue therapy and use alternative contraception. |
| Clinical Pearls |
| Griseofulvin (Fulvicin-U/F) is a fungistatic agent that binds to microtubules and inhibits fungal mitosis. It is effective only against dermatophytes (Trichophyton, Microsporum, Epidermophyton). It is not effective for Candida or tinea versicolor. It requires deposition in keratin for efficacy; duration of therapy is long (weeks to months depending on nail/hair involvement). Avoid in patients with porphyria or severe liver disease. May decrease efficacy of oral contraceptives and warfarin. Ultramicrosize formulations have better absorption; administer with fatty meals to enhance absorption. |
| Patient Advice | Take this medication with a meal high in fat (e.g., whole milk, peanut butter) to improve absorption. · Complete the full course of therapy even if symptoms improve; treatment may last weeks to months. · Avoid excessive sun exposure and use sunscreen, as this drug may increase sensitivity to sunlight. · Do not drink alcohol during treatment due to risk of rapid heart rate and flushing. · Use effective contraception if you are a woman of childbearing age and not on hormonal contraceptives, as it may reduce the effectiveness of birth control pills. · Monitor for signs of liver problems: yellowing of skin or eyes, dark urine, severe stomach pain. · Report any signs of new infection, rash, or persistent sore throat to your healthcare provider. |