Griseofulvin

Antifungal Benzofuran derivative

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO Microsize: 25-50 mg/kg; Ultramicrosize: 5-10 mg/kg q12h or q24h Duration: 4-8 weeks; continue for 2 weeks beyond clinical cure
Notes: Administer with a fatty meal to enhance absorption.
Cat PO Microsize: 25-50 mg/kg; Ultramicrosize: 5-10 mg/kg q12h or q24h Duration: 4-8 weeks; continue for 2 weeks beyond clinical cure
Notes: Administer with a fatty meal. Cats may require higher doses due to variable absorption.
Horse PO 5-10 mg/kg (microsize) q24h Duration: 4-8 weeks
Notes: May be administered as a paste or mixed with feed.
Cattle PO 10-20 mg/kg (microsize) q24h Duration: 4-8 weeks
Notes: Not commonly used in food animals due to withdrawal times and availability of other antifungals.
Small Ruminants (sheep/goats) PO 10-20 mg/kg (microsize) q24h Duration: 4-8 weeks
Notes: Use with caution; extra-label use may be required.
Rabbit PO 25-50 mg/kg (microsize) q24h Duration: 4-6 weeks
Notes: Administer with a fatty meal. Monitor for GI upset.

Clinical Indications & Species Uses

General Indications
  • Dermatophytosis (ringworm) caused by susceptible dermatophytes
Dog (Canine)
  • Dermatophytosis (ringworm) caused by Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes
  • Onychomycosis (fungal nail infections)
Cat (Feline)
  • Dermatophytosis (ringworm) caused by Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes
  • Onychomycosis
Horse (Equine)
  • Dermatophytosis (ringworm) caused by Trichophyton equinum, Microsporum gypseum
Cattle (Bovine)
  • Dermatophytosis (ringworm) caused by Trichophyton verrucosum
Small Ruminants (Sheep / Goat)
  • Dermatophytosis (ringworm) caused by Trichophyton verrucosum
Rabbit & Small Mammals
  • Dermatophytosis (ringworm) caused by Trichophyton mentagrophytes
Exotic & Other Species
  • Dermatophytosis in small mammals (e.g., guinea pigs, chinchillas) and reptiles (rarely)

Pharmacology & Mechanism of Action

Drug Class: Antifungal | Pharmacological Group: Benzofuran derivative

Mechanism of Action: Griseofulvin is a fungistatic antibiotic that inhibits fungal cell mitosis by binding to microtubules and interfering with the formation of the mitotic spindle. It disrupts the microtubule-associated protein (MAP) function, leading to arrest of fungal cell division. It is deposited in keratin precursor cells and binds to keratin, making the newly formed keratin resistant to fungal invasion. It is effective only against dermatophytes (e.g., Microsporum, Trichophyton, Epidermophyton) and has no activity against yeasts or bacteria.

Pharmacodynamics: Griseofulvin is active against dermatophytes that cause infections of skin, hair, and nails. It is fungistatic, meaning it inhibits fungal growth but does not kill the fungus directly. The drug is incorporated into keratin, which is then gradually replaced by resistant keratin as the infected tissue is shed. Clinical improvement is slow and depends on the rate of keratin turnover. It is ineffective against subcutaneous or systemic mycoses.

⚑ Pharmacokinetics Summary

Absorption: Griseofulvin is poorly absorbed from the gastrointestinal tract. Absorption is enhanced when administered with a high-fat meal. In dogs, oral bioavailability is approximately 40-70% depending on the formulation (microsize vs. ultramicrosize). Ultramicrosize formulations have better absorption.
Distribution: Griseofulvin distributes widely throughout the body, with high concentrations in the skin, hair, nails, liver, fat, and skeletal muscle. It crosses the placental barrier and is excreted in milk. It binds to keratin in the stratum corneum, providing a protective effect.
Metabolism: Griseofulvin is metabolized in the liver primarily by demethylation and glucuronidation. The major metabolite is 6-demethylgriseofulvin, which is inactive. Metabolism is inducible by phenobarbital and other hepatic enzyme inducers.
Excretion: Griseofulvin and its metabolites are excreted primarily in the urine (as glucuronides) and feces (as unchanged drug). A small amount is excreted in sweat and saliva. The elimination half-life is approximately 24 hours in dogs and 24-48 hours in cats.
Half-Life: Dogs: ~24 hours; Cats: ~24-48 hours; Horses: ~24 hours; Cattle: ~24 hours
Bioavailability: Oral bioavailability is variable: microsize ~40-70%, ultramicrosize ~70-90% (in humans; similar in animals).
Protein Binding: Griseofulvin is approximately 80% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 125 mg, 250 mg, 500 mg (microsize) (PO)
Oral Tablet 125 mg, 250 mg (ultramicrosize) (PO)
Oral Suspension 125 mg/5 mL (PO)
Oral Powder (for horses) Various (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to griseofulvin
  • Pregnancy (teratogenic in animals; contraindicated in pregnant animals, especially cats and horses)
  • Severe hepatic disease
  • Porphyria (griseofulvin can precipitate acute porphyria)
  • Concurrent use with anticoagulants (e.g., warfarin) may require dose adjustment
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment.
  • May cause teratogenic effects; avoid use in pregnant animals.
  • May cause bone marrow suppression; monitor CBC during prolonged therapy.
  • May cause photosensitivity; avoid excessive sunlight exposure.
  • In cats, griseofulvin can cause feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) positive cats to be more susceptible to bone marrow suppression.
  • Administer with fatty meals to enhance absorption.
  • Not effective against yeasts or systemic mycoses.
  • May interfere with oral contraceptives in humans; not relevant in animals.

Adverse Effects & Reactions

Common:

  • Vomiting
  • Diarrhea
  • Anorexia
  • Lethargy
  • Skin rash or pruritus

Serious / Severe:

  • Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
  • Hepatotoxicity
  • Teratogenic effects
  • Neurotoxicity (ataxia, tremors)

Rare:

  • Proteinuria
  • Photosensitivity
  • Angioedema
  • Stevens-Johnson syndrome

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Warfarin and other oral anticoagulants Griseofulvin may decrease the anticoagulant effect by inducing hepatic enzymes. Moderate
Phenobarbital and other hepatic enzyme inducers May increase metabolism of griseofulvin, reducing its efficacy. Moderate
Cyclosporine Griseofulvin may decrease cyclosporine levels by inducing metabolism. Moderate
Oral contraceptives (in humans) Griseofulvin may reduce effectiveness of oral contraceptives. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Ataxia
  • Tremors
  • Seizures
  • Hepatotoxicity
  • Bone marrow suppression

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids, monitor liver function and CBC. Seizures may be controlled with diazepam. No specific antidote.

Food Animal Withdrawal Times

πŸ₯© Meat: 14 daysπŸ₯› Milk: 3 days

Withdrawal times are not established for griseofulvin in food animals in many countries; consult local regulations. In the US, griseofulvin is not approved for food animals, so extra-label use requires extended withdrawal times (e.g., 30 days for meat, 7 days for milk) as per FARAD recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25Β°C (68-77Β°F)

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: FDA-approved for use in dogs and cats for dermatophytosis.

Extra-Label (Off-Label) Use: In the US, griseofulvin is not approved for use in food animals. Extra-label use in food animals is permitted under AMDUCA with veterinary supervision, but requires extended withdrawal times. In companion animals, it is FDA-approved for use in dogs and cats.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Griseofulvin is a classic antifungal for dermatophytosis, but its use has declined due to the availability of safer and more effective drugs like itraconazole and terbinafine. It is fungistatic and requires prolonged therapy. It is important to combine treatment with environmental decontamination and topical therapy to reduce reinfection. In cats, griseofulvin can cause bone marrow suppression, especially in FIV/FeLV-positive cats; therefore, itraconazole is often preferred. For food animals, griseofulvin is rarely used due to withdrawal times and availability of other antifungals. Always administer with a fatty meal to improve absorption. Monitor for adverse effects, especially hematologic and hepatic toxicity, during prolonged therapy.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)