Usage
- Griseofulvin is prescribed for fungal infections of the skin, hair, and nails (dermatomycoses) caused by susceptible dermatophytes such as Trichophyton, Microsporum, and Epidermophyton species. It is particularly effective against infections of the scalp (tinea capitis), body (tinea corporis), groin (tinea cruris), hand (tinea manuum), foot (tinea pedis), and nails (tinea unguium or onychomycosis). Topical therapy is generally preferred for mild, localized infections, while Griseofulvin is reserved for more extensive or resistant cases.
- Pharmacological Classification: Antifungal antibiotic.
- Mechanism of Action: Griseofulvin inhibits fungal growth by disrupting microtubule function, interfering with mitosis, and arresting cell division. It binds to keratin precursor cells, which then become resistant to fungal invasion.
Alternate Names
- Griseofulvin ultramicrosize, Griseofulvin microsize.
- Brand Names: Grifulvin V®, Gris-PEG® and others
How It Works
- Pharmacodynamics: Griseofulvin accumulates in keratin precursor cells, making them resistant to fungal invasion. It binds to fungal microtubules, disrupting mitosis and cell wall formation, ultimately leading to fungal cell death.
- Pharmacokinetics:
- Absorption: Absorption varies depending on particle size; ultramicrosize formulations are absorbed better than microsize. Absorption is enhanced with high-fat meals.
- Metabolism: Primarily metabolized in the liver to 6-desmethylgriseofulvin and its glucuronide conjugate.
- Elimination: Excreted primarily in the urine and feces.
- Mode of Action: Binds to tubulin, inhibiting microtubule polymerization and function, which disrupts fungal mitosis.
- Elimination Pathways: Primarily hepatic metabolism with renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Microsize: 500-1000 mg daily in single or divided doses.
- Ultramicrosize: 375-750 mg daily in single or divided doses.
- Duration of treatment depends on the site and severity of infection (weeks to months).
Children:
- Microsize: 10-20 mg/kg/day (max 1 g/day) once daily.
- Ultramicrosize: 5-10 mg/kg/day (max 750 mg/day) once daily.
Special Cases:
- Elderly Patients: Start with lower doses and monitor for adverse effects; consider age-related hepatic and renal function.
- Patients with Renal Impairment: No dose adjustment typically required.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment; use with caution in mild to moderate impairment with close monitoring of liver function.
- Patients with Comorbid Conditions: Porphyria is a contraindication. Use cautiously in patients with lupus erythematosus.
Clinical Use Cases
Griseofulvin is not typically used in the settings of intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It is indicated for the oral treatment of specific dermatophyte infections when topical therapy is inadequate.
Dosage Adjustments
Adjustments may be necessary based on individual response, infection severity, and location. Close monitoring is essential, especially with hepatic dysfunction.
Side Effects
Common Side Effects
Headache, dizziness, nausea, vomiting, diarrhea, abdominal discomfort, fatigue, insomnia, photosensitivity.
Rare but Serious Side Effects
Hepatotoxicity (jaundice, elevated liver enzymes), leukopenia, granulocytopenia, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, serum sickness-like reactions, peripheral neuropathy.
Long-Term Effects
Chronic use may rarely lead to liver damage or blood disorders.
Adverse Drug Reactions (ADR)
Severe skin reactions, hepatotoxicity, blood dyscrasias require immediate discontinuation and medical attention.
Contraindications
- Porphyria
- Hepatocellular failure
- Hypersensitivity to griseofulvin
- Pregnancy
Drug Interactions
- CYP450 Interactions: Induces CYP3A4, potentially decreasing the effectiveness of drugs metabolized by this enzyme (e.g., warfarin, oral contraceptives, cyclosporine).
- Other Interactions: Barbiturates, alcohol (disulfiram-like reaction). Antacids can reduce absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated) - Teratogenic effects observed. Effective contraception is mandatory during and for one month after treatment. Males should avoid fathering a child for 6 months post-treatment.
- Breastfeeding: Safety not established, use generally avoided.
Drug Profile Summary
- Mechanism of Action: Inhibits fungal mitosis via disruption of microtubule function.
- Side Effects: Headache, nausea, photosensitivity; rarely hepatotoxicity, severe skin reactions.
- Contraindications: Porphyria, liver failure, pregnancy.
- Drug Interactions: Warfarin, oral contraceptives, cyclosporine, barbiturates, alcohol.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; avoid during breastfeeding.
- Dosage: Adults: 375-1000mg/day; children: 5-20mg/kg/day. Dependent upon formulation.
- Monitoring Parameters: Liver function tests (long-term use), complete blood count.
Popular Combinations
- Topical antifungals are often used concomitantly, especially in the initial stages of treatment or for localized infections.
Precautions
- General Precautions: Evaluate liver and renal function, especially with prolonged use. Monitor for hypersensitivity reactions.
- Specific Populations: As detailed in the section above.
- Lifestyle Considerations: Avoid alcohol (Disulfiram-like reaction). Protect from sunlight (photosensitivity).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Griseofulvin?
A: Dosage depends on the formulation (microsize vs. ultramicrosize), patient age, and the infection being treated. See the Dosage section for details.
Q2: How long does it take for Griseofulvin to work?
A: Improvement may take several weeks, with treatment duration depending on the infection type and severity (e.g., weeks for skin infections, months for nail infections).
Q3: What are the most serious side effects of Griseofulvin?
A: Hepatotoxicity, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), and blood disorders are the most serious potential side effects.
Q4: Can Griseofulvin be used during pregnancy or breastfeeding?
A: Griseofulvin is contraindicated during pregnancy due to the risk of birth defects. It is generally avoided during breastfeeding due to limited safety data.
Q5: What should patients avoid while taking Griseofulvin?
A: Alcohol (due to a potential disulfiram-like reaction) and excessive sun exposure (due to photosensitivity) should be avoided.
Q6: Does Griseofulvin interact with other medications?
A: Yes, it can interact with several medications, including warfarin, oral contraceptives, cyclosporine, and barbiturates. Always review a patient’s medication list for potential interactions.
Q7: How should Griseofulvin be taken?
A: Griseofulvin should be taken with a high-fat meal to enhance absorption.
Q8: Are there any specific monitoring requirements for patients taking Griseofulvin?
A: Monitoring of liver function and complete blood counts is recommended, especially during long-term therapy.
Q9: What are the signs of a Griseofulvin overdose?
A: Nausea, vomiting, headache, numbness, tingling, confusion, vertigo.
Q10: What should be done in case of a Griseofulvin overdose?
A: There is no specific antidote. Supportive care, including gastric lavage and activated charcoal may be indicated.
