griseofulvin

Action and Spectrum

Actions and Spectrum: 

griseofulvin is an antifungal drug generally used to treat various fungal infections, especially those affecting the skin, hair, and nails. It belongs to a class of drugs known as antifungals and works by inhibiting the growth of fungi. 

The action of griseofulvin: griseofulvin binds to the microtubules in fungal cells, disrupting their function and preventing their replication. Microtubules form the fungal cell’s cytoskeleton, necessary for various cellular processes, including cell division. By interfering with microtubule formation, griseofulvin inhibits fungal cell division and growth. 

griseofulvin has a selective affinity for fungal cells, as it binds to the fungal microtubules more readily than the microtubules in human cells. This selectivity helps to minimize the adverse effects on human cells while targeting fungal infection. 

The spectrum of Activity: griseofulvin is primarily effective against dermatophytes, a group of fungi that commonly cause skin, hair, and nail infections. Some of the dermatophyte species susceptible to griseofulvin include: 

• Trichophyton species (e.g., Trichophyton rubrum, Trichophyton mentagrophytes) 
• Microsporum species (e.g., Microsporum canis) 
• Epidermophyton floccosum 

griseofulvin is not effective against all types of fungi. It is specifically designed to target dermatophytes and may not be effective against other fungal infections, such as Candida (yeast) infections or systemic fungal infections. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Headache 

Photosensitivity 

Fatigue 

Paresthesia  

Oral thrush 

Nausea 

Epigastric distress 

Gastrointestinal bleeding 

Angioneurotic edema  

Urticaria  

Leukopenia 

Dizziness 

Vomiting 

Hepatotoxicity 

Rash  

Insomnia 

Diarrhea 

Proteinuria 

Nephrosis 

Menstrual irregularities  

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: griseofulvin should not be used in individuals with known hypersensitivity or allergic reactions to griseofulvin or its components. Allergic reactions can range from mild- severe, skin rashes to systemic reactions, including anaphylaxis. 
• Porphyria: griseofulvin is contraindicated in individuals with porphyria, a group of infrequent genetic disorders that affect the production of heme, a component of red blood cells. griseofulvin can exacerbate the symptoms of porphyria and may lead to a life-threatening porphyric crisis. 
• Hepatic dysfunction: griseofulvin is primarily metabolized in the liver, and individuals with severe hepatic impairment or liver disease may have difficulty metabolizing the medication. This can lead to an accumulation of griseofulvin in the body, enhancing the risk of adverse effects. Caution should be exercised when using griseofulvin in patients with mild to moderate hepatic impairment. 
• Pregnancy and breastfeeding: griseofulvin is generally not recommended during pregnancy condition, especially during the first trimester, because of the potential risk of fetal harm. It may also pass into breast milk, adversely affecting the nursing infant.  
• Systemic lupus erythematosus: griseofulvin may exacerbate the symptoms of systemic lupus erythematosus (SLE) or cause drug-induced lupus-like syndrome. Therefore, it should be avoided or used cautiously in individuals with SLE. 
• Pre-existing blood disorders: griseofulvin can affect blood cell production and may cause or worsen pre-existing blood disorders, such as leukopenia, neutropenia, or thrombocytopenia. It should be used with caution in individuals with these conditions. 
• Children under two years old: griseofulvin is not recommended for use in children under the age of 2 years, as safety and efficacy in this age group have not been established. 

Caution 

• Hepatic function: griseofulvin is primarily metabolized in the liver, and individuals with impaired liver function may have difficulty metabolizing the medication. Caution should be exercised when using griseofulvin in patients with mild to moderate hepatic impairment. Liver function tests may be recommended before and during treatment with griseofulvin. 
• Renal function: griseofulvin is primarily excreted in the urine. While no dose adjustment is necessary for patients with renal impairment, caution should be exercised, and close monitoring of renal function may be warranted in patients with severe renal dysfunction. 
• Systemic lupus erythematosus: griseofulvin may exacerbate the symptoms of systemic lupus erythematosus (SLE) or cause drug-induced lupus-like syndrome. It should be used cautiously in individuals with SLE, and any new or worsening symptoms should be promptly reported to a healthcare professional. 
• Photosensitivity: griseofulvin has been associated with photosensitivity reactions, which can increase the risk of sunburn. Minimizing sun exposure, wearing protective clothing, and using sunscreen when taking griseofulvin are advisable to reduce the risk of photosensitivity reactions. 
• Interactions with other medications: griseofulvin can interact with various medications, including oral contraceptives, warfarin, cyclosporine, phenobarbital, and other drugs metabolized by the liver. These interactions can affect either griseofulvin or co-administered medication’s efficacy or safety. To avoid potential interactions, you must inform your healthcare provider about all your medications. 
• Pediatric population: Children commonly use griseofulvin to treat fungal infections. However, dosing and duration of treatment may vary based on the age and weight of the child. Caution should be exercised when using griseofulvin in pediatric patients, and a healthcare professional should carefully determine dosing. 
• Alcohol consumption: There is limited information regarding the interaction of griseofulvin with alcohol. However, alcohol consumption may increase the risk of liver toxicity associated with griseofulvin.

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: D
US FDA pregnancy category: X 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

griseofulvin is an antifungal medication that exhibits fungistatic activity against dermatophyte fungi. Its pharmacological action involves binding to fungal microtubules, disrupting their function, and inhibiting mitosis. This disruption of microtubule function prevents the formation of the fungal cell’s cytoskeleton, impeding fungal growth and replication.

griseofulvin is selectively taken up by fungal cells due to its greater affinity for fungal microtubules than human ones. The medication is primarily metabolized in the liver and excreted in the urine. While its exact mechanism of action is not fully understood, griseofulvin’s ability to inhibit fungal cell division has effectively treated various dermatophyte infections of the skin, hair, and nails. 

Pharmacodynamics: 

Mechanism of action: The action of griseofulvin involves its interaction with fungal microtubules, which are essential for various cellular processes, including mitosis (cell division) in fungi.  

• Disruption of fungal microtubules: griseofulvin enters fungal cells and binds to tubulin, a protein that forms microtubules. This binding alters the conformation and assembly of microtubules in the fungal cells. 
• Inhibition of mitosis: By binding to tubulin, griseofulvin disrupts the formation of functional microtubules, which are required for proper mitotic spindle formation during cell division. This inhibits mitosis in fungal cells, arresting their replication and growth. 
• Impact on fungal cell structures: The disruption of microtubule formation by griseofulvin also affects other cellular processes. It interferes with organizing fungal cell structures, including forming the cell wall and cell membrane. 
• Accumulation in actively growing tissues: griseofulvin has a particular affinity for keratin, a protein found in the skin, hair, and nails. It accumulates in the keratin precursor cells, which are incorporated into the developing keratinized tissues. This accumulation ensures that griseofulvin is present at the site of fungal infection, targeting the growing fungal cells. 

Pharmacokinetics: 

Absorption 

griseofulvin is administered orally and is absorbed from the gastrointestinal tract. However, its absorption is variable and incomplete. The presence of fat or a fatty meal enhances its absorption, so it is recommended to take griseofulvin with food. 

Distribution 

griseofulvin is extensively bound to plasma proteins, primarily albumin. It is distributed throughout the body, including the skin, hair, nails, and other tissues. The drug crosses the blood-brain barrier and is found in cerebrospinal fluid, albeit in lower concentrations than in plasma. 

Metabolism 

griseofulvin undergoes extensive metabolism in the liver. The primary metabolic pathway involves hydroxylation and subsequent conjugation with glucuronic acid. The major metabolite, 6-desmethylgriseofulvin, is also active against certain fungi—various factors, including genetic polymorphisms and drug interactions, influence griseofulvin’s metabolism. 

Elimination and Excretion 

The elimination half-life of griseofulvin is variable and can range from 9 to 24 hours. The drug and its metabolites are mainly excreted in the urine. Only a tiny portion of the dose is excreted unchanged, with the majority eliminated as metabolites. Approximately 30% to 50% of the administered dose is excreted into the urine within 24 to 48 hours, while a smaller portion is eliminated in the feces. 

Adminstartion

Administration: 

Oral administration 

griseofulvin is typically administered orally in the form of tablets or capsules.  

• Dosage: The griseofulvin dosage can vary depending on the specific fungal infection being treated, the patient’s age, weight, and overall health. Following the prescribed dosage instructions the healthcare professional provides or as indicated on the medication label is essential. 
• Timing: griseofulvin is usually taken once a day with a fatty meal or food containing fat. The presence of fat enhances its absorption in the gastrointestinal tract. It is generally recommended to take griseofulvin with meals to optimize its absorption. Taking it consistently at the same time each day can help ensure proper medication levels in the body. 
• Swallowing: The tablets or capsules should be swallowed whole with a glass of water. It is important not to crush, chew, or break the tablets unless specifically instructed by a healthcare professional, as it may affect the drug’s absorption or cause an unpleasant taste. 
• Duration of treatment: Treatment with griseofulvin can vary based on the type and severity of the fungal infection. It is essential to complete the entire course of treatment as prescribed, even if symptoms improve before the treatment period ends. Stopping the medication prematurely may lead to incomplete eradication of the infection and increase the risk of recurrence. 
• Pediatric considerations: The griseofulvin dosage is typically based on the child’s weight in pediatric patients. Pediatric formulations may be available to facilitate accurate dosing. A healthcare professional should determine the dosage and duration of treatment in children. 
• Follow-up: It is essential to follow up with the healthcare professional as scheduled to monitor the response to treatment and assess for any potential side effects or complications. Laboratory tests, such as periodic liver function tests, may be recommended during treatment with griseofulvin. 
• Adherence: It is crucial to adhere to the prescribed treatment regimen and take griseofulvin as directed by the healthcare professional. Skipping doses or not completing the entire course of treatment can compromise the effectiveness of the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: griseofulvin 

Pronounced: [ GRIS-ee-oh-FUL-vin ] 

Why do we use griseofulvin? 

griseofulvin is an antifungal medication with several uses in treating fungal infections. Here are some common uses of griseofulvin: 

• Dermatophyte infections: griseofulvin is primarily used to treat dermatophyte infections, which are fungal infections affecting skin, hair, and nails. It is commonly used for the treatment of: 
• Tinea corporis (ringworm of the body) 
• Tinea cruris (jock itch) 
• Tinea pedis (athlete’s foot) 
• Tinea capitis (scalp ringworm) 
• Tinea barbae (ringworm of the beard) 
• Tinea unguium (onychomycosis/nail fungus) 
• Superficial fungal infections: griseofulvin may also be used for the treatment of other superficial fungal infections that are caused by susceptible organisms, such as: 
• Tinea versicolor (a fungal infection causing discoloration of the skin) 
• Cutaneous candidiasis (skin infection caused by Candida yeast) 
• Pityriasis rosea (a self-limiting skin condition that may have a fungal component) 

It is important to note that griseofulvin is ineffective against all fungal infections. It explicitly targets dermatophytes and is less effective against other fungi, such as Candida species (yeast). The choice of antifungal treatment depends on the specific fungal infection and the judgment of the prescribing healthcare professional. 

griseofulvin is often used as a first-line treatment for dermatophyte infections, especially in cases where topical antifungal medications are ineffective or when the infection is widespread or involves the nails. However, the use of griseofulvin has declined over time due to the availability of newer antifungal agents with broader spectra and improved efficacy.