Griseofulvin

Brand Names

• Gris-PEG (ultramicrosize)

• Grifulvin V (microsize)

• Grisactin (500 or Ultra)

• Fulvicin P/G or Fulvicin U/F

• Grisovin-FP (Common in some markets)

MECHANISM OF ACTION

Griseofulvin acts by inhibiting fungal cell division (mitosis). It binds to fungal microtubules and interferes with the formation of the mitotic spindle by affecting tubulin function, thereby preventing proper chromosome separation. This results in a fungistatic effect, stopping the growth of dermatophytes. The drug also gets deposited in keratin precursor cells of skin, hair, and nails, making newly formed keratin resistant to fungal infection.

PHARMACOKINETICS

 Absorption: Poor and variable oral absorption; significantly improved when taken with fatty or high-fat meals

Distribution: Widely distributed to keratin-rich tissues (skin, hair, nails); binds strongly to keratin precursor cells, providing site-specific antifungal action.

Metabolism: Hepatic metabolism mainly via demethylation and conjugation (liver enzyme induction also occurs).

Elimination: Excreted primarily in urine as metabolites; a small amount is eliminated in feces.

PHARMACODYNAMICS

Griseofulvin shows fungistatic pharmacodynamic action, meaning it inhibits fungal growth rather than directly killing fungi. It works by binding to fungal microtubules and disrupting mitotic spindle formation, thereby blocking cell division in dermatophytes. Its effect is most prominent in actively growing fungal cells. Additionally, the drug accumulates in keratin precursor cells of skin, hair, and nails, and is gradually incorporated into keratin, making newly formed tissues resistant to fungal invasion. This selective action explains its effectiveness against dermatophyte infections of keratinized tissues.

ADMINISTRATION

Griseofulvin is administered orally. It is best absorbed from the gastrointestinal tract when taken with a fatty meal or milk, as fat enhances its absorption. The drug is usually given in divided doses depending on the severity and site of infection. Because it accumulates in keratinized tissues like skin, hair, and nails, treatment is typically long-term, often continuing for several weeks to months until the infected tissue is completely replaced by healthy keratin.

DOSAGE AND STRENGTH

Griseofulvin is given orally in doses that depend on the infection and patient age. In adults, the usual dose ranges from 500 mg to 1000 mg per day in one or two divided doses, while in children it is typically 10–20 mg/kg/day (higher doses may be used for severe infections). It is available in tablet strengths of 125 mg, 250 mg, and 500 mg, as well as oral suspensions. The ultramicrosize form allows better absorption and may require lower doses. Treatment is usually prolonged, lasting weeks to months depending on the site of infection.

DRUG INTERACTIONS 

Griseofulvin has several important drug interactions mainly due to its ability to induce hepatic microsomal (CYP450) enzymes. It can reduce the effectiveness of drugs such as warfarin, oral contraceptives, and cyclosporine by increasing their metabolism. Alcohol intake may cause a disulfiram-like reaction (flushing, headache, nausea), so it should be avoided. Barbiturates may decrease its antifungal effect by increasing its metabolism

FOOD INTERACTIONS 

Griseofulvin has an important food interaction: its absorption is significantly increased when taken with fatty or high-fat meals (such as milk, butter, or oily food). This is because the drug is poorly soluble in water and fat improves its gastrointestinal absorption.

CONTRAINDICATIONS

Griseofulvin is contraindicated in patients with hypersensitivity to the drug or any of its components. It should not be used in pregnancy because it has potential teratogenic effects, and it is also avoided in severe hepatic impairment since it is metabolized in the liver. It is contraindicated in patients with porphyria as it may precipitate acute attacks. Caution is also advised in individuals with a history of systemic lupus erythematosus (SLE) as it may exacerbate symptoms.

Side Effects

• Gastrointestinal: Nausea, vomiting, diarrhea, stomach pain, and heartburn.

• Neurological: Headache (very common), dizziness, and fatigue.

• Skin/Allergic: Rashes, urticaria (hives), and itching.

OVER DOSE 

Griseofulvin overdose is uncommon and usually causes mainly gastrointestinal and central nervous system symptoms. It may present with nausea, vomiting, diarrhea, headache, dizziness, confusion, and occasionally skin reactions or photosensitivity.

TOXICITY 

Griseofulvin toxicity is rare and usually seen with prolonged or high-dose therapy. It mainly affects the central nervous system and liver, leading to symptoms such as headache, dizziness, confusion, and occasionally hepatotoxicity.