TERBINOL

Indications

• Onychomycosis
• Tinea pedis (athlete's foot)
• Tinea corporis (ringworm)
• Tinea cruris (jock itch)
• Tinea capitis (scalp fungus)

Dosage

Adults: For onychomycosis, the typical adult dosage is 250 mg orally once daily for

Mechanism of action

Terbinafine inhibits the enzyme squalene monooxygenase, preventing the conversion of squalene to 2,3-oxydosqualene, a crucial step in ergosterol synthesis. This inhibition leads to decreased ergosterol levels, which are normally incorporated into the fungal cell wall, and results in the accumulation of squalene. The accumulation of squalene generates vesicles that weaken the cell wall, ultimately leading to fungal cell death.

Pharmacodynamics

As an antifungal, terbinafine demonstrates a high affinity for squalene epoxidase, effectively preventing ergosterol formation. It has a long duration of action due to its extensive tissue distribution and long terminal elimination half-life. In overdose situations, terbinafine has a wide therapeutic index, with rare instances of overdose occurring even at doses higher than the therapeutic range. Regular liver function tests are advisable for patients on oral terbinafine to monitor potential liver injury.

Pharmacokinetics

Terbinafine is well absorbed after oral administration, with peak plasma concentrations achieved in approximately 2 hours. It is extensively distributed in body tissues, particularly in skin and nail keratin. Terbinafine is metabolized in the liver and has a half-life of about 200-400 hours, allowing for once-daily dosing in many instances. It is primarily excreted in urine, with less than 5% of the drug being eliminated unchanged.

Interactions

• terbinafine+galantamine: Moderate (increases exposure)
• terbinafine+risperidone: Moderate (increases exposure)
• terbinafine+atomoxetine: Moderate (increases exposure)
• terbinafine+eliglustat: Moderate (increases exposure)
• terbinafine+fesoterodine: Moderate (increases exposure)
• rifampicin+terbinafine: Moderate (decreases exposure)
• terbinafine+fluoxetine: Moderate (increases exposure)
• terbinafine+anticholinesterases, centrally acting: Moderate (increases exposure)
• terbinafine+antipsychotics, second generation: Moderate (increases exposure)
• terbinafine+tricyclic antidepressants: Moderate (increases exposure)

Precautions

• Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.

Pregnancy

Terbinafine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Terbinafine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Cream
• Spray

Mechanism of action

Terbinafine inhibits the enzyme squalene monooxygenase (also called squalene epoxidase), preventing the conversion of squalene to 2,3-oxydosqualene, a step in the synthesis of ergosterol. This inhibition leads to decreased ergosterol, which would normally be incorporated into the cell wall, and accumulation of squalene. Generation of a large number of squalene containing vesicles in the cytoplasm may leach other lipids away from, and further weaken, the cell wall.

Pharmacodynamics

Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells. Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long. Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide. Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.