TERBINAFINE AND RELATED AGENTS
- USES: Terbinafine is used for the treatment of onychomycosis of toenails or fingernails secondary to dermatophytes (tinea unguium). PHARMACOLOGY: Terbinafine is an allylamine antifungal. It inhibits biosynthesis of ergosterol via inhibition of squalene epoxidase enzyme resulting in fungal cell death. OVERDOSE: Limited data. Anticipate toxic effects similar to adverse events reported (predominantly dermatologic manifestations and gastrointestinal irritation). Doses up to 5 g (20 times the therapeutic daily dose) have been associated with nausea, vomiting, abdominal pain, rash, headache, dizziness and frequent urination. ADVERSE EVENTS: COMMON: Various dermatologic adverse reactions, including pustular and psoriasis-like eruptions, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome have commonly occurred with oral terbinafine therapy. Hypersensitivity reactions and cutaneous and systemic lupus erythematosus have also been reported. Headache, nausea, vomiting, diarrhea, dyspepsia, liver enzyme abnormalities, pruritus, flatulence and abdominal pain can develop following oral therapy. INFREQUENT: Ocular disturbances, taste impairment and smell disturbance (sometimes prolonged and may be permanent), leukopenia, renal impairment and hepatotoxicity are infrequent occurrences following therapy. RARE: Hematologic effects including, neutropenia, agranulocytosis, and thrombocytopenia have occurred rarely following chronic oral terbinafine therapy. Cases of liver failure leading to liver transplant or death have occurred with oral therapy. In most cases, individuals had underlying hepatic events and systemic conditions. Hypersensitivity reactions and cutaneous lupus erythematosus have been reported following terbinafine therapy.
Range of Toxicity:
TERBINAFINE AND RELATED AGENTS
- TOXICITY: Limited data. Doses up to 5 g (20 times the therapeutic daily adult dose) have been associated with mild toxicity (ie, nausea, vomiting, abdominal pain, dizziness, rash, frequent urination and headache). THERAPEUTIC DOSE: TINEA CAPITIS: ORAL GRANULES: ADULT: Weighing greater than 35 kg: 250 mg/day for 6 weeks. PEDIATRIC: For children weighing between 25 and 35 kg: 187.5 mg/day for 6 weeks and weighing less than 25 kg: 125 mg/day for 6 weeks.
TERBINAFINE AND RELATED AGENTS
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe vomiting and/or diarrhea. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Monitor CBC with differential and vital signs for evidence of infection in a symptomatic patient or following chronic exposure. Severe neutropenia has developed in some cases; the effects were reversible upon discontinuation of terbinafine, with or without supportive care. Monitor for bleeding as indicated; blood transfusions and/or platelets may be necessary. In patients with an acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Obtain baseline liver enzymes in patients following a significant or chronic exposure.
- Decontamination: PREHOSPITAL: Toxicity after an acute ingestion is not anticipated; activated charcoal is unlikely to be necessary following a minor ingestion. It is not known if gastric decontamination will be useful in treating acute terbinafine ingestions. HOSPITAL: Toxicity after an acute ingestion is unlikely, and is often only expected with chronic use. Consider activated charcoal only if coingestants with significant toxicity are involved.
- Airway management: Airway support is unlikely to be necessary following a minor or moderate ingestion. Ensure adequate ventilation and perform endotracheal intubation early in patients with a terbinafine overdose (eg, severe allergic reactions, severe bleeding, hemodynamic instability).
- Antidote: None.
- Myelosuppression: Administer colony stimulating factors in patients who develop severe neutropenia or neutropenic sepsis that does not improve with the discontinuation of terbinafine. During postmarketing experience, pancytopenia, thrombocytopenia and anemia have also been reported with oral therapy. Filgrastim: 5 mcg/kg/day IV or subQ. Sargramostim: 250 mcg/m(2)/day IV over 4 hours. Monitor CBC with differential and platelet count daily for evidence of bone marrow suppression until recovery has occurred. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage. Patients with severe neutropenia should be in protective isolation. Transfer to a bone marrow transplant center should be considered.
- Monitoring of patient: Terbinafine serum levels are not clinically useful. Monitor fluids and electrolyte status following significant vomiting and/or diarrhea. Monitor CBC with differential and liver enzymes in symptomatic patients or as indicated. Long-term administration of terbinafine may cause hepatotoxicity and/or hematoxicity (ie, leukopenia, thrombocytopenia, neutropenia).
- Enhanced elimination procedure: Due to the high degree (greater than 99%) of protein binding of terbinafine, it is unlikely that hemodialysis will be effective.
- Patient disposition: HOME CRITERIA: Patients who are asymptomatic or have minimal gastrointestinal symptoms following exposure to terbinafine and are otherwise improving may be managed at home. OBSERVATION CRITERIA: Patients who develop significant symptoms (ie, hypersensitivity, allergic reactions) or evidence of laboratory abnormalities (ie, increased liver enzymes, hematologic effects) need to have ongoing monitoring until they are clearly improving and clinically stable. ADMISSION CRITERIA: Only patients with systemic toxicity (ie, serious skin reactions, hepatotoxicity and hematologic effects) may require admission. CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.