What are the risks associated with oral terbinafine (antifungal medication)?

From the Guidelines

Oral terbinafine is associated with significant risks, including rare but serious adverse reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as hepatic toxicity, particularly in patients with pre-existing liver disease 1. The most common side-effects of oral terbinafine are gastrointestinal, including nausea, diarrhea, or taste disturbance, and dermatological events, such as rash, pruritus, urticaria, or eczema, which occur in 49% and 23% of patients, respectively 1. Key risks to consider when prescribing oral terbinafine include:

• Hepatic toxicity, which can be severe and is more likely to occur in patients with active or chronic liver disease, making it essential to avoid its use in such patients and to monitor liver function tests in those with a history of heavy alcohol consumption, hepatitis, or hematological abnormalities 1
• Serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, which are rare but can be life-threatening 1
• Gastrointestinal side effects, including nausea, diarrhea, and taste disturbances, which are common but usually manageable 1
• Potential drug interactions, particularly with medications metabolized by the cytochrome P450 2D6 isoenzyme, which should be considered when prescribing oral terbinafine 1. It is crucial to carefully weigh the benefits and risks of oral terbinafine and to monitor patients closely for signs of adverse reactions, particularly those with pre-existing medical conditions or taking concomitant medications 1.

From the FDA Drug Label

Liver failure, sometimes leading to liver transplant or death, has occurred with the use of oral terbinafine. Obtain pretreatment serum transaminases. Prior to initiating treatment and periodically during therapy, assess liver function tests. Discontinue terbinafine tablets if liver injury develops. Taste disturbance, including taste loss, has been reported with the use of terbinafine tablets. Taste disturbance can be severe, may be prolonged, or may be permanent. Discontinue terbinafine tablets if taste disturbance occurs. Smell disturbance, including loss of smell, has been reported with the use of terbinafine tablets. Smell disturbance may be prolonged, or may be permanent. Discontinue terbinafine tablets if smell disturbance occurs. Depressive symptoms have been reported with terbinafine use. Prescribers should be alert to the development of depressive symptoms. Severe neutropenia has been reported. If the neutrophil count is less than or equal to 1000 cells/mm3, terbinafine tablets should be discontinued. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported with oral terbinafine use. If signs or symptoms of drug reaction occur, treatment with terbinafine tablets should be discontinued.

The risks associated with oral terbinafine include:

• Liver failure, which can lead to liver transplant or death
• Taste disturbance, including taste loss, which can be severe, prolonged, or permanent
• Smell disturbance, including loss of smell, which can be prolonged or permanent
• Depressive symptoms
• Severe neutropenia
• Serious skin/hypersensitivity reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome 2, 2, 2.

From the Research

Risks Associated with Oral Terbinafine

The use of oral terbinafine, an antifungal medication, is associated with several risks, including:

• Hepatotoxicity, as reported in studies 3, 4, 5, 6
• Hypersensitivity syndrome reaction, which can involve multiple systems and is idiosyncratic in nature, as described in 7
• Cholestatic liver disease, as documented in 5
• Severe acute liver injury, which is a known but unusual complication of terbinafine exposure, as reviewed in 6
• Minor gastrointestinal upset, headache, and skin reactions, as listed in 4

Precautions and Monitoring

To minimize the risk of worsening hepatotoxicity, precautions such as:

• Consultation with a hepatologist
• Limiting terbinafine exposure to less than 6 weeks
• Monitoring of liver function tests
• Patient education on the signs and symptoms of liver injury, as recommended in 3
• Liver function assessment before treatment and periodic monitoring 4-6 weeks after initiation of treatment, as suggested in 6

Important Considerations

It is essential for physicians to be aware of the possible development of a hypersensitivity syndrome reaction in a patient on terbinafine who experiences an adverse event with multisystem involvement, as highlighted in 7. Prompt recognition and determination of the extent of systemic involvement are crucial for the proper management of the patient.