Summary

Terbinafine can significantly interact with selective serotonin reuptake inhibitors (SSRIs) by inhibiting the CYP2D6 enzyme, potentially leading to increased SSRI blood levels and enhanced side effects. This interaction requires careful monitoring and possible dose adjustments to ensure patient safety.

Introduction

Terbinafine is an antifungal medication belonging to the allylamine class, primarily used to treat fungal infections of the skin, hair, and nails, including onychomycosis and dermatophyte infections. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medications commonly prescribed for depression, anxiety disorders, and other psychiatric conditions. SSRIs work by blocking the reuptake of serotonin in the brain, increasing its availability at synaptic sites. Common SSRIs include fluoxetine, sertraline, paroxetine, citalopram, and escitalopram.

Mechanism of Interaction

The interaction between terbinafine and SSRIs occurs through cytochrome P450 enzyme inhibition, specifically CYP2D6. Terbinafine is a potent inhibitor of the CYP2D6 enzyme, which is responsible for metabolizing many SSRIs, particularly paroxetine, fluoxetine, and to a lesser extent, sertraline. When terbinafine inhibits CYP2D6, it reduces the metabolism of these SSRIs, leading to increased plasma concentrations and prolonged half-lives. This enzyme inhibition can persist for several weeks after terbinafine discontinuation due to its long elimination half-life and irreversible binding to the enzyme.

Risks and Symptoms

The primary clinical risks of this interaction include increased SSRI-related side effects such as nausea, headache, dizziness, sexual dysfunction, and sleep disturbances. More serious concerns include an elevated risk of serotonin syndrome, particularly when combined with other serotonergic medications. Patients may experience enhanced CNS effects including sedation, confusion, and impaired cognitive function. The interaction is most clinically significant with paroxetine and fluoxetine, which are heavily dependent on CYP2D6 metabolism. Elderly patients and those with reduced kidney or liver function may be at higher risk for adverse effects.

Management and Precautions

Healthcare providers should carefully assess the necessity of concurrent use and consider alternative antifungal agents when possible. If co-administration is required, close monitoring for SSRI-related side effects is essential, particularly during the first few weeks of treatment. SSRI dose reduction may be necessary, especially for paroxetine and fluoxetine. Patients should be educated about potential symptoms of increased SSRI effects and advised to report any new or worsening side effects immediately. Consider using SSRIs with less CYP2D6 dependence, such as citalopram or escitalopram, when clinically appropriate. Monitor for signs of serotonin syndrome and discontinue both medications if suspected. Regular follow-up appointments should be scheduled to assess treatment response and adverse effects.

Terbinafine interactions with food and lifestyle

Terbinafine should be taken with food to improve absorption and reduce gastrointestinal side effects. Alcohol consumption should be avoided or limited during terbinafine treatment due to the potential for increased risk of liver toxicity, as both terbinafine and alcohol can affect liver function. Patients should also avoid excessive caffeine intake, as terbinafine can reduce caffeine metabolism, potentially leading to increased caffeine effects such as jitteriness, insomnia, and rapid heartbeat.