The following case demonstrates the terbinafine amitriptyline interaction as well as another interaction you should be aware of!
JS is a 63-year-old female. Past medical history includes hypertension, CHF, ASCVD, recent fungal infection, depression, insomnia, breast cancer, and neuropathy.
- Terbinafine 250 mg QD
- Omeprazole 20 mg QD
- Lisinopril 5 mg QD
- Carvedilol 6.25 mg BID
- Amitriptyline 100 mg HS
- Tamoxifen 20 mg QD
- Aspirin 81 mg QD
The terbinafine has recently been added to this patient’s regimen for a fungal infection. After a week of treatment, this patient is now reporting an increase in fatigue and feels that her cognition is not as sharp as it should be. Her fatigue and change in cognition have affected her work as a financial planner. She wants to stop the terbinafine and start something else due to her perceived adverse effects.
So what is really going on here? It is possible that terbinafine is contributing to these adverse effects, but I don’t suspect that it is a direct effect of the drug. Terbinafine can inhibit CYP2D6. A major metabolic pathway for the breakdown of amitriptyline is through CYP2D6. The terbinafine amitriptyline interaction can lead to increased effects of amitriptyline and thus, the higher potential for adverse effects that she is reporting. Instead of changing terbinafine, a reduction in the dose of amitriptyline might be considered.
What other interaction is important here? Also, recall that tamoxifen is activated by CYP2D6. Another way to put it is that tamoxifen is a prodrug and needs decent activity of CYP2D6 to have its beneficial effects. The terbinafine is potentially leading to a reduced effect from the tamoxifen and could increase the risk of breast cancer (the likely use) recurring in this patient. I’ve discussed tamoxifen drug interactions in the past including this one with a commonly used antidepressant.
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