A 55-year-old man taking ketoconazole for a fungal infection requires an oral antihistamine for allergic rhinitis. Which agent can be co-prescribed with the least risk of ventricular arrhythmia?
- A Fexofenadine ✓
- B Astemizole
- C Terfenadine
- D Ebastine
Correct answer: A. Fexofenadine
Explanation
Terfenadine and astemizole depend entirely on CYP3A4 metabolism for clearance. Ketoconazole inhibits CYP3A4, causing parent drug accumulation, hERG potassium channel blockade, QT prolongation and torsades de pointes. Fexofenadine is the active carboxylic acid metabolite of terfenadine, is not significantly CYP3A4 dependent, and does not block cardiac potassium channels even at high levels, making it the safest choice here. Ebastine also requires CYP3A4 activation to carebastine.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.