Terfenadine was withdrawn worldwide after reports of fatal torsades de pointes. Its active carboxylic acid derivative remains in use and does not carry this risk because it:

• A Is hydroxyzine, which lacks any affinity for HERG channels at therapeutic doses
• B Is loratadine, which is fully protein bound and cannot cross into myocardium
• C Is cetirizine, which is renally cleared and therefore cardioprotective
• D Is fexofenadine, which does not block cardiac potassium channels and undergoes negligible hepatic CYP3A4 metabolism ✓

Explanation

Terfenadine blocked delayed rectifier potassium channels encoded by HERG, prolonging QT, especially when CYP3D4 inhibitors like ketoconazole or erythromycin raised parent compound levels. Fexofenadine is its active metabolite, retains H1 selectivity, does not block cardiac potassium channels, and is minimally metabolised by CYP3D4, being largely excreted unchanged in faeces and bile. Loratadine is a separate prodrug, not the terfenadine metabolite, eliminating option B.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.