A patient receiving cetuximab for colorectal cancer reports new-onset generalized muscle cramps. Serum magnesium is 1.1 mg/dL. The most likely mechanism is:

• A Drug-induced pancreatitis with secondary hypomagnesemia
• B Immune complex deposition in the glomerulus causing renal magnesium wasting
• C EGFR blockade in the distal convoluted tubule impairing magnesium reabsorption ✓
• D Chelation of magnesium by the antibody in the circulation

Explanation

EGFR is expressed in the distal convoluted tubule, where it upregulates TRPM6 channels responsible for magnesium reabsorption. Cetuximab blocks this pathway, producing renal magnesium wasting that can be severe and symptomatic with cramps, tetany, and arrhythmias, requiring IV replacement. The rash seen with cetuximab reflects EGFR in skin keratinocytes; hypomagnesemia reflects the same receptor in kidney, an exam-favourite pairing.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.