A TB patient who had been taking rifampicin twice weekly at high dose develops fever, chills, myalgia, headache, and malaise beginning 1 to 2 hours after each dose, along with mild hemolysis. What is the mechanism of this syndrome?

• A Direct hepatocellular necrosis from accumulated rifampicin metabolites
• B Type IV delayed hypersensitivity to isoniazid given concurrently
• C Cumulative adrenal suppression causing steroid withdrawal-like symptoms
• D Immune-mediated hypersensitivity with antibodies to rifampicin-drug complexes induced by intermittent high-dose therapy ✓

Explanation

The rifampicin flu syndrome occurs with intermittent high-dose administration (twice weekly), not with daily therapy. Antibodies directed against rifampicin bound to plasma proteins mediate fever, chills, myalgia, and sometimes hemolytic anemia, thrombocytopenia, or acute renal failure. Switching to uninterrupted daily dosing usually abolishes the syndrome, confirming its immunologic basis tied to pulsatile exposure.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.