Primaquine-Induced Methemoglobinemia: A Case Report

Methemoglobinemia is a life-threatening side effect of several drugs, including primaquine. When endogenous counter-oxidative stress mechanisms are overwhelmed, hemoglobin is oxidized to methemoglobin. This "oxygen scavenger" leads to tissue hypoxia, despite adequate alveolar gas exchange. A 47-year-old male under immunosuppression after a reno-pancreatic transplant was admitted to the ICU for respiratory failure following suspected Pneumocystis jirovecii pneumonia (PJP), and empiric treatment was started. After ICU admission, treatment with cotrimoxazole was switched to primaquine due to hematological toxicity. Progressively, the oxygenated hemoglobin fraction declined despite normal PaO₂ levels. Concurrently, methemoglobin levels rose, suggesting primaquine as the culprit. Treatment was switched to pentamidine, and ascorbic acid was administered. Methemoglobin levels subsequently lowered, and oxygen saturation normalized. G6PDH activity levels were within the normal range. Pentamidine was continued for a total of 21 days while the patient slowly recovered. Methemoglobinemia is a rare complication of primaquine treatment with severe consequences. A discrepancy between PaO₂ and the oxygenated hemoglobin fraction should raise awareness of this diagnosis and prompt immediate action.