Jornal de Toxicologia Clínica
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Primaquine-Induced Asymptomatic Methemoglobinemia Treated with N-Acetylcysteine: A Case Report

Losso Lorenzo*, Bartalesi Filippo, Camiciottoli Gianna, Ciambellotti Lorenzo, Gambassi Francesco, Lagi Filippo, Mancarini Jessica, Mannaioni Guido, Ieri Alessandra

Introduction: Primaquine-induced methemoglobinemia is a rare pathological condition typically characterized by mild-moderate symptoms driven by an increase in Methaemoglobin (MetHb) levels (normal value <1%), which can lead to primaquine discontinuation, with major consequences for the management of the underlying disease. Primaquine increases MetHb levels through a pro-oxidant environment promoted by its metabolites. To this aim, we tested the hypothesis that N-Acetyl Cysteine (NAC), by acting as a reducing agent, could be safe and effective in the treatment of primaquine-induced methemoglobinemia not requiring methylene blue treatment.

Methods: We report a 41-years-old woman affected by multiple sclerosis, in treatment with immune-modulatory therapy, who was hospitalized for the management of Pneumocystis jirovecii Pneumonia (PJP) treated with primaquine 30 mg/day and clindamycin 1800 mg/day. At the time of admission MetHb was <1% and after nine days of treatment, a mild increase in MetHb levels was observed (9%). The increase in MetHb was ascribed to primaquine, after ruling out other causes, including Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. NAC-based antioxidant therapy was introduced at the dose of 3600 mg/day (per os) in order to allow second-line primaquine treatment for PJP.

Results: MetHb levels gradually decreased until the physiological range. Given primaquine and its metabolites halflife, NAC therapy lasted one week longer than the duration of primaquine therapy (total 19 days). No adverse drug reaction to NAC therapy has been reported.

Conclusion: NAC-based antioxidant therapy has been proved effective and safe for the treatment of primaquineinduced methemoglobinemia.