Objective: Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology. Data Sources: Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. Study Selection and Data Extraction: Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. Data synthesis: For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases. Relevance to Patient Care and Clinical Practice: This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. Conclusions: These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days.

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