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Drug-induced electrolyte abnormalities have been increasingly reported and may be associated with considerable morbidity and/or mortality. In clinical practice, hypernatraemia (serum sodium higher than 145 mmol/L) is usually of multifactorial aetiology and drug therapy not infrequently is disregarded as a contributing factor for increased serum sodium concentration. Strategies to prevent this adverse drug effect involve careful consideration of risk factors and clinical and laboratory evaluation in the course of treatment. Herein, we review evidence-based information via PubMed and EMBASE and the relevant literature implicating pharmacologic treatment as an established cause of hypernatraemia and discuss its incidence and the underlying pathophysiologic mechanisms.