Lithium Toxicity Secondary to Lithium—Losartan Interaction

Abstract

Objective:

To report a case of lithium toxicity following lithium and losartan coadministration in a diabetic patient.

Case Summary:

A 61-year-old white male with a history significant for bipolar disorder, hypertension, and diabetes was admitted to the Veterans Affairs Medical Center—based Nursing Home Care Unit for long-term intravenous antibiotic therapy for osteomyelitis. He developed lithium toxicity at a dose previously tolerated (1,350 mg/day) following administration of losartan 50 mg on the day before and day of evidence of toxicity. The drugs had been used concurrently prior to admission without evidence of toxicity; however, adherence to treatment could not be confirmed and concurrent dehydration may have been a contributing factor. Lithium toxicity was evidenced by irritability, tremors, confusion, and disorientation. Results of laboratory studies were significant for an elevated lithium concentration, hyponatremia, and slight elevations of serum creatinine and blood urea nitrogen. All other laboratory values were within normal limits.

Discussion:

Losartan, an angiotensin-receptor blocker (ARB), is commonly used for treatment of hypertension and heart failure as well as for renoprotection in diabetic patients. It has been shown to interact with lithium, resulting in lithium intoxication, most likely as a result of natriuresis leading to hyponatremia. Hyponatremia and a decrease in the glomerular filtration rate through the action of both angiotensin-converting enzyme inhibitors and ARBs enhance the renal tubular reabsorption of lithium, thus leading to potentially toxic serum concentrations of lithium. An objective causality assessment revealed that the interaction was probable.

Conclusions:

The temporal fashion in which the episode occurred indicated that a lithium—losartan interaction was probably the cause of lithium toxicity in this patient. Clinicians need to be aware of potential lithium—ARB interactions resulting in an increased risk of lithium toxicity associated with concurrent use of these drugs.