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Lithium Intoxication as a Result of an Interaction with Rofecoxib

Vice Head, Drug Information Center, Division of Clinical Pharmacology & Toxicology, Department of Internal Medicine, University Hospital, Basel, Switzerland

Sabin S Egger, MS

PhD Student, Division of Clinical Pharmacology & Toxicology, Department of Internal Medicine, University Hospital, Basel

Sophie Crespo, MD

Resident Physician, Intensive Care Unit, Department of Internal Medicine, University Hospital, Basel

Willi L Probst, MD

Senior Resident Physician, Department of Geriatrics, Felix Platter Hospital, Basel

Stephan Krähenbühl, MD PhD

Head, Division of Clinical Pharmacology & Toxicology, Department of Internal Medicine, University Hospital, Basel

Reprints: Alexandra E Rätz Bravo MS, Division of Clinical Pharmacology & Toxicology, University Hospital, Hebelstrasse 2, CH 4031 Basel, Switzerland, fax 41 61 265 4560, raetza{at}uhbs.ch

OBJECTIVE: To report the occurrence of lithium intoxication in a patient with bipolar disorder after adding rofecoxib to the medication regimen.

CASE SUMMARY: A 68-year-old woman with bipolar disorder under long-term treatment with lithium, carbamazepine, pipamperon, and mirtazapine was prescribed rofecoxib 25 mg twice daily for the treatment of leg pain. Within one week, she showed progressive hypokinesia and tremor, which was treated with propranolol. Subsequently, she developed bradycardia, necessitating treatment with isoproterenol. Her lithium serum concentration had doubled compared with those before rofecoxib, and her renal function had deteriorated. After stopping lithium and rofecoxib, her laboratory values and neurologic signs improved or normalized within 2 days. An objective causality assessment revealed a probable relationship between concomitant use of the drugs and the resulting symptoms.

DISCUSSION: As of May 24, 2004, only 3 cases of reversible lithium intoxication as a result of a possible interaction with rofecoxib or celecoxib have been previously reported. The mechanism of the interaction between lithium and cyclooxygenase (COX) 2 selective inhibitors is most probably related to inhibition of renal synthesis of prostaglandins, which are important for the maintenance of renal perfusion and tubular function. Impairment of renal blood flow, leading to a decrease in the glomerular filtration rate, and increased proximal tubular absorption are the most likely mechanisms by which COX-2 selective inhibitors reduce lithium clearance.

CONCLUSIONS: Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.

Key Words: drug interactions, lithium, renal failure, rofecoxib

Published Online, June 8, 2004. www.theannals.com, DOI 10.1345/aph.1E034

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