Lithium intoxication as a result of an interaction with rofecoxib.
OBJECTIVE
To report the occurrence of lithium intoxication in a patient with bipolar disorder after adding rofecoxib to the medication regimen.


METHODS
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.


CONCLUSIONS
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.
Rätz Bravo
Alexandra E
AE
Department of Internal Medicine, University Hospital, Basel, Switzerland. raetza@uhbs.ch
Egger
Sabin S
SS
Crespo
Sophie
S
Probst
Willi L
WL
Krähenbühl
Stephan
S
D000368:Aged; D018692:Antimanic Agents / Q000506:poisoning* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D051546:Cyclooxygenase 2; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D018020:Lithium Compounds / Q000506:poisoning* / Q000627:therapeutic use; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D013450:Sulfones
D018692:Antimanic Agents; D007527:Isoenzymes; D007783:Lactones; D018020:Lithium Compounds; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases