Interaction between naproxen and lithium./nClinical background: A 35-year-old woman with depressive
Fråga: Interaction between naproxen and lithium. Clinical background: A 35-year-old woman with depressive symptoms has been treated with lithium, the dose unknown, for one and a half years. Treatment with naproxen, 250 mg when required, is desirable because of dysmenorrhoea and also because of migraine. It is not known whether the patient is treated with any other drugs. What is the risk for an interaction between naproxen and lithium?
Sammanfattning: There is conclusive evidence that naproxen increases lithium serum concentrations and may increase the risk of lithium toxicity. The magnitude of the effect appears to vary considerably from patient to patient. Careful monitoring of serum lithium levels should be done and a reduction in lithium dosage may be needed in some cases. In the present case the combination of naproxen and lithium should preferably be avoided considering the intermittent treatment with naproxen and the difficulty in adjusting the lithium dosage to this intermittent naproxen treatment. An alternative anti-inflammatory agent should be considered, for instance sulindac combined with lithium drug monitoring.
Svar: It has been documented that nonsteroidal anti-inflammatory drugs can increase serum lithium levels. Such an interaction has occurred in patients with normal renal function. The effect on serum lithium levels varies greatly among different nonsteroidal anti-inflammatory drugs, indomethacin seeming to be the most potent (1,2).
The interaction of lithium with sulindac and naproxen was studied in six sulindac-treated and seven naproxen-treated patients, all with steady-state lithium serum concentrations (1,2). The addition of naproxen 750 mg/day for six days resulted in a steady increase in serum lithium concentrations. Sulindac failed to affect serum lithium levels and lithium clearance. The results with naproxen showed marked interindividual variations ranging from no increase to a 41.9 per cent increase (mean increase, 16 per cent) in serum levels within five days. There was a corresponding decrease in lithium clearance in naproxen-treated patients.
Decreased clearance and increased serum concentrations of lithium have been reported resulting in toxicity on some occasions after the concomitant administration of lithium with naproxen (5).
In one case report a woman in her early 60s treated with lithium long term had been prescribed ibuprofen 400 mg four times daily. Her serum lithium concentrations had earlier been satisfactory. A week later she arrived at the accident and emergency department with symptoms of stupor, confusion, and ataxia. Her serum lithium concentration was approximately five times higher than the therapeutic level and she had renal failure with a serum creatinine concentration of 500 umol/l (2).
The mechanism behind this interaction between lithium and naproxen appears to be a naproxen-induced reduction of renal clearance of lithium. It has been proposed that renal tubular prostaglandins are involved in the excretion of lithium and that the anti-prostaglandin effects of NSAIDs interfere with renal lithium elimination (4,6).
If naproxen therapy is initiated during lithium therapy, monitoring for serum lithium concentration should be done (4,6,7), every 4-5 days, until the extent of drug interaction is assessed (6,7). Careful consideration should precede the decision to use these drugs simultaneously since lithium has a narrow therapeutic range and symptoms of toxicity may result from the increased plasma lithium concentration (7). Careful patient monitoring and possible lithium dosage adjustment should be made to prevent lithium intoxication (6,7). If appropriate for the patient, use of an anti-inflammatory agent that is not likely to increase lithium concentrations, such as sulindac (clinoril) or aspirin, should be considered (4,5), although serum lithium levels were increased in one patient treated with aspirin, which may however have been due to variations in sodium intake (5).