Drug Interaction Report

MONITOR CLOSELY: Concomitant use of angiotensin II receptor antagonists (ARBs) may increase the serum concentrations of lithium. The exact mechanism of the interaction is unknown, but may be related to the blockade of angiotensin II type 1 receptor by the ARB causing decreased sodium reabsorption (natriuresis) and increased lithium reabsorption in the proximal convoluted tubule (PCT). Increased steady-state lithium concentrations and lithium toxicity, including death, have been described in multiple case reports with various ARBs in association with the interaction, sometimes with a delayed onset of up to several weeks after coadministration.

MANAGEMENT: Given the narrow therapeutic index of lithium, caution is advised during coadministration with angiotensin II receptor antagonists, particularly in the elderly or patients with other risk factors (e.g., sodium restriction, renal impairment, congestive heart failure, dehydration, concomitant use of diuretics or NSAIDs). The labeling for some ARBs recommends avoiding this combination, while the labeling of others suggest they may be coadministered if necessary, but with additional monitoring. If coadministration is necessary, lithium product labeling recommends more frequent monitoring of serum lithium levels and renal function, as well as possible lithium dose reductions. Patients and their caregivers should be advised to seek medical attention if they experience potential signs and symptoms of lithium toxicity (e.g., drowsiness, dizziness, confusion, muscle weakness, vomiting, diarrhea, polydipsia, polyuria, tinnitus, tremor, ataxia, and blurred vision). Individual product labeling should be consulted for further guidance.

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GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

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MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

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