From the Guidelines
Lithium and lisinopril can have potentially serious interactions when taken together, with the most significant concern being that lisinopril can increase lithium blood levels, potentially leading to lithium toxicity. The interaction between lithium and lisinopril is a result of lisinopril's effect on the kidneys, which can reduce their ability to clear lithium from the body 1. This can lead to elevated lithium levels, increasing the risk of lithium toxicity. Patients taking both medications may experience symptoms of lithium toxicity, including:
- Tremor
- Confusion
- Lethargy
- Vomiting
- Diarrhea
- In severe cases, seizures or coma
If both medications are necessary, lithium levels should be monitored more frequently, especially when starting, stopping, or changing the dose of lisinopril. Dosage adjustments of lithium may be needed to prevent toxicity. Patients should stay well-hydrated and maintain consistent sodium intake, as changes in these factors can also affect lithium levels 1. Any signs of lithium toxicity should prompt immediate medical attention. This interaction is particularly important to monitor in older adults and those with kidney problems, who may be more susceptible to lithium accumulation.
From the FDA Drug Label
Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. When such combinations are used, the lithium dosage may need to be decreased, and more frequent monitoring of lithium plasma levels is recommended
- Major interactions between lithium and lisinopril (an ACE inhibitor) include:
- Increased risk of lithium toxicity due to reduced renal clearance of lithium
- Potential need to decrease lithium dosage when used concomitantly with lisinopril
- Recommendation for more frequent monitoring of lithium plasma levels when used with lisinopril 2
From the Research
Major Interactions between Lithium and Lisinopril
- The combination of lithium and lisinopril may increase the risk of lithium intoxication, as lisinopril can affect renal function and lithium clearance 3, 4, 5.
- Dehydration and concomitant use of hydrochlorothiazide can also contribute to lithium intoxication when combined with lisinopril 3.
- Switching from one ACE inhibitor to another, such as from fosinopril to lisinopril, can lead to significant changes in serum lithium levels and increase the risk of lithium toxicity 4.
- Patients taking lithium and lisinopril should be closely monitored for changes in serum lithium levels, especially during the first 4-6 weeks after switching to lisinopril or when dehydration occurs 4, 5.
- The concomitant use of diuretics, such as thiazide diuretics, with lithium can also increase the risk of lithium toxicity, and the risk of interactions varies with the site of pharmacological action of the diuretic in the renal tubule 6.
- ACE inhibitors, including lisinopril, may impair lithium elimination, and further investigations are needed to identify patients at risk 6.