Lithium Toxicity Due to Drug Interactions

Lithium carbonate (ESKALITH; LITHOBID; LITHONATE), which is used to treat bipolar (also called manic/depressive) disorder, can interact with drugs for cardiovascular diseases.

This may result in a dangerous condition known as lithium toxicity. This condition occurs when lithium blood levels are increased. In severe cases, this can cause seizures, coma and even death.

Symptoms of lithium toxicity are nonspecific gastrointestinal symptoms such as nausea, vomiting, diarrhea and loss of appetite. These symptoms are often accompanied by other warning signs such as lethargy, slurred speech, tremors and disorientation.

Patients are at greatest risk of lithium toxicity in the one- to three-week period following the start of the interacting drug.

But lithium drug interactions tend to be gradual, and it sometimes takes up to two or three weeks after starting the interacting drug before lithium toxicity becomes evident.

What drugs interact with lithium?

When lithium is taken with a drug with which it interacts, it is almost always the blood level of lithium (rather than the potency of the second drug) that is affected by the interaction.

Angiotensin converting enzyme (ACE) inhibitors
These drugs are commonly used to treat heart failure and other cardiovascular diseases. They may increase the risk of lithium toxicity by affecting blood flow through the kidneys. See Table 1 below for a list of ACE inhibitors.

There are a number of case reports of lithium toxicity with concurrent use of an ACE inhibitor. In one epidemiologic study, the use of ACE inhibitors was associated with a substantial increase in the risk of hospitalization due to lithium toxicity.

Angiotensin receptor blockers (ARBs)
These drugs and ACE inhibitors have similar effects on kidney function, and both have been associated with lithium toxicity.

See Table 2 for a list of ARBs.

Diuretics
Diuretics such as furosemide (LASIX) act on the kidneys to increase the elimination of sodium in the urine. The kidneys try to fight this by reabsorbing as much sodium as possible from the kidney tubules. Unfortunately, sodium and lithium are so similar that the kidneys can’t distinguish one from the other. So the kidneys avidly reabsorb more lithium, leading to reduced lithium elimination and lithium toxicity.

Because there is conflicting evidence as to which diuretics are the most likely to produce lithium toxicity, it is best to be alert for the interaction with any diuretic — especially when the diuretic is added to stable lithium therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs)
There are many case reports of lithium toxicity following the concurrent use of NSAIDs (See Table 3), but this interaction clearly does not result in a clinically important interaction in many patients.

Some patients develop reduced kidney function when taking NSAIDs, and it may be that these are thepeople at greatest risk of developing lithium toxicity.

But in any case, using NSAIDs with lithium is cause for increased vigilance for lithium toxicity.

What You Can Do

Protect yourself by making sure that all of your prescribing physicians and pharmacists are aware of all of the different medications and dietary supplements you are taking.

If possible, get all of your prescriptions filled at one pharmacy or an affiliated group of pharmacies that will check all of your medications for drug interactions. Pharmacy-based computerized drug interaction detection systems are not perfect, but they can detect drug interactions effectively if they have a complete and timely record of all of the medications you are taking.

Keep in mind that it may take a few weeks before lithium toxicity becomes manifest.

Table 1. Angiotensin Converting Enzyme (ACE) Inhibitors

* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills

Table 2. Angiotensin Receptor Blockers (ARBs)

** Limited Use in Worst Pills, Best Pills
*** Do Not Use Until 2009 in Worst Pills, Best Pills (This drug to be reclassified in 2010.)

Table 3. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills