Carbamazepine with Lithium Interaction Details

Brand Names Associated with Carbamazepine

Brand Names Associated with Lithium

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Additive risk of toxic side effects

Interaction Summary

Concomitant use of lithium and carbamazepine may increase the risk of toxic side effects. Case reports have described the development of neurotoxicity during concurrent administration of lithium and carbamazepine despite normal therapeutic levels of either drug  A case report of lithium toxicity following carbamazepine-induced renal failure has also been described .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of lithium and carbamazepine may increase the risk of toxic side effects.

Mechanism Of Interaction

Unknown

Literature Reports

A) A potential interaction between lithium and carbamazepine has been reported . The patient, a 22-year-old woman with bipolar affective disorder, developed neurotoxicity despite therapeutic plasma levels of both drugs. Previous reports of neurotoxicity due to either of these agents have occurred when recommended plasma levels were exceeded. Toxicity due to carbamazepine was not observed in this case when the plasma level was 6.9 mcg/mL (therapeutic: 8 to 12 mcg/mL). Similarly, no neurotoxicity occurred with plasma lithium levels of 0.9 mEq/L (therapeutic: 0.6 to 1.4 Eq/L). However, when the drugs were administered concurrently, neurotoxicity, characterized by unsteady gait, truncal tremors, ataxia, horizontal nystagmus, hyperreflexia of all four limbs, and occasional muscle fasciculation, occurred within three days. Plasma levels of lithium and carbamazepine were 0.9 mEq/L and 7.6 mcg/mL, respectively. Upon discontinuation of carbamazepine, neurologic symptoms subsided within three days. Therapeutic plasma levels of these two drugs administered concomitantly may lead to acute neurotoxicity .

B) Neurotoxic syndromes developed in five manic patients treated with a combination of lithium and carbamazepine, although all five had therapeutic plasma levels of both drugs . The clinical picture of the patients consisted of symptoms of confusion, drowsiness, generalized weakness, lethargy, coarse tremor, hyperreflexia, and cerebellar signs. Patients with previous lithium-induced neurotoxicity and those with underlying CNS disease or metabolic disease appeared to be at greater risk for developing the neurotoxicity when the combination of the two drugs was utilized .

C) An analysis of the data from other researchers  was performed . The analysis demonstrated no synergistic toxicity between the two drugs, but noted on a hypothetical plot of blood levels of both drugs that lithium appears to contribute more significantly to the toxicity observed. The authors further concluded that usually used therapeutic ranges cannot be used in monitoring for toxicity when two drugs are used together and a two-dimensional plot of serum levels may be of assistance in ascertaining the safe range of serum levels with combinations of drugs .

D) Over a three-year period, some drug combinations were observed to cause a greater risk of asterixis (flapping tremor) in patients on a regimen of multiple psychopharmacologic agents. With regard to carbamazepine, clozapine, and lithium, the incidence of asterixis was greatest in those patients that were on at least two of these three agents. Serum levels of all three drugs were within normal therapeutic ranges, suggesting an additive effect of combination therapy rather than the effect of a single agent .

E) Lithium intoxication occurred in a patient following carbamazepine-induced renal failure. A 33-year-old male diagnosed with bipolar manic-depressive disorder was treated with lithium for the last 18 months. Carbamazepine 600 mg was added to his drug regimen. Serum lithium levels were 1.08 mEq/L and serum carbamazepine concentration was 8 mcg/mL two weeks later. Upon admission he was stuporous but arousable. His serum creatinine was 6.5 mg/dL, and serum carbamazepine concentration was 11 mcg/mL and serum lithium concentration was 3.5 mEq/L. After 2 L of normal saline was administered, this patient developed pulmonary edema. After one session of hemodialysis, serum lithium concentrations decreased to 1.3 mEq/L, and serum creatinine decreased to 3.5 mg/dL. Three weeks later serum creatinine was 1.0 mg/dL and lithium concentrations were within the therapeutic range. Renal failure was most likely caused by carbamazepine induced interstitial nephritis. Patients who are treated with lithium and carbamazepine should be followed carefully to prevent carbamazepine-induced interstitial nephritis. The presence of fever, eosinophiluria, urinary leukocyte casts, and the patients improvement after withdrawal of carbamazepine support the diagnosis of interstitial nephritis. Patients who are treated with lithium and carbamazepine should be followed carefully to prevent carbamazepine-induced interstitial nephritis .

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

Lithium Overview

• Lithium is used to treat and prevent episodes of mania (frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lithium is in a class of medications called antimanic agents. It works by decreasing abnormal activity in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.