Lamotrigine with Carbamazepine Interaction Details

Brand Names Associated with Lamotrigine

Brand Names Associated with Carbamazepine

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

Interaction Effect

Reduced lamotrigine efficacy

Interaction Summary

Concomitant use of lamotrigine (metabolized predominantly by glucuronic acid conjugation) with carbamazepine, which is known to induce glucuronidation, has resulted in a 40% decrease in plasma concentrations of lamotrigine. Dose increases of lamotrigine may be necessary to maintain efficacy, especially in patients receiving adjunctive antiepileptics, in patients with bipolar disorder, and in pediatric patients. Dosage of lamotrigine may need to be subsequently decreased when the inducer is discontinued. Lamotrigine dose should be adjusted as clinically indicated.

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concomitant use of lamotrigine (metabolized predominantly by glucuronic acid conjugation) with carbamazepine, which is known to induce glucuronidation, has resulted in a 40% decrease in plasma concentrations of lamotrigine. Dose increases of lamotrigine may be necessary to maintain efficacy, especially in patients receiving adjunctive antiepileptics, in patients with bipolar disorder, and in pediatric patients. Dosage of lamotrigine may need to be subsequently decreased when the inducer is discontinued. Lamotrigine dose should be adjusted as clinically indicated.

Mechanism Of Interaction

Hepatic induction of lamotrigine metabolism

Literature Reports

A) In drug interactions studies, the addition of carbamazepine decreased lamotrigine steady-state concentrations by approximately 40% .

B) While lamotrigine alone has a steady-state elimination half-life of between 25 to 37 hours, coadministration of carbamazepine reduces the half-life to approximately 14 or 15 hours . Lamotrigine clearance ranged from 0.021 to 0.035 L/h/kg (0.35 to 0.59 mL/min/kg) in healthy volunteers given lamotrigine alone . Comparable values during combination therapy ranged from 0.044 to 0.084 L/h/kg (0.73 to 1.4 mL/min/kg) . Carbamazepine was found to decrease incrementally the half-life of lamotrigine by 1.7 hours for every 100 mg of carbamazepine within the dosing range of 800 to 1600 mg daily .

C) If phenytoin or carbamazepine (or any prodrugs) is used in pregnant women, there is a substantially increased risk of teratogenicity with many combinations of other anticonvulsants. The teratogenicity of these drugs is largely or wholly related to the levels of the reactive epoxide metabolites . The epoxide/parent drug ratio is generally increased when phenytoin or carbamazepine is combined with each other, any other drugs that induce cytochrome P450 enzymes (3A4, 2C9, 2C19), or drugs which inhibit epoxide hydrolase, such as valproic acid, progabide, and lamotrigine . Such combinations increase the risk of major birth defects 3- to 4-fold over monotherapy and about 10-fold over background rates.

D) No pharmacokinetic interaction between carbamazepine and lamotrigine was found in children. Three adolescents and eleven children with intractable generalized epilepsy who had been treated with carbamazepine for longer than one year started lamotrigine 1 mg/kg/day divided into two daily dosages. The lamotrigine dose was increased by 1 mg/kg/day every other week until clinical response or side effects occurred. The mean carbamazepine levels did not change significantly from baseline when lamotrigine was coadministered (29.9 mmol/L vs. 28.8 mmol/L). In addition, the plasma concentrations of the active metabolite of carbamazepine, carbamazepine-10,11-epoxide, significantly decreased from 6.4 mmol/L to 2.4 mmol/L with lamotrigine therapy .

E) Carbamazepine reduces the plasma levels of lamotrigine. A 65-year-old male suffering from complex partial epilepsia for 40 years was receiving carbamazepine (400 mg three times daily) and lamotrigine (200 mg three times daily). Seizures occurred at least twice a week. Steroids, ipratropium bromide and a beta-agonist were used for an obstructive lung disease. A current pneumonia was being treated with an oral amoxicillin preparation. A trough lamotrigine was 1.7 mcmol/mL and a trough carbamazepine was 11 mcmol/mL. The patient continued to suffer from seizures. Carbamazepine was gradually replaced by levitiracetam (1500 mg twice daily) within 4 weeks. After 4 weeks of levitiracetam therapy the patient's carbamazepine plasma levels were 1.3 mcmol/mL and lamotrigine plasma levels were 12.1 mcmol/mL. Lamotrigine levels increased rapidly after reductions in the carbamazepine dose. Levetiracetam and lamotrigine combination was well tolerated and seizures stopped completely after 4 weeks. A drug interaction should be considered when carbamazepine and lamotrigine result in ineffective antiepileptic therapy .

F) The clearance of lamotrigine may double during concomitant therapy with carbamazepine . In addition, increased serum concentrations of carbamazepine-10,11-epoxide (an active metabolite of carbamazepine) and neurotoxicity have been reported during concomitant administration of carbamazepine and lamotrigine . Other investigators have found that lamotrigine had no effect on either carbamazepine or its metabolite .

Lamotrigine Overview

• Lamotrigine extended-release (long-acting) tablets are used with other medications to treat certain types of seizures in patients who have epilepsy. All types of lamotrigine tablets (tablets, orally disintegrating tablets, and chewable tablets) other than the extended-release tablets are used alone or with other medications to treat seizures in people who have epilepsy or Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). All types of lamotrigine tablets other than the extended-release tablets are also used to increase the time between episodes of depression, mania (frenzied or abnormally excited mood), and other abnormal moods in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lamotrigine has not been shown to be effective when people experience the actual episodes of depression or mania, so other medications must be used to help people recover from these episodes. Lamotrigine is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

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.

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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.