Carbamazepine with Isoniazid Interaction Details

Brand Names Associated with Carbamazepine

Brand Names Associated with Isoniazid

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

Interaction Effect

Increased carbamazepine exposure and increased risk of isoniazid-induced hepatotoxicity

Interaction Summary

The concomitant use of carbamazepine, a CYP3A4 substrate, and isoniazid, a CYP3A4 inhibitor, may increase the exposure of carbamazepine and may also result in isoniazid-induced hepatotoxicity . Concomitant use increased carbamazepine serum concentrations and toxicity at isoniazid doses of 200 mg daily or more . If carbamazepine is used concomitantly with isoniazid, closely monitor carbamazepine levels and adjust the carbamazepine dosage as needed .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of carbamazepine, a CYP3A4 substrate, and isoniazid, a CYP3A4 inhibitor, may result in increased carbamazepine exposure. Concomitant use also increases the risk of isoniazid-induced hepatotoxicity. If coadministration is required, closely monitor carbamazepine levels and adjust the carbamazepine dosage as needed.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of carbamazepine by isoniazid

Literature Reports

A) Five days after concurrent use of carbamazepine with isoniazid 300 mg daily, a patient presented with ataxia, headache, vomiting, drowsiness, and confusion. Carbamazepine serum levels had increased from 5 mcg/mL to 15 mcg/mL. The patient was also receiving phenytoin, with levels increasing from 13 to 18 mcg/mL; this was considered to be in the therapeutic range and not related to an interaction with carbamazepine. Upon withdrawal of the isoniazid, the carbamazepine level decreased to 6 mcg/mL within 7 days, and the phenytoin level remained at 18 mcg/mL; the patient's symptoms disappeared at day 2. However, it is difficult to rule out the effects of phenytoin as a possible cause of toxicity, since some patients may present with toxic symptoms at these serum concentrations .

B) Administration of isoniazid to a patient receiving chronic carbamazepine therapy resulted in significant decreases in carbamazepine clearance as well as delayed isoniazid-induced hepatotoxicity. This was presumably related to inhibition of carbamazepine's microsomal enzyme metabolism by isoniazid and increased metabolism of isoniazid to the hepatotoxic metabolite (acetylhydrazine) by carbamazepine .

C) One study reported a case of carbamazepine toxicity following the addition of antituberculosis medication to chronic anticonvulsant medication. Carbamazepine levels had previously been 8.5 to 9.5 mcg/mL without evidence of toxicity. Isoniazid 300 mg daily was well tolerated for 3 days prior to the introduction of rifampin 600 mg daily. Within 24 hours of initiation of rifampin, the patient developed nausea, ataxia, confusion and drowsiness. The carbamazepine level was noted to be 16.9 mcg/mL. The authors suggest that rifampin may have augmented the enzyme-inhibiting effects of isoniazid, resulting in carbamazepine toxicity .

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.

Isoniazid Overview

• Isoniazid is used with other drugs to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Isoniazid is also used with other drugs to treat people with latent (resting or nongrowing) TB including those in close contact with people who have active TB, a positive tuberculin skin test, human immunodeficiency virus (HIV), and those with pulmonary fibrosis (scarring of the lungs with an unknown cause). Isoniazid is in a class of medications called antituberculosis agents. It works by killing the bacteria that cause tuberculosis.

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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.