Carbamazepine with Erythromycin Interaction Details

Brand Names Associated with Carbamazepine

Brand Names Associated with Erythromycin

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

Interaction Effect

Increased exposure of carbamazepine; decreased exposure of erythromycin

Interaction Summary

The concomitant use of carbamazepine (CYP3A4 inducer and substrate) and erythromycin (CYP3A4 inhibitor and substrate) may decrease exposure of erythromycin and increase exposure of carbamazepine . Concomitant administration in healthy volunteers resulted in significant increases in carbamazepine half-life and 24-hour postdose serum concentrations, and decreases in carbamazepine oral clearance and in maximum carbamazepine-10,11-epoxide metabolite serum concentrations . If coadministering carbamazepine and erythromycin, monitor carbamazepine levels and dosage adjustments of erythromycin and/or carbamazepine may be warranted .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

The concomitant use of erythromycin (CYP3A4 inhibitor and substrate) and carbamazepine (CYP3A4 inducer and substrate) may result in a decreased exposure of erythromycin and increased exposure of carbamazepine. If coadministering carbamazepine and erythromycin, monitor carbamazepine levels and dosage adjustments of erythromycin and/or carbamazepine may be warranted .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of carbamazepine by erythromycin; induction of CYP3A4-mediated metabolism of erythromycin by carbamazepine

Literature Reports

A) Toxicity following concomitant administration of carbamazepine and erythromycin was reported in 6 pediatric patients. Toxicity occurred in less than 2 days with erythromycin therapy in 5 patients; in the sixth patient, the interaction was not observed until the eighth day of erythromycin therapy when the dose was doubled from 27 to 55 mg/kg/day. Carbamazepine serum concentrations decreased to baseline levels within 8 to 12 hours of discontinuing erythromycin, suggesting that normalization of carbamazepine metabolism occurs rapidly .

B) Concomitant administration of erythromycin and carbamazepine in healthy volunteers resulted in significant increases in carbamazepine half-life and 24-hour postdose serum concentrations, as well as decreases in carbamazepine oral clearance. Decreases in maximum carbamazepine-10,11-epoxide serum concentrations, AUC, and the carbamazepine-10,11-epoxide to carbamazepine ratio were also observed during combined therapy. In this study, carbamazepine was given in daily doses of 300 mg to 400 mg orally for 17 consecutive days; subjects were given placebo erythromycin every 6 hours on days 12, 13 and 14, then erythromycin base 250 mg every 6 hours for the final 3 days. It is suggested that erythromycin significantly inhibits the epoxide-diol metabolic pathway required for transformation of carbamazepine to carbamazepine-10,11-epoxide. Wide individual variability was seen in this study; individual changes in oral clearance ranged from plus 23% to minus 41%, suggesting the unpredictability of this interaction. Close patient monitoring is advised when these 2 agents are given concurrently or when one agent is discontinued .

C) Increases in carbamazepine serum concentrations were observed in 4 children during concurrent erythromycin and carbamazepine therapy. All children developed signs of toxicity (nausea, vomiting, ataxia, dizziness) within several days of initiation of erythromycin therapy, which subsided after erythromycin was discontinued and was associated with reduction in carbamazepine serum concentrations. The onset of the interaction generally occurred 3 to 4 days after addition of erythromycin to the carbamazepine regimen .

D) Concomitant carbamazepine and erythromycin stearate therapy was reported to result in carbamazepine toxicity and SIADH in a 41-year-old epileptic woman .

E) A report of the interaction between erythromycin ethylsuccinate and carbamazepine was described in a 6-year-old girl with tonic-clonic seizures. The patient had been maintained on carbamazepine 60 mg/kg/day (serum level 12 mcg/mL) and developed symptoms of carbamazepine toxicity (vomiting, lethargy, ataxia, nystagmus, cogwheeling movements) after five days of erythromycin ethylsuccinate therapy (250 mg 4 times daily), with concomitant increases in carbamazepine serum levels to 26 mcg/mL. Following withdrawal of erythromycin, serum concentrations of carbamazepine returned to normal levels, with resolution of symptoms .

F) Two cases describing the interaction of carbamazepine and erythromycin in children resulting in carbamazepine toxicity were reported by .

G) Concomitant administration of erythromycin and carbamazepine was reported to result in sinus arrest and AV block in a 10-year-old boy secondary to carbamazepine toxicity. The patient recovered following supportive therapy and the EKG normalized when carbamazepine serum levels returned to the therapeutic range. This patient had no preexisting cardiac symptoms .

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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.