Verapamil with Carbamazepine Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 03, 2023

Interaction Effect

Increased exposure of carbamazepine; decreased exposure of CYP3A4 substrates

Interaction Summary

In a single case report, the addition of diltiazem to long-term use of carbamazepine produced carbamazepine toxicity within a few days; toxicity resolved with carbamazepine dosage reduction. The concomitant use of carbamazepine, a CYP3A4 inducer and substrate, and a CYP3A4 inhibitor and substrate may decrease exposure of the CYP3A4 substrate and may also increase exposure of carbamazepine. If coadministered, monitor carbamazepine levels and dosage adjustments of either carbamazepine or the CYP3A4 substrate may be warranted .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

The concomitant use of carbamazepine, a CYP3A4 inducer and substrate, and a CYP3A4 inhibitor and substrate may decrease exposure of the CYP3A4 substrate and may also increase exposure of carbamazepine. If coadministered, monitor carbamazepine levels and dosage adjustments of either carbamazepine or the CYP3A4 substrate may be warranted.

Mechanism Of Interaction

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

Literature Reports

A) A 49-year-old man with childhood epilepsy and long-term use of carbamazepine developed carbamazepine toxicity within a week after initiating concurrent diltiazem. During a hospital admission for acute allograft dysfunction of a kidney transplant received 27 years earlier, cyclosporine was changed to tacrolimus and felodipine was changed to diltiazem. Additional medications were prednisoLONE. sodium valproate, metoprolol, simvastatin, and aspirin, and additional medical history included hypertension, old lacunar infarct, and pulmonary TB (11 years after completed treatment). About a week after the initial hospitalization, the patient presented with a 4-day history of lethargy, tinnitus, and blurred vision. He had a broad-based gait and bilateral bidirectional nystagmus on funduscopy but no other abnormal neurologic, ocular, or other physical exam findings; he was afebrile and hemodynamically stable. CT of the brain excluded acute intracranial pathology, and CBC and blood chemistries were normal. His trough carbamazepine level was 64.2 mcmol/L (normal, 16.9 to 50.8 mcmol/L), and he was diagnosed with carbamazepine toxicity secondary to coadministration of diltiazem. The suspected mechanism of interaction was the inhibition of carbamazepine metabolism by diltiazem via the CYP450 pathway. Carbamazepine was withheld for a day and restarted at a lower dose; carbamazepine level at hospital discharge was 41.7 mcmol/L. His tinnitus and visual impairment completely resolved during outpatient follow-up .

Verapamil Overview

• Verapamil is used to treat high blood pressure and to control angina (chest pain). The immediate-release tablets are also used alone or with other medications to prevent and treat irregular heartbeats. Verapamil is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart and slows electrical activity in the heart to control the heart rate.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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.