Carbamazepine with Nirmatrelvir Interaction Details
Brand Names Associated with Carbamazepine
- Carbamazepine
- Carbatrol®
- Epitol®
- Equetro®
- Tegretol®
- Tegretol®-XR
- Teril®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Increased carBAMazepine exposure and reduced nirmatrelvir/ritonavir exposure
Interaction Summary
CarBAMazepine is contraindicated when used in combination with nirmatrelvir/ritonavir due to potential loss of virologic response and possible resistance, as well as increased carBAMazepine exposure. After coadministration of carBAMazepine 300 mg twice daily (for 16 doses, after 1 week of titration) and nirmatrelvir 300 mg/ritonavir 100 mg twice daily (for 5 doses), the Cmax and AUC of nirmatrelvir significantly decreased by about 43.2% and 55.5%, respectively. Also, nirmatrelvir/ritonavir cannot be started immediately after discontinuation of carBAMazepine (a potent CYP3A inducer) due to the delayed offset of the recently discontinued CYP3A inducer.
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
CarBAMazepine is contraindicated when used in combination with nirmatrelvir/ritonavir due to potential loss of virologic response and possible resistance, as well as increased carBAMazepine exposure. Also, nirmatrelvir/ritonavir cannot be started immediately after discontinuation of carBAMazepine (a potent CYP3A inducer) due to the delayed offset of the recently discontinued CYP3A inducer.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated carBAMazepine metabolism by nirmatrelvir/ritonavir; induction of CYP3A4-mediated nirmatrelvir/ritonavir metabolism by carBAMazepine
Literature Reports
A) After coadministration of carBAMazepine 300 mg twice daily (for 16 doses, after 1 week of titration) and nirmatrelvir 300 mg/ritonavir 100 mg twice daily (for 5 doses), the Cmax and AUC of nirmatrelvir significantly decreased by about 43.2% and 55.5%, respectively (N=9) .
B) When the ombitasvir, paritaprevir, ritonavir, and dasabuvir combination was coadministered with carBAMazepine 200 mg once daily followed by 200 mg twice daily, ritonavir Cmax and AUC were reduced by 83% and 87%, ombitasvir Cmax and AUC were reduced by 31% and 31%, paritaprevir Cmax and AUC were reduced by 66% and 70%, dasabuvir Cmax and AUC we reduced by 55% and 70% .
C) A 36-year-old HIV-positive patient maintained on carBAMazepine and phenytoin to control seizures experienced dizziness and progressive gait disorder after the addition of ritonavir to his antiretroviral treatment. The patient was well-managed for over a year when his antiretroviral therapy, consisting of lamivudine, didanosine and saquinavir was augmented with ritonavir 600 mg twice a day. At that time, serum phenytoin and carBAMazepine levels were normal at 16.5 mcg/mL and 6.5 mcg/mL, respectively. Approximately 2 months later, the patient presented with dizziness and impaired gait. CarBAMazepine serum levels were measured at 18 mcg/mL while phenytoin levels remained normal (14.7 mcg/mL). CarBAMazepine was discontinued and replaced with primidone, resulting in resolution of the gait disorder and continued seizure control. Viral load remained undetectable .
D) A case report demonstrated a severe interaction between ritonavir and carBAMazepine resulting in carBAMazepine toxicity. A 36-year-old patient with AIDS with a history of alcoholism, IV drug use, hepatitis B and C virus infection, tuberculosis, and seizures developed elevated plasma carBAMazepine levels leading to CNS disorders while receiving concomitant treatment with ritonavir. His anticonvulsant medication regimen consisted of carBAMazepine 400 mg 3 times daily, phenytoin 200 mg in the morning and 100 mg at night. Two days after initiation of the new antiretroviral schedule (after 4 ritonavir doses), he presented with diplopia, disorientation, drowsiness, vertigo, and severe ataxia. carBAMazepine plasma levels were increased by 99.4% to 16.6 mg/L, and his phenytoin concentration decreased by 32.7% to 7 mg/L. CarBAMazepine concentration returned to the therapeutic range 2 days after carBAMazepine dosage was reduced to 200 mg 3 times daily, ritonavir was discontinued and nelfinavir 1000 mg twice daily was initiated. Symptoms of toxicity disappeared as well. Blood concentrations of antiepileptics should be monitored during the first 24 to 48 hours when ritonavir is added to carBAMazepine and phenytoin treatment regiments. Reduction of the carBAMazepine dose may prevent toxicity .
Carbamazepine Overview
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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:
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.