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Patients taking the commonly prescribed epilepsy drug carbamazepine (CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL) should be aware that it has clinically important interactions with numerous other prescription and over-the-counter medications.
Carbamazepine was initially approved by the Food and Drug Administration (FDA) in 1968 for treatment of a form of excruciating facial pain called trigeminal neuralgia or tic douloureux.[1] Trigeminal neuralgia pain typically occurs on one side of the...
Patients taking the commonly prescribed epilepsy drug carbamazepine (CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL) should be aware that it has clinically important interactions with numerous other prescription and over-the-counter medications.
Carbamazepine was initially approved by the Food and Drug Administration (FDA) in 1968 for treatment of a form of excruciating facial pain called trigeminal neuralgia or tic douloureux.[1] Trigeminal neuralgia pain typically occurs on one side of the face, is electric shock-like, and starts and ends suddenly. Carbamazepine is considered first-line therapy for this disorder.[2]
The drug also is now FDA-approved for treating generalized (tonic-clonic or grand mal) seizures, certain types of partial (focal) seizures and mixed seizures, and as a mood stabilizer for treating manic episodes or mixed manic-depressive episodes in certain types of bipolar disorder.[3],[4]
Drugs that affect carbamazepine levels[5],[6]
Like many drugs, carbamazepine is metabolized (broken down or chemically modified) by substances in the liver called enzymes. Carbamazepine is particularly susceptible to interactions with other drugs that inhibit a specific liver enzyme called CYP3A4 that is involved in the breakdown of carbamazepine. Inhibition of this enzyme can lead to significantly increased blood levels of the drug and carbamazepine toxicity.
The top part of Table 1, below, provides examples of just some of the many drugs that may increase carbamazepine blood levels, potentially leading to carbamazepine toxicity. These include certain antibiotics, antidepressants, antifungal drugs and the atypical antipsychotic olanzapine (ZYPREXA, ZYPREXA ZYDIS), among others. Signs of carbamazepine toxicity include dizziness, light-headedness, fainting, a rapid or slow heart rate, drowsiness, nausea, vomiting, loss of appetite and problems with walking and coordination.
Table 1. Examples of Oral Drugs That May Affect Carbamazepine Blood Levels
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| Drugs that may increase carbamazepine blood levels | ||
| clarithromycin* | generic only | Antibiotic |
| desipramine* | NORPRAMIN | Tricyclic antidepressant |
| fluconazole | DIFLUCAN | Antifungal drug |
| fluoxetine* | PROZAC, SARAFEM | Selective serotonin reuptake inhibitor/antidepressant |
| isoniazid | generic only | Antibiotic for tuberculosis |
| itraconazole** | ONMEL, SPORANOX, TOLSURA | Antifungal drug |
| ketoconazole*** | generic only | Antifungal drug |
| olanzapine* | ZYPREXA, ZYPREXA ZYDIS | Atypical antipsychotic |
| quinine | QUALAQUIN | Antimalarial drug |
| ritonavir | NORVIR | Antiviral drug for HIV infection |
| voriconazole | VFEND | Antifungal drug |
| Drugs that may decrease carbamazepine blood levels | ||
| methsuximide | CELONTIN | Epilepsy drug |
| phenobarbital* | LUMINAL, SOLFOTON | Barbiturate/epilepsy drug |
| phenytoin | DILANTIN, PHENYTEK | Epilepsy drug |
| primidone | MYSOLINE | Epilepsy drug |
| rifampin | RIFADIN, RIMACTANE | Antibiotic/tuberculosis drug |
| theophylline* | ELIXOPHYLLIN, THEO-24, THEOCHRON | Asthma drug |
†Brand-name combination products were excluded.
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use Except for Serious Fungal Infections by Worst Pills, Best Pills News
***Designated as Do Not Use by Worst Pills, Best Pills News
Other drugs can accelerate the breakdown of carbamazepine by the CYP3A4 liver enzyme, potentially resulting in low levels of carbamazepine and inadequate seizure control (see the bottom part of Table 1 for examples). Such drugs include several other epilepsy drugs, including phenytoin (DILANTIN, PHENYTEK).
Because of the potential harm that may result from these interactions in patients taking carbamazepine, blood levels of this drug should be monitored closely when such patients start or stop any drug that may alter carbamazepine levels.
Carbamazepine affects levels of other drugs[7],[8]
In addition to being affected by other drugs, carbamazepine itself can interfere with the effectiveness of many other drugs, most commonly by decreasing the blood levels of the interacting drugs (see Table 2, below, for examples). The drugs that carbamazepine may affect in this manner include certain antifungal drugs, antidepressants, antipsychotic drugs, calcium channel blockers for hypertension and the cholesterol-lowering drug simvastatin (FLOLIPID, ZOCOR), among others. Notably, several drugs that affect carbamazepine levels also are simultaneously affected by carbamazepine.
Table 2. Examples of Oral Drugs That May be Affected by Carbamazepine
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| alprazolam* | XANAX | Benzodiazepine sedative/sleeping pill |
| bupropion** | APLENZIN, FORFIVO XL, WELLBUTRIN | Antidepressant/smoking cessation drug |
| clozapine** | CLOZARIL, VERSACLOZ | Atypical antipsychotic |
| cyclosporine | GENGRAF, NEORAL, SANDIMMUNE | Immunosuppressant/organ transplant drug |
| everolimus | AFINITOR, AFINITOR DISPERZ, ZORTRESS | Immunosuppressant/organ transplant drug |
| felodipine | generic only | Calcium channel blocker/hypertension drug |
| haloperidol** | generic only | Typical antipsychotic |
| itraconazole*** | ONMEL, SPORANOX, TOLSURA | Antifungal drug |
| methadone** | METHADOSE | Opioid |
| nifedipine, long-acting** | PROCARDIA XL | Calcium channel blocker/hypertension drug |
| nortriptyline** | PAMELOR | Tricyclic antidepressant |
| olanzapine** | ZYPREXA, ZYPREXA ZYDIS | Atypical antipsychotic |
| phenytoin | DILANTIN, PHENYTEK | Epilepsy drug |
| quetiapine** | SEROQUEL | Atypical antipsychotic |
| risperidone** | RISPERDAL | Atypical antipsychotic |
| simvastatin**** | FLOLIPID, ZOCOR | Cholesterol-lowering statin |
| theophylline** | ELIXOPHYLLIN, THEO-24, THEOCHRON | Asthma drug |
| voriconazole | VFEND | Antifungal drug |
| warfarin | JANTOVEN | Anticoagulant/blood thinner |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***The 80-milligram dose of simvastatin is designated as Do Not Use.
Other important drug interactions[9]
Some of the other notable drug interactions for carbamazepine include the following:
- Concomitant use of carbamazepine with the bipolar disorder drug lithium (LITHOBID) may increase the risk of neurological toxicity.
- Concomitant use of carbamazepine with hormonal birth control pills may render these contraceptives ineffective, increasing the risk of unintended pregnancy.
- Concomitant use of carbamazepine with the tuberculosis drug isoniazid (available in generic only) increases the risk of isoniazid-induced liver toxicity.
What You Can Do
If you need treatment with carbamazepine, review all your other medications with your doctor to assess for potentially significant drug interactions. If any of your medications interact with carbamazepine, you may need to adjust the dosage of carbamazepine, the interacting drug or both. You also may need to undergo more frequent monitoring of the blood levels of carbamazepine or, in some cases, the interacting drug, or your doctor may advise you to take a different drug. Be aware that other drugs not listed in this article also may have dangerous interactions with carbamazepine.
References
[1] Food and Drug Administration. Medical officer review of NDA 16-608. April 19, 1967. https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/016608_Med_rvw.pdf. Accessed January 10, 2021.
[2] Ho CC, Khan SA, Whealy MA. Trigeminal neuralgia. UpToDate. August 3, 2020.
[3] Novartis. Label: carbamazepine (TEGRETOL). March 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053&type=display. Accessed January 10, 2021.
[4] Validus Pharmaceuticals. Label: carbamazepine (EQUETRO). September 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021710s11s012lbl.pdf. Accessed January 10, 2021.
[5] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “carbamazepine.” Accessed January 10, 2021.
[6] Novartis. Label: carbamazepine (TEGRETOL). March 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053&type=display. Accessed January 10, 2021.
[7] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “carbamazepine.” Accessed January 10, 2021.
[8] Novartis. Label: carbamazepine (TEGRETOL). March 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053&type=display. Accessed January 10, 2021.
[9] Ibid.
