Total cholesterol in patients taking ERC-CBZ also rose 12% to 13% in the double-blind studies.2,3 Consider dietary and/or cholesterol-lowering medications in patients taking ERC-CBZ who are at high risk for cardiovascular events.
In the 6-month open-label study, headache, dizziness, and benign rash were most frequently reported. No serious adverse events related to the study drug were reported.
Table 2
Carbamazepine’s common to rare side effects
| Common | Infrequent |
| Ataxia | Hyponatremia (asymptomatic to symptomatic, reversed by demeclocycline or lithium) |
| Benign rash | Liver enzyme elevations |
| Benign white blood cell count suppression (reversed by lithium) | Tremor |
| Decreased thyroid hormones | Weight gain |
| Diplopia | Rare/serious |
| Dizziness | Agranulocytosis |
| Fatigue, sedation | Aplastic anemia |
| Increased cholesterol | Hyponatremia (symptomatic) |
| Nausea | Severe rash
|
| Spina bifida (following in utero exposure) |
INTERACTIONS WITH OTHER MEDICATIONS
Because of its potent induction of CYP 3A4 enzymes,6 carbamazepine in any form may substantially lower blood levels of several compounds metabolized principally by CYP 3A4 isoenzymes (Table 3), including typical antipsychotics such as haloperidol and the atypical antipsychotic aripiprazole. Even so, patients often improve with combination carbamazepine/haloperidol therapy despite lower haloperidol blood levels.
If a patient is taking oral contraceptives, inform her primary care physician or OB/GYN when prescribing carbamazepine. Because the anticonvulsant lowers circulating estrogen, a higher contraceptive dosage or alternate birth-control method should be considered to prevent unwanted pregnancy.
Most other drug-drug interactions have been well-delineated and can be avoided. Inform the patient and his or her primary care physician when giving carbamazepine concomitantly with any drug.
Numerous medications can also increase serum carbamazepine levels, causing problems in a patient already near his or her side-effect threshold (Table 4). Reduce the carbamazepine dosage to avoid these adverse effects.
Table 3
Carbamazepine decreases serum concentrations of these drugs
| Antipsychotics | Analgesics |
| Buprenorphine | Aripiprazole* |
| Methadone | Clozapine |
| Antimicrobials | Haloperidol* |
| Caspofungin | Olanzapine* |
| Doxycycline | Risperidone* |
| Anticoagulants | Thiothixene |
| Warfarin*† | Ziprasidone* |
| Anticonvulsants | Antivirals |
| Carbamazepine*† | Delavirdine |
| Lamotrigine*† | Protease inhibitors† |
| Oxcarbazepine | Anxiolytics/sedatives |
| Phenobarbital | Alprazolam* |
| Phenytoin | Steroids |
| Topiramate | Estrogen in hormonal contraceptives*† |
| Valproate*‡ | Mifepristone |
| Zonisamide | Prednisolone* |
| Antidepressants | Stimulants |
| Bupropion* | Methylphenidate* |
| Citalopram* | Modafinil* |
| Mirtazapine | Others |
| Tricyclics | Cisplatin |
| Doxorubicin | |
| Theophylline | |
| * Carbamazepine is often given with this medication. | |
| † Potentially serious interaction. | |
| ‡ Less-serious interaction likely with carbamazepine. | |
Table 4
These drugs increase serum carbamazepine and may cause toxicity
| Anticonvulsants | Macrolide antibiotics |
| Valproate (increases carbamazepine 10, 11-epoxide levels)*† | Clarithromycin*† |
| Antidepressants | Erythromycin*† |
| Fluoxetine*‡ | Flurithromycin*† |
| Fluvoxamine*‡ | Josamycin*† |
| Nefazodone*‡ | Ponsinomycin*† |
| Antimicrobials | Triacetyloleandromycin*† |
| Isoniazid† | Others |
| Quinupristin/dalfopristin | Acetazolamide |
| Calcium channel blockers | Cimetidine§ |
| Diltiazem*† | Danazol |
| Verapamil*† | d-Propoxyphene‡ |
| Hypolipidemics | Ketoconazole† |
| Gemfibrozil | Niacinamide |
| Nicotinamide | Omeprazole |
| Ritonavir† | |
| Ticlopidine | |
| * Carbamazepine is often given with this medication. | |
| † Potentially serious interaction. | |
| ‡ Less-serious interaction likely with carbamazepine. | |
| § Data on interactions with carbamazepine unclear. | |
CLINICAL IMPLICATIONS
Long-acting carbamazepine suitable for single nighttime dosing should facilitate adherence and reduce daytime side effects. Consider ERC-CBZ for patients not responding adequately to lithium or valproate, as individual response to any of these three drugs can vary greatly. Sideeffect tolerability (such as less weight gain with carbamazepine than with valproate) also could help guide drug choice. In patients with rapid cycling, carbamazepine plus lithium may be more effective than either drug alone.
New data suggest that carbamazepine offers acute antidepressant effects in some individuals and in long-term depression treatment.5 More research is needed to identify depressed patients most likely to respond to this agent.
For now, when using ERC-CBZ, we can draw from the larger experience with immediate-release carbamazepine to treat epilepsy, bipolar disorder, and related mood disorders. Once you master carbamazepine’s pharmacokinetic interactions with other commonly used agents, ERC-CBZ in slowly titrated, single nighttime dosages should simplify the compound’s administration and tolerability.
Related resources
- Carbamazepine (extended-release) Web site. www.equetro.com.
- Post RM, Speer AM, Obrocea GV, Leverich GS. Acute and prophylactic effects of anticonvulsants in bipolar depression. Clin Neurosci Res 2002;2:228-51.
- Denicoff KD, Smith-Jackson EE, Disney ER, et al. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry 1997;58:470-8.
Drug brand names
- Aripiprazole • Abilify
- Carbamazepine (extended-release) • Equetro
- Carbamazepine (immediate-release) • Tegretol, others
- Haloperidol • Haldol
- Lithium • Eskalith, others
- Valproate • Depakote
Disclosure
Dr. Post reports no current financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.