Carbamazepine dosing

In patients converted from carbamazepine, the typical maintenance doses of oxcarbazepine are 1.5 times the carbamazepine dose. 

Carbamazepine is more widely used for treating chronically agitated dementia patients. Its onset of action is delayed by several days to a couple of weeks therefore, other tranquilizing medications such as antipsychotics may need to be used when first starting carbamazepine. Carbamazepine doses have problematic side effects that require blood monitoring, and it also interacts with many medications. 

Carbamazepine Dose-related double vision, vertigo, gastrointestinal disturbance Idiosyncratic agranulocytosis, Stevens-Johnson syndrome, aplastic anemia... 

FIGURE 6—19. The anticonvulsant and mood stabilizer carbamazepine is a substrate for CYP450 3A4. It can also induce the metabolism of 3A4 by inducing more copies of the enzyme to be formed, thereby raising the enzyme activity of 3A4. Over time, therefore, carbamazepine doses may need to be increased to compensate for this increased metabolism. 

Both patients recovered with normalization of the serum sodium when the carbamazepine dose was tapered. 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

An epileptic patient taking carbamazepine 400 mg in the morning and 600 mg in the evening developed symptoms of toxicity (dizziness, nausea, ataxia and diplopia) within 2 days of starting to take diltiazem 60 mg three times daily. His serum carbamazepine levels had risen by about 40% to 21 mg/L, but fell once again when the diltiazem was stopped. No interaction occurred when the diltiazem was replaced by nifedipine 20 mg three times daily. Other case reports describe carbamazepine toxicity and a rise in serum levels of up to fourfold in a total of 11 patients given diltiazem. " One patient required a 62% reduction in the carbamazepine dose. Another patient had a marked fall in serum carbamazepine levels of 54% when diltiazem was stopped. For a further case report involving diltiazem, see Nifedipine, below. 

A 58-year-old man, taking carbamazepine 1 g daily for epilepsy developed visual disturbances with diplopia, and was found to have a carbamazepine level of 11 micrograms/mL (therapeutic range 4 to 10 micrograms/mL). Previous levels had not exceeded 5.4 micrograms/mL. The patient said that one month previously he had started to eat one whole grapefruit each day. The levels restabilised at 5.1 micrograms/mL after the carbamazepine dose was reduced to 800 mg daily. ... 

Five patients developed elevated serum carbamazepine levels and toxicity when nefazodone was given. A study in healthy subjects using lower carbamazepine doses found only modest increases in carbamazepine levels, and no evidence of toxicity when nefazodone was given. Carbamazepine markedly reduces nefazodone levels. 

A minor to modest fall in carbamazepine levels may occur, but there may be a moderate to marked rise in the active epoxide metabolite. Therefore, be alert for signs of toxicity, which may indicate high levels of carbamazepine-10,11-epoxide and a need to reduce the carbamazepine dose. 

However, a further study of the efficacy of remaeemide and carbamazepine in combination found fhaf abouf fwo-fhirds offhe 120 patients treated needed 14 to 50% reductions in their carbamazepine dose, to ensure levels remained in the therapeutic range. ... 

Mawer GE, Jamieson V, Lucas SB, Wild JM. Adjustment of carbamazepine dose to offset the effects of the interaction with remaeemide hydrochloride in a double-blind, multicentre, addon drug trial (CR2237) in refractory epilepsy. Epilepsia (1999) 40,190-6. 

Kerr BM, Maitinez-L e JM, Viteri C, Tot J, Edrfy AC, Levy RH. Carbamazepine dose requirements during stiripentol therapy influence of cytochrcxne P-450 inhibitiOTi by stiripen-toL Epilepsia (1991) 32,267-74. 

Topiramate plasma levels may be reduced by carbamazepine. Carbamazepine levels are not affected by topiramate. However, one report suggests that the toxicity seen when topiramate is added to maximum tolerated doses of carbamazepine may respond to a reduction in the carbamazepine dose. 

In a study in 12 epileptic patients topiramate titrated up to a maximum of 400 mg twice daily had no effect on the steady-state plasma levels of carbamazepine 300 to 800 mg every 8 hours or on its main metabolite, carbamazepine-10,11-epoxide. An earlier study in epileptic patients also reported that topiramate does not affect the pharmacokinetics of carbamazepine. In contrast, another report describes 2 patients taking a maximum tolerated dose of carbamazepine who started treatment with topiramate and subsequently developed symptoms suggestive of carbamazepine toxicity. In both these cases, the symptoms resolved when the carbamazepine dose was reduced, and this enabled continued titration of the topiramate dose in one. A review of the clinical use of these two drugs found another 23 cases that fitted this pattern. Carbamazepine levels were not reported. ... 

An HIV-positive patient who had a serum carhamazepine level of 10.3 mg/L while taking carbamazepine 400 mg three times daily reported feeling very drowsy within 9 days of starting to take tenofovir, lamivudine and lopinavir/ritonavir 400/100 mg twice daily. His carhamazepine serum level was found to have increased by 46%, to 15 mg/L. The carbamazepine dose was reduced to 400 mg twice daily, and 2 days later the carbamazepine level was 7.4 mg/L. ... 

Makmor-Bakry M, Sills GJ, Hitiris N, Butler E, Wilson EA, Brodie MJ. Genetic variants in microsomal epoxide hydrolase influence carbamazepine dosing. Clin Neuropharmacol 2009 32(4) 205-12. 

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