Carbamazepine (Tegretol, Novartis; Carbatrol, Shire)
Carbamazepine has been in use in Europe since the 1950's and the United States since the 1960's. No drug has been shown to be more effective for partial seizures.
Advantages of carbamazepine include its effectiveness in partial and secondarily generalized seizures, and probably primarily generalized seizures. It is not effective for absence, atonic or myoclonic seizures. Carbamazepine is less sedating than are the barbiturates, and it probably is equivalent to phenytoin in this regard. Carbamazepine does not produce cosmetic side effects. Blood levels of carbamazepine easily are measured and an increase in dose produces a smooth increase in blood levels.
The typical carbamazepine dose in adults is 600 - 1,600 mg orally divided into 3 or 4 doses. These doses can safely be exceeded for intractable epilepsy patients. Therapeutic serum levels range 4 - 12 mg/L. Carbamazepine is metabolized to the 10, 11-epoxide, which may contribute to hidden toxicity to the medication.
Disadvantages of carbamazepine include the need to dose on a three or four times daily basis. This problem is partially obviated by the Tegretol-XR or the Carbatrol dosing forms, each of which can be taken twice daily. Carbamazepine can cause GI upset and double vision. It can lead to reversible decreases in white count, distinct from aplastic anemia, but still in need of following. Serum sodium declines in about 5 percent of people on chronic carbamazepine, sometimes limiting its use.
Rare cases of liver toxicity necessitate monitoring of blood tests. At least as many people are allergic to carbamazepine as to phenytoin: in one European study over 10 percent of people started on carbamazepine monotherapy developed a rash. Carbamazepine tablets inactivate easily in hot, moist environments (e.g., bathrooms) or in the sun. This problem can occur with all seizure medications, but particularly with carbamazepine.
If you use the Tegretol-XR form, you should know that empty pills are excreted in the stool - this is normal. Neither Tegretol-XR nor Carbatrol should be cut into pieces, since the intact capsule confers the slow release.
Summary Data for Carbamazepine
Pill sizes
Tegretol
100 mg (round, speckled white, chewable),
200 mg (oblong and pink);
Tegretol-XR100 mg (round orange pill with a T)
200 mg (round red pill with a T)
400 mg (round brown pill with a T)
Carbatrol
200 mg (turquoise/black & "200"¯)
300 mg (turquoise/black & "300"¯)
Liquid for oral: suspension 100 mg/5 ml
Injectable: None available.
Typical adult dose: Start with 100 mg twice a day. Increase 100 mg every 3-7 days to 400 - 1600 mg per day. It is not practical to load CBZ in an emergency.
Typical pediatric dose: 10-35 mg/kg/d, divided into 2-4 doses.
Metabolism: Liver (CYP 3A4). Becomes the epoxide. Excreted in urine.
Half-life: around 12 hours after a few weeks of use.
Therapeutic plasma concentrations: 4-12 mcg/ml.
Pregnancy: Category D - known to cause birth defects in humans.
Drugs that raise CBZ levels: Grapefruit juice (not a drug, but can seriously raise CBZ levels), antifungals, cimetidine, diltiazem, erythomycins (very significant), fluoxetine, isoniazid, omeprazole, protease inhibitors, propoxyphene (highly significant), verapamil. Felbamate and valproate incease the epoxide metabolite.
Drugs that lower CBZ levels: felbamate (but increases epoxide metabolite), methsuximide, phenobarbital, phenytoin.
CBZ increases effects of: acetaminophen toxicity, benzodiazepines, clozapine bone marrow toxicity, lithium, MAO inhibitors (serious toxic interaction)
CBZ decreases effects of other drugs: acetaminophen efficacy, antipsychotics, antifungals, buproprion, buspirone, coumadin, cyclosporin, felbamate, lamotrigine, methadone, narcotics, neuromuscular blockers, oral contraceptives, protease inhibitors, quetiapine, quinidine, risperidone, theophylline, thyroid hormone, tiagabine, topiramate, tricyclics, valproate, zonisamide.
Dangerous Side Effects
Blood toxicity, liver toxicity, Stevens-Johnson skin rash, severe lowering of serum sodium, birth defects, worsening of certain seizure types (atypical absence).
Common Side Effects
Blurred vision, GI upset.
Other Side Effects
Mild weight gain, unsteadiness, dizziness, mild lowering of blood counts, mild water retention and lowering of serum sodium, rash, mouth sores, sensitivity to the sun, behavior and personality changes, sexual dysfunction, inactivation of birth control pills.