Oxcarbazepine (Trileptal, Novartis)
Oxcarbazepine (Trileptal) is not yet well known in the US medical community, but is a drug of some importance in the treatment of partial and secondarily generalized seizures. The Food and Drug Administration (FDA) has approved use of Trileptal as a first-line drug in monotherapy (as a single drug).
Oxcarbazepine is structurally identical to carbamazepine (Tegretol), except for a double-bond oxygen molecule (a keto group) on the 10-11 position of the triple-ring structure. This oxygen molecule prevents metabolism to the epoxide form of the drug. Since the epoxide form accounts for some of the toxicity of Tegretol, Trileptal may have a better therapeutic/toxic profile, at least in some users. Trileptal is not effective against absence or myoclonic seizures.
Trileptal is a different drug from Tegretol / Tegretol-XR / Carbatrol, although in the same family. Advantages of Trileptal over the older carbamazepines include: fewer drug interactions, need to take only twice daily, less auto-induction in the liver (the phenomenon of lower blood levels on constant dose because of increased liver clearance in the first 2 months of use), less interference with oral contraceptives; possibly better therapeutic ratio. The side effects of oxcarbazepine are similar to those of carbamazepine.
A side effect seen more with Trileptal than Tegretol is hyponatremia, or low blood sodium. The blood sodium is low, not from a deficiency of salt, but because of greater retention of water, which dilutes the sodium. Normal serum sodium is 135-145 mEq/L. At serum sodium concentrations less than 120 mEq/L, people can become confused and experience worsening of seizures.
Effects tend to be more severe in cases of rapid reduction of sodium, compared to declines over many weeks. Excessively rapid correction of low sodium also can cause problems. I usually reduce or discontinue Trileptal or Tegretol for serum sodium less than 125 mEq/L,but each case should be considered in the context of how much the drug is helping the seizures, and whether there are good alternatives.
No drug, old or new, has been proven to be more effective than is carbamazepine (Tegretol) for partial seizures. Given that oxcarbazepine has similar effectiveness to that of carbamazepine, and may have fewer side effects (except for hyponatremia), it stands out as a first-line dug for many patients. I sometimes use it as a first drug of choice for partial seizures, with or without secondary generalization. The reasons against using it in all patients (versus the more traditional Tegretol or Dilantin) are higher cost and less of a long-term track record.
Summary Data for Oxcarbazepine
Pill sizes: 150, 300 600 mg all tan, scored tablets.
Liquid for oral: 300 mg/5 ml suspension. Injectable: None, although the active metabolite, monohydroxy derivative has been in clinical trials for intravenous use.Typical adult dose: The manufacturer recommends a starting dose of 600 mg per day. Dr. Fisher says his experience shows this results in excessive toxicity. If seizures are not very severe or frequent, he begins with 300 mg/d (150 mg twice a day), and increases 150 mg per week to a target daily dose of 1,200 - 2,400 mg/d. If a patient is on Tegretol, then he immediately switches to approximately the same daily milligrams of Trileptal, and over the next few weeks, increase to 1.5 times the daily milligrams of Tegretol.
Typical pediatric dose: Start with 8-10 mg/kg/d (maximum 600 mg/d), and increase over several weeks to 20-50 mg/kg/d.
Metabolism: Metabolized outside the liver to the mono-hydroxy derivative (MHD), which is the active compound. The MHD then is eliminated by glucuronidation in the liver.
Half-life: The active MHD metabolite has a half-life of 8-10 hrs, longer in patients with kidney disease.
Serum levels: MHD metabolite 12-30 mcg/ml.
Pregnancy: Category C - can cause birth defects in animals, unknown in humans.
Drugs that raise OXC levels:
Drugs that lower OXC levels: Dilantin, phenobarbital, carbamazepine.
OXC increases effects of: Dilantin, tricyclic antidepressants.
OXC decreases effects of other drugs: Lamotrigine, felodipine, dihydropyridine calcium blockers, Verapamil, oral contraceptives.
Dangerous Side Effects
Worsening of seizures (especially atypical absence) with toxic doses.
Common Side Effects
Blurred vision, sedation, dizziness, unsteadiness, GI upset.
Other Side Effects
Behavior or mood changes, headaches, rash, inactivation of birth control pills.