Anti-epileptics: Side Effects

• All probably have some effect on behavior and school performance
• phenobarbital causes cognitive impairment and behavioral side effects most frequently (in up to 50% of children). Decline in intelligence quotient, decreased attention, depression, or hyperactivity has been reported in
  50% or more of patients receiving phenobarbital. Sedation is dose-related, but cognitive impairment can be idiosyncratic.
• Primidone is metabolized to phenobarbital and may result in similar effects, especially aggressive behavior or personality changes.
• valproic acid
  • least likely to affect behavior and cognitive performance adversely.
  • Valproic acid does not produce rage attacks; in fact, it has been used for their treatment.
  • can be associated with weight gain, thrombocytopenia, tremor, and fulminant hepatic failure, particularly in children younger than age 3 years who are receiving multiple antiepileptic medications.
• Carbamazepine
  • rarely causes significant leukopenia or hepatotoxicity and seldom produces hyponatremia.
  • Macrolides such as erythromycin and  azithromycin should be used very cautiously or, if possible, avoided in children receiving carbamazepine because these drugs compete for hepatic metabolism, leading to increasing carbamazepine levels and acute toxicity.
• Phenytoin is similar to carbamazepine in efficacy for seizures, but it is used less commonly in children because of significant cosmetic adverse effects, including
  • hirsutism, gingival hyperplasia, and facial coarsening.
  • Phenytoin is poorly absorbed from the gastrointestinal tracts of infants and metabolized at a variable rate in the liver.
• Lamotrigine is used in a number of refractory seizure disorders and generally is well tolerated
  • occasional drowsiness, headache, and blurred vision.
  • associated with the development of maculopapular rash that may progress to Stevens-Johnson syndrome during the early months of use, especially when administered with valproate. The development of such a rash should prompt immediate drug discontinuation.
  • In an attempt to avoid these reactions, lamotrigine is administered initially at a low dose and very gradually increased over months, particularly if valproate also is being administered.
• Gabapentin, a second or add-on drug for partial seizures, usually is well tolerated.
  • not metabolized by the  liver and is excreted unchanged by the kidneys, it has no significant drug interactions.
  • Adverse effects include very occasional fatigue, dizziness, headache, and weight gain.
• Benzodiazepines, such as clonazepam or clorazepate, can produce significant behavioral abnormalities as well as drowsiness and irritability.

  Topamax

  - inhibits carbonic anhydrase, thereby increasing renal excretion of bicarb, so watch out for metabolic acidosis. Decreases in serum bicarb are mild to moderate, rarely severe.  Acute metabolic acidosis can cause hyperventilation, fatigue, anorexia, cardiac arrythmias, and stupor.
  - monitor serum bicarb when starting therapy or increasing dose. Reduce dose or dc topamax if metabolic acidosis develops.

   

References:
Freeman JM, Vining EP, Pillas DJ, eds. Seizures and Epilepsy in Childhood: A Guide for Parents. 2nd ed. Baltimore, Md: Johns Hopkins University Press; 1997 Freeman JM, Vining EP. Decision making and the child with afebrile seizures. Pediatr Rev. 1992;13:305-310 Haslam RH. Nonfebrile seizures. Pediatr Rev. 1997;18:39-49 Haslam RH. Seizures in childhood. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co;  2000:1813-1829