Safety of Anticonvulsants​​


The following agents are strongly porphyrinogenic, have been associated with acute attacks and should be avoided:

  • phenobarbital
  • primidone
  • phenytoin
  • mephenytoin
  • ethosuximde
  • methosuximide.

Use with only extreme caution

The following agents are of contentious safety, and are best avoided:

  • carbamazepine
  • valproic acid
  • topiramate
  • vigabatrin

Carbamazepine is of contentious safety. Some authors have described patients who tolerated it well whereas they had reacted poorly to other anticonvulsants. However, there are also a number of reports detailing clinical and biochemical deterioration in porphyria on carbamazepine; it is also porphyrinogenic in experimental systems and in human volunteers. We suggest that it be avoided.

Several lists have suggested that valproic acid is safe. However, review of the literature reveals a number of reports of clinical deterioration following valproic acid therapy or of failure to resolve until it was discontinued; it is also porphyrinogenic in both experimental systems and in normal human volunteers. We suggest that it be avoided.

Topiramate is a CYP inducer and should therefore be avoided, although there are no data on its clinical use.


The following agents appear to be the safest for use in porphyria:

  • clonazepam
  • gabapentin
  • lamotrigine

Clonazepam is weakly porphyrinogenic in experimental systems, and there are isolated reports of a rise in urine precursors on clonazepam therapy. However, several authors report that patients whose porphyria had deteriorated on agents such as phenytoin and carbamazepine were maintained in complete safety on clonazepam. It has been used safely on both a short- and a long-term basis in Cape Town for patients with active porphyria, and we regard it as a safe agent.

Gabapentin appears safe. Several patients in Cape Town have successfully used gabapentin for chronic control of epilepsy.

Lamotrigine is very little metabolised, and one would predict it is safe, though data are lacking .

Immediate Control of Seizures

There is no evidence that a single injection of a benzodiazepine such as diazepam is dangerous; we suggest diazepam or preferably clonazepam for the termination of seizures.