Anticonvulsant hypersensitivity syndrome: cross-reactivity with tricyclic antidepressant agents.
BACKGROUND
Aromatic anticonvulsant agents such as carbamazepine and phenytoin can induce anticonvulsant hypersensitivity syndrome (AHS) at a frequency of 1 in 10,000 to 1 in 1,000 treated patients. The hypersensitivity syndrome is a potentially life-threatening adverse drug reaction with multiorgan involvement, and incidental reexposure must be strictly avoided. Patients and treating physicians must be informed and educated about the causal drug and its potential immunologic or toxicologic cross-reactivity with other compounds. It has been well established that for future antiepileptic drug therapy, carboxamides (carbamazepine and oxcarbazepine), phenytoin, and barbiturates (phenobarbital and primidone) have to be avoided owing to their high degree of cross-reactivity. Other anticonvulsant agents, such as valproic acid, benzodiazepines, and gabapentin, may be prescribed.


OBJECTIVE
To present the clinical data for and to describe the potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant agents in patients with carbamazepine- and phenytoin-induced AHS.


METHODS
The knowledge of cross-reactivity among aromatic anticonvulsant agents mainly emerged from clinical experience and observations because diagnostic challenge tests are not advisable. Thirty-six patients with the diagnosis of AHS were instructed to contact our unit if the symptoms relapsed.


RESULTS
Despite better knowledge of AHS, one third of the patients had avoidable recurrences after exposure to cross-reactive drugs. Besides the known cross-reactivity among aromatic anticonvulsant agents, we observed a recurrence of the hypersensitivity syndrome in 5 patients after the administration of tricyclic antidepressant agents.


CONCLUSIONS
The important potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant drugs should be brought to the attention of treating physicians.
Seitz
Cornelia S
CS
Department of Dermatology, Venerology, and Allergology, University of Würzburg, Würzburg, Germany.
Pfeuffer
Petra
P
Raith
Petra
P
Bröcker
Eva B
EB
Trautmann
Axel
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000588:Amines / Q000627:therapeutic use; D000639:Amitriptyline / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D003429:Cross Reactions; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004316:Doxepin / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D010672:Phenytoin / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D012882:Skin Tests / Q000706:statistics & numerical data; D013577:Syndrome; D014635:Valproic Acid / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D003509:Cyclohexanecarboxylic Acids; D001569:Benzodiazepines; D004316:Doxepin; D000639:Amitriptyline; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; D000077206:Gabapentin