Cross Hypersensitivity Syndrome between Phenytoin and Carbamazepine

Pharm World Sci. 2005 Jun;27(3):170-4. doi: 10.1007/s11096-004-1736-z.


Objective: To evaluate the incidence of cross anticonvulsant hypersensitivity syndrome (AHS) between phenytoin (PHT) and carbamazepine (CBZ) in hospitalized patients.

Method: Retrospective chart review about the cross AHS was retrieved from pharmacy adverse drug reaction program from 1998 to 2002 in a 450-bed teaching hospital.

Main outcome measures: AHS was defined as the appearance of at least two symptoms with the first anticonvulsant drug (ACD). Cross AHS was considered if after withdrawal of a first ACD because of hypersensitivity symptoms, a new episode with similar or new symptoms appeared after exposure to a second ACD. The following symptoms were considered- rash, fever, hepatotoxicity, lymphadenopathies or hematological disturbances.

Results: Cross AHS between PHT and CBZ was observed in nine cases (45). After the cross-reaction event, four of them were treated with valproic acid, two with vigabatrin, two with phenobarbital and one with no treatment without developing further AHS.

Conclusions: AHS is a severe complication of aromatic ACD that can compromise the future choice of therapy. Because of the high incidence of clinical cross-reaction between these two drugs, non-aromatic ACD alternatives, must be considered.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects*
  • Carbamazepine / adverse effects*
  • Child
  • Child, Preschool
  • Cross Reactions
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / enzymology
  • Drug Hypersensitivity / epidemiology*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Phenytoin / adverse effects*
  • Retrospective Studies


  • Anticonvulsants
  • Carbamazepine
  • Phenytoin