Multidisciplinary adverse drug reaction surveillance program.

Initial experience with a multidisciplinary adverse drug reaction (ADR) surveillance program at a 350-bed community hospital center is described. The pharmacy and quality-review (QR) departments developed a program that was incrementally incorporated into the hospital's overall QR activity. After inservice training, nurses and QR personnel were asked to complete an "alert" card for every suspected ADR and send it to the pharmacy. In addition, medical records were reviewed retrospectively for disease classification codes related to drug toxicity and unspecified adverse effects. Laboratory and utilization-review personnel also conducted retrospective reviews. A pharmacist reviewed all ADR reports and categorized each according to the severity of the reaction and the probability that it was drug related. For each reaction classified as severe, the patient's chart underwent physician peer review for appropriateness of therapy, avoidability of the reaction, and adequate documentation; related patient-care issues were addressed by the medical staff as part of routine quality-review activities. When problems with prescribing were identified, the pharmacy and therapeutics committee intervened with the prescribers or recommended further medical staff review. Drugs repeatedly associated with ADRs became the focus of drug-use reviews. The number of ADR reports increased from 0 to 134 in the first 11 months of the program. A multidisciplinary approach to ADR reporting increased the number and quality of ADR reports.

Phenytoin-induced hypersensitivity reactions.

A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old black woman with a two-month history of seizure disorder was admitted to a hospital with nausea, vomiting, fever, lymphadenopathy, diffuse maculopapular rash, left-upper-quadrant tenderness, and hepatomegaly. She was receiving phenytoin sodium 300 mg/day; carbamazepine 200 mg four times daily had been discontinued four days before admission because of leukopenia. Phenytoin was discontinued after admission; however, phenytoin 1 g i.v. was given for a tonic-clonic seizure two days after admission, after which swelling of the face and legs and pruritus developed. Over the next few days, signs and symptoms of hepatotoxicity progressed, and she became comatose. Seizures were treated with diazepam. She began to recover after 10 days of supportive therapy and was discharged several weeks later on primidone therapy. Serious phenytoin hypersensitivity reactions may appear as dermatologic, lymphoid, or hepatic syndromes. Fever, rash, and lymphadenopathy often accompany hepatic injury. Encephalopathy and death may occur. Proposed mechanisms for phenytoin hypersensitivity include antigen-antibody reactions, alteration of lymphocyte function, and an enzyme abnormality causing the production of toxic metabolites. Treatment is supportive; phenobarbital and carbamazepine may be used with caution as alternate anticonvulsant therapy. The possibility of phenytoin hypersensitivity reactions should be considered when patients receiving phenytoin have unusual symptoms, particularly fever, rash, and lymphadenopathy.