Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978-1985.

Between September 1978 and December 1985, 450 case reports of serious respiratory and cardiovascular events and 32 case reports of death attributed to ophthalmic timolol were received by the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects. Two hundred sixty-seven patients (55%) experienced a cardiac arrhythmia or a bronchospasm-related event. The median age was 68 years (n = 365). Fifty-five percent of the patients were women and 45% were men (n = 41). Of the 212 persons for whom medical history was provided, 129 (61%) had respiratory disease, 65 (31%) had cardiovascular disease, 13 (6%) had other illnesses, and five (2%) had no underlying illness. Of the 318 patients for whom data on duration of drug use were available 106 (33%) experienced their adverse event within one week of beginning timolol therapy: 73 (23%) had their events on the first day of therapy. Of 192 patients for whom information was available 177 (92%) improved after the drug was discontinued.

Food and Drug Administration monitoring of adverse drug reactions.

Food and Drug Administration requirements for reporting adverse drug reactions (ADRs), processing of ADR reports, and actions in response to these reports are described. FDA requires that drug manufacturers report ADRs to the FDA Division of Epidemiology and Surveillance; 90% of the ADR reports received are from manufacturers. Of the remaining 10%, one third are from pharmacists. FDA regulations were revised in 1985 to specifically define reportable ADRs and procedures for reporting; manufacturers are required to report within 15 days reactions that are serious and unlabeled. For newly approved drugs, reports on ADRs must be submitted quarterly for three years; subsequently, annual reporting is required. Any increase in the frequency of serious, labeled reactions must be reported. Serious reactions not listed in the product labeling must be reported for products marketed before 1962 for which new drug applications or abbreviated new drug applications were not filed. ADR information received by FDA is coded into standard terms and entered in a computerized database for evaluation by reviewers. If an important reaction is suspected, the report is entered in a tracking system for further monitoring. ADR reports may result in requirements for changes in product labeling, "Dear Doctor" letters, requirement of further study by the manufacturer, or withdrawal of the product. Information about ADRs is communicated to health-care practitioners in product labeling and in the literature. Pharmacists are encouraged to report suspected serious and unlabeled reactions to FDA so that the medical community and the public can benefit from current information about drug safety.

Rifampicin-induced renal failure.

Renal failure is a rare complication associated with the use of rifampicin for the treatment of tuberculosis, usually occurring well into the course of therapy. The following is a report of 2 cases of rifampicin-induced renal insufficiency. In the first case oligo-anuric renal failure occurred on the thirteenth day of treatment, after the patient had taken only 9 doses of medication. The second case occurred in a patient who developed renal failure while on daily therapy in the hospital. A literature review revealed 83 other reported cases of rifampicin-induced renal insufficiency. Intermittent or interrupted therapy appears to be a significant risk factor for the development of this complication.

Juvenile discitis.

Over a period of three years four girls and two boys presented with discitis. All were less than 5 years old at presentation, and each had a short history of symptoms. Three were initially thought to have pathological defects of the abdomen. All children showed abnormal posturing with exaggerated lumbar lordosis. Diagnosis was essentially clinical. All cultures were sterile. The erythrocyte sedimentation rate was increased in all the children and all had mild pyrexia. Symptoms lasted from two to 8 weeks. Discitis should be considered in any child with fever, abnormal posturing, and refusal to walk. Early recognition may avoid unnecessary diagnostic and treatment procedures.