Subject(s)
Anti-Bacterial Agents/adverse effects , Fever/chemically induced , Gentamicins/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Child , Child, Preschool , Drug Administration Schedule , Endotoxins , Female , Gentamicins/administration & dosage , Humans , Male , Middle AgedABSTRACT
This report summarizes postmarketing adverse events reported to the Food and Drug Administration (FDA) that describe unusual or abnormal fat distribution in association with anti-retroviral therapies. Reports associated will protease inhibitors were compared to those associated with non-protease inhibitor antiretroviral therapies. The Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) of the FDA MEDWATCH post-marketing surveillance system served as the database. Four protease inhibitors (saquinavir, indinavir, nelfinavir, and ritonavir) and seven nonprotease inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, nevirapine, and delavirdine) were searched for reports relating to: weight increase, unusual fat deposition, Cushing's syndrome, or Cushingoid appearance. Each drug was searched for its "life" from time of initial approval through a uniform database cutoff of March 18, 1998. A total of 62 cases of abnormal fat accumulation were reported in association with one or several of the four approved protease inhibitors compared to three cases reported in association with the seven non-protease inhibitor based therapies. Case descriptions varied, and included abdominal fat accumulation, breast enlargement, thick necks, buffalo humps, multiple lipomatous growths, Cushingoid features, centralized fat redistribution, and mesenteric, omental, and retroperitoneal fat accumulation. Some subjects switched or stopped their antiretroviral therapy, others underwent surgery to remove the fat, and many considered their symptoms disabling. The pathophysiologic mechanism for these events remains unclear and a causal link to a specific drug or drug class is uncertain. Patients and clinicians reporting to the MEDWATCH system, however, have clearly associated the development of abnormal body fat with protease inhibitors as opposed to other antiretroviral therapies.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Adipose Tissue/drug effects , Anti-HIV Agents/adverse effects , Body Composition/drug effects , Cushing Syndrome/chemically induced , HIV Protease Inhibitors/adverse effects , Adult , Adverse Drug Reaction Reporting Systems , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , United States , United States Food and Drug AdministrationABSTRACT
Trends in the reporting of serious adverse events directly to FDA between 1992 and 1994 and the quality of reports before and after the June 1993 launching of MedWatch were studied. Computerized data were used to assess changes between 1992 and 1994 in the proportion of adverse-event reports to FDA classified as serious. To evaluate the quality of reports, every third report received during April 1993 (sample size, 254) and April 1994 (263) was evaluated for 21 variables and to determine whether the event was serious. For the first analysis, a serious adverse event was defined as one that resulted in death, hospitalization or prolongation of hospitalization, or disability; for the second, the outcome of a threat to life was also included. The proportion of reports that were serious increased from 34% in 1992 to 49% in 1994. The overall quality of the reports made in 1994 was higher than that of the 1993 reports. In particular, significantly higher percentages of reports in 1994 indicated whether the drug was a new molecular entity, indicated whether the event was serious, and gave laboratory and clinical information in support of the event diagnosis. Reports from pharmacists increased both in number and in quality. Physicians' reports were of high quality in both years, but the number of reports they made decreased. The proportion of adverse-event reports classified as serious increased between 1992 and 1994, and the quality of event reporting to FDA improved since the introduction of MedWatch.
Subject(s)
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Health Personnel/statistics & numerical data , Humans , Product Surveillance, Postmarketing , Quality Assurance, Health Care , United States , United States Food and Drug AdministrationABSTRACT
OBJECTIVE: To report the first five cases of amphotericin B overdose with secondary cardiac complications in a pediatric population. Treatment is also presented. SETTING: Hospital. PATIENTS: Two infants and three children inpatients receiving amphotericin B. INTERVENTIONS AND RESULTS: Cardiac complications were observed in five pediatric patients who received between 4.6 and 40.8 mg/kg/d of amphotericin B. Cardiac arrest occurred in all patients, and four patients died. A detailed description of the cardiac event is provided for one patient who was on a cardiac monitor during the adverse reaction. Hydrocortisone prophylaxis and verapamil therapy were the primary therapies used in patient 1 (the only survivor). Evaluation of the literature provides substantial evidence for the use of hydrocortisone in prevention of cardiac arrhythmias. CONCLUSIONS: Amphotericin B overdose can be fatal in children and infants. The presentation in humans appears similar to that in dogs where cardiac arrhythmias occurred at doses of 5-15 mg/kg. Hydrocortisone may decrease the incidence of mortality associated with cardiac arrhythmias in children receiving amphotericin B overdoses. Animal studies are necessary to evaluate this observation and potential disadvantages of hydrocortisone usage.
