Regulatory Affairs Syndicator

A nationwide investigation of a possible protamine drug-product defect.

Ann Pharmacother. 1992 May;26(5):643-4

Authors: Herrera CR, Grasela TH, Walawander CA

OBJECTIVE: To follow-up a report submitted to FDA Spontaneous Reporting System, we investigated the hypothesis that there was not a striking increase in unexpected deaths within four hours after elective coronary artery bypass surgery associated with protamine sulfate use. DESIGN: Surveys were mailed to clinical pharmacists at 521 hospitals participating in the Drug Surveillance Network. Questionnaires were to be completed with the assistance of cardiac surgeons and anesthesiologists. Hospitals responding with a suspected problem with protamine were contacted via telephone. RESULTS: Surveys were received from clinical pharmacists at 380 hospitals (73 percent response rate) and 29 hospitals reported the occurrence of potential problems associated with protamine during coronary artery bypass graft surgery. Telephone interviews of the positive responders yielded six cases of possible myocardial decomposition potentially associated with protamine. There was no association with a specific distributor, however, and none of the hospitals reported a dramatic increase in serious adverse events around the time of index cases. CONCLUSIONS: There was no evidence of a widespread public health problem with protamine and a product recall was not necessary. The high response rate and the ability to follow-up with telephone interviews suggests that the Drug Surveillance Network is an effective mechanism for investigating possible outbreaks of serious adverse events in the hospital setting.

PMID: 1591423 [PubMed - indexed for MEDLINE]

Necrotizing soft tissue infections reported with nonsteroidal antiinflammatory drugs.

Ann Pharmacother. 1997 Sep;31(9):1034-9

Authors: Kahn LH, Styrt BA

BACKGROUND: Recent reports of necrotizing fasciitis in children with varicella who received a nonsteroidal antiinflammatory drug (NSAID) recall earlier concerns regarding the possibility of relationships between infections and NSAIDs. We searched the Food and Drug Administration’s Spontaneous Reporting System (SRS) for necrotizing soft tissue infections reported in conjunction with the use of NSAIDs, to identify common features. METHODS: A computer search of NSAID listings in the adverse event database recovered reports with codes for selected infection and necrosis-related diagnostic categories. From review of individual reports classified under these codes, cases were selected if the terms "necrotizing fasciitis," "necrotic," or "gangrenous" appeared in the adverse drug reaction description. Demographic, drug use, and disease course information were gathered. FINDINGS: Thirty-three cases were identified, of which 10 were fatal. Over two-thirds of the patients were younger than 40 years. Thirty (91%) had a possible portal of entry for infection. Most received NSAIDs for acute conditions including varicella, trauma, and postoperative or postpartum pain; 7 received an NSAID by intramuscular injection. Specific NSAIDs accounting for most reports were also among those likely to be most heavily used in the relevant populations. INTERPRETATION: Common features of these rare case reports of necrotizing soft tissue infections with NSAID use include characteristics such as age, portal of infection entry, indication for NSAID use, route of administration, and individual NSAIDs. The total number of SRS cases does not suggest that necrotizing infection is frequent with NSAIDs or likely without other risk factors. Controlled observational studies would help to define any causal contribution of these factors to the evolution of severe infection.

PMID: 9296245 [PubMed - indexed for MEDLINE]