Examining product risk in context. Market withdrawal of zomepirac as a case study.

OBJECTIVE To examine changes in the prescribing of analgesics after the market entry and subsequent withdrawal of zomepirac sodium, a nonsteroidal anti-inflammatory drug (NSAID), following repeated reports of zomepirac-related deaths. DESIGN To evaluate this natural quasi experiment, we conducted time-series analyses to compare prescribing in two cohorts of primary care physicians from July 1980 through September 1983. SETTING Study physicians provided outpatient pharmaceutical care to patients enrolled in the New Jersey Medicaid program. PARTICIPANTS We identified 260 primary care physicians who provided 10 or more prescriptions for zomepirac (zomepirac prescribers) and 308 who provided 10 or more prescriptions for NSAIDs other than zomepirac (other-NSAID prescribers) in Medicaid during the study period. MAIN OUTCOME MEASURES Monthly rates of prescribing for zomepirac and several categories of substitute analgesics among Medicaid patients seen by study physicians. MAIN RESULTS Zomepirac accounted for a stable 11.0% of analgesic prescribing among the zomepirac-prescriber cohort; label changes and manufacturer product-risk warnings 11 months before the product's withdrawal from the market had no impact on use. After market entry, zomepirac prescribers reduced use of other NSAIDs and propoxyphene (hydrochloride or napsylate) in comparison with other-NSAID prescribers (-8.1% and -2.8% of total analgesic prescribing, respectively; P < .001). After the product's withdrawal from the market, zomepirac prescribers showed significant increases in relative prescribing of other NSAIDs (+6.8%; P < .001), propoxyphene (+2.1%; P < .05), and analgesics containing barbiturates (+2.7%; P < .001). CONCLUSIONS The sudden withdrawal of zomepirac from the market resulted in substitutions not only of other NSAIDs, but also of alternative analgesics that carry risks of habituation and adverse effects. Apparent gains in patient safety resulting from market withdrawal of medications must be evaluated in comparison with risks of medications likely to be substituted.

[1]  D. Knapp,et al.  Utilization of analgesic drugs in office-based ambulatory care: National Ambulatory Medical Care Survey, 1980-81. , 1984, Advance data.

[2]  R. Shochet,et al.  Analytic Reviews : Neuropsychiatric Toxicity of Meperidine , 1988 .

[3]  G. Heidrich,et al.  Central nervous system excitatory effects of meperidine in cancer patients , 1983, Annals of neurology.

[4]  W. Ray,et al.  Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. , 1992, Journal of gerontology.

[5]  S B Soumerai,et al.  Withdrawing payment for nonscientific drug therapy. Intended and unexpected effects of a large-scale natural experiment. , 1990, JAMA.

[6]  V. Smith.  Anaphylactic shock, acute renal failure, and disseminated intravascular coagulation. Suspected complications of zomepirac. , 1982, JAMA.

[7]  M. Henman,et al.  Impact of a Nationwide Limited Prescribing List: Preliminary Findings , 1987, Drug intelligence & clinical pharmacy.

[8]  K. Corre,et al.  Adverse drug reaction processing in the United States and its dependence on physician reporting: zomepirac (Zomax) as a case in point. , 1988, Annals of emergency medicine.

[9]  J. Avorn,et al.  Improving drug prescribing in primary care: a critical analysis of the experimental literature. , 1989, The Milbank quarterly.

[10]  J. Avorn,et al.  Effect of government and commercial warnings on reducing prescription misuse: the case of propoxyphene. , 1987, American Journal of Public Health.

[11]  D. Brahams.  Triazolam suspended , 1991, The Lancet.

[12]  B. Strom,et al.  The effect of indication on hypersensitivity reactions associated with zomepirac sodium and other nonsteroidal antiinflammatory drugs. , 1987, Arthritis and rheumatism.

[13]  J. Avorn,et al.  Physician motivations for nonscientific drug prescribing. , 1989, Social science & medicine.

[14]  W. Barclay.  AMA drug evaluations. , 1977, JAMA.

[15]  Stephen B. Soumerai,et al.  Payment Restrictions for Prescription Drugs under Medicaid , 1987 .

[16]  D. Makuc,et al.  Analysis of interrupted time series mortality trends: an example to evaluate regionalized perinatal care. , 1981, American journal of public health.

[17]  S. Soumerai,et al.  A critical analysis of studies of state drug reimbursement policies: research in need of discipline. , 1993, The Milbank quarterly.

[18]  M. Weintraub,et al.  Consequences of the 1989 New York State triplicate benzodiazepine prescription regulations. , 1991, JAMA.

[19]  E. Lesnefsky,et al.  Near fatal bronchospasm induced by zomepirac sodium. , 1982, Annals of allergy.

[20]  D. Kennedy,et al.  Utilization of nonsteroidal antiinflammatory drugs. , 1985, Arthritis and rheumatism.

[21]  Erwin K. Kastrup,et al.  Drug facts and comparisons , 1977 .

[22]  S. Gortmaker,et al.  Reducing infant mortality in rural America: evaluation of the Rural Infant Care Program. , 1987, Health services research.

[23]  A. Mack,et al.  Effect of regulatory withdrawal of drugs and prescription recommendations on the pattern of self-poisonings in Oslo. , 2009, Acta medica Scandinavica.

[24]  S B Soumerai,et al.  Payment restrictions for prescription drugs under Medicaid. Effects on therapy, cost, and equity. , 1987, The New England journal of medicine.

[25]  Smith Vt.  Anaphylactic Shock, Acute Renal Failure, and Disseminated Intravascular Coagulation: Suspected Complications of Zomepirac , 1982 .

[26]  S. Soumerai,et al.  Effects of professional and media warnings about the association between aspirin use in children and Reye's syndrome. , 1992, The Milbank quarterly.