An evaluation of the quinolone-theophylline interaction using the Food and Drug Administration spontaneous reporting system.

A review of the Food and Drug Administration's spontaneous reporting system identified 48 reports of adverse events in patients who received concomitant therapy with ciprofloxacin (n = 39) or norfloxacin (n = 9) and theophylline. The mean (SD) age of these cases was 68.4 (18.5) years; 25 patients (52%) were female. The mean percent change in theophylline concentrations was 114%, with a range of 32% to 308% following the addition of a quinolone to the patient's theophylline regimen. Fourteen (36%) of the 39 patients receiving ciprofloxacin and three (33%) of the nine patients receiving norfloxacin experienced a seizure. The accumulated evidence suggests that extreme caution should be used when quinolones are prescribed in conjunction with theophylline, particularly in elderly patients. Further research is required to identify risk factors that will more specifically predict the magnitude of the interaction.

National adverse drug reaction surveillance. 1986.

The collection of adverse drug reaction (ADR) reports by the Food and Drug Administration serves to provide additional information on the toxic reactions of drugs that often cannot be known before a drug is marketed. In 1986, a total of 53,547 ADR reports were received; 56% of these were made by US health care professionals based on observations made during usual clinical practice. The 1986 total represents an increase of 14% in ADR reporting over 1985, continuing a trend begun in 1981. While these increases are encouraging, US reporting rates are far below many other countries, and further encouragement of reporting must be done. Of these ADR reports, 24% involved serious reactions and 20% involved new drugs. An ADR report should be seen as a professional responsibility; reports are carefully analyzed and used.

Neonatal anuria with maternal angiotensin-converting enzyme inhibition.

The use of angiotensin-converting enzyme inhibitors as antihypertensives has increased rapidly since the introduction of captopril in 1981. Seven cases of neonatal renal failure have been reported in patients with exposure to angiotensin-converting enzyme inhibitors that continued to the time of delivery. Two cases resulted in death of the newborn; the other five patients recovered after peritoneal dialysis. Because the relative frequency of normal outcomes is unknown, these data are insufficient for incidence-rate estimates or risk/benefit analyses. However, given the potential neonatal morbidity and mortality associated with late-pregnancy exposure to angiotensin-converting enzyme inhibitors, alternative therapies in the third trimester should be given consideration. If these drugs must be used in this context, the clinician should be prepared to deal with renal failure and hypotension in the newborn. The Food and Drug Administration invites reports of adverse pregnancy outcomes associated with such exposure.

Cataracts associated with allopurinol therapy.

The National Registry of Drug-Induced Ocular Side Effects has accumulated 30 cases of suspected allopurinol-induced lens changes. The cataracts associated with this antihyperuricemic agent are initially anterior and posterior lens capsule changes with anterior subcapsular vacuoles. With time, wedge-shaped anterior and posterior cortical haze occurs, along with dense posterior subcapsular cataracts. Histologic studies of these cataracts showed no unique or identifying features. These cases do not prove a cause-and-effect relationship, but raise the suspicion that allopurinol may be cataractogenic in some patients. Additional case reports and lens material should be sent to the National Registry of Drug-Induced Ocular Side Effects, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.

Hematologic reactions to carbonic anhydrase inhibitors.

The National Registry of Drug-Induced Ocular Side Effects has received 79 case reports of suspected hematopoietic toxicity caused by carbonic anhydrase inhibitors. Twenty-six of these suspected cases (32%) resulted in death secondary to aplastic anemia, thrombocytopenia, or agranulocytosis. In 54 of these 79, adverse reactions (68%) occurred during the first six months of therapy.

Use and reported adverse effects of new chemical entities.

Reports submitted to the FDA through 1987 of adverse drug reactions (ADRs) to new chemical entities (NCEs) approved after 1983 are described, and estimates of each NCE's proportionate use in hospitals and within its therapeutic class are reported. This review was limited to those domestic spontaneous ADR reports submitted to the FDA by healthcare professionals. NCEs accounted for approximately 20% of the total number of domestic spontaneous ADR reports received in 1987, 22% of the reports of serious ADRs, and 24% of the reports that listed death as an outcome. Data on the use of these NCEs were obtained through the U.S. Pharmaceutical Market--Drugstores and Hospitals and the National Prescription Audit. Of the 93 drugs designated as NCEs in 1987, 65 had measurable use, with 41% of those used principally in hospitals. Most hospital-use NCEs were injectable antimicrobial agents, surgical drugs, and radioactive diagnostic agents. Because NCEs account for a disproportionate share of the ADRs reported to the FDA, and because of the high use of NCEs in hospitals, hospital pharmacists should be aware of the importance of monitoring and reporting serious ADRs associated with NCEs.

National adverse drug reaction surveillance: 1985.

The Food and Drug Administration received about 37,000 adverse drug reaction reports in 1985. Seventy-one percent of the reports involved toxic reactions to usual doses of drugs and were sent by medical care professionals directly to the Food and Drug Administration or to pharmaceutical manufacturers. In terms of severity, 2% of reports involved death while 21% involved hospitalization. The highest proportions of hospitalization or death were found for reports describing cardiovascular, hematologic, or respiratory effects. Nearly half of the reported deaths were in patients more than 59 years of age. The majority of reports described an adverse drug reaction occurring within two weeks of initial exposure to the suspected drug. Adverse drug reaction reporting by physicians is crucial to ensuring that pharmaceutical products are used appropriately.

Low cost, manual drug use review of Medicaid recipients to screen prescriber and pharmacist performance.

A manual drug use review (DUR) methodology to screen outpatient prescribing which would meet the needs of large third-party programs that cannot afford elaborate computerized DUR was developed and pilot tested. A Medicaid drugs data base was used for the pilot test. A probability sample of 100 recipients over a three-month period was selected for the DUR. The drugs for each recipient, listed by their generic composition and amount, were recorded. Then a priori, explicit, screening criteria were developed for these generics. These criteria delineated drugs of choice, daily dose and refill patterns and, as appropriate, therapy length, drug holidays, and disease-drug and drug-drug interactions. Only 11% of recipients had prescribing patterns which passed all the screens. The most frequent screening failure was due to the prescribing of a drug which was not a drug of choice. In nearly all of the cases which failed the other screens, an alert pharmacist with patient records should have noticed these problems. An analysis showed that the initial start-up cost for the manual DUR was estimated at $1053 (not including personnel fringe benefits); for subsequent quarterly review, the cost was estimated to be about $530. The project showed that manual DUR can effectively and efficiently screen prescribing in a large third-party program.