[Parenteral iron therapy: problems and possible solutions]. / Parenterale Eisentherapie: Probleme und mögliche Lösungen.

To investigate whether there are differences in the frequency of ADRs (adverse drug reactions) to parenteral iron preparations, we compared the results of 4 different data collections which contain observations in particular on i.m. or i.v. iron dextran and i.v. iron hydroxide sucrose complex, primarily in relation to anaphylactic/anaphylactoid reactions and common exanthemas. 1. In 206 patients of the department of general internal medicine in a city/teaching hospital (in association with the Swiss Foundation for Comprehensive Hospital Drug Monitoring--CHDM), 4 probably allergic reactions to i.m. iron dextran were found, one with acute severe dyspnea, cyanosis and flush, 3 with slight generalized, probably allergic reactions. Data from the USA on i.v. iron dextran do not show marked differences in the frequency of ADRs as compared with our data with i.m. administration. 2. A group of 400 otherwise healthy patients of the obstetric department of Zurich University Hospital were treated with i.v. iron sucrose for anemia due to iron loss during pregnancy or following childbirth. Seven generalized skin reactions, 4 in the form of flush and 3 of common exanthema, occurred. 3. In a retrospective study on patients on maintenance hemodialysis with chronic renal insufficiency and anemia, a questionnaire was answered by the medical heads of 17 selected hemodialysis units in Switzerland. Response was 100%. During around 8100 patient-years with approximately 160,000 ampoules of iron sucrose (with 100 mg elementary iron), not a single life threatening reaction was observed; only 5-7 situations of rapidly reversible blood pressure fall occurred, some 10 with flush, and one each with urticaria and vomiting/diarrhea. 4. The relatively good tolerance of i.v. iron sucrose in patients with chronic renal failure may be due either to reduced immune competence in patients with chronic renal insufficiency and/or to the use of the preparation itself, or probably both. 5. In ADRs of allergic appearance to iron sucrose, the 7 generalized skin reactions occurred on the first day of the injections, as did those under iron dextran. Preexisting hypersensitivity must be taken into consideration. 6. If our experience is confirmed, preventive measures with i.v. iron sucrose, mainly in patients with chronic renal insufficiency, could be reduced.

Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone sodium for 4 weeks. Efficacy and outpatient treatment feasibility.

UNLABELLED: OBJECTIVE--To evaluate the efficacy and safety of ceftriaxone sodium in the treatment of streptococcal endocarditis. DESIGN--An open, multicenter, noncomparative study with a follow-up of patients for 4 months to 5 years. SETTING--Internal medicine wards and outpatient clinics of hospitals of various sizes in three European countries. PATIENTS--Fifty-nine patients with defined criteria for streptococcal endocarditis. INTERVENTION--Ceftriaxone sodium administered at a once-daily dose of 2 g for 4 weeks. MAIN OUTCOME MEASURES--Clinical outcome and microbiological cure rate. RESULTS--Among the 59 patients, 55 completed the treatment and were followed up for 4 months to 5 years. No patients showed evidence of relapse. Treatment was completely uneventful in 42 patients (71%). A cardiac valve was replaced in four patients (7%) receiving antimicrobial therapy and in six patients (10%) who had completed antimicrobial therapy. One of the 10 valves taken for culture at surgery was positive, but only for microorganisms that were different from the microorganism isolated before the treatment. The treatment had to be interrupted in four patients because of drug allergy. Other side effects were mild except for two cases of reversible neutropenia. The treatment was easy to administer: 27 patients (46%) had no permanent intravenous catheter at any time, seven patients (12%) had such a catheter for less than 4 days. Twenty-three patients (39%) were discharged from the hospital less than 2 weeks after admission. CONCLUSIONS: --Ceftriaxone sodium administered at a once-daily dose of 2 g appears to be an effective and safe treatment of streptococcal endocarditis. In hospitals, this agent may be more convenient to administer than penicillin G with or without aminoglycosides. Some patients may even be treated as outpatients.

Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Results from the Comprehensive Hospital Drug Monitoring Berne (CHDM).

The hospital prevalence rate for upper gastrointestinal ulcerative disease in 28,531 inpatients consecutively admitted in two teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM) in Berne, from 1974 to 1985, was 2.2% (1.8% for gastric or duodenal ulcer, and 0.4% for erosive gastritis). This was based on the evaluation of 634 patients after exclusion of the subgroup of patients with hepatic cirrhosis or upper gastrointestinal neoplasia. After exclusion of patients on anticoagulant therapy (n = 73), 561 (= 100%) patients could be further studied. Of them, 33.3% (n = 187) were found to have been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, within 21 days prior to confirmation of the diagnosis. The observed relative risk (RR) of developing a substantial acute upper gastrointestinal bleeding (Hb less than 10 g/100 ml for men, and less than 9 g/100 ml for women, or a decrease in Hb of more than 25%) was 1.61 when patients exposed to NSAIDs (n = 187) were compared to patients not exposed to those drugs (n = 374). Although there was no significant sex difference overall, the RR for gastrointestinal bleeding differed considerably in the various age-groups; it was elevated in men under 40 years (RR = 2.86) and in women over 60 years of age (RR = 1.89), as compared to the mean RR of 1.61.

Risk factors for adverse drug reactions--epidemiological approaches.

Age by itself is not an important risk factor for ADRs. Age-related changes are the consequence of a number of individual factors, for example morbidity associated with polypharmacy, decline in renal or liver function in the elderly, hypoalbuminaemia, reduced body weight, etc. The relationship between gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be assessed globally in large cohort studies with access to computerized data, but complete accuracy requires access to the original patient records. The increase in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in non-users. About a quarter of ADRs in hospitalized patients seem not to arise from purely pharmacological mechanisms. They are mainly due to allergic, anaphylactoid, or idiosyncratic reactions and to intolerance. In such non-pharmacological reactions, the time of exposure, reaction time, and even dosage may be important factors in identification of the causal drug. The use of benzodiazepines can be optimized by taking into account potency, time of action and the different syndromes encountered after withdrawal. Following long-term use problems of relapse and rebound are being increasingly recognized, in addition to organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due to neuroleptics are common. The rates of these ADRs differ markedly between various drugs, even after dosages and co-medications are taken into account. Epidemiological screening for potentially carcinogenic drugs can only be done in large cohorts of patients with pre-recorded full information sets as may be found in an HMO (Health Maintenance Organization). The findings of several such studies have been published in specialist cancer journals.(ABSTRACT TRUNCATED AT 250 WORDS)

[Exanthema during frequent use of antibiotics and antibacterial drugs (penicillin, especially aminopenicillin, cephalosporin and cotrimoxazole) as well as allopurinol. Results of The Berne Comprehensive Hospital Drug Monitoring Program]. / Exantheme unter häufig angewandten Antibiotika und antibakteriellen Chemotherapeutika (Penicilline, speziell Aminopenicilline, Cephalosporine und Cotrimoxazol) sowie Allopurinol. Ergebnisse aus dem Komprehensiven Spital-Drug-Monitoring Bern (CHDMB).

Of 19,653 patients hospitalized in the medical divisions of two teaching hospitals, 3980 were treated with an aminopenicillin, 808 with other penicillins, 427 with a cephalosporin, 2619 with cotrimoxazole and 846 with allopurinol. The first part of the study deals only with the incidence of exanthemas definitely or probably due to a specific drug on the basis of clinical considerations. The exanthema incidence is 8.0% for aminopenicillins, 4.7% for other penicillins, 1.9% for cephalosporins and 2.8% for cotrimoxazole. The second part of the study employs a cross-tabulation to determine the incidence of exanthemas definitely and probably drug-induced, and the temporal relationship of these reactions to aminopenicillin and allopurinol exposure. The observed risks of developing an exanthema are as follows: aminopenicillin without allopurinol 10.1%, aminopenicillin combined with allopurinol 7.2%, allopurinol without aminopenicillin 3.0%, neither of the two drugs 1.5%. The increased incidence of exanthemas observed by the Boston Collaborative Drug Surveillance Program (BCDSP) in patients concomitantly treated with aminopenicillin and allopurinol was not confirmed by our results. Our hypothesis is that the time of exposure to aminopenicillins might have been shorter for patients of the BCDSP who were not treated in connection with neoplastic disease and did not receive allopurinol. The incidence of aminopenicillin induced exanthemas increases severalfold with the duration of exposure time during the first 2-3 weeks. In the CHDMB, on the other hand, exposure time does not differ between the patients treated with aminopenicillin alone or in combination with allopurinol.

[Drug fever caused by the antidepressive agent nomifensine (Alival)]. / Arzneifieber auf das Antidepressivum Nomifensin (Alival).

During 1979 4 patients were observed who developed short episodes of fever as high as 104 degrees F after oral intake of 25--100 mg nomifensine (Alival). In all four cases a clear fever spike was produced by reexposure to the drug. The reaction time was 4--6 hours. this drug-induced fever appeared initially 2--4 weeks after the commencement of Alival therapy. No other cause for the fever was identifiable. In one patient an allergic alveolitis was suspected to be a further reaction. In another patient a concomitant granulomatous hepatitis was possibly also due to this drug. It is probable that the febrile reactions have an allergic mechanism. Allergologic investigations have not yet been completed.

[Neurologic aspects of cranial arteritis]. / Neurologische Aspekte der Arteriitis cranialis

This study describes 44 cases of cranial arteritis (41 of whome had been established by arterial biopsy). Special attention has been payed to the type and the significance of initial symptoms. The majority of the patients were from 65-80 years, the youngest 55 years old. The frequency was slightly higher in the male than in the female. All the patients except for two suffered from pain in the area of the head or the face. Ocular disorders had been found in 62% of the cases, commonly represented by blindness of one eye, decreased vision, papillar edema and eventually by occlusion of the retineal artery. The sedimentation rate of red blood cells showed acceleration between 32 and 130 mm after 1 hour. In the average a laps of time of one month was noted between the appearance of the first subjective symptoms and the moment when diagnosis was made. The administration of 60-80 mg Prednisone daily was followed by a decrease in the clinical signs within a few days to 3 weeks. It is important that therapy be started with a high dosis of Prednisone and that it should be reduced to smaller doses given during several years.