Cetuximab infusion reactions: French pharmacovigilance database analysis.

OBJECTIVES: To compare characteristics of patients exhibiting cetuximab infusion reactions or another adverse drug reaction related to cetuximab and to identify factors associated with the severity of cetuximab infusion reactions. METHODS: All cases of adverse drug reaction reported with cetuximab from 1985 to 2010 were extracted from the French Pharmacovigilance database. The severity of infusion reactions was assessed according to the NCI-CTCAE criteria (v4.0). Multiple logistic regression analysis was performed to identify factors associated with the severity of infusion reactions. RESULTS: Among the 602 adverse drug reaction reported with cetuximab during the study period, 374 infusion reactions were identified. Indication is more likely to be head and neck than colorectal cancer among patients experiencing an infusion reaction (p < 0.001). Among the seven deaths related to an infusion reaction, five patients were treated for head and neck cancer. Infusion reactions were more likely to be severe when they occurred during the first administration (OR = 7.40 95% CI [2.21-24.71]), adjusted for age, sex, region of France, quarter of the year, indication, year of occurrence, and premedication. CONCLUSION: Our study found that reports of infusion reactions more often concerned patients treated for head and neck cancer, that in these patients the adverse drug reaction was more often fatal and severe infusion reactions were more likely during the first administration. In daily practice, the close monitoring of patients during the first infusion, especially patients with head and neck cancer, is recommended. Considering the possible immunoglobulin E-mediated mechanism, reliable tests for their detection need to be readily available.

Joint symptoms in patients on bupropion therapy.

OBJECTIVE: To describe joint symptoms related to bupropion therapy. METHODS: We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. RESULTS: Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. CONCLUSION: Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case.

Cytochrome P450 interactions and clinical implication in rheumatology.

There are many potential drug interactions that involve the complex cytochromes P450 (CYP) enzyme system when treatments for chronic inflammatory rheumatic diseases are used. This iatrogenic risk is increased in patients taking multiple drugs such as those with rheumatoid arthritis or gout, whatever the type of CYP interaction (substrate, inducer, or inhibitor of one of the CYP isoenzymes). Some of these CYP interactions may have clinical consequences, sometimes serious (overdose or therapeutic failure) and are often unrecognized by clinicians. The aim of this article is first of all to act as a reminder of the metabolic role of membrane-bound CYP enzymes in the liver in the oxidation of drugs and the potential types of interaction (drug substrate, inducer, or inhibitor or indirectly by the modulation of CYP activity through its powerful antiinflammatory activity). Secondly, the different factors that modulate the enzymatic activity of CYP will be described that may contribute to variations in drug metabolism and therefore modify the benefit-risk ratio of the drug. Thirdly, an analysis based on a review of the literature will present the different known interactions via CYP for drugs used in clinical practice in rheumatic diseases: analgesics, antiinflammatory drugs, conventional disease-modifying antirheumatic drugs and biologic agents. To limit the clinical consequences of these CYP interactions, it is recommended to focus on drugs that are really essential, to systematically identify the rheumatic patients most at risk before prescribing, and thus to adopt therapeutic strategies that reduce iatrogenic risk.

Assessment of the use of hypolipidemic agents (HAs), mainly statins, in elderly subjects aged 80 years and more in Burgundy: analysis of 13,211 patients.

Only few studies have investigated the use of HA in elderly subjects and there are no data in very elderly subjects. We assessed the prescription of HA and analyzed the relationship between such prescriptions and frailty markers among persons aged 80 and more in an observational study. We recorded the prescriptions for 13,211 patients aged 80-109 years and affiliated to the "Mutualité-Sociale-Agricole (MSA)" of Burgundy over a 1-month period. The prescription of a HA among all included patients, and the existence of serious long-term disease(s) (LTD), polypharmacy or a prescription of cardiovascular drugs among patients receiving a HA were recorder. Among the 13,211 patients, 3412 aged 80-98 years were treated with an HA. The main HA were statins (70.4%), and fibrates were used in 27.3% of cases. Of these 3412 patients, 2250 had one or several LTD mainly coronaropathy, hypertension, diabetes mellitus or peripheral artery disease. The mean number of drugs per prescription was 6.37. Among subjects treated with HA, 40% also received antiplatelets, 35.6% ß-blockers and 30% inhibitors of the renin-angiotensin system. For 99% of the patients, the prescription of HA was a renewal. Prescribers were mainly general practitioners (96.8%). Statins are the most widely prescribed HA even among very elderly subjects. However, after 80 years the prescription of HA, mainly statins, decreases with aging. This could be explained by polypathology, polypharmacy and the deterioration in metabolic functions which are markers of frailty. This study should encourage research into the use of statins in very elderly subjects.