SUMMARY AimTo appraise the tolerance and efficacy of an induction of tolerance protocol to infliximab permitting the re-administration of the drug to patients with Crohn's disease having had infusion reactions requiring suspension of treatment. MethodsFourteen patients were included in the induction of tolerance protocol. Each infusion of infliximab (5 mg/kg) was divided into 11 escalating 15 min increments over a 3-h time period. The induction of tolerance procedure was repeated for subsequent infusions. ResultsTen patients (71.4%) received all the three infusions for the induction treatment. Nine (64.3%) had a significant response and six (48.8%) still benefited from infliximab infusions. Seven patients (50%) achieved a complete remission, after a mean of 2.5 (two to three) infusions. Four patients (28.6%) had no response and the protocol was stopped. Three patients (21.4%) experienced mild immediate hypersensitivity reactions, which were controlled, two patients (14.2%) experienced severe immediate hypersensitivity reactions, leading to interruption of the treatment and one patient developed a delayed hypersensitivity reaction. ConclusionOur induction of tolerance protocol allows some patients who have experienced severe or repetitive infusion reactions to infliximab to be safely retreated with the drug in a hospitalized setting, with a clinical response achieved in a majority of these patients.

While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. First, amoxicillin solubility in water was assessed within the range of 25 to 300 mg/mL. Then, amoxicillin solutions were prepared at different concentrations (25, 50, 125, 250 mg/mL) and stored in different conditions (5±2°C, 25±1°C, 30±1°C and 37±1°C) to investigate the influence of concentration and temperature on the chemical stability of amoxicillin. Finally, its stability was assessed under optimized conditions using a fully validated HPLC-UV stability-indicating method. Degradation products of amoxicillin were investigated by accurate mass determination using high-resolution mass spectrometry. Amoxicillin displayed limited water solubility requiring reconstitution at concentrations below or equal to 150 mg/mL. Amoxicillin degradation were time, temperature as well as concentration-dependent, resulting in short-term stability, in particular at high concentrations. Four degradation products of amoxicillin have been identified. Among them, amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction and may accumulate in the patient. Optimized conditions allowing for continuous infusion of high-dose amoxicillin has been determined: amoxicillin should be reconstituted at 25 mg/mL and stored up to 12 hours at room temperature (22 ± 4°C) or up to 24 hours between 4 and 8°C.

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