4CPS-027 Desensitisation protocol for liposomal amphothericin B: a case report

E. Wilhelmi, C. Salazar, R. Farré, M. Duero, A. Machinena, M. Gómez
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Abstract

Background and importance Liposomal amphotericin B (ANBL) is an effective and safe treatment, however non-IgE-mediated hypersensitivity reactions have been described. Aim and objectives To describe the ANBL desensitisation protocol in a patient with leishmaniasis who developed a demonstrated hypersensitivity reaction to the drug. Material and methods A 16-year-old male, 85 kg, with severe corticodependent eosinophilic asthma, was admitted for prolonged fever, cholestatic hepatitis, splenomegaly and thrombocytopenia. Visceral leishmaniasis was diagnosed and ANBL treatment was started at 3 mg/kg intravenously (IV) to be administered over 2 hours. During the perfusion the patient presented back pain and headache, which subsided when the perfusion was interrupted. Later, the perfusion was restarted at a slower rate; however, he developed erythematous plaques, discomfort, tachycardia and fever, as a result of which the perfusion was stopped. The ANBL prick test was negative. It has been described that in non-IgE reactions there is a release of cytokines that trigger the symptoms of fever, hypotension, etc. Desensitisation to the antigen produced by the initial cytokine cascade is possible. Second-line alternatives for leishmaniasis were not considered adequate, so it was decided to restart ANBL with a desensitisation protocol, which consisted of administering the drug in three steps, progressively increasing the infusion rate and concentration until administration of the full dose was reached. Low initial doses of antigen produce progressive depletion of activating signals and inhibition of mediator release, thus reducing clinical reactivity. Results In our case, desensitisation consisted of only two steps: 1/10 dilution at a concentration of 0.2 mg/mL (25 mg/ 125mL) and the full dose at 1 mg/mL (250 mg/250mL) of ANBL in 5% glucose serum because there are no stability data for a more dilute preparation of ANBL (1/100). The first dilution was administered in five perfusion rhythms starting at 2.5 mL/hour in 15 min, given good tolerance, the speed was progressively increased every 15 min: 5 mL/hour, 10 mL/hour, 20 mL/hour up to 40 mL/hour. Subsequently, the full dose of ANBL was administered in four rhythms, starting at 10 mL/hour, and increasing to 20 mL/hour, 40 mL/hour to 60 mL/hour, which was maintained until the full dose was reached. Premedication with paracetamol plus IV dexchlorpheniramine was necessary. Conclusion and relevance The use of an ANBL desensitisation protocol has proven to be a safe option, which has allowed the administration of treatment without the appearance of adverse effects.
两性霉素B脂质体脱敏方案:1例报告
背景和重要性脂质体两性霉素B (ANBL)是一种有效和安全的治疗方法,然而非ige介导的超敏反应已被描述。目的和目的描述一名利什曼病患者的ANBL脱敏方案,该患者对该药表现出超敏反应。材料与方法16岁男性,85公斤,患有严重的皮质依赖性嗜酸性粒细胞性哮喘,因长期发热、胆汁淤积性肝炎、脾肿大和血小板减少而入院。诊断为内脏利什曼病,并开始以3mg /kg静脉注射(IV) ANBL治疗,持续2小时。灌注过程中患者出现腰痛和头痛,灌注中断后症状消退。随后,以较慢的速度重新开始灌注;但患者出现红斑斑块、不适、心动过速及发热,并停止灌注。ANBL点刺试验为阴性。据描述,在非ige反应中,有细胞因子的释放,引发发烧、低血压等症状。对最初细胞因子级联反应产生的抗原脱敏是可能的。利什曼病的二线替代方案被认为不够,因此决定用脱敏方案重新启动ANBL,该方案包括分三步给药,逐步增加输注速度和浓度,直到达到全剂量。低初始剂量抗原产生的激活信号的逐渐消耗和抑制介质释放,从而降低临床反应性。在我们的病例中,脱敏只包括两个步骤:1/10稀释浓度为0.2 mg/mL (25 mg/ 125mL)和1 mg/mL (250 mg/250mL) ANBL在5%葡萄糖血清中的全剂量,因为没有更稀释的ANBL制备(1/100)的稳定性数据。第一次稀释在15分钟内以2.5 mL/小时开始的5个灌注节律进行,给予良好的耐受性,每15分钟逐渐增加速度:5ml /小时,10ml /小时,20ml /小时直到40ml /小时。随后,以4个节律给药ANBL全剂量,从10 mL/小时开始,逐渐增加到20 mL/小时、40 mL/小时至60 mL/小时,一直维持到达到全剂量。前用药对乙酰氨基酚加静脉注射右氯苯那敏是必要的。结论和相关性使用ANBL脱敏方案已被证明是一种安全的选择,它允许在没有出现不良反应的情况下进行治疗。
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