CURRENT DRUG DESENSITIZATION PRACTICES

Drug hypersensitivity reactions (DHRs) present significant and increasingly complex challenges in clinical practice, particularly when the culprit drug is indispensable for treatment and no alternative with equivalent efficacy, safety, or accessibility is available. In such circumstances, drug desensitiza-tion represents a well-defined, reproducible, and clinically effective immunomodulatory approach that enables the safe re-administration of essential medications by inducing temporary immune tolerance without compromising therapeutic efficacy. This chapter presents a comprehensive overview based on current literature, addressing the immunological basis of DHRs ranging from well-characterized im-munoglobulin E (IgE)-mediated pathways to non-IgE and mixed mechanisms, the association between phenotypes and endotypes, and the clinical utility of biomarkers such as tryptase, drug-specific IgE, and the basophil activation test. Indications for desensitization primarily include selected immediate Type I reactions and mild Type Iv reactions in cases where the responsible drug is vital, whereas Type II (cytotoxic) and Type III (immune complex-mediated) hypersensitivity reactions, as well as severe cutaneous adverse reactions, are considered contraindications. When indicated, desensitiza-tion strategies include rapid and slow protocols, tailored to the timing and immunological profile of DHRs. Depending on the clinical context, various routes of administration are employed, including oral, intravenous, and subcutaneous methods; in intravenous applications, two main strategies are employed: traditional multi-bag protocols and single-bag strategies utilizing programmable pumps that allow controlled escalation of infusion rates. Premedication strategies, including H1/H2 antihis-tamines, corticosteroids, antipyretics, and adjunctive agents such as omalizumab, tailored to individ-ual clinical characteristics, are discussed in the context of preventing and managing breakthrough reactions, with particular emphasis on appropriate timing and dose adjustment. Continuous clinical monitoring, readiness for emergency intervention, and strict adherence to safety protocols are critical for early recognition and effective management of breakthrough reactions during desensitization. Clin-ical applications encompass desensitization strategies for a wide range of agents, primarily including chemotherapeutics, biologics, antibiotics, antituberculosis drugs, and nonsteroidal anti-inflammatory drugs, thus ensuring the continuation of first-line therapies in patients with limited alternative treat-ment options. Finally, ongoing advances in the understanding of underlying mechanisms, validation of predictive biomarkers, refinement of dose-escalation algorithms, and strengthened standardization are expected to further advance the personalization of drug desensitization, thereby enhancing patient safety, procedural efficiency, and overall clinical efficacy.