Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Issue 6 ¦ 2022 2268 Review Article: Mechanisms and Efficacy of Using Diphenhydramine as a Chemotherapy Premedication Fauziah Hasdin*, Dinda Monika, Bambang Subakti Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia Correspondence author: Fauziah Hasdin, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia E-mail: fauziahhasdin01@gmail.com DOI: 10.47750/pnr.2022.13.S06.295 The use of chemotherapeutic agents can cause side effects that have a negative impact on the patient's quality of life and have the potential to cause unexpected reactions. This reaction is known as a hypersensitivity reaction where. This reaction occurs at therapeutic doses that resemble an allergic reaction. The effects of these reactions can range from mild to life-threatening. The use of diphenhydramine as a chemotherapy premedication has been widely studied for its effectiveness in reducing the risk of hypersensitivity and toxicity from the use of chemotherapeutic agents. Therefore, this review article aims to provide an understanding of the importance of the use of premedication, as prevention of hypersensitivity reactions and reduce the potential for toxicity from the use of chemotherapeutic agents. The method used in this literature study is to identify and review various research articles through the MeSH PubMed database, ScienceDirect with the keywords “Diphenhydramine”, “Prevention”, “Premedication”, “Hypersensitivity Reaction” “Toxicity” and “Chemotherapy” as relevant references. An analysis was conducted on relevant research articles related to the mechanism and efficacy of diphenhydramine in the use of chemotherapy.The research article that forms the basis for writing this literature study, as a whole, shows that the use of diphenhydramine as an anti- histamine is one of the effective prophylaxis that can be used before the use of chemotherapy agents to minimize the occurrence of unwanted hypersensitivity and toxicity effects. Keywords: Diphenhydramine, Hypersensitivity, Toxicity, Chemotherapeutic Agent. INTRODUCTION Cancer incidence is expected to increase from 17 million to 26 million between 2018 and 2040 1 . The increase in cancer cases, perhaps benefiting from the use of chemotherapy, has led to rapid development of chemotherapeutic agent design 1– 3 .However, chemotherapeutic agents in cancer patients can potentially cause fatal hypersensitivity reactions 4 . A hypersensitivity reaction is defined as an unexpected reaction to chemotherapy use 5–7 . The risk of hypersensitivity reactions will increase with the cycle of therapy and the type of chemotherapy used. Symptoms of hypersensitivity from the use of chemotherapeutic agents can include difficulty breathing, redness, hypotension, nausea and tachycardia 6 . Hypersensitivity reactions can occur within seconds or minutes after drug administration which is characterized by an anaphylactic reaction 5 . The use of chemotherapeutic agents that cause hypersensitivity reactions can still be used by carrying out prevention and treatment methods 8 . One method of preventing and treating hypersensitivity reactions due to the use of antineoplastics is the use of antihistamines 9 . Antihistamines are considered to be able to suppress hypersensitivity reactions caused by high levels of histamine in cancer patients by reducing the immunotherapy response so that they can be used as adjuvant agents 10 . Diphenhydramine is a first-generation histamine H1 receptor antagonist, which is commonly used to reverse the effects of histamine on capillaries, thereby reducing the symptoms of allergic reactions 11 . Diphenhydramine is the first generation of injectable antihistamines with a rapid onset of action 12 . The use of diphenhydramine as an antihistamine is one of the premedications that have been empirically introduced to reduce reactions related to chemotherapy infusions 13 . Therefore, this literature study aims to provide a review regarding antihistamines, especially diphenhydramine as a preventive option for the prevention of HSRs in patients receiving chemotherapy therapy, and to determine the mechanism and efficacy of diphenhydramine in HSRs against neoplastic agents. Method The method used in this review article uses a systematic review to identify studies related to the mechanism and efficacy of diphenhydramine as a chemotherapy premedication. We identified various research articles through the MeSH PubMed database, ScienceDirect with the keywords “Diphenhydramine”, “Prevention”, “Premedication”, “Hypersensitivity Reaction” “Toxicity” and “Chemotherapy” as relevant references. We grouped studies related to inclusion related to relevant articles and excluded duplicate articles, review articles, duplicated data and articles that were not relevant to the use of diphenhydramine, chemotherapeutic agents, or their effect on the condition of HSRs, IR or toxic effects caused by