Metamizole Dipyrone AND THE Liver A Revirw OF THE Literature PDF

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Metamizole (Dipyrone) and the Liver: A Review of the Literature

The Journal of Clinical Pharmacology 2019, 00(0) 1–10  C 2019 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology DOI: 10.1002/jcph.1512

Mathias Lutz, MD

Abstract Metamizole, also known as dipyrone, was introduced to the market nearly a century ago. Due to its excellent analgesic, antipyretic, and spasmolytic properties combined with its mostly favorable gastrointestinal tolerability, the drug was extensively applied worldwide during the first decades after its market introduction. Although rare, agranulocytosis is a well-known adverse event of metamizole and led to its withdrawal from the market in a number of countries beginning in the 1960s. Nevertheless, metamizole is still a frequently used drug worldwide either legally (by prescription in some countries, over the counter in other countries) or without official approval (especially by immigrants knowing the drug from their home countries) or even illegally (due to its growing application as an adulterant in illicit drugs). Metamizole undergoes extensive metabolism in the liver and cases of potential metamizole-associated hepatotoxicity have been described. Here, the literature is extensively reviewed for the first time regarding hepatic effects associated with the use of metamizole.

Keywords dipyrone, hepatotoxicity, liver, liver disease, drug-drug interactions, drug metabolism, metamizole

Nearly 100 years have passed since metamizole, also known as dipyrone, was introduced to the market in 1922.1,2 Due to its chemical structure belonging to the class of pyrazolones and its analgesic, antipyretic, and (however weak) antiphlogistic effects, metamizole is classified as a nonsteroidal anti-inflammatory drug (NSAID).3–5 Compared to the other agents of this heterogeneous group, metamizole also offers additional spasmolytic properties.6,7 In combination with its mostly favorable gastrointestinal tolerability, this profile led to an extensive clinical application of metamizole during the initial period after its market introduction.8–10 However, an increasing number of side effects of metamizole have been reported over the following decades affecting the cardiovascular system (ie, hypotension and arrhythmia), the respiratory system (ie, bronchospasm, especially in asthmatic patients), and the skin (ie, maculopapular rash), among others.11–15 While most of these side effects rapidly disappear after discontinuation of the drug and/or are manageable in a clinical setting, metamizole-induced agranulocytosis, whose first description dates back to 1936, poses a serious threat to the patient’s life.16,17 Defined as a granulocyte count of...