Sodium Metamizole: Regulatory Status around the World, Safety Problems and Medication Errors

Abstract

Sodium metamizole (SM), analgin, was recalled from the pharmaceutical market by the regulatory authorities of some countries in the mid-60s because of side effects (agranulocytosis). However, there has been a trend towards a steady increase in its prescription rates in the recent decades. The aim of the study was to characterise the regulatory status of SM in different countries of the world, to assess the effectiveness and safety, and to analyse available data on medication errors in real clinical practice. According to the reviewed publications, SM is the most frequently used analgesic in surgical practice in German-speaking countries, the third most frequently prescribed analgesic in Switzerland, and a widely used one even in the countries where it has previously been recalled, such as the USA. The increase in the use of SM, according to experts, is due to the opioid crisis and the high risk of cardiotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs). In chronic pain, the efficacy of SM is superior to that not only of paracetamol, but also of NSAIDs; in postoperative pain and acute primary headache, it is not lower than that of other commonly used analgesics. SM has a pronounced analgesic effect in cancer patients; high doses are comparable to narcotic analgesics in effectiveness but have a significantly more favourable safety profile. Randomised and observational studies confirm that the short-term use of SM is quite safe, including in terms of the risk of developing myelosuppressive side effects. When administered as a course of less than 2 weeks, SM is characterised by a lower frequency of adverse events compared to opioids and an approximately equal one compared to placebo and paracetamol, while longer courses are associated with an increased risk of agranulocytosis. Adverse drug reactions may result from medication errors. The risk of lethal outcome associated with agranulocytosis increases when SM is co-administered with methotrexate or used in elderly patients. In the Russian Federation, SM is an over-the-counter medicinal product approved for a wide range of pain types; it can be used as a highly effective analgesic provided that the dose, route, and frequency of administration are appropriate, the baseline characteristics of patients are taken into account, and unreasonably long courses (more than 2 weeks) are avoided.