Metamizole and the Price of Pain Relief

Pain relief is essential in healthcare, but what happens when the remedy itself becomes the problem? Metamizole, a widely used non-opioid analgesic, sparks a long-standing debate due to its powerful pain-relieving and fever-reducing properties, yet severe, sometimes fatal side effects plague it. The primary concern is the drug’s association with agranulocytosis, a life-threatening condition where white blood cell counts dramatically decrease, leaving the body vulnerable to infections. While some healthcare systems argue that the risk is manageable with proper monitoring, others have imposed outright bans. The challenge for pharmacovigilance experts and healthcare professionals is balancing the drug’s therapeutic benefits with its potential dangers.

The Perilous Case of Metamizole-Induced Agranulocytosis

The DrugCard platform recently uncovered a tragic case published in Duodecim, a Finnish medical journal. A young man was prescribed Litalgin – a combination of metamizole and pitofenone – for abdominal pain. He developed agranulocytosis, which led to neutropenic sepsis and disseminated intravascular coagulation (DIC). His condition deteriorated rapidly, resulting in the amputation of all four limbs due to severe tissue necrosis. This devastating case serves as a stark reminder of the potential risks of metamizole and highlights the importance of heightened vigilance in monitoring patients on this medication. Even with existing safety measures, such severe reactions raise concerns about whether the benefits of metamizole truly outweigh the risks.

A Drug with a Troubled History

Metamizole, first introduced in the 1920s, was banned in several countries, including the United States and the United Kingdom, due to its association with agranulocytosis. Yet, paradoxically, it remains available in many European, Latin American, and Asian countries, where healthcare providers prescribe it under various brand names. The safety debate surrounding metamizole continues as healthcare systems across the world grapple with its risks and benefits. In 2017, Finland took regulatory action due to the ongoing risk of agranulocytosis from Litalgin. Authorities introduced additional safety measures, including patient warning cards, risk communications about agranulocytosis, and mandatory blood monitoring for prolonged use. Despite these precautions, severe cases of agranulocytosis persist, fueling ongoing questions about the drug’s safety and whether stricter regulations – or even complete withdrawal – are necessary. This disparity in global regulation adds complexity to the debate, leaving the pharmacovigilance community divided.

New Safety Measures: Raising Awareness and Early Detection

In response to persistent safety concerns, the European Medicines Agency (EMA) and the Committee for Medicinal Products for Human Use (CMDh) have introduced new safety measures to minimize the risks of agranulocytosis linked to metamizole. On 18 September 2024, the EMA’s safety committee, PRAC, recommended updates to the product information for all metamizole-containing medicines. The goal is to raise awareness about the symptoms of agranulocytosis, such as fever, chills, sore throat, and painful sores in mucosal areas like the mouth, nose, throat, and genital regions.

These updates help healthcare professionals and patients recognize early signs of agranulocytosis, which can occur during treatment or shortly after stopping the medication. Early detection is key to preventing potentially fatal infections. Healthcare professionals must now inform patients about the risks, advise them to stop taking metamizole, and seek immediate medical attention if they develop symptoms.

Who Should Avoid Metamizole?

The updated safety measures also specify that patients at increased risk for agranulocytosis should not use metamizole. This includes individuals with a history of agranulocytosis caused by metamizole or similar medicines, as well as those with conditions affecting bone marrow or blood cell production. Healthcare professionals must prevent prescribing metamizole to these patients, emphasizing the importance of patient safety. If symptoms of agranulocytosis appear, conduct blood tests immediately and suspend treatment until the results are available.

The European Medicines Agency updated its safety recommendations, which the CMDh endorsed. The European Commission made these recommendations legally binding on 22 November 2024, reflecting ongoing efforts to ensure patient safety.

Metamizole: Risk vs. Benefit?

Despite the safety measures in place, the controversy surrounding metamizole’s safety persists. Healthcare professionals continue to recognize the benefits of metamizole for pain and fever management. However, the potential for severe adverse reactions, such as agranulocytosis, demands careful consideration. The ongoing debate about whether the benefits outweigh the risks is crucial for both healthcare professionals and pharmacovigilance experts. As new cases of agranulocytosis are reported, the question remains: should metamizole remain a part of pain management protocols, or is it time for a complete reevaluation of its place in modern medicine?