LivingWhy should we be careful with Nolotil?

Why should we be careful with Nolotil?

 

Nolotil (trade name) or metamizole (active ingredient) is a medicine for pain and fever that has a long history of use. The main indication for the use of metamizole is usually moderate or severe pain . Also, it is used for fever when other medications such as paracetamol are not suitable or sufficient. In 2020, it will be one hundred years and 50 since it began to be widely used around the world. At the same time, the age period of use only increased the contradictions of this drug. It is known that the use of Nolotil is discouraged and even prohibited in some countries of the world, but is it so dangerous?

Almost 50 years of history

Sweden first banned it in 1974, returned it to pharmacies in 1995, banned it again, and relatively recently allowed it again. Nolotil has been banned in the US, Japan, and Western Europe, and is not licensed in the UK. The debates about the appropriateness of the restrictions have not stopped there, especially in recent years. [9]

This attitude is related to a side effect of Nolotil. This is a rare but very serious side effect in the form of a blood disease: agranulocytosis . The greatest risk, based on available data, exists in people over 65 years of age and in people with suppressed immune systems . Agranulocytosis means that the bone marrow does not produce white blood cells, the body is not resistant to infection, and severe blood poisoning can occur. Against the background of these diseases, shortness of breath and inflammation of the larynx may occur. It is considered a dangerous complication of such conditions: pneumonia, enteropathy (necrotic), and toxic hepatitis.

The inflection point

The events that changed the fate of Nolotil took place in Spain , where it is still widely prescribed. Specifically, there were many consequences of agranulocytosis, including deaths, especially among British tourists.

A medical translator from Madrid, Cristina García del Campo , began intensively collecting data on the side effects of Nolotil in 2017. Considering the work she does, she realized that there are many hospitalized British people who used Nolotil. Deaths have occurred in the elderly who even survived malignant diseases and then used Nolotil, contracted sepsis and died.

Later, he traveled throughout Spain to collect data on side effects. Those who contacted her were Britons living in Spain. There is no strong evidence yet that genetics influences the side effects of metamizole. But the statistics indicate a potentially higher sensitivity of the Northern European population, especially the British . The data collected began to arouse suspicion among health professionals.

A hospital heard…

The Hospital Costa del Sol , in Marbella, carried out a statistical study on the cases of agranulocytosis among its patients. It turned out that in a five-year study, two-thirds of the patients were foreigners and up to a third of the patients were British. Based on this study, it was concluded that agranulocytosis is more common in the British and that the use of this drug should be avoided.

The incidence of agranulocytosis is indeed different between populations and shows wide geographic variation. For example, in Sweden a study tells us that out of 1,439 prescriptions, 1 case occurs, while in Greece there is one case for every 133,000-466,000 patients who use metamizol.

For this reason, well-designed studies that yield consistent results are necessary, and that can present data that definitively decide the fate of this drug. Because in addition to the side effects, the advantages should be noted. It has not been calculated how many lives Nolotil has saved as an antipyretic (especially in combination with other drugs) when other antipyretics (for example, paracetamol) were not capable of lowering the temperature. In this case, there are those who defend that its advantage has no limits and, in many countries, it is widely used by doctors. A special advantage of metamizol (Nolotil) compared to other nonsteroidal anti-inflammatory drugs ( NSAIDs ) such as ibuprofen or dexketoprofen (Enantyum) is its better profile in terms of teratogenic effects (interfering with fetal formation). And even outside of pregnancy , it is especially indicated for those who need this treatment and other NSAIDs are contraindicated or pose a greater risk.

The official statement

The data collected by Cristina García del Campo were assumed by the Spanish Agency for Medicines and Health Products (AEMPS) . This has given rise to new guidelines for the issuance and sale of Nolotil. Its sale and dispensing in pharmacies and hospitals to patients who cannot be controlled for a long time is prohibited. These are mainly tourists. However, García del Campo, as well as the families of the deceased Britons, call for a total ban on Nolotil in Spain.

The AEMPS issued updated information after consulting with the Health Products Safety Committee. The statement states that metamizole should only be used for a short time, with blood monitoring if longer treatment is needed. All possible tests should be performed in patients to be administered Nolotil, to avoid the risk of agranulocytosis. These recommendations are especially important for remarkably prolonged treatments. Furthermore, it is important to bear in mind that metamizol should not be used in patients in whom these controls are not possible, such as those who visit the country as tourists.

Studies are lacking to better establish the risk-benefit relationship

Metamizole remains a stigmatized medication in various settings due to reports of its association with agranulocytosis. Despite this, its use is well established in many countries, where it represents one of the most widely used analgesics in the treatment of postoperative pain, both in adults and children, but also in other indications. Future randomized controlled clinical trials should be organized to assess its safety and efficacy, because the benefits of metamizole must be weighed against the risk of metamizole-induced adverse effects, especially when compared to other NSAIDs. It is the only way to define its place in contemporary pharmacotherapy relative to the treatment of pain.

A popular hypothesis

It is necessary to determine in detail why the British and Scandinavians are so sensitive to Nolotil. One of the most interesting hypotheses is the possibility that they have more proteins that regulate the immune response, the so-called HLA alleles . If the presence of these proteins is determined, the sensitivity to metamizole could be determined, as well as the degree of risk of side effects. This type of screening would greatly help the proper use of this analgesic.

References:

Andrade, S., Bartels, D. B., Lange, R., Sandford, L., & Gurwitz, J. (2016). Safety of metamizole: a systematic review of the literature. Journal of clinical pharmacy and therapeutics, 41(5), 459–477. https://doi.org/10.1111/jcpt.12422

Ibáñez, L., Vidal, X., Ballarín, E., & Laporte, J. R. (2005). Agranulocytosis associated with dipyrone (metamizol). European journal of clinical pharmacology, 60(11), 821–829. https://doi.org/10.1007/s00228-004-0836-y

Mérida Rodrigo, L., Faus Felipe, V., Poveda Gómez, F., & García Alegría, J. (2009). Metamizole-induced agranulocytosis: a potential problem in the British population. Spanish Clinical Journal, 209(4), 176–179. https://doi.org/10.1016/s0014-2565(09)71310-4

Miljkovic, MN, Ranchic, NK, Simic, RM, Stamenkovic, DM, & Dragojevic-Simic, VM (2018). Metamizole: Current Status of Safety and Efficacy. Hospital Pharmacology, 5 (3), 694-704. doi: 10.5937 / hpimj1803694M

Shah R. R. (2019). Metamizole (dipyrone)-induced agranulocytosis: Does the risk vary according to ethnicity? Journal of clinical pharmacy and therapeutics, 44(1), 129–133. https://doi.org/10.1111/jcpt.12768

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