Nolotil, banned for tourists

A pack of Nolotil, the most commonly bought brand of metamizole in Spain.
A pack of Nolotil, the most commonly bought brand of metamizole in Spain. / SUR
  • The health authorities recommend that this drug should not be prescribed for foreign visitors after discovering that several British people suffered serious side effects. Ten died

She has spent over a year moving heaven and earth to try to demonstrate that what she suspected was true. After one of the patients Cristina García de Campo had helped as an interpreter at the hospital in Denia died from sepsis (a serious infection), she discovered that there had been several similar cases in the previous months. "That didn't seem normal to me," she says.

It continued to bother her for months, until one day she decided to look at the medical histories of the patients with whom she had worked, most of whom were British or from northern Europe. She found they had all been treated with Nolotil, a commonly-used analgesic which is recommended for acute pain and as an antipyretic when other alternatives were not effective.

In Spain it has been sold for the past 50 years and its use has doubled in the past decade, but the greatest increase has been in the past five years, from 14.6 million packets consumed in 2013 to 22.8 million in 2017. So Cristina wondered whether those cases of sepsis had been associated with the use of Nolotil. She did think for a moment that maybe she was seeing ghosts where there weren't any and she guessed that nobody would take any notice of her, but "I couldn't sit back and do nothing," she decided. She explained her concerns to the hospital management; "I believe we have a public health problem," she said.

The response

From then on, Cristina's life would never be the same. She began to make enquiries on her own account, and made contact with groups of British expats on social media, asking if they had ever suffered any adverse reaction to taking metamizole (the active principle in Nolotil). She was surprised by the response.

"I was told about 100 cases and 21 deaths," she says. Recently, the British media has reported that about ten people from the UK had died after taking metamizole in Spain. Armed with that information, Cristina contacted the Spanish Medications Agency (Aemps), and met officials there last summer. She didn't have to wait long for a reaction.

The misgivings were taken into account by the Ministry of Health, which issued a serious warning about the risks of suffering one of the side effects of metamizole, known as agranulocytosis, and asked medical professionals not to give it to patients "in cases where they cannot be checked (ie the floating population)." This means that Nolotil can no longer be prescribed for tourists, because they cannot be monitored by doctors here to prevent problems arising if they were to experience symptoms of agranulocytosis. The Ministry also warned of a greater risk among older patients, and said it should only be taken by medical prescription.

"This disorder occurs when the chemical composition of a medication comes into contact with normal white blood cells and, even, the precursors of the white blood cells in the bone marrow, and causes the immune system to destroy them. It's a type of allergy to the leukocytes. The normal values can change very suddenly and fall to zero in 24 hours, and that can cause serious infections and the possibility of death," explains Isidro Jarque, a haematologist at La Fe hospital in Valencia, and a member of the Spanish Haematology and Haemotherapy Society.

He says it has been known for years that Nolotil is one of the most important causes of agranulocytosis. "It is the one most commonly used and associated with this complication, but it's by no means the only one," he stresses. With regard to prognosis, there should be no problem if it is detected on time because there are drugs which quickly recover the level of leukocytes.

"Normally, it is treated with a stimulating factor for granulocytic colonies, which considerably shortens recovery time. Antibiotics might also be used and even hospitalisation if the infection is serious, but if there are no complications a patient can be home in a week," says Jarque.

The Aemps says it had reviewed the situation in Spain after learning of the recent notification from the Spanish Pharmovigilance System about cases of agranulocytosis, particularly of British origin.

Cristina García says she feels that all her efforts have been rewarded. "I feel as if I had aged ten years," she admits. She had also written to the British government to ask why Nolotil is not sold in the UK.

"I believed there could be some relationship, that they would have some evidence that British people are more likely to suffer agranulocytosis, but they told me they had never sold it because of the side effects of this medication in general," she says.

Britain is not the only country to veto the sale of Nolotil; in Sweden it has been prohibited for human use since 1974, and in the USA since 1997. Over the years, Japan, Australia, Iran and some EU countries, (where it is permitted for veterinary use) have also banned it. However, in Germany (its country of origin), Spain, Russia, Brazil and Israel, among other nations, it is one of the most commonly-prescribed drugs to alleviate pain and lower temperature.

Is there a genetic predisposition? Sources at the Spanish Medications Agency say that although there have been discussions for some years about a greater susceptibility to agranulocytosis in the northern European population and certain genetic factors have been studied, "with the information available we cannot confirm or rule out a higher risk among populations with specific ethnic characteristics," they say.

Isidro Jarque admits there could be a genetic predisposition to suffer agranulocytosis, "but like intolerances, having that predisposition doesn't mean you suffer it; the patient would have to come into contact with the medication. That's why people shouldn't self-medicate, because there could be unexpected side effects," he says.

Cristina García del Campo is pleased with the results of what she began to investigate a year ago. She says the Denia hospital is currently carrying out a study into the incidence of metamizole on the foreign population, which will be one of the biggest studies so far. The Costa del Sol hospital in Marbella did a study of its own ten years ago.

"They found that agranulocytosis caused by metamizole is an adverse effect which occurs more often in British people," she says.