A patients group representing several British victims has launched legal action against the Spanish Government over claims it failed to safeguard people against the potentially fatal side effects of one of the country’s most popular painkillers, involved in a series of serious illnesses, sepsis, amputations and deaths.
The drug metamizole, commonly sold in Spain under the brand name Nolotil, is banned in several countries, including Britain, the US, India and Australia, reports The Guardian.
It can cause a condition known as agranulocytosis, which reduces white blood cells, increasing the risk of potentially fatal infection.
The Association of Drug Affected Patients (ADAF), which said adverse reactions to the drugs have led to sepsis, organ failure and amputations, has identified about 350 suspected cases of agranulocytosis between 1996 and 2023, including those of 170 Britons living in Spain or who were holidaying there.
The ADAF is examining more than 40 fatalities in which it considers the drug may have led, or contributed, to death, and demanding an investigation into the drug and new controls.
It filed its action on 14 November in the national court in Madrid.
Cristina García del Campo, founder of the organisation, said: “This drug has destroyed people’s lives and it should now be withdrawn. One woman took three tablets and had to have part of her feet amputated and several fingers. Even if it doesn’t kill you, once you’ve had sepsis your body is never the same.”
Metamizole was first produced commercially in Germany in 1922 and was available worldwide until it was found there was a risk of it causing agranulocytosis. It was withdrawn in about 30 countries, but is still widely available across the EU. In South Africa, notes MedicalBrief, a warning about the risk of drug-induced liver injury associated with the use of metamizole-containing medicines, was issued a two years ago. (see below).
Studies have shown a dramatic variation in the estimated incidence of agranulocytosis in response to the drug, from about one in 2 000 to less than 1.1 per million users.
A European Medicines Agency report in December 2018 suggested the “potential to induce agranulocytosis may be associated with the genetic characteristics of certain populations”.
García del Campo, a translator from Alicante, started investigating when one of her clients, an Irishman, fell seriously ill, with infections racking his body. He was admitted to hospital in the city of Dénia and died on 18 November 2017 of sepsis and multi-organ failure.
She said: “I was the last person with him and all the time I was with him, I kept asking: ‘Why is this happening? How could someone go from being fine to having this terrible infection?’”
She started compiling worrying recent reports she had heard locally involving agranulocytosis and sepsis. Then she spread out all the case files and medical notes she had gathered on six cases. It struck her that everyone involved had been on metamizole.
One of the patients, Paddy Clancy (80), a British expatriate who lives in Jávea, said last week that he nearly died after being given metamizole following a shoulder operation in September 2017. He became so ill doctors put him into an induced coma to give his body the best chance of fighting the infection.
His wife was told his kidneys are packing up and his organs are shutting down, that the white blood cells in his body, which usually fight infection, had been severely depleted.
Clancy emerged from the coma after 39 days. He had lost 22kg and could not stand, but has gradually recovered. His records confirm the disorder that nearly killed him: “agranulocytosis associated with metamizole”.
García del Campo was finding many similar cases. An Irish holidaymaker, William Smyth (66), died in April 2016 from multi-organ failure after being prescribed Nolotil for shoulder pain.
Mary Ward (59), who lived in Spain, died in March 2006 after taking Nolotil following an operation in Marbella and contracting agranulocytosis and complications.
In another case, a woman in her 60s required amputations after taking the drug and developing sepsis.
It is said that agranulocytosis is an extremely rare reaction to metamizole, but García del Campo was soon being inundated with reports.
She said the cases appeared to show that the British and Irish community were more susceptible.
A study in April 2009 had looked into 13 cases of agranulocytosis involving dipyrone (another name for metamizole) at the Hospital Costa del Sol in Marbella, with five cases involving Britons. It concluded: “Dipyrone-related agranulocytosis is an adverse effect more frequent in (the) British population, and its use must be avoided.”
The ADAF has submitted evidence in its case from a regional health official who says a local study in five Health Departments in Spain had “surprisingly” found that the British population had a susceptibility to metamizole in the order of “80 to 120 times higher” than the Spanish.
That report has not been published and there is no comprehensive and robust epidemiological evidence to date to support the theory that British or Irish people may be more susceptible to the drug’s side effects.
In October 2018, less than a year after García del Campo had started her campaign, Spain’s medicines and health products agency, the AEMPS, brought out new guidelines for metamizole. It recommended its use be avoided in tourists (described as the “floating population”) and that patients should be advised of symptoms of agranulocytosis.
García del Campo says the new guidelines have been widely breached. She said patients were not being warned of the risks and that the drug could be obtained without the required prescription.
The ADAF legal action, against the Spanish Ministry of Health and the AEMPS, says the drug is being offered to patients without proper controls. It calls for a ban on giving the drug to citizens from countries where metamizole has been withdrawn and a new analysis of the risk factors relating to agranulocytosis.
It also says the information sheet for the drug needs to be revised.
Francisco Almodóvar, the lawyer representing the ADAF, said: “We have testimonies of British people telling their stories. We can support the evidence with clinical records. It is a very significant public health issue.”
The company that makes Nolotil, Boehringer Ingelheim, said: “Nolotil is a prescription drug. Its ingredient metamizole has been used by patients for almost 100 years, with an established and well known safety profile.
“Agranulocytosis is described as a very rare frequency adverse reaction in the current prescribing information. It is a known adverse reaction for decades and the available scientific information has confirmed the well known safety profile of metamizole.
“The side effect of agranulocytosis is addressed in the current product information… which addresses current knowledge about risks associated with Nolotil use. We welcome any information which helps us to improve the benefit-risk profile and the safe use of our medicines.”
In March 2021, Sanofi-Aventis South Africa (Pty) Ltd and Adcock Ingram Ltd, in agreement with the South African Health Products Regulatory Authority (SAHPRA), issued a warning letter to health professionals across the country about the risk of drug-induced liver injury (DILI) associated with the use of metamizole-containing medicines.
It provided background information related to the warning, and said liver injury was “observed to be predominantly of a hepatocellular pattern with an onset of a few days to months following treatment initiation with metamizole-containing medicines”.
“Signs and symptoms included elevated serum hepatic enzymes with or without jaundice, frequently in the context of other drug hypersensitivity reactions (e.g., skin rash, blood dyscrasias, fever and eosinophilia) or accompanied by features of autoimmune hepatitis. There are cases reporting liver injury recurrence upon re-administration.”
It said available data indicated an immuno-allergic mechanism. “In general, metamizole-containing medicines induced liver injury may progress to potentially serious outcomes, such as acute hepatic failure requiring liver transplantation.”
DHCP-Letter-Metamizole-Final_approved_signed-02Mar21
The Guardian article – ‘They thought I had cancer’: painkiller banned in UK linked to Britons’ deaths in Spain (Open access)