Spain Investigates Metamizole Risks In Expat Britons
Executive Summary
Metamizole is in the safety spotlight again after the Spanish regulator said it was investigating reports of deaths and serious side-effects in expatriate and holidaymaking Britons caused by the painkiller.
The European Medicines Agency says it is keeping an eye on developments in Spain after the country's medicines agency, the AEMPS, confirmed that it is gathering information on adverse reaction reports with the painkiller and antipyretic metamizole, in light of reports that at least 10 Britons have died after taking the product in Spain.
Local Spanish news sources have been reporting cases of serious side-effects of metamizole, including agranulocytosis, and deaths in people from the UK over the past few years. There have been suggestions that northern Europeans are more likely than other populations to experience these side-effects. Last year, the expatriate publication The Olive Press launched a campaign to ban what it called the “deadly painkiller Nolotil in Spain.” The matter came to the fore after the UK newspaper The Times ran a report saying that “more than 100 British and Irish expatriates and holidaymakers in Spain” had suffered “devastating side-effects after taking the drug.”
The EMA is “aware that the Spanish national competent authority (AEMPS) is investigating the issue," the agency said in an emailed statement. "The Agency is closely following the matter and will react accordingly if deemed necessary.”
The EMA already has the safety of metamizole in its sights, albeit for another reason. More than 50 medicines containing the substance are under review by its drug evaluation committee, the CHMP, because of what the agency calls “substantial” differences in their labeling among the EU member states concerning the recommended maximum daily dosages and the contraindications on its use in pregnant and breastfeeding women. (Also see "Metamizole Safety In Spotlight As EMA Tackles Pregnancy/Lactation Labeling Disarray" - Pink Sheet, 4 Jun, 2018.)
Metamizole is a decades-old medicine that is also known as dipyrone and is used to treat severe pain and fever that cannot be controlled with other treatments. It is available in 19 EU countries, with Bulgaria, Germany and Hungary among those with the highest number of different brands. However, it is not available in many countries, including the UK, Denmark, France and Sweden.
In Spain the drug is sold as Nolotil by Boehringer Ingelheim and as Buscapina Compositum by Sanofi, as well as by numerous generics companies including Cinfa, Stada and Teva.
The AEMPS said that “the risk of leukopenia, agranulocytosis and possibly sepsis is already known for metamizole” and is described in the medicine’s labeling. Studies suggest that the risk of agranulocytosis in Spain is very low, but “there are no formal, well designed studies on the incidence of agranulocytosis with metamizole in patients of anglo-saxon or Nordic origin compared with those from other geographic areas,” the agency told the Pink Sheet.
It said it was collating information on adverse reaction cases that it has identified but that have not yet been formally reported, and on cases already notified to the Spanish pharmacovigilance system. “In the great majority of cases notified, there is a lack of relevant information to evaluate the impact of this adverse reaction in these populations, which we are waiting to receive.” The AEMPS is collecting more detailed information on these cases together with the autonomous pharmacovigilance centers for evaluation, it added.
Some publications have mentioned a higher frequency of hospitalizations due to agranulocytosis associated with metamizole in these kinds of patients, the AEMPS said, adding that it was “important to point out that this medicine is not authorized in all countries of the EU.”
A spokesperson for Boehringer Ingelheim said there was "no scientific evidence/data on country specific populations that are prone to develop any side-effects." The company had "submitted all available safety and effectiveness data collected during approx. 60 years (since the product launch) for the approved indications with the marketing authorization application," the spokesperson said.
"Health authorities as well as Boehringer Ingelheim are continuously monitoring the risk-benefit profile of Nolotil. Current prescribing information adequately addresses current knowledge about any risks associated with Nolotil use." The company's priority "is always to assure the health and wellbeing of our patients and we take seriously every case where a patient suffers an adverse event," the spokesperson added.
From the editors of Scrip Regulatory Affairs.