Spanish health agency AEMPS warns of a ‘potentially fatal combination’ when mixing these drugs

Image of a doctor and patient. Credit: Andrei_R/

A warning about a ‘potentially fatal combination’ when mixing specific drugs was issued by the Spanish Agency for Medicines and Health Products (AEMPS).


The Spanish Agency for Medicines and Health Products (AEMPS) – which reports to the Ministry of Health – issued a warning today, Tuesday, February 21, about the ‘potentially fatal risks’ of the joint administration of two drugs used to combat shingles and cancer.

As pointed out in a statement from the agency, despite the fact that the Ministry of Health has warned about this problem on several occasions, the Spanish Pharmacovigilance System for Medicines for Human Use (SEFV-H) continues to receive notifications of serious cases due to the joint administration of these drugs.

Specifically, six new cases of this interaction have been reported since 2017, all of them serious and four of them fatal. The high mortality rate is due to the co-use of brivudine and fluoropyrimidines.

Brivudine is a drug used as an inhibitor of varicella-zoster virus replication. It is prescribed for the early treatment of acute herpes zoster in immunocompetent adults. Two medicines containing this active ingredient are currently authorised in Spain: Nervinex and Brivudine Aristo.

AEMPS warned that these medicines cannot be mixed with fluoropyrimidines, such as capecitabine, 5-fluorouracil, tegafur, floxuridine or flucytosine, which are used to treat cancer. In addition, a waiting period of at least four weeks must be observed between the end of brivudine treatment and the start of fluoropyrimidine administration.

“Brivudine, through its main metabolite, bromovinyl uracil, exerts an irreversible inhibition of dihydropyrimidine dehydrogenase. This is an enzyme that regulates the metabolism of both natural nucleosides (e.g. thymidine) and pyrimidine-type drugs (fluoropyrimidines) such as capecitabine or 5-fluorouracil (5-FU)”, explained the agency.

It added: “As a consequence of enzyme inhibition, overexposure and increased toxicity of fluoropyrimidines can be life-threatening”.

In case of accidental administration of brivudine to patients who have recently received, or are receiving, fluoropyrimidines, both treatments should be stopped and appropriate measures taken to reduce toxicity.

Health recommends immediate hospitalisation and measures to prevent systemic infections and dehydration. Symptoms of fluoropyrimidine drug toxicity include nausea, vomiting, diarrhoea and, in severe cases, stomatitis, mucositis, toxic epidermal necrolysis, neutropenia and bone marrow depression.

Among its recommendations to patients, the AEMPS pointed out the importance of not taking Nervinex or Brivudina Aristo if they are receiving any medicine for the treatment of cancer or the medicine Ancotil for a fungal infection, “and should be avoided during the entire treatment period”, among other precautions.

Finally, the AEMPS highlighted that the interaction between brivudine and 5-fluoropyrimidines is fully described in the label and packaging leaflet of medicines containing this active substance, and a warning is also included on the packaging of the medicine.


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Written by

Chris King

Originally from Wales, Chris spent years on the Costa del Sol before moving to the Algarve where he is a web reporter for The Euro Weekly News covering international and Spanish national news. Got a news story you want to share? Then get in touch at