The EMA warns of several deaths due to the prolonged use of drugs that combine ibuprofen and codeine

The European Medicines Agency (EMA) has issued a warning about the risks of long-term use of medicines containing ibuprofen and codeine.

Taking both active ingredients together, used to treat pain, can cause "serious kidney and gastrointestinal damage, even fatal, especially when taken for longer and at higher doses than recommended," the agency's Pharmacovigilance Committee has warned. .

The EMA states that it has received news in recent months of several deaths related to this type of drug, although none of them have been registered in Spain, according to the Spanish Agency for Medicines and Health Products (AEMPS).

Treatments that combine ibuprofen and codeine can only be purchased with a prescription.

In Spain there are seven authorized medicines that use this formulation, although currently only three of them are for sale in pharmacies, according to the General Council of Pharmacists Associations.

They are Neobrufen with Codeine —another version without codeine not affected by the alert is sold— and two presentations of Astefor, one in capsules and the other in sachets.

All of them contain 400 milligrams of ibuprofen and 30 of codeine.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild and moderate pain, among other ailments.

Codeine is one of those considered minor opioids that can also be used for less intense pain.

The combined use of both active ingredients has

advantage: as their mechanisms of action are completely different, the use of both has a greater therapeutic effect and makes it possible to deal with moderate pain without having to resort to more powerful opioids.

“The use of these drugs is only justified for short periods of time, because prolonged use has many side effects in addition to those now reported by the EMA.

Codeine causes persistent constipation and ibuprofen is harsh on the digestive system.

If the pain becomes chronic, there are other effective and safer therapeutic options," says María Ángeles Canos, head of the Pain Unit at Hospital La Fe (Valencia).

According to data from the Ministry of Health, the combination of ibuprofen and codeine is the tenth most used type of opioid in Spain and accounts for 1.17% of the total consumption of this type of drug.

The daily dose consumption per 1,000 inhabitants —DHD, the most widely used measure— is 0.083, according to these data.

The trend of its use in Spain is downward and has fallen by 71% in the last decade (consumption was 0.2915 DHD in 2011).

“On the pain treatment scale, the combination of ibuprofen and codeine would be the third level.

The first is paracetamol and nolotil.

The second, NSAIDs.

And for more severe pain, other types of opioids are used.

But, as the EMA says, it is not a good option for prolonged treatments.

At its level, moreover, it has been displaced by other combinations such as tramadol with paracetamol”, explains Vicente Baos, a family doctor at the Collado Villalba Pueblo health center (Madrid).

The EMA warns that the repeated use of codeine with ibuprofen can also lead to dependence due to the addictive potential of opioids, which increases the risk of dangerous side effects.

"The Pharmacovigilance Committee has reviewed numerous cases of renal, gastrointestinal and metabolic poisoning related to abuse" of these presentations, the agency said in a statement.

“Its prolonged use can damage the kidneys, preventing them from properly purifying acids from the blood to the urine (acidosis).

Malfunctioning kidneys can also lower blood potassium levels,” he adds.

The Agency alerts the Member States about the sale in some countries of this type of medicine without a prescription, something that in Spain no longer occurs, according to all the sources consulted.

This newspaper tried to acquire them this Monday in six pharmacies in the city of Barcelona alleging intense joint pain and all of them refused by not presenting the prescription.

The most repeated advice was to make an appointment with the doctor (five) and four of them suggested taking ibuprofen 400 milligrams provisionally until the consultation.

The EMA notice will mean that the prospectuses and technical data sheets of these drugs will be modified to include warnings about the risks detected, something that has already begun to be done, although the complete substitution process may take a few weeks.

A spokesman for the AEMPS confirmed that this body, dependent on the Ministry of Health, is preparing an informative note to transmit the EMA's conclusions to the health system, which will be published in the next few hours.

According to Agency sources, in Spain "it is not necessary to adopt more measures, such as the withdrawal of medicines or warnings to the population."

Carlos Fernández Moriano, responsible for scientific dissemination of the General Council of Pharmaceutical Associations, affirms that this sector is "waiting for the AEMPS to issue the corresponding information note to transmit it to all the associations in Spain to reinforce the messages to all associates ”.