Adverse reactions from anaesthetics containing articaine (Septanest®, Septocaine®, Ubistesin®, Ubistesin Forte®)

This is a follow-up on the Danish Medicines Agency’s announcement from 17 August 2005 “Study of adverse reactions from anaesthetics for dental treatment” (link in the fact box to the right).

In 2005, the Danish Medicines Agency initiated a study of the local anaesthetic articaine, which is used in dental care and elsewhere. The reason was that the Danish Medicines Agency had received information about occurrences of sensory impairment (paraesthesia, nerve damage) in patients who had been given local anaesthesia in the lower part of the mouth or the lower jaw (mandibular block) with articaine.
This information raised a suspicion that articaine might cause nerve damage and that the risk of using articaine is greater than the risk of using alternatives (mepivacaine, prilocaine, lidocaine).

Articaine is used in 57 countries, and it is estimated that around 100 million patients are treated with articaine every year. In Denmark, it is suspected that articaine is neurotoxic.
The suspicion is based on:

• an increased number of damages reported to the Danish Dental Association’s Patient Insurance Scheme
• adverse reaction reports submitted to the Danish Medicines Agency
• a number of open observation studies carried out in Denmark
• notifications in the literature about the result of relatively retrospective statements about patients, as well as experimental animal studies.

The below chart illustrates the number of reports on articaine received in Denmark in 2005 and up to today:

The increase in August and September may be due to a discussion in the media from the middle of August (stimulated reporting). Many of the reports submitted in August and ahead concern adverse reactions observed some time ago. Based on these reports, it is not possible to determine a causal relation between the adverse reactions observed and the medicinal product used.

The below figure illustrates the development in the sale of anaesthetics containing articaine:

Neurotoxicity has not been observed in prospective blinded randomised studies with a sufficient number of patients. Thus, it is not sufficiently scientifically documented that articaine can cause nerve damage. The existing studies are either retrospective reviews of patient material or studies not including enough patients to show very rarely occurring adverse reactions. In addition, the literature contains conflicting information.

The authorities in other EU countries have only registered very few reports on suspected neurological adverse reactions from local anaesthetics. Moreover, the other EU authorities are not in possession of any information arousing suspicion that articaine’s safety profile has changed significantly since it was granted marketing authorisation.

The Danish Medicines Agency believes that further studies are required. It is necessary to make animal trials with a view to examining whether/to what extent articaine may cause nerve damage. Furthermore, it is necessary to examine a large number of patients in prospective blinded and randomised studies. The Danish Medicines Agency is going to urge the marketing authorisation holder to perform such studies.

Anaesthetics containing articaine can still be used according to the current summaries of product characteristics (link to the summaries of product characteristics, SPC, in the fact box at the top of this page).

Doctors and patients are encouraged to report to the Danish Medicines Agency if suspecting adverse reactions (link to a reporting form in the fact box at the top of this page).

For further information, please contact Chief Medical Officer Doris I. Stenver on tel.: +45 4488 9247 or mobile: +45 2246 0979.

The Danish Medicines Agency, 30 March 2006