The Spanish medicines agency, AEMPS, warns against severe methemoglobinemia after using large quantities of EMLA Cream (2.5% lidocaine + 2.5% prilocaine) (1). The well known methemoglobin-forming capacity of parenteral prilocaine is based on oxidation of the hemoglobin iron by the prilocaine metabolite o-toluidine (a-t 1994; no. 12: 120). The blood loses capacity to transport oxygen. Characteristic results are headaches, fatigue, lethargy, confusion and breathlessness as well as cyanosis of the skin and mucosa.

AEMPS overviews eleven reports on methemoglobinemia with EMLA. Symptoms begin about one to two hours after using the anaesthetic cream (1). Nine of the patients used it in preparation for photo-epilation (1). To relieve pain, the external agent with anaesthetising effects is applied thickly to the area of skin to be treated and covered with an occlusive dressing. In the patients affected by methemoglobinemia, the maximum dose for adults of the prescription-only cream of 60 g, which is also given in the German Summary of Product Characteristics (SPC) (2), was exceeded (1).

The German Federal Institute for Drugs and Medical Devices (BfArM) overviews two reports from Germany on methemoglobinemia including one involving an infant aged three months who was treated with 20 g to 25 g in preparation for elective dye laser therapy for naevus flammeus. The child had to be ventilated for several days (3). Of five other reports from outside Germany which are known to the BfArM, at least three are caused by overdose with the use of 90 g cream in the case of a 36-year old woman and a two-year old child with subsequent coma and 120 g in a 14-year old girl* before laser hair removal (3).

Because of the seriousness of the events and the conspicuous connection with use before photo-epilation, the Spanish authority warns that the restrictions on use should be strictly observed: 60 g cream at the most over a maximum area of 600 cm2 in adults, which is equivalent to about the size of a DIN A4 sheet of paper (1). Simultaneous use of other methemoglobin formers, such as sulphonamides or nitrate-containing products, should be avoided. In cases of clinically relevant methemoglobinemia, tolonium chloride (TOLUIDINBLAU) injected slowly is used as an antidote (2).

1

Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): Posibles efectos adversos del uso de EMLA Crema aplicada sobre superficies extensas de piel, 15 June 2012; http://www.aemps.gob.es/informa/notasInformativas/ medicamentosUsoHumano/seguridad/ciudadanos/2012/docs/NI-MUH_FV_09-2012.pdf

2

AstraZeneca: SPC EMLA, as at Aug. 2011

3

BfArM: letter dated 8 Aug. 2012

*

Report from Spain and so possibly included in the eleven reports mentioned initially.