Topical Anaesthesia in Infants

The Therapeutic Goods Administration (TGA) has issued a safety update regarding the use of prilocaine/lidocaine cream (e.g. EMLA®) in infants. This follows two serious adverse events involving seizures and methaemoglobinaemia. Both cases occurred in neonates and are believed to have involved overdose.

Methaemoglobinaemia is a potentially life-threatening condition where methaemoglobin, the oxidised form of haemoglobin, accumulates in the blood. As this form of haemoglobin cannot bind oxygen, raised levels can lead to hypoxia.

Infants may be more likely to develop methaemoglobinaemia due to:

• A higher proportion of foetal haemoglobin, which is more readily oxidised to methaemoglobin compared to adult haemoglobin; and
• Lower activity of NADH cyb5r reductase, the enzyme responsible for reducing methaemoglobin back to haemoglobin.

The manufacturer advises against using EMLA® in pre-term infants with a gestational age of less than 37 weeks, and in infants up to 12 months of age who are receiving treatment with a methaemoglobin-inducing agent. Examples of methaemoglobin-inducing agents include dapsone, sulphonamides, other local anaesthetics, and nitrites and nitrates. EMLA® is also contraindicated in glucose-6-phosphate dehydrogenase deficiency and congenital or idiopathic methaemoglobinaemia as these patients have a higher risk of drug-induced methaemoglobinemia.

The EMLA® product label and package insert have been updated to emphasise the importance of adhering to the maximum recommended dose and application time. The TGA is also in the process of ensuring these updates are applied to generic products.