Risk of overdose in infants when using prilocaine/lidocaine cream (EMLA and generics)

Summary

We have received 2 serious adverse event cases in neonates in which EMLA (topical prilocaine/lidocaine cream) was applied for a circumcision procedure. Both cases were likely to have involved overdose.

Prilocaine/lidocaine cream (EMLA and various generics) is used for topical anaesthesia of the skin before various minor procedures.

Overdose of EMLA can cause serious adverse effects including methaemoglobinaemia, which in severe cases can lead to seizures or even death.

Methaemoglobinaemia is a condition in which elevated methaemoglobin in the blood disrupts the haemoglobin that transports oxygen around the body. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination and cyanosis. Complications may include seizures and heart arrhythmias.

When EMLA and other lidocaine/prilocaine topical cream preparations are provided over the counter without a prescription, consumers may not routinely receive advice on use from a health professional.

What health professionals should do

Health professionals should instruct parents and carers to use no more than the recommended amount of EMLA on the child’s skin, and to leave it on the skin for only the recommended length of time.

When preparing infants for circumcision, the recommended amount is 1 g applied to the prepuce for a maximum of 1 hour.

In general, you should provide clear instructions about using any topical anaesthetic, emphasising the recommended amount and length of application.

Use of EMLA

The registered indications for EMLA are topical anaesthesia of:

• the skin prior to insertion of IV catheters, blood sampling, vaccination; superficial surgical procedures, including split skin grafting
• leg ulcers to facilitate mechanical cleansing and debridement
• the genital skin prior to superficial surgical procedures or infiltration anaesthesia
• the skin prior to minor superficial cosmetic procedures.

Adverse events reported to us

Our publicly searchable Database of Adverse Event Notifications contains:

• 1 report of ‘seizure’ (1 of the reports mentioned below)
• 3 reports of ‘methaemoglobinaemia’, 2 of which are in patients under 1 year of age (which includes 1 of the cases mentioned below).

In October 2024, the Therapeutic Goods Administration (TGA) received 2 serious reports (1 case of seizure and 1 case of methaemoglobinaemia) following the topical administration of EMLA in preparation for circumcision. The TGA conducted a signal investigation to review these cases and found both were likely to have involved an overdose of the topical anaesthetic.

The following reports triggered this signal investigation:

• A 3-week-old male neonate hospitalised with a seizure following the reported administration of 3-4 g of EMLA on the penile shaft for circumcision. The child was not exposed to any other medicines and was treated supportively.
• A 3-week-old male neonate hospitalised with cyanosis and in respiratory distress following a circumcision and 3 g of EMLA applied topically to the shaft of his penis. The child was diagnosed with methaemoglobinaemia.

Response to adverse event notifications

The risk of methaemoglobinaemia and seizure in overdose were previously described in the EMLA Product Information (PI) and Consumer Medicine Information (CMI). In response to these adverse event notifications, the product label, package insert and CMI have been updated to emphasise the need to not exceed the maximum recommended dose or application time, as well as highlight that children, particularly those under 3 months of age, are at an increased risk of serious adverse effects in overdose. The package insert also now specifies a maximum length of application (maximum of 1 hour) for neonates and infants (0-3 months) when used for circumcision. We are currently working with sponsors (pharmaceutical companies) of the generic products to update their PIs, CMIs, product labels and package inserts.

Disclaimer

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Medicine Safety Updates are written by staff from the Pharmacovigilance Branch.

• Editor: Dr Daniel Dascombe
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• Contributors: Dr Steph Cheung and Renae Mura