The Health Sciences Authority (HSA) and its Pharmacovigilance Advisory Committee (PVAC) have recently reviewed the safety profile of promethazine in children following the action taken by the US Food and Drug Administration (FDA) to contraindicate the use of promethazine hydrochloride preparations (e.g. Phenergan®) in children younger than 2 years old.
From our review of the risks versus benefits of promethazine, it was concluded that the risk of serious adverse drug reactions outweighs the potential benefits of the drug in young children. To reflect this safety concern, HSA is currently working with pharmaceutical companies to include the following information in the affected package inserts/patient information leaflets:
- Promethazine is contraindicated in children less than 6 months old;
- It is not recommended for use in children less than 2 years old;
- Caution should be exercised when used in children 2 years of age and older.
Summary of HSA’s review
Promethazine containing preparations are widely used in children for their antihistamine, antiemetic, and sedative properties. Since its approval in the US in 1951, serious and life-threatening adverse events have been reported with promethazine when used in children. Between the period 1969 – 2003, there were 125 cases of serious adverse events reported in patients below 17 years of age. The serious adverse events include respiratory depression, apnoea, cardiac arrest, seizures, dystonic reactions and hallucinations. For the cases involving respiratory depression (38 reports), about 57% occurred in young patients between 1.5 months – 2 years old. Based on the US FDA's analysis, respiratory depression occurred over a wide range of doses (0.45 mg/kg – 6.4 mg/kg of promethazine). Another point highlighted by the US FDA was that serious outcomes such as death, disability, life-threatening events, and hospitalisation occurred with all routes of administration (oral, rectal and parenteral).
A review of the product information of promethazine containing preparations in countries such as the UK and Australia showed they contain cautionary statements on the use of promethazine in young children. For instance, the product information of promethazine containing elixirs carries the precaution that the product is not recommended for children under 2 years of age.
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Conclusion
Although there have been no local reports of fatal ADRs associated with promethazine, HSA is aware of cases of apnoea occurring in very young children. In view of the unpredictable nature of the adverse events and their serious outcomes, healthcare professionals should exercise caution when prescribing promethazine to young children.
