The European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has confirmed that hydroxyzine is associated with a “small but definite risk” of serious heart rhythm anomalies, in a review published on 13 February 2015. The conclusion is likely to bring important changes to the use of hydroxyzine-containing medicines across the EU.
Hydroxyzine has been used for almost 60 years as an antihistamine, antipsychotic, anxiolytic and sedative across a range of indications. It is currently marketed under several names, including Atarax (hydroxyzine hydrochloride; Alliance Pharmaceuticals) and Vistaril (hydroxyzine pamoate; Pfizer).
The PRAC started its benefits-risk review in April 2014 in response to a notification by Hungary, the lead member state for signals for this active ingredient. The referral was prompted by a desire to consider the implications of research published in 2011 which identified, among other things, the potential for hydroxyzine to cause arrhythmias at lower concentrations than previously thought.
The PRAC review has confirmed that hydroxyzine poses an increased risk of QT-interval prolongation and of torsade de pointes, which can cause arrhythmia and cardiac arrest. The risk does not vary between indications, the PRAC found, and can increase significantly when hydroxyzine is combined with other medications.
The committee considers that hydroxyzine-containing medicines can continue to be used, but that a series of measures should be put in place to minimise the risks. They include: reducing the dosage; avoiding its use in the elderly and in patients at highest risk of arrhythmia (including specifically those already receiving medication to reduce the heart rate or that increase the risk of QT prolongation); and closely monitoring patients. The product information should be updated accordingly, and further research is also recommended.
Hydroxyzine should be used, the PRAC believes, at the lowest effective dose for the shortest time possible, and should not exceed 100mg per day in adults, 50mg in the elderly (and only when its use is unavoidable) and 2mg per kilogram of body weight in children (up to 40kg). Currently, the highest recommended daily dose for adults is 300mg.
The PRAC’s recommendations will now be considered by the EMA’s Co-ordination Group for Mutual Recognition and Decentralised Procedures — Human (CMDh) at its next monthly meeting, scheduled for 23-25 February 2015.
Depending on whether the CMDh agrees by consensus or by majority vote, the measures could be implemented directly by the 24 member states where hydroxyzine-containing medicines have been authorised, or forwarded to the European Commission for the adoption of a legally-binding EU-wide decision.