In order to investigate the many issues surrounding brand and generic prescribing, including the issue of switching between AEDs, an expert group of the Commission on Human Medicines (CHM) was set up.⁵ The CHM reviewed spontaneous adverse reactions received by MHRA as well as publications that reported potential harm arising from generic switching of AEDs. These published reports were in patients who were previously stabilised on a branded product.

In their review the CHM considered a number of key factors:

• The bioequivalence standards that are applied to generic AEDs.
• The implications on safety and efficacy where a formulation shows a difference in bioavailability despite being defined as bioequivalent.
• Switching from branded originator to generic or between different generic products.
• The influence of a drug’s solubility and permeability on the bioavailability of different formulations.

A review of the published studies did not show clear evidence of actual harm arising from switching between formulations. The CHM found that reports of loss of seizure control and worsening of side effects that coincided with a product switch could be explained as chance associations.

However, a causal relationship between product switching and adverse events could not be ruled out in all cases. In addition, given the limitations of observational studies, a lack of strong evidence did not completely rule out the risk of patient harm occurring as a direct result of switching.

The CHM review therefore concluded that, for certain AEDs, there is a need to maintain continuity of supply of the same manufacturer’s product – whether that is a brand or a generic. This is in line with NICE guidance and further reinforces the need for caution if a switch is necessary. The CHM noted that problems relating to variation in bioequivalence were of significant concern for some AEDs but less so for others with a wider therapeutic range or higher solubility.

The key question is – for which AEDs is the continuity of supply of the same formulation most essential?

⁵ Formulation switching of antiepileptic drugs: A report on the recommendations of the Commission on Human Medicines from July 2013; Medicines and Healthcare Products Regulatory Agency; July 2013. http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con341226.pdf