Antiepileptic drugs: updated advice on switching between different manufacturers’ products
In addition to the 3 risk-based categories of antiepileptic drugs, patient-related factors should be considered when deciding whether it is necessary to maintain continuity of supply for a specific product.
Advice for healthcare professionals:
- core advice from 2013 remains in effect for prescribing antiepileptic drugs to manage epilepsy
- consult the 3 categories of antiepileptic drugs when deciding whether it is necessary to maintain continuity of supply of a specific manufacturer’s product
- as well as the classification, when evaluating whether continuity of supply should be maintained for category 2 or 3 drugs, consider:
- perception by patients of differences in supply, for example differences in product presentations
- co-morbid autism, mental health issues, or learning disability
- if you think a patient should be maintained on a specific manufacturer’s product, prescribe either by specifying brand name or by using the generic drug name and name of the manufacturer
CHM review and update
In November 2013, we issued advice about switching between different manufacturers’ products of an oral antiepileptic drug.
In September 2016, the Commission of Human Medicines (CHM) reviewed this advice following feedback and requests for clarification from patients and healthcare professionals. CHM maintained their previous advice that when considering switching, antiepileptic drug could be classified into 3 categories and that, although the reports of loss of seizure control and/or worsening of side effects occur around the time of switching between products could be explained as chance associations, the effect of switching could not be ruled out in all cases.
For drugs in Category 3, therapeutic equivalence between branded and generic products (and between different generics) can be assumed, but other factors are important when considering whether switching is appropriate. Differences between alternative products (for example, product name, packaging, appearance, and taste) may be perceived negatively by patients and/or carers, and may lead to dissatisfaction, anxiety, confusion, dosing errors, and reduced adherence. In addition, difficulties for patients with co-morbid autism, mental health problems, or learning disability should also be considered.
For drugs in Category 2 similar considerations apply. It may also be necessary to consider clinical factors such as seizure frequency, treatment history, and the potential implications for the individual of having a breakthrough seizure.
The table below summarises the different categories of drugs, and advice for prescribing.
Category
Category 1
Drugs
Carbamazepine, Phenobarbital, Phenytoin, Primidone
More details on classification
For these drugs, there are clear indications that clinically relevant differences between different manufacturers’ products might occur, even when the pharmaceutical forms are the same and bioequivalence has been shown
Advice for prescribing
Ensure that the patient is maintained on a specific manufacturer’s product.
Category
Category 2
Drugs
Clobazam, Clonazepam, Eslicarbazepine, Lamotrigine, Oxcarbazepine, Perampanel, Retigabine, Rufinamide, Topiramate, Valproate, Zonisamide
More details on classification
Drugs that do not fit into Category 1 or 3
Advice for prescribing
Base the need for continued supply of a particular manufacturer’s product on clinical judgement and consultation with patient and/or carer, taking into account factors such as seizure frequency and treatment history. Take into account patient/carer-related factors such as their negative perceptions about alternative products and/or other issues related to the patient should also be taken into account.
Category
Category 3
Drugs
Brivaracetam, Ethosuximide, Gabapentin, Lacosamide, Levetiracetam, Pregabalin, Tiagabine, Vigabatrin
More details on classification
These drugs show all the following characteristics: High solubility across the relevant range of pHs; Essentially complete absorption after oral administration; Dose-response curves for efficacy and safety are not steep; Therapeutic Index is not narrow
Advice for prescribing
For these drugs, the potential for clinically relevant differences to exist between different manufacturers’ products is considered to be extremely low. However, consider other patient/carer-related factors, such as negative perceptions about alternative products and/or other issues related to the patient.
Article citation: Drug Safety Update volume 11, issue 4; November 2017: 5.