Antiepileptic drugs: new advice on switching between different manufacturers’ products for a particular drug
Different antiepileptic drugs ( AEDs ) vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers’products of a particular drug may cause adverse effects or loss of seizure control.
Antiepileptic drugs have been divided into three risk-based categories to help healthcare professionals decide whether it is necessary to maintain continuity of supply of a specific manufacturer’s product.
Bioequivalence and antiepileptic drugs
When a generic medicinal product is shown to be bioequivalent to the originator ( reference ) product, as defined by the relevant regulations and guidelines, it follows that the products can be considered to be clinically equivalent. However, concerns about switching between different manufacturers’ products of an oral antiepileptic drug have been raised by patients and prescribers. These include switching between branded originator and generic products, and between different generic products of a particular drug. The main reasons for these concerns are the narrow therapeutic index of some antiepileptic drugs and the potentially serious consequences of therapeutic failure. Drug-drug interactions and the relatively low solubility or bioavailability ( or both ) of some antiepileptic drugs are other important factors.
Potential risk from switching between different manufacturers’products
The Commission on Human Medicines ( CHM ) reviewed spontaneous adverse reactions received by MHRA ( Medicines and Healthcare Products Regulatory Agency ) and publications that reported potential harm arising from switching of antiepileptic drugs in patients previously stabilised on a branded product to a generic. Following this review, CHM concluded that reports of loss of seizure control and/or worsening of side effects around the time of switching between products could be explained as chance associations, but that a causal role of switching could not be ruled out in all cases.
New categorisation to help minimise risk
The CHM considered the characteristics of antiepileptic drugs and advised that they could be classified into three categories based on therapeutic index, solubility, and absorption to help prescribers and patients decide whether it was necessary to maintain continuity of supply of a specific manufacturer’s product. These categories are listed below:
Category 1 - Phenytoin, Carbamazepine, Phenobarbital, Primidone - For these drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product
Category 2 - Valproate, Lamotrigine, Perampanel, Retigabine, Rufinamide, Clobazam, Clonazepam, Oxcarbazepine, Eslicarbazepine, Zonisamide, Topiramate - For these drugs, the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with patient and/or carer, taking into account factors such as seizure frequency and treatment history
Category 3 - Levetiracetam, Lacosamide, Tiagabine, Gabapentin, Pregabalin, Ethosuximide, Vigabatrin - For these drugs, it is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors.
Advice for prescribers
Different antiepileptic drugs vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers’ products of a particular drug may cause adverse effects or loss of seizure control.
Antiepileptic drugs have been divided into three categories to help healthcare professionals decide whether it is necessary to maintain continuity of supply of a specific manufacturer’s product.
If it is felt desirable for a patient to be maintained on a specific manufacturer’s product, this should be prescribed either by specifying a brand name, or by using the generic drug name and name of the manufacturer ( otherwise known as the Marketing Authorisation Holder ). ( Xagena )
Source: Drug Safety Update 2013; volume 7 issue 4: A1
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