Prescribing Antiepileptic Drugs: Lamotrigine and Levetiracetam
Key Messages
1. Any generic switching should only be carried out following an informed
discussion with the patient and/or carer. The MHRA leaflet3 may be
useful in consultations.
2. Patients should be asked whether they have previously experienced
problems when switching between brands and generics or if they have
been told by their doctor that they must not switch between brands or
generics.
3. If a patient on lamotrigine is to be maintained on a specific
manufacturer’s product, then this can either be achieved by prescribing
the brand Lamictal or by indicating a specific generic on the prescription.
4. The community pharmacy or GP dispensary must endeavour to maintain
consistency of supply of a specific manufacturer’s generic product if it is
indicated on the prescription. Any substitution should only be carried out
in conjunction with the prescriber and patient/carer
5. Any substitution with a different manufacturer’s generic product is to be
identified to the patient/carer upon collection to reduce the potential for
anxiety and poor adherence to therapy.
6. The evidence suggests that it is reasonable for most patients to receive
generic levetiracetam. The drug has a wide therapeutic index and unless
there are specific concerns around the impact of lack of seizure control
in well controlled patients, generic prescribing could be considered after
consultation with the patient and/or carer.
7. Non adherence to antiepileptic therapy may be associated with a 20%
higher rate of seizures and a threefold increase in mortality. Promoting
the importance of good medicines adherence, and offering reassurance
about the effectiveness of treatment is critical, especially when any
switching is considered.
Introduction
The aim of this document is to clarify the local position with regard to the new
recommendations on the prescribing and dispensing of Anti-Epileptic Drugs (AEDs)
published in the MHRA Drug Safety Update in November 20131, specifically around
the use of generic products. Specific detail is included within Appendix 1.
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A letter to the BMJ published in December 2013 highlighted that whilst considerable
savings were possible through the use of generics, 35-50% of patients with epilepsy
may be non-adherent to their dosing regimens and that generic switching may
increase this percentage further. Non adherence may be associated with a 20%
higher rate of seizures and a threefold increase in mortality, leading to considerable
increases in healthcare costs2.
The Local Position
Local discussions have focussed primarily on the prescribing of the drugs lamotrigine
and levetiracetam. Both products are available as generics, but fall into different
therapeutic categories.
Lamotrigine is a Category 2 drug where the MHRA advises that the need for
continued supply of a manufacturer’s product should be based on clinical judgement
and consultation with the patient and/or carer, taking into account factors such as
seizure frequency and treatment history.
There are a number of manufacturers of generic lamotrigine, and patients may often
receive different generics when prescriptions are dispensed.
Levetiracetam is a Category 3 drug where the MHRA advises that it is usually
unnecessary to ensure that patients are maintained on a specific manufacturer’s
product unless there are specific reasons such as patient’s anxiety.
Prescribing data indicates that the use of generic levetiracetam in Cornwall and Isles
of Scilly is significantly lower than the England average. Approximately £60,000 per
annum could be saved if generic prescribing rates rose to the England average.
The Cornwall Area Prescribing Committee (CAPC) sought advice from local
neurologists, specialist nurses, and paediatric consultants on the issue of generic
prescribing of AEDs, with specific reference to lamotrigine and levetiracetam. There
were obvious concerns around loss of seizure control, patients’ anxiety and reduced
adherence to dosing regimens, and continuity of supply of certain generics. It was
also noted that ‘tablet identifier’ materials from The Epilepsy Society only referred to
brands of drugs.
The CAPC acknowledged the concerns and agreed the following recommendations
in line with those from the MHRA:
1. Most patients taking lamotrigine should be maintained on a specific product.
This does not necessarily mean that prescriptions should be routinely written
as Lamictal, but that prescriptions could include the generic drug name and
name of generic manufacturer.
2. Pharmacies and GP dispensaries should ensure the continuity of a particular
manufacturer’s generic product when the prescription specifies it. If the
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3.
4.
5.
6.
7.
8.
9.
prescribed product is unavailable, the need for continuity of treatment may
dictate that a different manufacturer’s product is required. This should be
discussed with the prescriber and patient/carer.
Where any switching has taken place, the new product should be identified to
the patient/carer at the point of collection, and reassurance given around the
use of a product the patient/carer may be unfamiliar with.
New initiations of levetiracetam will be for the generic, unless clinical need
dictates otherwise. Any new requests for Keppra may be queried with the
initiating healthcare professional.
Patients stabilised on branded Keppra who are seizure-free will not be
routinely expected to switch to a generic. However, there may still be an
opportunity to review therapy and discuss with patients their views on
switching - they should not be forced to switch.
Patients on Keppra who still experience seizures will be reviewed and a
switch to the generic may be considered if clinically appropriate. (This may be
part of a wider review of the effectiveness of the current treatment regimen).
The change should be discussed with the patient to reduce the risk of anxiety
and poor adherence to prescribed medicine
Any changes to patients’ prescribed AEDs will be communicated to the
supplying dispensary or pharmacy so that messages can be reinforced. This
will also allow for Keppra stock to be run down
Industry/Charity ‘tablet identifiers’ should not be used for medicines where
generic products exist and may be prescribed. Where there is concern around
the appearance of an AED, the supplying pharmacy/GP dispensary should be
requested to identify prescribed AEDs to the patient.
The leaflet for patients3 may be useful in discussions
References
1. MHRA Drug Safety Update, Volume 7 Issue 4 November 2013
2. Letter to BMJ, Dec 13 ‘New advice on switching antiepileptic drugs might be a
false economy’
3. Leaflet for patients: Antiepileptic drugs: changing between different
manufacturers’ products
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Appendix 1: MHRA Drug Safety Advice
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 AED 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 AEDs and the potentially serious consequences of therapeutic failure.
Drug–drug interactions and the relatively low solubility or bioavailability (or both) of
some AEDs are other important factors1.
Potential risk from switching between different manufacturers’ products
The Commission on Human Medicines (CHM) reviewed spontaneous adverse
reactions received by MHRA and publications that reported potential harm arising
from switching of AEDs 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 AEDs 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
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
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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 error
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