Category 1
Phenytoin, carbamazepine p. 196 , phenobarbital,
primidone p. 217. For these drugs, doctors are advised to
ensure that their patient is maintained on a specific
manufacturer’s product.
Category 2
Valproate,lamotrigine,perampanel,rufinamide,
clobazam p. 218 ,clonazepam p. 219 ,oxcarbazepine
p. 204 ,eslicarbazepine acetate,zonisamide p. 215 ,
topiramate p. 212. For these drugs, the need for continued
supply of a particular 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.
Category 3
Levetiracetam p. 203 ,lacosamide p. 201 ,tiagabine
p. 211 ,gabapentin p. 200 ,pregabalin,ethosuximide
p. 198 ,vigabatrin p. 214. For these drugs, it is usually
unnecessary to ensure that patients are maintained on a
specific manufacturer’s product unless there are specific
concerns such as patient anxiety, and risk of confusion or
dosing errors.
Antiepileptic hypersensitivity syndrome
Antiepileptic hypersensitivity syndrome is a rare but
potentially fatal syndrome associated with some
antiepileptic drugs (carbamazepine, lacosamide,
lamotrigine, oxcarbazepine, phenobarbital, phenytoin,
primidone, and rufinamide p. 207 ); rarely cross-sensitivity
occurs between some of these antiepileptic drugs. Some
other antiepileptics (eslicarbazepine acetate, stiripentol
p. 210 , and zonisamide) have a theoretical risk. The
symptoms usually start between 1 and 8 weeks of exposure;
fever, rash, and lymphadenopathy are most commonly seen.
Other systemic signs include liver dysfunction,
haematological, renal, and pulmonary abnormalities,
vasculitis, and multi-organ failure. If signs or symptoms of
hypersensitivity syndrome occur, the drug should be
withdrawn immediately, the child should not be re-exposed,
and expert advice should be sought.
Risk of suicidal thoughts and behaviour
The MHRA has advised (August 2008 ) that all antiepileptic
drugs are associated with a small increased risk of suicidal
thoughts and behaviour. Symptoms may occur as early as
one week after starting treatment. Children and their parents
or carers should be advised to seek medical advice if the child
develops any mood changes, distressing thoughts, or
feelings about suicide or harming themselves, and should be
referred for appropriate treatment if necessary.Interactions
Interactions between antiepileptics are complex and may
increase toxicity without a corresponding increase in
antiepileptic effect. Interactions are usually caused by
hepatic enzyme induction or inhibition; displacement from
protein binding sites is not usually a problem. These
interactions are highly variable and unpredictable.
Withdrawal
Antiepileptic drugs should be withdrawn under specialist
supervision. Avoid abrupt withdrawal, particularly of
barbiturates and benzodiazepines, because this can
precipitate severe rebound seizures. Reduction in dosage
should be gradual and, in the case of barbiturates,
withdrawal of the drug may take months.
The decision to withdraw antiepileptic drugs from a
seizure-free child, and its timing, is often difficult and
depends on individual circumstances. Even in children who
have been seizure-free for several years, there is a significant
risk of seizure recurrence on drug withdrawal.
Drugs should be gradually withdrawn over at least
2 – 3 months by reducing the daily dose by 10 – 25 %atintervals of 1 – 2 weeks. Benzodiazepines may need to be
withdrawn over 6 months or longer.
In children receiving several antiepileptic drugs, only one
drug should be withdrawn at a time.
Monitoring
Routine measurement of plasma concentrations of
antiepileptic drugs is not usually justified, because the target
concentration ranges are arbitrary and often vary between
individuals. However, plasma-drug concentrations may be
measured in children with worsening seizures, status
epilepticus, suspected non-compliance, or suspected
toxicity. Similarly, haematological and biochemical
monitoring should not be undertaken unless clinically
indicated.
Plasma concentration of some medications may change
during pregnancy and monitoring may be required (see
underPregnancy).
Driving
If a driver has a seizure (of any type) they must stop driving
immediately and inform the Driver and Vehicle Licensing
Agency (DVLA).
Patients who have had afirst unprovoked epileptic seizure
or a single isolated seizure must not drive for 6 months;
driving may then be resumed, provided the patient has been
assessed by a specialist asfit to drive and investigations do
not suggest a risk of further seizures.
Patients with established epilepsy may drive a motor
vehicle provided they are not a danger to the public and are
compliant with treatment and follow up. To continue
driving, these patients must be seizure-free for at least one
year (or have a pattern of seizures established for one year
where there is no influence on their level of consciousness or
the ability to act); also, they must not have a history of
unprovoked seizures.
Patients who have had aseizure while asleepare not
permitted to drive for one year from the date of each seizure
unless:
.a history or pattern of sleep seizures occurringonlyever
while asleep has been established over the course of at
least one year from the date of thefirst sleep seizure; or
.an established pattern of purely asleep seizures can be
demonstrated over the course of three years if the patient
has previously had seizures whilst awake (or awake and
asleep).
The DVLA recommends that patients should not drive during
medication changes or withdrawal of antiepileptic drugs, and
for 6 months after their last dose. If a seizure occurs due to a
prescribed change or withdrawal of epilepsy treatment, the
patient will have their driving license revoked for 1 year;
relicensing may be considered earlier if treatment has been
reinstated for 6 months and no further seizures have
occurred.Pregnancy
Young women of child-bearing potential should discuss with
a specialist the impact of both epilepsy, and its treatment, on
the outcome of pregnancy.
There is an increased risk of teratogenicity associated with
the use of antiepileptic drugs (especially if used during the
first trimester and particularly if the patient takes two or
more antiepileptic drugs). Valproate is associated with the
highest risk of serious developmental disorders (up to
30 – 40 % risk) and congenital malformations (approx. 10 %
risk). Valproate mustnotbe used in females of childbearing
potential unless the conditions of the Pregnancy Prevention
Programme are met and alternative treatments are
ineffective or not tolerated; during pregnancy, it must not be
used for epilepsy, unless it is the only possible treatment.
There is also an increased risk of teratogenicity with
phenytoin, primidone, phenobarbital, lamotrigine, and
carbamazepine. Topiramate carries an increased risk of
congenital malformations (including cleft palate,192 Epilepsy and other seizure disorders BNFC 2018 – 2019
Nervous system4