Cluster headache rarely responds to standard anal- CLONIDINE HYDROCHLORIDE U
4 Cluster headache rarely responds to standard anal- CLONIDINE HYDROCHLORIDE U
gesics. Sumatriptan given by subcutaneous injection Indications
is the drug of choice for the treatment of cluster head- prevention of recurrent migraine (but see
ache. Alternatively, 100% oxygen at a rate of 7–12 notes above), vascular headache, menopausal flush-
litres/minute is useful in aborting an attack. ing; hypertension (section 2.5.2)
Cautions depressive illness, concurrent antihyper- Prophylaxis of cluster headache is considered if the tensive therapy; acute porphyria (section 9.8.2);
attacks are frequent, or last over 3 weeks, or if the interactions: Appendix 1 (clonidine)
attacks cannot be treated effectively. Verapamil or lith- Side-effects dry mouth, sedation, dizziness, nausea,
ium [both unlicensed use] are used for prophylaxis. nocturnal restlessness; occasionally rashes
Ergotamine, used on an intermittent basis is an alter- Dose
native for patients with short bouts, but it should not be used for prolonged periods. Methysergide is effective
50 micrograms twice daily, increased after 2 weeks to but must be used with extreme caution (section 4.7.4.2)
75 micrograms twice daily if necessary; CHILD not and only if other drugs cannot be used or if they are not recommended
effective.
Clonidine (Non-proprietary) AU Tablets , clonidine hydrochloride 25 micrograms. Net price 112-tab pack = £11.00
4.8 Antiepileptic drugs
Dixarit c (Boehringer Ingelheim) AU
Tablets , blue, s/c, clonidine hydrochloride 25 micr- ograms. Net price 112-tab pack = £7.11
4.8.1 Control of epilepsy
c 4.8.2 Catapres Drugs used in status epilepticus AU
4.8.3 Febrile convulsions
Section 2.5.2 (hypertension)
METHYSERGIDE U
4.8.1 Control of epilepsy
Indications prevention of severe recurrent migraine, cluster headache and other vascular headaches in
The object of treatment is to prevent the occurrence of patients who are refractory to other treatment and
seizures by maintaining an effective dose of one or more whose lives are seriously disrupted (important: hos-
antiepileptic drugs. Careful adjustment of doses is pital supervision only, see notes above); diarrhoea
necessary, starting with low doses and increasing gra- associated with carcinoid syndrome
dually until seizures are controlled or there are signifi- Cautions history of peptic ulceration; avoid abrupt
cant adverse effects. withdrawal of treatment; after 6 months withdraw
When choosing an antiepileptic drug, the seizure type, (gradually over 2 to 3 weeks) for reassessment for at
concomitant medication, co-morbidity, age, and sex least 1 month (see also notes above); interactions:
should be taken into account. For women of child- Appendix 1 (ergot alkaloids)
bearing age, see Pregnancy and Breast-feeding, p. 250.
BNF 57
4.8.1 Control of epilepsy 249
The dose frequency is often determined by the plasma-
Levetiracetam
drug half-life, and should be kept as low as possible to no interactions with levetiracetam reported encourage adherence with the prescribed regimen. Most antiepileptics, when used in the usual dosage,
Oxcarbazepine
may be given twice daily. Lamotrigine, phenobarbital, sometimes lowers plasma concentration of carbamaze- and phenytoin, which have long half-lives, can be given
pine (but may raise concentration of an active metabo- once daily at bedtime. However, with large doses, some
lite of carbamazepine) antiepileptics may need to be given more frequently to
sometimes raises plasma concentration of phenytoin avoid adverse effects associated with high peak plasma-
often raises plasma concentration of phenobarbital drug concentration. Young children metabolise anti- epileptics more rapidly than adults and therefore require
Phenobarbital or Primidone more frequent doses and a higher dose in proportion to
often lowers plasma concentration of carbamazepine, their body-weight.
clonazepam, lamotrigine, and of phenytoin (but may also raise phenytoin concentration), tiagabine, val-
MHRA/CHM advice proate, and zonisamide Suicidal behaviour and antiepileptic drugs
sometimes lowers plasma concentration of ethosuximide Antiepileptic drugs have been associated with a
Phenytoin
small increased risk of suicidal thoughts and beha- often lowers plasma concentration of clonazepam, carba- viour; this can occur as early as 1 week after starting
mazepine, lamotrigine, an active metabolite of oxcarba- treatment. Patients should be advised to seek med-
zepine, and of tiagabine, topiramate, valproate, and ical advice if they develop mood changes or suicidal
zonisamide
thoughts. often raises plasma concentration of phenobarbital sometimes lowers plasma concentration of ethosuximide,
Management When monotherapy with a first-line and primidone (by increasing conversion to phenobar- antiepileptic drug has failed, monotherapy with a sec-
bital)
ond drug should be tried. The changeover from one
Pregabalin
antiepileptic drug to another should be cautious, slowly no interactions with pregabalin reported withdrawing the first drug only when the new regimen has been established. Combination therapy with 2 or
Rufinamide
more antiepileptic drugs may be necessary, but the sometimes raises plasma concentration of phenytoin
concurrent use of antiepileptic drugs enhances toxicity
Topiramate
entral C
and the risk of drug interactions (see below). If combi- sometimes raises plasma concentration of phenytoin
nation therapy does not bring about worthwhile bene-
Valproate
fits, revert to the regimen (monotherapy or combination sometimes lowers plasma concentration of an active therapy) that provided the best balance between toler-
nervous
metabolite of oxcarbazepine
ability and efficacy. often raises plasma concentration of an active metabolite of carbamazepine, and of lamotrigine, primidone, phe-
Interactions Interactions between antiepileptic drugs nobarbital, and phenytoin (but may also lower)
syst
are complex and may enhance toxicity without a corre- sponding increase in antiepileptic effect. Interactions
sometimes raises plasma concentration of ethosuximide,
em
are usually caused by hepatic enzyme induction or hepatic primidone, (and tendency for significant increase in enzyme inhibition ; displacement from protein binding sites is
phenobarbital level), and rufinamide not usually a problem. These interactions are highly
Vigabatrin
variable and unpredictable. often lowers plasma concentration of phenytoin Significant interactions that occur between antiepilep-
sometimes lowers plasma concentration of phenobarbital, tics themselves are as follows:
and primidone
Note Check under each drug for possible interactions when For other important interactions see Appendix 1; for two or more antiepileptic drugs are used
advice on hormonal contraception and enzyme-indu- cing drugs (including antiepileptics), see section 7.3.1
Carbamazepine
and section 7.3.2.
often lowers plasma concentration of clobazam, clonaze- pam, lamotrigine, an active metabolite of oxcarbaze-
Withdrawal Antiepileptic drugs should be withdrawn pine, and of phenytoin (but may also raise phenytoin
under specialist supervision. Abrupt withdrawal, parti- concentration), tiagabine, topiramate, valproate, and
cularly of the barbiturates and benzodiazepines, should zonisamide
be avoided because this may precipitate severe rebound plasma concentration of ethosuximide,
seizures. Reduction in dosage should be gradual and, in sometimes lowers and primidone (but tendency for corresponding
the case of barbiturates, withdrawal of the drug may increase in phenobarbital level)
take months.
Ethosuximide The decision to withdraw antiepileptic drugs from a sometimes raises plasma concentration of phenytoin
seizure-free patient, and its timing, is often difficult and depends on individual circumstances. Even in
Gabapentin patients who have been seizure-free for several years, no interactions with gabapentin reported
there is a significant risk of seizure recurrence on drug Lamotrigine
withdrawal.
sometimes raises plasma concentration of an active meta- In patients receiving several antiepileptic drugs, only bolite of carbamazepine (but evidence is conflicting)
one drug should be withdrawn at a time.
Driving Patients suffering from epilepsy may drive a motor vehicle (but not a heavy goods or public service vehicle) provided that they have had a seizure-free period of one year or, if subject to attacks only while asleep, have established a 3-year period of asleep attacks without awake attacks. Patients affected by drowsiness should not drive or operate machinery.
Guidance issued by the Drivers Medical Unit of the Driver and Vehicle Licensing Agency (DVLA) recom- mends that patients should be advised not to drive during withdrawal of antiepileptic drugs, or for 6 months afterwards (see also Drugs and Driving under General Guidance, p. 3).
Pregnancy and breast-feeding
There is an
increased risk of teratogenicity associated with the use of antiepileptic drugs (reduced if treatment is limited to
a single drug). In view of the increased risk of neural tube and other defects associated, in particular, with carbamazepine, lamotrigine, oxcarbazepine, pheny- toin, and valproate, women taking antiepileptic drugs who may become pregnant should be informed of the possible consequences. Those who wish to become pregnant should be referred to an appropriate specialist for advice. Women who become pregnant should be counselled and offered antenatal screening (alpha- fetoprotein measurement and a second trimester ultra- sound scan).
To counteract the risk of neural tube defects, adequate folate supplements are advised for women before and during pregnancy (section 9.1.2).
The concentration of antiepileptic drugs in the blood can change during pregnancy, particularly in the later stages. The dose of antiepileptic drugs should be mon- itored carefully during pregnancy and after birth, and adjustments made on a clinical basis.
Routine injection of vitamin K (section 9.6.6) at birth effectively counteracts any antiepileptic-associated risk of neonatal haemorrhage.
Breast-feeding is acceptable with all antiepileptic drugs, taken in normal doses, with the possible exception of the barbiturates, and also some of the more recently introduced ones, see Appendix 5.