BNF for Children 2011-2012

216 4.8.1 Control of the epilepsies BNFC 2011–20124 Central nervous systemRufinamidesometimes lowers plasma concentration of carbamazepinesometimes raises plasma concentration of phenytoinStiripentoloften raises plasma concentration of carbamazepine,clobazam, phenobarbital, primidone-derived phenobarbital,and phenytoinTopiramatesometimes raises plasma concentration of phenytoinValproatesometimes lowers plasma concentration of an activemetabolite of oxcarbazepineoften raises plasma concentration of lamotrigine, phenobarbital,primidone-derived phenobarbital, phenytoin(but may also lower), and an active metabolite of carbamazepinesometimes raises plasma concentration of ethosuximideand rufinamideVigabatrinoften lowers plasma concentration of phenytoinWithdrawal Antiepileptics should be withdrawn underspecialist supervision. Avoid abrupt withdrawal, particularlyof barbiturates and benzodiazepines because thiscan precipitate severe rebound seizures. Reduction indosage should be gradual and, in the case of barbiturates,the withdrawal process may take months.The decision to withdraw antiepileptics from a seizurefreechild, and its timing, depends on individual circumstancessuch as the type of epilepsy and its cause. Evenin children who have been seizure-free for several years,there is a significant risk of seizure recurrence on drugwithdrawal.Drugs should be gradually withdrawn over at least 2–3months by reducing the daily dose by 10–25% at intervalsof 1–2 weeks. Benzodiazepines may need to bewithdrawn over 6 months or longer.In children receiving several antiepileptic drugs, onlyone drug should be withdrawn at a time.Monitoring Routine measurement of plasma concentrationsof antiepileptic drugs is not usually justified,because the target concentration ranges are arbitraryand often vary between individuals. However, plasmadrugconcentrations may be measured in children withworsening seizures, status epilepticus, suspected noncompliance,or suspected toxicity. Similarly, haematologicaland biochemical monitoring should not be undertakenunless clinically indicated.Driving Older children with epilepsy may drive a motorvehicle (but not a large goods or passenger carryingvehicle) provided that they have been seizure-free forone year or, if subject to attacks only while asleep, haveestablished a 3-year period of asleep attacks withoutawake attacks. Those affected by drowsiness should notdrive or operate machinery.Guidance issued by the Drivers Medical Unit of theDriver and Vehicle Licensing Agency (DVLA) recommendsthat patients should be advised not to driveduring medication changes or withdrawal of antiepilepticdrugs, and for 6 months afterwards.Patients who have had a first or single epileptic seizuremust not drive for 6 months (5 years in the case of largegoods or passenger carrying vehicles) after the event;driving may then be resumed, provided the patient hasbeen assessed by a specialist as fit to drive because noabnormality was detected on investigation.Pregnancy Young women of child-bearing potentialshould discuss with a specialist, the impact of bothepilepsy, and its treatment, on the outcome ofpregnancy.There is an increased risk of teratogenicity associatedwith the use of antiepileptic drugs (especially if usedduring the first trimester and if the patient takes two ormore antiepileptic drugs). Valproate is associated withthe highest risk of major and minor congenital malformations,and with developmental delay. Valproateshould not be prescribed unless there is no safer alternativeand only after a careful discussion of the risks;doses greater than 1 g daily are associated with anincreased risk of teratogenicity. There is also anincreased risk of teratogenicity with phenytoin, primidone,phenobarbital, lamotrigine, and carbamazepine.There is not enough evidence to establish the risk ofteratogenicity with other antiepileptic drugs.Prescribers should also consider carefully the choice ofantiepileptic therapy in pre-pubescent girls who maylater become pregnant.Young women of child-bearing potential who take antiepilepticdrugs should be given contraceptive advice.Some antiepileptic drugs can reduce the efficacy ofhormonal contraceptives, and the efficacy of some antiepilepticsmay be affected by hormonal contraceptives(see section 7.3.1 and interactions of antiepileptics,Appendix 1).Young women who want to become pregnant should bereferred to a specialist for advice in advance of conception.For some women, the severity of seizure or theseizure type may not pose a serious threat, and drugwithdrawal may be considered; therapy may beresumed after the first trimester. If treatment with antiepilepticdrugs must continue throughout pregnancy,then monotherapy is preferable at the lowest effectivedose.Once an unplanned pregnancy is discovered it is usuallytoo late for changes to be made to the treatment regimen;the risk of harm to the mother and fetus fromconvulsive seizures outweighs the risk of continuedtherapy. The likelihood of a young woman who is takingantiepileptic drugs having a baby with no malformationsis at least 90%, and it is important that women do notstop taking essential treatment because of concern overharm to the fetus.To reduce the risk of neural tube defects, folate supplementation(section 9.1.2) is advised before conceptionand throughout the first trimester.The concentration of antiepileptic drugs in the plasmacan change during pregnancy. Doses of phenytoinp. 224, carbamazepine, and lamotrigine should beadjusted on the basis of plasma-drug concentrationmonitoring; the dose of other antiepileptic drugs shouldbe monitored carefully during pregnancy and after birth,and adjustments made on a clinical basis. Plasma-drugconcentration monitoring during pregnancy is also usefulto check compliance. Additionally, in patients takingtopiramate or levetiracetam, it is recommended thatfetal growth is monitored.