thrombocytopenia.urine abnormalities.vasculitis.
vomiting.weight increased
SIDE-EFFECTS, FURTHER INFORMATION
Hepatic dysfunctionWithdraw treatment immediately if
persistent vomiting and abdominal pain, anorexia,
jaundice, oedema, malaise, drowsiness, or loss of seizure
control.
PancreatitisDiscontinue treatment if symptoms of
pancreatitis develop.
lCONCEPTION AND CONTRACEPTIONThe MHRA advises
that all women and girls of childbearing potential being
treated with valproate medicines must be supported on a
Pregnancy Prevention Programme—pregnancy should be
excluded before treatment initiation and highly effective
contraception must be used during treatment.
lPREGNANCYFormigraine prophylaxis[unlicensed] and
bipolar disorder, the MHRA advises that valproate must not
be used. Forepilepsy, the MHRA advises valproate must
not be used unless there is no suitable alternative
treatment; in such cases, access to counselling about the
risks should be provided (see Healthcare Professional
Guide for more information) and a Risk Acknowledgement
Form signed by both specialist and patient. If valproate is
to be used during pregnancy, the lowest effective dose
should be prescribed in divided doses to avoid peaks in
plasma-valproate concentrations; doses greater than 1 g
daily are associated with an increased risk of
teratogenicity. Neonatal bleeding (related to
hypofibrinaemia). Neonatal hepatotoxicity also reported.
MonitoringSpecialist prenatal monitoring should be
instigated when valproate has been taken in pregnancy.
The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
clinical basis.
lBREAST FEEDINGPresent in milk—risk of haematological
disorders in breast-fed newborns and infants.
lHEPATIC IMPAIRMENTAvoid if possible—hepatotoxicity
and hepatic failure may occasionally occur (usually infirst
6 months). Avoid in active liver disease.
lRENAL IMPAIRMENT
Dose adjustmentsReduce dose.
lMONITORING REQUIREMENTS
▶Monitor closely if dose greater than 45 mg/kg daily.
▶Monitor liver function before therapy and duringfirst
6 months especially in patients most at risk.
▶Measure full blood count and ensure no undue potential
for bleeding before starting and before surgery.
lEFFECT ON LABORATORY TESTSFalse-positive urine tests
for ketones.
lTREATMENT CESSATIONgIn bipolar disorder, avoid
abrupt withdrawal; if treatment with valproate is stopped,
reduce the dose gradually over at least 4 weeks.h
lPRESCRIBING AND DISPENSING INFORMATIONThe
Pregnancy Prevention Programme is supported by the
following materials provided by the manufacturer:Patient
Guide,Guide for Healthcare Professionals,Risk
Acknowledgement Form, and for pharmacists,Patient Cards
andStickers with warning symbols; the MHRA has also
produced a patient information sheet providing advice for
women and girls taking valproate medicines.
CONVULEX®Patients being treated for epilepsy may need
to be maintained on a specific manufacturer’s branded or
generic oral valproic acid product.
lPATIENT AND CARER ADVICE
Valproate use by women and girlsThe MHRA advises women
and girls shouldnotstop taking valproate withoutfirst
discussing it with their doctor.
Blood or hepatic disordersPatients or their carers should be
told how to recognise signs and symptoms of blood or liverdisorders and advised to seek immediate medical attention
if symptoms develop.
PancreatitisPatients or their carers should be told how to
recognise signs and symptoms of pancreatitis and advised
to seek immediate medical attention if symptoms such as
abdominal pain, nausea, or vomiting develop.
Pregnancy Prevention ProgrammePharmacists must ensure
that female patients have a patient card—see also
Important safety information.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug. Forms available from special-order
manufacturers include: oral suspension, oral solution
Gastro-resistant capsule
CAUTIONARY AND ADVISORY LABELS8, 10, 21, 25
▶Convulex(Pfizer Ltd)A
Valproic acid 150 mgConvulex 150 mg gastro-resistant capsules|
100 capsuleP£ 3. 68
Valproic acid 300 mgConvulex 300 mg gastro-resistant capsules|
100 capsuleP£ 7. 35
Valproic acid 500 mgConvulex 500 mg gastro-resistant capsules|
100 capsuleP£ 12. 25Vigabatrin
lINDICATIONS AND DOSE
Adjunctive treatment of focal seizures with or without
secondary generalisation not satisfactorily controlled
with other antiepileptics (under expert supervision)
▶BY MOUTH
▶Neonate:Initially 15 – 20 mg/kg twice daily, to be
increased over 2 – 3 weeks to usual maintenance dose,
usual maintenance 30 – 40 mg/kg twice daily (max. per
dose 75 mg/kg).▶Child 1–23 months:Initially 15 – 20 mg/kg twice daily
(max. per dose 250 mg), to be increased over 2 – 3 weeks
to usual maintenance dose, usual maintenance
30 – 40 mg/kg twice daily (max. per dose 75 mg/kg)
▶Child 2–11 years:Initially 15 – 20 mg/kg twice daily (max.
per dose 250 mg), to be increased over 2 – 3 weeks to
usual maintenance dose, usual maintenance
30 – 40 mg/kg twice daily (max. per dose 1. 5 g)
▶Child 12–17 years:Initially 250 mg twice daily, to be
increased over 2 – 3 weeks to usual maintenance dose,
usual maintenance 1 – 1. 5 g twice daily
▶BY RECTUM
▶Child 1–23 months:Initially 15 – 20 mg/kg twice daily
(max. per dose 250 mg), to be increased over 2 – 3 weeks
to usual maintenance dose, usual maintenance
30 – 40 mg/kg twice daily (max. per dose 75 mg/kg)
▶Child 2–11 years:Initially 15 – 20 mg/kg twice daily (max.
per dose 250 mg), to be increased over 2 – 3 weeks to
usual maintenance dose, usual maintenance
30 – 40 mg/kg twice daily (max. per dose 1. 5 g)
▶Child 12–17 years:Initially 250 mg twice daily, to be
increased over 2 – 3 weeks to usual maintenance dose,
usual maintenance 1 – 1. 5 g twice daily
Monotherapy in the management of infantile spasms in
West’s syndrome (under expert supervision)
▶BY MOUTH
▶Neonate:Initially 15 – 25 mg/kg twice daily, to be
adjusted according to response over 7 days to usual
maintenance dose; usual maintenance 40 – 50 mg/kg
twice daily (max. per dose 75 mg/kg).▶Child 1 month–1 year:Initially 15 – 25 mg/kg twice daily,
to be adjusted according to response over 7 days to
usual maintenance dose; usual maintenance
40 – 50 mg/kg twice daily (max. per dose 75 mg/kg)214 Epilepsy and other seizure disorders BNFC 2018 – 2019
Nervous system4