www.medicinesforchildren.org.uk/sodium-valproate-andpregnancy-information-girls-and-young-women
Medicines for Children leaflet: Sodium valproate and pregnancy -
information for parents and carers www.medicinesforchildren.
org.uk/sodium-valproate-and-pregnancy-information-parentsand-carers
EPISENTA ® CAPSULES Patients and carers should be
counselled on the administration of capsules.
EPISENTA ® GRANULES Patients and carers should be
counselled on the administration of granules.
EPILIM CHRONOSPHERE ® Patients and carers should be
counselled on the administration of granules.
l MEDICINAL 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
CAUTIONARY AND ADVISORY LABELS 8, 10, 21, 25
Sodium valproate 500 mg Epilim Chrono 500 tablets |
30 tablet P £8.73 | 100 tablet P £29.10 DT = £29.10
▶ Epival CR (Chanelle Medical UK Ltd) A
Sodium valproate 300 mg Epival CR 300mg tablets | 100 tablet P £17.47 DT = £17.47
Sodium valproate 500 mg Epival CR 500mg tablets | 100 tablet P £29.10 DT = £29.10
CAUTIONARY AND ADVISORY LABELS 5, 8, 10, 25
▶ Sodium valproate (non-proprietary) A
CAUTIONARY AND ADVISORY LABELS 8, 10, 21
Sodium valproate 100 mg Epilim 100mg crushable tablets |
30 tablet P £1.68 | 100 tablet P £5.60 DT = £5.60
▶ Sodium valproate (non-proprietary) A
Sodium valproate 100 mg per 1 ml Sodium valproate 400mg/4ml
solution for injection ampoules | 5 ampoule P £57.90 DT = £57.90
▶ Episenta (Desitin Pharma Ltd) A
Sodium valproate 100 mg per 1 ml Episenta 300mg/3ml solution
for injection ampoules | 5 ampoule P £35.00 DT = £35.00
CAUTIONARY AND ADVISORY LABELS 8, 10, 21, 25
▶ Episenta (Desitin Pharma Ltd) A
Sodium valproate 150 mg Episenta 150mg modified-release
capsules | 100 capsule P £7.00 DT = £7.00
Sodium valproate 300 mg Episenta 300mg modified-release
capsules | 100 capsule P £13.00 DT = £13.00
CAUTIONARY AND ADVISORY LABELS 8, 10, 21
▶ Sodium valproate (non-proprietary) A
Sodium valproate 40 mg per 1 ml Sodium valproate 200mg/5ml
oral solution sugar free sugar-free | 300 ml P £7.37–£9.38 DT =
Sodium valproate 40 mg per 1 ml Epilim 200mg/5ml liquid sugarfree | 300 ml P £7.78 DT = £8.70
Epilim 200mg/5ml syrup | 300 ml P £9.33 DT = £9.33
CAUTIONARY AND ADVISORY LABELS 8, 10, 21, 25
▶ Epilim Chronosphere MR (Sanofi) A
Sodium valproate 50 mg Epilim Chronosphere MR 50mg granules
sachets sugar-free | 30 sachet P £30.00 DT = £30.00
Sodium valproate 100 mg Epilim Chronosphere MR 100mg granules
sachets sugar-free | 30 sachet P £30.00 DT = £30.00
Sodium valproate 250 mg Epilim Chronosphere MR 250mg granules
sachets sugar-free | 30 sachet P £30.00 DT = £30.00
Sodium valproate 500 mg Epilim Chronosphere MR 500mg granules
sachets sugar-free | 30 sachet P £30.00 DT = £30.00
Sodium valproate 750 mg Epilim Chronosphere MR 750mg granules
sachets sugar-free | 30 sachet P £30.00 DT = £30.00
Sodium valproate 1 gram Epilim Chronosphere MR 1000mg
granules sachets sugar-free | 30 sachet P £30.00 DT = £30.00
▶ Episenta (Desitin Pharma Ltd) A
Sodium valproate 500 mg Episenta 500mg modified-release
granules sachets sugar-free | 100 sachet P £21.00 DT = £21.00
Sodium valproate 1 gram Episenta 1000mg modified-release
granules sachets sugar-free | 100 sachet P £41.00 DT = £41.00
Adjunctive therapy of refractory generalised tonic-clonic
seizures in patients with severe myoclonic epilepsy in
infancy (Dravet syndrome) in combination with
clobazam and valproate (under expert supervision)
▶ Adult: Doses of up to 50 mg/kg daily in 2–3 divided
doses should be continued for as long as efficacy is
DOSE EQUIVALENCE AND CONVERSION
▶ Stiripentol capsules and oral powder sachets are not
bioequivalent. If a switch of formulation is required,
manufacturer advises this is done under clinical
supervision in case of intolerance.
l CONTRA-INDICATIONS History of psychosis in the form of
l INTERACTIONS → Appendix 1: antiepileptics
▶ Uncommon Diplopia . fatigue . photosensitivity reaction . skin reactions
▶ Rare or very rare Thrombocytopenia
l ALLERGY AND CROSS-SENSITIVITY Antiepileptic
hypersensitivity syndrome theoretically associated with
stiripentol. See under Epilepsy p. 305 for more
l PREGNANCY See also Pregnancy in Epilepsy p. 305.
Monitoring The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
l BREAST FEEDING Present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises avoid (no
l RENAL IMPAIRMENT Avoid—no information available.
l MONITORING REQUIREMENTS Perform full blood count and
liver function tests prior to initiating treatment and every
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (September
2017) that stiripentol (Diacomit ®) is accepted for use
within NHS Scotland in conjunction with clobazam and
valproate as adjunctive therapy of refractory generalised
tonic-clonic seizures in patients with severe myoclonic
epilepsy in infancy whose seizures are not adequately
controlled with clobazam and valproate.
330 Epilepsy and other seizure disorders BNF 78
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(November 2017) that stiripentol (Diacomit ®) is
recommended for use within NHS Wales for use in
conjunction with clobazam and valproate as adjunctive
therapy of refractory generalized tonic-clonic seizures in
patients with severe myoclonic epilepsy in infancy (SMEI,
Dravet syndrome) whose seizures are not adequately
controlled with clobazam and valproate.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 1, 8, 13, 21
EXCIPIENTS: May contain Aspartame
▶ Diacomit (Alan Pharmaceuticals)
Stiripentol 250 mg Diacomit 250mg oral powder sachets |
60 sachet P £284.00 DT = £284.00
Stiripentol 500 mg Diacomit 500mg oral powder sachets | 60 sachet P £493.00 DT = £493.00
CAUTIONARY AND ADVISORY LABELS 1, 8, 21
▶ Diacomit (Alan Pharmaceuticals)
Stiripentol 250 mg Diacomit 250mg capsules | 60 capsule P £284.00 DT = £284.00
Stiripentol 500 mg Diacomit 500mg capsules | 60 capsule P £493.00 DT = £493.00
Adjunctive treatment for focal seizures with or without
secondary generalisation that are not satisfactorily
controlled by other antiepileptics (with enzyme-inducing
▶ Child 12–17 years: Initially 5–10 mg daily in 1–2 divided
doses, then increased in steps of 5–10 mg/24 hours
every week; maintenance 30–45 mg daily in
▶ Adult: Initially 5–10 mg daily in 1–2 divided doses,
then increased in steps of 5–10 mg/24 hours every
week; maintenance 30–45 mg daily in 2–3 divided
Adjunctive treatment for focal seizures with or without
secondary generalisation that are not satisfactorily
controlled by other antiepileptics (without enzymeinducing drugs)
▶ Child 12–17 years: Initially 5–10 mg daily in 1–2 divided
doses, then increased in steps of 5–10 mg/24 hours
every week; maintenance 15–30 mg daily in
▶ Adult: Initially 5–10 mg daily in 1–2 divided doses,
then increased in steps of 5–10 mg/24 hours every
week; maintenance 15–30 mg daily in 2–3 divided
l CAUTIONS Avoid in Acute porphyrias p. 1058
CAUTIONS, FURTHER INFORMATION Tiagabine should be
avoided in absence, myoclonic, tonic and atonic seizures
due to risk of seizure exacerbation.
l INTERACTIONS → Appendix 1: antiepileptics
▶ Common or very common Abdominal pain . behaviour
▶ Uncommon Drowsiness . psychosis . skin reactions
▶ Rare or very rare Delusions . hallucination
l PREGNANCY See also Pregnancy in Epilepsy p. 305.
Monitoring The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment (risk of increased exposure);
Dose adjustments Manufacturer advises dose reduction
and/or longer dose interval with careful titration in mild to
Medicines for Children leaflet: Tiagibine for preventing seizures
www.medicinesforchildren.org.uk/tiagabine-preventingseizures
Driving and skilled tasks May impair performance of skilled
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
CAUTIONARY AND ADVISORY LABELS 21
Tiagabine (as Tiagabine hydrochloride monohydrate)
5 mg Gabitril 5mg tablets | 100 tablet P £52.04 DT = £52.04
Tiagabine (as Tiagabine hydrochloride monohydrate)
10 mg Gabitril 10mg tablets | 100 tablet P £104.09 DT = £104.09
Tiagabine (as Tiagabine hydrochloride monohydrate)
15 mg Gabitril 15mg tablets | 100 tablet P £156.13 DT = £156.13
Monotherapy of generalised tonic-clonic seizures or focal
seizures with or without secondary generalisation
▶ Child 6–17 years: Initially 0.5–1 mg/kg once daily (max.
per dose 25 mg) for 1 week, dose to be taken at night,
then increased in steps of 250–500 micrograms/kg
twice daily, dose to be increased by a maximum of
25 mg twice daily at intervals of 1–2 weeks; usual dose
50 mg twice daily (max. per dose 7.5 mg/kg twice daily),
if child cannot tolerate titration regimens
recommended above then smaller steps or longer
interval between steps may be used; maximum 500 mg
▶ Adult: Initially 25 mg once daily for 1 week, dose to be
taken at night, then increased in steps of 25–50 mg
every 1–2 weeks, dose to be taken in 2 divided doses;
usual dose 100–200 mg daily in 2 divided doses,
adjusted according to response, doses of 1 g daily have
been used in refractory epilepsy; maximum 500 mg per
Adjunctive treatment of generalised tonic-clonic seizures
or focal seizures with or without secondary
generalisation | Adjunctive treatment for seizures
associated with Lennox-Gastaut syndrome
▶ Child 2–17 years: Initially 1–3 mg/kg once daily (max.
per dose 25 mg) for 1 week, dose to be taken at night,
then increased in steps of 0.5–1.5 mg/kg twice daily,
dose to be increased by a maximum of 25 mg twice
daily at intervals of 1–2 weeks; usual dose
2.5–4.5 mg/kg twice daily (max. per dose 7.5 mg/kg
twice daily), if child cannot tolerate recommended
titration regimen then smaller steps or longer interval
between steps may be used; maximum 400 mg per day
▶ Adult: Initially 25–50 mg once daily for 1 week, dose to
be taken at night, then increased in steps of 25–50 mg
every 1–2 weeks, dose to be taken in 2 divided doses;
usual dose 200–400 mg daily in 2 divided doses;
maximum 400 mg per day continued→
BNF 78 Epilepsy and other seizure disorders 331
▶ Adult: Initially 25 mg once daily for 1 week, dose to be
taken at night, then increased in steps of 25 mg every
week; usual dose 50–100 mg daily in 2 divided doses;
l CAUTIONS Avoid in Acute porphyrias p. 1058 .risk of
metabolic acidosis .risk of nephrolithiasis—ensure
adequate hydration (especially in strenuous activity or
l INTERACTIONS → Appendix 1: antiepileptics
disorders . feeling abnormal . fever (in children). gait
abnormal . gastrointestinal discomfort. gastrointestinal
children). hypokalaemia . hypotension . influenza like
stiffness . palpitations . pancreatitis . paranasal sinus
hypersecretion . peripheral coldness . peripheral
acidosis . severe cutaneous adverse reactions (SCARs). unresponsive to stimuli
SIDE-EFFECTS, FURTHER INFORMATION Topiramate has
starting treatment. Choroidal effusions resulting in
anterior displacement of the lens and iris have also been
reported. If raised intra-ocular pressure occurs: seek
specialist ophthalmological advice; use appropriate
measures to reduce intra-ocular pressure and stop
topiramate as rapidly as feasible.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
perform pregnancy test before the initiation of
treatment—a highly effective contraceptive method is
advised in women of child-bearing potential; patients
should be fully informed of the risks related to the use of
l PREGNANCY Increased risk of major congenital
malformations following exposure during the first
trimester. For migraine prophylaxis manufacturer advises
avoid. For epilepsy manufacturer advises consider
alternative treatment options. See also Pregnancy in
Monitoring Manufacturer advises in case of administration
during first trimester, careful prenatal monitoring should
It is recommended that the fetal growth should be
The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Use with caution in moderate to
severe impairment—clearance may be reduced.
l RENAL IMPAIRMENT Use with caution.
Dose adjustments ▶ In adults Half usual starting and
maintenance dose if eGFR less than
—reduced clearance and longer time
to steady-state plasma concentration.
▶ In children Half usual starting and maintenance dose if
estimated glomerular filtration less than
—reduced clearance and longer time
to steady-state plasma concentration.
l DIRECTIONS FOR ADMINISTRATION
TOPAMAX ® CAPSULES Swallow whole or sprinkle contents
of capsule on soft food and swallow immediately without
l PRESCRIBING AND DISPENSING INFORMATION
Switching between formulations Care should be taken when
switching between oral formulations in the treatment of
epilepsy. The need for continued supply of a particular
manufacturer’s product should be based on clinical
judgement and consultation with the patient or their
carer, taking into account factors such as seizure
frequency and treatment history.
Patients being treated for epilepsy may need to be
maintained on a specific manufacturer’s branded or
Medicines for Children leaflet: Topiramate for preventing seizures
www.medicinesforchildren.org.uk/topiramate-preventingseizures
TOPAMAX ® CAPSULES Patients or carers should be given
advice on how to administer Topamax ® Sprinkle capsules.
l MEDICINAL 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
▶ Topiramate (Non-proprietary)
Topiramate 10 mg per 1 ml Topiramate 50mg/5ml oral suspension
sugar free sugar-free | 150 ml P £129.00 DT = £129.00
Topiramate 20 mg per 1 ml Topiramate 100mg/5ml oral suspension
sugar free sugar-free | 280 ml P £195.69 DT = £195.69
CAUTIONARY AND ADVISORY LABELS 3, 8
▶ Topiramate (Non-proprietary)
Topiramate 25 mg Topiramate 25mg tablets | 60 tablet P £10.00 DT = £6.12
Topiramate 50 mg Topiramate 50mg tablets | 60 tablet P £36.75 DT = £9.33
Topiramate 100 mg Topiramate 100mg tablets | 60 tablet P £37.54 DT = £14.83
Topiramate 200 mg Topiramate 200mg tablets | 60 tablet P £57.60 DT = £47.57
Topiramate 25 mg Topamax 25mg tablets | 60 tablet P £19.29
Topiramate 50 mg Topamax 50mg tablets | 60 tablet P £31.69
Topiramate 100 mg Topamax 100mg tablets | 60 tablet P £56.76 DT = £14.83
Topiramate 200 mg Topamax 200mg tablets | 60 tablet P £110.23 DT = £47.57
332 Epilepsy and other seizure disorders BNF 78
CAUTIONARY AND ADVISORY LABELS 3, 8
▶ Topiramate (Non-proprietary)
Topiramate 15 mg Topiramate 15mg capsules | 60 capsule P £26.21 DT = £26.21
Topiramate 25 mg Topiramate 25mg capsules | 60 capsule P £15.45 DT = £12.21
Topiramate 50 mg Topiramate 50mg capsules | 60 capsule P £55.08 DT = £55.08
Topiramate 15 mg Topamax 15mg sprinkle capsules | 60 capsule P £14.79 DT = £26.21
Topiramate 25 mg Topamax 25mg sprinkle capsules | 60 capsule P £22.18 DT = £12.21
Topiramate 50 mg Topamax 50mg sprinkle capsules | 60 capsule P £36.45 DT = £55.08
Adjunctive treatment of focal seizures with or without
secondary generalisation not satisfactorily controlled
with other antiepileptics (under expert supervision)
▶ 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
▶ Adult: Initially 1 g once daily, alternatively initially 1 g
daily in 2 divided doses, then increased in steps of
500 mg every week, adjusted according to response;
usual dose 2–3 g daily; maximum 3 g per day
▶ 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
l UNLICENSED USE Granules not licensed for rectal use.
Tablets not licensed to be crushed and dispersed in liquid.
Vigabatrin doses in BNF publications may differ from
l CONTRA-INDICATIONS Visual field defects
l CAUTIONS Elderly . history of behavioural problems . history of depression . history of psychosis
CAUTIONS, FURTHER INFORMATION Vigabatrin may worsen
absence, myoclonic, tonic and atonic seizures.
▶ Visual field defects Vigabatrin is associated with visual field
defects. The onset of symptoms varies from 1 month to
several years after starting. In most cases, visual field
defects have persisted despite discontinuation, and further
deterioration after discontinuation cannot be excluded.
Product literature advises visual field testing before
treatment and at 6-month intervals. Patients and their
carers should be warned to report any new visual
symptoms that develop and those with symptoms should
be referred for an urgent ophthalmological opinion.
Gradual withdrawal of vigabatrin should be considered.
l INTERACTIONS → Appendix 1: antiepileptics
impaired . depression . dizziness . drowsiness . eye
▶ Frequency not known Muscle tone increased
SIDE-EFFECTS, FURTHER INFORMATION Encephalopathic
symptoms Encephalopathic symptoms including marked
sedation, stupor, and confusion with non-specific slow
wave EEG can occur rarely -reduce dose or withdraw.
Visual field defects About one-third of patients
treated with vigabatrin have suffered visual field defects;
counselling and careful monitoring for this side-effect are
l PREGNANCY See also Pregnancy in Epilepsy p. 305.
Monitoring The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
l BREAST FEEDING Present in milk—manufacturer advises
Dose adjustments ▶ In adults Consider reduced dose or
increased dose interval if eGFR less than
▶ In children Consider reduced dose or increased dose
interval if estimated glomerular filtration rate less than
l MONITORING REQUIREMENTS Closely monitor
l DIRECTIONS FOR ADMINISTRATION
▶ With oral use The contents of a sachet should be dissolved
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