lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Oral solution
CAUTIONARY AND ADVISORY LABELS 8
▶Ethosuximide (Non-proprietary)
Ethosuximide 50 mg per 1 mlEthosuximide 250 mg/ 5 ml syrup|
200 mlP£ 173. 00 DT = £ 173. 00
Capsule
CAUTIONARY AND ADVISORY LABELS 8
▶Ethosuximide (Non-proprietary)
Ethosuximide 250 mgEthosuximide 250 mg capsules|
56 capsuleP£ 173. 00 DT = £ 173. 00
Fosphenytoin sodium
lDRUG ACTIONFosphenytoin is a pro-drug of phenytoin.
lINDICATIONS AND DOSE
Status epilepticus
▶BY INTRAVENOUS INFUSION
▶Child 5–17 years:Initially 20 mg(PE)/kg, dose to be
administered at a rate of 2 – 3 mg(PE)/kg/minute,
maximum 150 mg(PE)/minute, then 4 – 5 mg(PE)/kg
daily in 1 – 4 divided doses, dose to be administered at a
rate of 1 – 2 mg(PE)/kg/minute, maximum 100 mg
(PE)/minute, dose to be adjusted according to response
and trough plasma-phenytoin concentration
Prophylaxis or treatment of seizures associated with
neurosurgery or head injury
▶BY INTRAVENOUS INFUSION
▶Child 5–17 years:Initially 10 – 15 mg(PE)/kg, then
4 – 5 mg(PE)/kg daily in 1 – 4 divided doses, dose to be
administered at a rate of 1 – 2 mg(PE)/kg/minute,
maximum 100 mg(PE)/minute, dose to be adjusted
according to response and trough plasma-phenytoin
concentration
Temporary substitution for oral phenytoin
▶BY INTRAVENOUS INFUSION
▶Child 5–17 years:Same dose and same dosing frequency
as oral phenytoin therapy, intravenous infusion to be
administered at a rate of 1 – 2 mg(PE)/kg/minute,
maximum 100 mg(PE)/minute
DOSE EQUIVALENCE AND CONVERSION
▶Doses are expressed as phenytoin sodium equivalent
(PE); fosphenytoin sodium 1. 5 mg:phenytoin sodium
1 mg.lUNLICENSED USEFosphenytoin sodium doses inBNFC
may differ from those in product literature.
lCONTRA-INDICATIONSAcute porphyrias p. 603 .second-
degree heart block.sino-atrial block.sinus bradycardia.
Stokes-Adams syndrome.third-degree heart block
lCAUTIONSHeart failure.hypotension.injection solutions
alkaline (irritant to tissues).respiratory depression.
resuscitation facilities must be available
lINTERACTIONS→Appendix 1 : antiepileptics
lSIDE-EFFECTS
▶Common or very commonAsthenia.chills.dizziness.
drowsiness.dry mouth.dysarthria.euphoric mood.
headache.hearing impairment.hypotension.movement
disorders.nausea.nystagmus.sensation abnormal.skin
reactions.stupor.taste altered.tremor.vasodilation.
vertigo.vision disorders.vomiting
▶UncommonCardiac arrest.confusion.muscle complaints.
muscle weakness.nervousness.oral disorders.reflexes
abnormal.severe cutaneous adverse reactions (SCARs).
systemic lupus erythematosus (SLE).thinking abnormal
▶Frequency not knownAcute psychosis.agranulocytosis.
appetite disorder.atrial conduction depression (more
common if injection too rapid).atrioventricular block.
bone disorders.bone fracture.bone marrow disorders.
bradycardia.cardiotoxicity.cerebrovascular insufficiency.
circulatory collapse (more common if injection too rapid).
coarsening of the facial features.constipation.delirium.
Dupuytren’s contracture.encephalopathy.
granulocytopenia.groin tingling.hair changes.hepatic
disorders.hyperglycaemia.hypersensitivity.insomnia.
leucopenia.lymphadenopathy.nephritis
tubulointerstitial.Peyronie’s disease.polyarteritis nodosa
.polyarthritis.purple glove syndrome.respiratory
disorders.sensory peripheral polyneuropathy.
thrombocytopenia.tonic seizure.ventricular conduction
depression (more common if injection too rapid).
ventricularfibrillation (more common if injection too
rapid)
SIDE-EFFECTS, FURTHER INFORMATIONFosphenytoin has
been associated with severe cardiovascular reactions
including asystole, ventricularfibrillation, and cardiac
arrest. Hypotension, bradycardia, and heart block have
also been reported. The following are recommended:
monitor heart rate, blood pressure, and respiratory
function for duration of infusion; observe patient for at
least 30 minutes after infusion; if hypotension occurs,
reduce infusion rate or discontinue; reduce dose or
infusion rate in renal or hepatic impairment.
lALLERGY AND CROSS-SENSITIVITYCross-sensitivity
reported with carbamazepine.
lPREGNANCY
MonitoringChanges in plasma-protein binding make
interpretation of plasma-phenytoin concentrations
difficult—monitor unbound fraction.
The dose should be monitored carefully during
pregnancy and after birth, and adjustments made on a
clinical basis.
lBREAST FEEDINGSmall amounts present in milk, but not
known to be harmful.
lHEPATIC IMPAIRMENT
Dose adjustmentsConsider 10 – 25 % reduction in dose or
infusion rate (except initial dose for status epilepticus).
lRENAL IMPAIRMENT
Dose adjustmentsConsider 10 – 25 % reduction in dose or
infusion rate (except initial dose for status epilepticus).
lPRE-TREATMENT SCREENINGHLA-B* 1502 allele in
individuals of Han Chinese or Thai origin—avoid unless
essential (increased risk of Stevens-Johnson syndrome).
lMONITORING REQUIREMENTS
▶Manufacturer recommends blood counts (but evidence of
practical value uncertain).
▶With intravenous useMonitor heart rate, blood pressure,
ECG, and respiratory function for during infusion.
lDIRECTIONS FOR ADMINISTRATIONForintermittent
intravenous infusion(Pro-Epanutin®), giveinGlucose 5 %or
Sodium chloride 0. 9 %; dilute to a concentration of
1. 5 – 25 mg (phenytoin sodium equivalent (PE))/mL.
lPRESCRIBING AND DISPENSING INFORMATION
Prescriptions for fosphenytoin sodium should state the
dose in terms of phenytoin sodium equivalent (PE);
fosphenytoin sodium 1. 5 mg:phenytoin sodium 1 mg.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Solution for injection
ELECTROLYTES:May contain Phosphate
▶Pro-Epanutin(Pfizer Ltd)
Fosphenytoin sodium 75 mg per 1 mlPro-Epanutin 750 mg/ 10 ml
concentrate for solution for injection vials| 10 vialP£ 400. 00
(Hospital only)BNFC 2018 – 2019 Epilepsy and other seizure disorders 199
Nervous system4