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CAUTIONS, FURTHER INFORMATION The effectiveness of

clobazam may decrease significantly after weeks or

months of continuous therapy.

l INTERACTIONS → Appendix 1: clobazam

l SIDE-EFFECTS Appetite decreased . consciousness

impaired . constipation . drug abuse . dry mouth .fall . gait

unsteady . libido loss . movement disorders . muscle

spasms . nystagmus .respiratory disorder. severe

cutaneous adverse reactions (SCARs). skin reactions . speech impairment. weight increased

l BREAST FEEDING Benzodiazepines are present in milk, and

should be avoided if possible during breast-feeding.

Monitoring All infants should be monitored for sedation,

feeding difficulties, adequate weight gain, and

developmental milestones.

l RENAL IMPAIRMENT

Dose adjustments Start with small doses in severe

impairment.

l MONITORING REQUIREMENTS

▶ In children Routine measurement of plasma concentrations

of antiepileptic drugs is not usually justified, because the

target concentration ranges are arbitrary and often vary

between individuals. However, plasma drug

concentrations may be measured in children with

worsening seizures, status epilepticus, suspected

noncompliance, or suspected toxicity. Similarly,

haematological and biochemical monitoring should not be

undertaken unless clinically indicated.

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

generic clobazam product.

l PATIENT AND CARER ADVICE

Medicines for Children leaflet: Clobazam for preventing seizures

www.medicinesforchildren.org.uk/clobazam-preventingseizures-0

l NATIONAL FUNDING/ACCESS DECISIONS

NHS restrictions Clobazam is not prescribable in NHS

primary care except for the treatment of epilepsy; endorse

prescription ’SLS’.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: capsule, oral

suspension

Oral suspension

CAUTIONARY AND ADVISORY LABELS 2, 8, 19

▶ Clobazam (Non-proprietary)

Clobazam 1 mg per 1 ml Clobazam 5mg/5ml oral suspension sugar

free sugar-free | 150 ml P £90.00 DT = £90.00dsugar-free

|

Clobazam 2 mg per 1 ml

250 ml P £150.00dClobazam 10mg/5ml oral suspension sugar

free sugar-free | 150 ml P £95.00 DT = £95.00dsugar-free

|

Perizam

250 ml P

(Rosemont Pharmaceuticals Ltd)

£158.33d

Clobazam 1 mg per 1 ml Perizam 1mg/ml oral suspension sugar-free

|

Clobazam 2 mg per 1 ml

150 ml P £90.00 DT = £

Perizam

90.00d2mg/ml oral suspension sugar-free

|

Tapclob

150 ml

(Martindale Pharmaceuticals Ltd)

P £95.00 DT = £95.00d

Clobazam 1 mg per 1 ml Tapclob 5mg/5ml oral suspension sugarfree | 150 ml P £90.00 DT = £90.00dsugar-free | 250

Clobazam 2 mg per 1 ml

ml P £150.00d

Tapclob 10mg/5ml oral suspension sugarfree | 150 ml P £95.00 DT = £95.00dsugar-free | 250 ml P £158.34d

▶ Zacco (Thame Laboratories Ltd)

Clobazam 1 mg per 1 ml Zacco 5mg/5ml oral suspension sugar-free

|

Clobazam 2 mg per 1 ml

150 ml P £82.00 DT = £

Zacco

90.00

10

d

mg/5ml oral suspension sugar-free

| 150 ml P £87.00 DT = £95.00d

Tablet

CAUTIONARY AND ADVISORY LABELS 2, 8, 19

▶ Clobazam (Non-proprietary)

Clobazam 10 mg Clobazam 10mg tablets | 30 tablet P £3.65 DT

▶ Frisium

= £3.64d

(Sanofi)

Clobazam 10 mg Frisium 10mg tablets | 30 tablet P £2.51 DT =

£3.64d

eiiiF 342i

Clonazepam 31-Jul-2018

l INDICATIONS AND DOSE

All forms of epilepsy

▶ BY MOUTH

▶ Child 1–11 months: Initially 250 micrograms once daily

for 4 nights, dose to be increased over 2–4 weeks, usual

dose 0.5–1 mg daily, dose to be taken at night; may be

given in 3 divided doses if necessary

▶ Child 1–4 years: Initially 250 micrograms once daily for

4 nights, dose to be increased over 2–4 weeks, usual

dose 1–3 mg daily, dose to be taken at night; may be

given in 3 divided doses if necessary

▶ Child 5–11 years: Initially 500 micrograms once daily for

4 nights, dose to be increased over 2–4 weeks, usual

dose 3–6 mg daily, dose to be taken at night; may be

given in 3 divided doses if necessary

▶ Child 12–17 years: Initially 1 mg once daily for 4 nights,

dose to be increased over 2–4 weeks, usual dose

4–8 mg daily, dose usually taken at night; may be given

in 3–4 divided doses if necessary

All forms of epilepsy | Myoclonus

▶ BY MOUTH

▶ Adult: Initially 1 mg once daily for 4 nights, dose to be

increased over 2–4 weeks, usual dose 4–8 mg daily,

adjusted according to response, dose usually taken at

night; may be given in 3–4 divided doses if necessary

▶ Elderly: Initially 500 micrograms once daily for 4

nights, dose to be increased over 2–4 weeks, usual dose

4–8 mg daily, adjusted according to response, dose

usually taken at night; may be given in 3–4 divided

doses if necessary

Panic disorders (with or without agoraphobia) resistant to

antidepressant therapy

▶ BY MOUTH

▶ Adult: 1–2 mg daily

l UNLICENSED USE Clonazepam doses in BNF may differ

from those in product literature. Use for panic disorders

(with or without agoraphobia) resistant to antidepressant

therapy is an unlicensed indication.

IMPORTANT SAFETY INFORMATION

SAFE PRACTICE

Clonazepam has been confused with clobazam; care

must be taken to ensure the correct drug is prescribed

and dispensed.

l CONTRA-INDICATIONS Coma . current alcohol abuse . current drug abuse .respiratory depression

l CAUTIONS Acute porphyrias p. 1058 . airways obstruction . brain damage . cerebellar ataxia . depression . spinal ataxia . suicidal ideation

CAUTIONS, FURTHER INFORMATION The effectiveness of

clonazepam may decrease significantly after weeks or

months of continuous therapy.

l INTERACTIONS → Appendix 1: clonazepam

BNF 78 Epilepsy and other seizure disorders 337

Nervous system

4

l SIDE-EFFECTS Alopecia . bronchial secretion increased (in

children). concentration impaired . coordination abnormal . drooling (in children). hypersalivation (in children). incomplete precocious puberty (in children). increased

risk of fall (in adults). increased risk of fracture (in adults). muscle tone decreased . nystagmus . seizures . sexual

dysfunction . skin reactions . speech impairment

l BREAST FEEDING Present in milk, and should be avoided if

possible during breast-feeding.

Monitoring All infants should be monitored for sedation,

feeding difficulties, adequate weight gain, and

developmental milestones.

l RENAL IMPAIRMENT

Dose adjustments Start with small doses in severe

impairment.

l MONITORING REQUIREMENTS

▶ In children Routine measurement of plasma concentrations

of antiepileptic drugs is not usually justified, because the

target concentration ranges are arbitrary and often vary

between individuals. However, plasma drug

concentrations may be measured in children with

worsening seizures, status epilepticus, suspected

noncompliance, or suspected toxicity. Similarly,

haematological and biochemical monitoring should not be

undertaken unless clinically indicated.

l PRESCRIBING AND DISPENSING INFORMATION The RCPCH

and NPPG recommend that, when a liquid special of

clonazepam is required, the following strength is used:

2 mg/5 mL.

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

generic oral clonazepam product.

l PATIENT AND CARER ADVICE

Medicines for Children leaflet: Clonazepam for preventing seizures

www.medicinesforchildren.org.uk/clonazepam-preventingseizures-0

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: orodispersible

tablet, oral suspension, oral solution

Tablet

CAUTIONARY AND ADVISORY LABELS 2, 8

▶ Clonazepam (Non-proprietary)

Clonazepam 500 microgram Clonazepam 500microgram tablets |

100

Clonazepam 2 mg

tablet P £30

Clonazepam

.00 DT = £28

2

.31

mg tablets

d

| 100 tablet P £30.00 DT = £29.23d

Oral solution

CAUTIONARY AND ADVISORY LABELS 2, 8

EXCIPIENTS: May contain Ethanol

▶ Clonazepam (Non-proprietary)

Clonazepam 100 microgram per 1 ml Clonazepam

500micrograms/5ml oral solution sugar free sugar-free | 150

Clonazepam 400 microgram per 1 ml

ml P £78.00 DT = £76.94d

Clonazepam 2mg/5ml oral

solution sugar free sugar-free | 150 ml P £108.36 DT =

£108.36d

2.1 Status epilepticus

Other drugs used for Status epilepticus Diazepam, p. 343 . Fosphenytoin sodium, p. 314 . Phenobarbital, p. 335 . Phenytoin, p. 323

ANTIEPILEPTICS › BARBITURATES

Thiopental sodium

(Thiopentone sodium)

l INDICATIONS AND DOSE

Status epilepticus (only if other measures fail)

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: 75–125 mg for 1 dose, to be administered as a

2.5% (25 mg/mL) solution

Induction of anaesthesia

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: Initially 100–150 mg, to be administered over

10–15 seconds usually as a 2.5% (25 mg/mL) solution,

followed by 100–150 mg after 0.5–1 minute if required,

dose to be given in fit and premedicated adults;

debilitated patients or adults over 65 years may require

a lower dose or increased administration time,

alternatively initially up to 4 mg/kg (max. per dose

500 mg)

Anaesthesia of short duration

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: Initially 100–150 mg, to be administered over

10–15 seconds usually as a 2.5% (25 mg/mL) solution,

followed by 100–150 mg after 0.5–1 minute if required,

dose to be given in fit and premedicated adults;

debilitated patients or adults over 65 years may require

a lower dose or increased administration time,

alternatively initially up to 4 mg/kg (max. per dose

500 mg)

Reduction of raised intracranial pressure if ventilation

controlled

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: 1.5–3 mg/kg, repeated if necessary

IMPORTANT SAFETY INFORMATION

Thiopental sodium should only be administered by, or

under the direct supervision of, personnel experienced

in its use, with adequate training in anaesthesia and

airway management, and when resuscitation equipment

is available.

l CONTRA-INDICATIONS Acute porphyrias p. 1058 . myotonic dystrophy

l CAUTIONS Acute circulatory failure (shock) . avoid intraarterial injection . cardiovascular disease . elderly . fixed

cardiac output. hypovolaemia .reconstituted solution is

highly alkaline (extravasation causes tissue necrosis and

severe pain)

l INTERACTIONS → Appendix 1: thiopental

l SIDE-EFFECTS

▶ Common or very common Arrhythmia . myocardial

contractility decreased

▶ Frequency not known Appetite decreased . circulatory

collapse . cough . electrolyte imbalance . extravasation

necrosis . hypotension .respiratory disorders . skin

eruption . sneezing

l PREGNANCY May depress neonatal respiration when used

during delivery.

l BREAST FEEDING Breast-feeding can be resumed as soon

as mother has recovered sufficiently from anaesthesia.

l HEPATIC IMPAIRMENT Manufacturer advises caution.

Dose adjustments Manufacturer advises dose reduction.

l RENAL IMPAIRMENT Caution in severe impairment.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Patients given sedatives and

analgesics during minor outpatient procedures should be

very carefully warned about the risk of driving or

undertaking skilled tasks afterwards. For a short general

338 Epilepsy and other seizure disorders BNF 78

Nervous system

4

anaesthetic the risk extends to at least 24 hours after

administration. Responsible persons should be available to

take patients home. The dangers of taking alcohol should

also be emphasised.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: solution for

injection

Powder for solution for injection

▶ Thiopental sodium (Non-proprietary)

Thiopental sodium 500 mg Thiopental 500mg powder for solution

for injection vials | 10 vial P £69.00 | 25 vial P £172.50

HYPNOTICS, SEDATIVES AND

ANXIOLYTICS › BENZODIAZEPINES

eiiiF 342i

Lorazepam 02-Aug-2018

l INDICATIONS AND DOSE

Short-term use in anxiety

▶ BY MOUTH

▶ Adult: 1–4 mg daily in divided doses, for debilitated

patients, use elderly dose

▶ Elderly: 0.5–2 mg daily in divided doses

Short-term use in insomnia associated with anxiety

▶ BY MOUTH

▶ Adult: 1–2 mg daily, to be taken at bedtime

Acute panic attacks

▶ BY INTRAMUSCULAR INJECTION, OR BY SLOW INTRAVENOUS

INJECTION

▶ Adult: 25–30 micrograms/kg every 6 hours if required;

usual dose 1.5–2.5 mg every 6 hours if required,

intravenous injection to be administered into a large

vein, only use intramuscular route when oral and

intravenous routes not possible

Conscious sedation for procedures

▶ BY MOUTH

▶ Adult: 2–3 mg, to be taken the night before operation;

2–4 mg, to be taken 1–2 hours before operation

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: 50 micrograms/kg, to be administered

30–45 minutes before operation

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 50 micrograms/kg, to be administered

60–90 minutes before operation

Premedication

▶ BY MOUTH

▶ Adult: 2–3 mg, to be taken the night before operation;

2–4 mg, to be taken 1–2 hours before operation

▶ BY SLOW INTRAVENOUS INJECTION

▶ Adult: 50 micrograms/kg, to be administered

30–45 minutes before operation

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 50 micrograms/kg, to be administered

60–90 minutes before operation

Status epilepticus | Febrile convulsions | Convulsions

caused by poisoning

▶ BY SLOW INTRAVENOUS INJECTION

▶ Child 1 month–11 years: 100 micrograms/kg (max. per

dose 4 mg) for 1 dose, then 100 micrograms/kg after

10 minutes (max. per dose 4 mg) if required for 1 dose,

to be administered into a large vein

▶ Child 12–17 years: 4 mg for 1 dose, then 4 mg after

10 minutes if required for 1 dose, to be administered

into a large vein

▶ Adult: 4 mg for 1 dose, then 4 mg after 10 minutes if

required for 1 dose, to be administered into a large vein

l UNLICENSED USE

▶ In children Not licensed for use in febrile convulsions. Not

licensed for use in convulsions caused by poisoning.

IMPORTANT SAFETY INFORMATION

ANAESTHESIA

Benzodiazepines should only be administered for

anaesthesia by, or under the direct supervision of,

personnel experienced in their use, with adequate

training in anaesthesia and airway management.

l CONTRA-INDICATIONS Avoid injections containing benzyl

alcohol in neonates . chronic psychosis (in adults). CNS

depression . compromised airway . hyperkinesis . not for

use alone to treat depression (or anxiety associated with

depression) (in adults). obsessional states . phobic states . respiratory depression

l CAUTIONS Muscle weakness . organic brain changes . parenteral administration

CAUTIONS, FURTHER INFORMATION

▶ Paradoxical effects A paradoxical increase in hostility and

aggression may be reported by patients taking

benzodiazepines. The effects range from talkativeness and

excitement to aggressive and antisocial acts. Adjustment

of the dose (up or down) sometimes attenuates the

impulses. Increased anxiety and perceptual disorders are

other paradoxical effects.

▶ Special precautions for parenteral administration When given

parenterally, facilities for managing respiratory depression

with mechanical ventilation must be available. Close

observation required until full recovery from sedation.

l INTERACTIONS → Appendix 1: lorazepam

l SIDE-EFFECTS

GENERAL SIDE-EFFECTS

▶ Common or very common Apnoea . asthenia . coma . disinhibition . extrapyramidal symptoms . hypothermia . memory loss . speech slurred . suicide attempt

▶ Uncommon Allergic dermatitis . constipation . sexual

dysfunction

▶ Rare or very rare Agranulocytosis . hyponatraemia . pancytopenia . SIADH .thrombocytopenia

SPECIFIC SIDE-EFFECTS

▶ Rare or very rare

▶ With oral use Saliva altered

▶ Frequency not known

▶ With parenteral use Leucopenia

l BREAST FEEDING Benzodiazepines are present in milk, and

should be avoided if possible during breast-feeding.

l RENAL IMPAIRMENT

Dose adjustments Start with small doses in severe

impairment.

l DIRECTIONS FOR ADMINISTRATION

▶ With intravenous use in children For intravenous injection,

dilute with an equal volume of Sodium Chloride 0.9% (for

neonates, dilute injection solution to a concentration of

100 micrograms/mL). Give over 3–5 minutes; max. rate

50 micrograms/kg over 3 minutes.

▶ With intramuscular use in adults For intramuscular injection,

solution for injection should be diluted with an equal

volume of water for injections or sodium chloride 0.9%

(but only use when oral and intravenous routes not

possible).

▶ With intravenous use in adults For slow intravenous injection,

solution for injection should preferably be diluted with an

equal volume of water for injections or sodium chloride

0.9%.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Patients given sedatives and

analgesics during minor outpatient procedures should be

very carefully warned about the risks of undertaking

BNF 78 Status epilepticus 339

Nervous system

4

 


▶ With rectal use Dissolve contents of sachet in small amount

of water and administer rectally [unlicensed use].

l PATIENT AND CARER ADVICE Patients and their carers

should be warned to report any new visual symptoms that

develop.

Medicines for Children leaflet: Vigabatrin for preventing seizures

www.medicinesforchildren.org.uk/vigabatrin-preventingseizures

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 solution

Powder

CAUTIONARY AND ADVISORY LABELS 3, 8, 13

▶ Sabril (Sanofi)

Vigabatrin 500 mg Sabril 500mg oral powder sachets sugar-free | 50 sachet P £24.60 DT = £24.60

Tablet

CAUTIONARY AND ADVISORY LABELS 3, 8

▶ Sabril (Sanofi)

Vigabatrin 500 mg Sabril 500mg tablets | 100 tablet P £44.41

DT = £44.41

BNF 78 Epilepsy and other seizure disorders 333

Nervous system

4

Zonisamide 20-Feb-2019

l INDICATIONS AND DOSE

Monotherapy for treatment of focal seizures with or

without secondary generalisation in adults with newly

diagnosed epilepsy

▶ BY MOUTH

▶ Adult: Initially 100 mg once daily for 2 weeks, then

increased in steps of 100 mg every 2 weeks, usual

maintenance dose 300 mg once daily; maximum

500 mg per day

Adjunctive treatment for refractory focal seizures with or

without secondary generalisation

▶ BY MOUTH

▶ Child 6–17 years (body-weight 20–54 kg): Initially 1 mg/kg

once daily for 7 days, then increased in steps of

1 mg/kg every 7 days, usual maintenance 6–8 mg/kg

once daily (max. per dose 500 mg once daily), dose to

be increased at 2-week intervals in patients who are

not receiving concomitant carbamazepine, phenytoin,

phenobarbital or other potent inducers of cytochrome

P450 enzyme CYP3A4

▶ Child 6–17 years (body-weight 55 kg and above): Initially

1 mg/kg once daily for 7 days, then increased in steps

of 1 mg/kg every 7 days, usual maintenance

300–500 mg once daily, dose to be increased at 2-week

intervals in patients who are not receiving

concomitant carbamazepine, phenytoin, phenobarbital

or other potent inducers of cytochrome P450 enzyme

CYP3A4

▶ Adult: Initially 50 mg daily in 2 divided doses for

7 days, then increased to 100 mg daily in 2 divided

doses, then increased in steps of 100 mg every 7 days,

usual maintenance 300–500 mg daily in 1–2 divided

doses, dose to be increased at 2-week intervals in

patients who are not receiving concomitant

carbamazepine, phenytoin, phenobarbital or other

potent inducers of cytochrome P450 enzyme CYP3A4

l CAUTIONS Elderly . low body-weight or poor appetite—

monitor weight throughout treatment (fatal cases of

weight loss reported in children). metabolic acidosis—

monitor serum bicarbonate concentration in children and

those with other risk factors (consider dose reduction or

discontinuation if metabolic acidosis develops).risk

factors for renal stone formation (particularly

predisposition to nephrolithiasis)

CAUTIONS, FURTHER INFORMATION Avoid overheating and

ensure adequate hydration especially in children, during

strenuous activity or if in warm environment (fatal cases of

heat stroke reported in children).

l INTERACTIONS → Appendix 1: antiepileptics

l SIDE-EFFECTS

▶ Common or very common Alopecia . anxiety . appetite

decreased . ataxia . bradyphrenia . concentration impaired . confusion . constipation . depression . diarrhoea . dizziness . drowsiness .fatigue .fever. gastrointestinal discomfort. hypersensitivity . influenza like illness . insomnia . memory

loss . mood altered . nausea . nystagmus . paraesthesia . peripheral oedema . psychosis .rash (consider

discontinuation). skin reactions . speech disorder.tremor . urolithiases . vision disorders . vomiting . weight

decreased

▶ Uncommon Behaviour abnormal . gallbladder disorders . hallucination . hypokalaemia . increased risk of infection . leucopenia .respiratory disorders . seizures . suicidal

tendencies .thrombocytopenia

▶ Rare or very rare Agranulocytosis . angle closure glaucoma . anhidrosis . bone marrow disorders . coma . dyspnoea . eye pain . heat stroke . hepatocellular injury . hydronephrosis . leucocytosis . lymphadenopathy .

metabolic acidosis . myasthenic syndrome . neuroleptic

malignant syndrome . pancreatitis .renal failure .renal

tubular acidosis .rhabdomyolysis . severe cutaneous

adverse reactions (SCARs). urine abnormal

▶ Frequency not known Sudden unexplained death in

epilepsy

l ALLERGY AND CROSS-SENSITIVITY Contra-indicated in

sulfonamide hypersensitivity.

Antiepileptic hypersensitivity syndrome theoretically

associated with zonisamide. See under Epilepsy p. 305 for

more information.

l CONCEPTION AND CONTRACEPTION Manufacturer advises

women of childbearing potential should use effective

contraception during treatment and for one month after

last dose—avoid in women of childbearing potential not

using effective contraception unless clearly necessary and

the potential benefit outweighs risk; patients should be

fully informed of the risks related to the use of zonisamide

during pregnancy.

l PREGNANCY Manufacturer advises use only if clearly

necessary and the potential benefit outweighs risk—

toxicity in animal studies; patients should be fully

informed of the risks related to the use of zonisamide

during 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

clinical basis.

l BREAST FEEDING Manufacturer advises avoid for 4 weeks

after last dose.

l HEPATIC IMPAIRMENT Avoid in severe impairment.

Dose adjustments Initially increase dose at 2-week

intervals if mild or moderate impairment.

l RENAL IMPAIRMENT

Dose adjustments Initially increase dose at 2-week

intervals; discontinue if renal function deteriorates.

l TREATMENT CESSATION Avoid abrupt withdrawal (consult

product literature for recommended withdrawal regimens

in children).

l PRESCRIBING AND DISPENSING INFORMATION

Switching between formulations Care should be taken when

switching between oral formulations. 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 may need to be maintained on a specific

manufacturer’s branded or generic zonisamide product.

l PATIENT AND CARER ADVICE Children and their carers

should be made aware of how to prevent and recognise

overheating and dehydration.

Medicines for Children leaflet: Zonisamide for preventing seizures

www.medicinesforchildren.org.uk/zonisamide-preventingseizures

l NATIONAL FUNDING/ACCESS DECISIONS

Scottish Medicines Consortium (SMC) decisions

SMC No. 949/14

The Scottish Medicines Consortium has advised (March

2014) that zonisamide (Zonegran ®) is accepted for

restricted use within NHS Scotland as adjunctive

treatment of focal seizures, with or without secondary

generalisation, in adolescents and children aged 6 years

and above. It is restricted to use on advice from specialists

in paediatric neurology or epilepsy.

334 Epilepsy and other seizure disorders BNF 78

Nervous system

4

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

solution

Capsule

CAUTIONARY AND ADVISORY LABELS 3, 8, 10

▶ Zonisamide (Non-proprietary)

Zonisamide 25 mg Zonisamide 25mg capsules | 14 capsule P £8.82 DT = £6.45

Zonisamide 50 mg Zonisamide 50mg capsules | 56 capsule P £47.04 DT = £33.60

Zonisamide 100 mg Zonisamide 100mg capsules | 56 capsule P £62.72 DT = £4.74

▶ Zonegran (Eisai Ltd)

Zonisamide 25 mg Zonegran 25mg capsules | 14 capsule P £8.82 DT = £6.45

Zonisamide 50 mg Zonegran 50mg capsules | 56 capsule P £47.04 DT = £33.60

Zonisamide 100 mg Zonegran 100mg capsules | 56 capsule P £62.72 DT = £4.74

ANTIEPILEPTICS › BARBITURATES

Phenobarbital

(Phenobarbitone)

l INDICATIONS AND DOSE

All forms of epilepsy except typical absence seizures

▶ BY MOUTH

▶ Child 1 month–11 years: Initially 1–1.5 mg/kg twice daily,

then increased in steps of 2 mg/kg daily as required;

maintenance 2.5–4 mg/kg 1–2 times a day

▶ Child 12–17 years: 60–180 mg once daily

▶ Adult: 60–180 mg once daily, dose to be taken at night

Status epilepticus

▶ BY INTRAVENOUS INJECTION

▶ Adult: 10 mg/kg (max. per dose 1 g), dose to be

administered at a rate not more than 100 mg/minute,

injection to be diluted 1 in 10 with water for injections

▶ BY SLOW INTRAVENOUS INJECTION

▶ Neonate: Initially 20 mg/kg, dose to be administered at a

rate no faster than 1 mg/kg/minute, then 2.5–5 mg/kg

1–2 times a day.

▶ Child 1 month–11 years: Initially 20 mg/kg, dose to be

administered at a rate no faster than 1 mg/kg/minute,

then 2.5–5 mg/kg 1–2 times a day

▶ Child 12–17 years: Initially 20 mg/kg (max. per dose 1 g),

dose to be administered at a rate no faster than

1 mg/kg/minute, then 300 mg twice daily

DOSE EQUIVALENCE AND CONVERSION

▶ For therapeutic purposes phenobarbital and

phenobarbital sodium may be considered equivalent in

effect.

l CAUTIONS Avoid in Acute porphyrias p. 1058 . children . debilitated . elderly . history of alcohol abuse . history of

drug abuse .respiratory depression (avoid if severe)

CAUTIONS, FURTHER INFORMATION Consider vitamin D

supplementation in patients who are immobilised for long

periods or who have inadequate sun exposure or dietary

intake of calcium.

l INTERACTIONS → Appendix 1: antiepileptics

l SIDE-EFFECTS

GENERAL SIDE-EFFECTS

Agranulocytosis . anticonvulsant hypersensitivity

syndrome . behaviour abnormal . bone disorders . bone

fracture . cognitive impairment. confusion . depression . drowsiness . folate deficiency . hepatic disorders . memory

loss . movement disorders . nystagmus .respiratory

depression . skin reactions

SPECIFIC SIDE-EFFECTS

▶ With oral use Anxiety . hallucination . hypotension . megaloblastic anaemia . severe cutaneous adverse

reactions (SCARs).thrombocytopenia

▶ With parenteral use Agitation . anaemia . aplastic anaemia . Dupuytren’s contracture . hypocalcaemia . irritability . toxic epidermal necrolysis

Overdose For details on the management of poisoning, see

Active elimination techniques, under Emergency

treatment of poisoning p. 1359.

l ALLERGY AND CROSS-SENSITIVITY Antiepileptic

hypersensitivity syndrome associated with phenobarbital.

See under Epilepsy p. 305 for more information.

l PREGNANCY

Monitoring The dose should be monitored carefully during

pregnancy and after birth, and adjustments made on a

clinical basis.

l BREAST FEEDING Avoid if possible; drowsiness may occur.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate impairment; avoid in severe impairment.

l RENAL IMPAIRMENT Use with caution.

l MONITORING REQUIREMENTS

▶ Plasma-phenobarbital concentration for optimum

response is 15–40 mg/litre (60–180 micromol/litre);

however, monitoring the plasma-drug concentration is

less useful than with other drugs because tolerance occurs.

l TREATMENT CESSATION Avoid abrupt withdrawal

(dependence with prolonged use).

l DIRECTIONS FOR ADMINISTRATION

▶ With oral use For administration by mouth, tablets may be

crushed.

▶ With intravenous use in adults Solution for injection must be

diluted before intravenous administration.

▶ With intravenous use in children For intravenous injection,

dilute to a concentration of 20 mg/mL with Water for

Injections; give over 20 minutes (no faster than

1 mg/kg/minute).

l PRESCRIBING AND DISPENSING INFORMATION Some

hospitals supply alcohol-free formulations of varying

phenobarbital strengths.

The RCPCH and NPPG recommend that, when a liquid

special of phenobarbital is required, the following strength

is used: 50 mg/5 mL.

Switching between formulations Different formulations of oral

preparations may vary in bioavailability. Patients should

be maintained on a specific manufacturer’s product.

l PATIENT AND CARER ADVICE

Medicines for Children leaflet: Phenobarbital for preventing

seizures www.medicinesforchildren.org.uk/phenobarbitalpreventing-seizures

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: tablet, capsule, oral

suspension, oral solution

Tablet

CAUTIONARY AND ADVISORY LABELS 2, 8

▶ Phenobarbital (Non-proprietary)

Phenobarbital 15 mg Phenobarbital 15mg tablets | 28 tablet P £24.95 DT = £16.71c

Phenobarbital 30 mg Phenobarbital 30mg tablets | 28 tablet P £5.99 DT = £0.69c

Phenobarbital 60 mg Phenobarbital 60mg tablets | 28 tablet P £7.99 DT = £6.67c

Solution for injection

EXCIPIENTS: May contain Propylene glycol

▶ Phenobarbital (Non-proprietary)

Phenobarbital sodium 30 mg per 1 ml Phenobarbital 30mg/1ml

solution for injection ampoules | 10 ampoule P £98.42 DT =

£98.42c

BNF 78 Epilepsy and other seizure disorders 335

Nervous system

4

Phenobarbital sodium 60 mg per 1 ml Phenobarbital 60mg/1ml

solution for injection ampoules | 10 ampoule P £103.84 DT =

£103.84c

Phenobarbital sodium 200 mg per 1 ml Phenobarbital 200mg/1ml

solution for injection ampoules | 10 ampoule P £84.66 DT =

£84.66c

Oral solution

CAUTIONARY AND ADVISORY LABELS 2, 8

EXCIPIENTS: May contain Alcohol

▶ Phenobarbital (Non-proprietary)

Phenobarbital 3 mg per 1 ml Phenobarbital 15mg/5ml elixir | 500 ml P £83.00–£83.01 DT = £83.01c

Primidone

l INDICATIONS AND DOSE

All forms of epilepsy except typical absence seizures

▶ BY MOUTH

▶ Child 1 month–1 year: Initially 125 mg daily, dose to be

taken at bedtime, then increased in steps of 125 mg

every 3 days, adjusted according to response;

maintenance 125–250 mg twice daily

▶ Child 2–4 years: Initially 125 mg once daily, dose to be

taken at bedtime, then increased in steps of 125 mg

every 3 days, adjusted according to response;

maintenance 250–375 mg twice daily

▶ Child 5–8 years: Initially 125 mg once daily, dose to be

taken at bedtime, then increased in steps of 125 mg

every 3 days, adjusted according to response;

maintenance 375–500 mg twice daily

▶ Child 9–17 years: Initially 125 mg once daily, dose to be

taken at bedtime, then increased in steps of 125 mg

every 3 days, increased to 250 mg twice daily, then

increased in steps of 250 mg every 3 days (max. per

dose 750 mg twice daily), adjusted according to

response

▶ Adult: Initially 125 mg once daily, dose to be taken at

bedtime, then increased in steps of 125 mg every

3 days, increased to 500 mg daily in 2 divided doses,

then increased in steps of 250 mg every 3 days,

adjusted according to response; maintenance

0.75–1.5 g daily in 2 divided doses

Essential tremor

▶ BY MOUTH

▶ Adult: Initially 50 mg daily, then adjusted according to

response to up to 750 mg daily, dose to be increased

over 2–3 weeks

l CAUTIONS Avoid in Acute porphyrias p. 1058 . children . debilitated . elderly . history of alcohol abuse . history of

drug abuse .respiratory depression (avoid if severe)

CAUTIONS, FURTHER INFORMATION Consider vitamin D

supplementation in patients who are immobilised for long

periods or who have inadequate sun exposure or dietary

intake of calcium.

l INTERACTIONS → Appendix 1: antiepileptics

l SIDE-EFFECTS

▶ Common or very common Apathy . ataxia . drowsiness . nausea . nystagmus . visual impairment

▶ Uncommon Dizziness . headache . hypersensitivity . skin

reactions . vomiting

▶ Rare or very rare Arthralgia . blood disorder. bone

disorders .Dupuytren’s contracture . megaloblastic

anaemia (may be treated with folic acid) . personality

change . psychotic disorder. severe cutaneous adverse

reactions (SCARs). systemic lupus erythematosus (SLE)

▶ Frequency not known Bone fracture

l ALLERGY AND CROSS-SENSITIVITY Antiepileptic

hypersensitivity syndrome associated with primidone. See

under Epilepsy p. 305 for more information.

l PREGNANCY

Monitoring The dose should be monitored carefully during

pregnancy and after birth, and adjustments made on a

clinical basis.

l HEPATIC IMPAIRMENT May precipitate coma.

Dose adjustments Reduce dose.

l RENAL IMPAIRMENT Use with caution.

l MONITORING REQUIREMENTS

▶ Monitor plasma concentrations of derived phenobarbital;

plasma concentration for optimum response is

15–40 mg/litre (60–180 micromol/litre).

l TREATMENT CESSATION Avoid abrupt withdrawal

(dependence with prolonged use).

l PRESCRIBING AND DISPENSING INFORMATION

Switching between formulations Different formulations of oral

preparations may vary in bioavailability. Patients being

treated for epilepsy should be maintained on a specific

manufacturer’s product.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: capsule, oral

suspension

Tablet

CAUTIONARY AND ADVISORY LABELS 2, 8

▶ Primidone (Non-proprietary)

Primidone 50 mg Primidone 50mg tablets | 100 tablet P £110.00–£112.37 DT = £111.58

Primidone 250 mg Primidone 250mg tablets | 100 tablet P £99.65–£121.94 DT = £114.51

HYPNOTICS, SEDATIVES AND

ANXIOLYTICS › BENZODIAZEPINES

eiiiF 342i

Clobazam 29-Mar-2019

l INDICATIONS AND DOSE

Adjunct in epilepsy

▶ BY MOUTH

▶ Child 6–17 years: Initially 5 mg daily, dose to be

increased if necessary at intervals of 5 days,

maintenance 0.3–1 mg/kg daily, daily doses of up to

30 mg may be given as a single dose at bedtime, higher

doses should be divided; maximum 60 mg per day

▶ Adult: 20–30 mg daily, then increased if necessary up

to 60 mg daily

Anxiety (short-term use)

▶ BY MOUTH

▶ Adult: 20–30 mg daily in divided doses, alternatively

20–30 mg once daily, dose to be taken at bedtime;

increased if necessary up to 60 mg daily in divided

doses, dose only increased in severe anxiety (in

hospital patients), for debilitated patients, use elderly

dose

▶ Elderly: 10–20 mg daily

l UNLICENSED USE

▶ In children Not licensed as monotherapy.

IMPORTANT SAFETY INFORMATION

SAFE PRACTICE

Clobazam has been confused with clonazepam; care

must be taken to ensure the correct drug is prescribed

and dispensed.

l CONTRA-INDICATIONS Chronic psychosis (in adults). hyperkinesis . not for use alone to treat anxiety associated

with depression (in adults). obsessional states . phobic

states .respiratory depression

l CAUTIONS Muscle weakness . organic brain changes

336 Epilepsy and other seizure disorders BNF 78

Nervous system

4

mcq general

 

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