Drugs List

Therapeutic Indications

Uses

Seizures linked with Lennox-Gastaut Syndrome: adjunct (with valproate)
Seizures linked with Lennox-Gastaut Syndrome: adjunct (without valproate)

Administration

If the patients has difficulty in swallowing, the tablets may be crushed and added to water.

Contraindications

Children under 1 year
Breastfeeding
Severe hepatic impairment

Precautions and Warnings

Females of childbearing potential
Suicidal ideation
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Lactose intolerance
Pregnancy
Shortened QT interval

Patients at risk of suicide should be closely supervised
Advise patient blurred vision may affect ability to drive/operate machinery
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Consider prescribing by manufacturer to ensure seizure control maintenance
Folic acid 5mg daily required pre-conception to end of 1st trimester
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
May cause an increase in seizure frequency or onset of new seizure types
Advise patients/carers to seek medical advice if suicidal intent develops
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if drug-related rash or other hypersensitivity reactions occur
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient of increased risk of falls
Advise patients to report skin rash

Assess benefits and risk on continued therapy if patients develop new seizure types and/or an increased frequency of status epilepticus that is different from the baseline condition.

Dizziness, somnolence, ataxia and gait disturbances have been associated with rufinamide therapy. These effects could increase the risk of falls. Patients and their carers should be advised to exercise caution until they are aware of how they respond to rufinamide therapy.

Antiepileptic drug hypersensitivity syndrome is a rare but potentially fatal syndrome associated with some antiepileptic drugs. Patients usually present with fever, rash, lymphadenopathy and other organ system involvement. Other possible symptoms include liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure. If signs or symptoms of hypersensitivity syndrome occur, the drug should be withdrawn immediately and expert advice sought. Patients must be closely monitored if they develop a rash during therapy.

Pregnancy and Lactation

Pregnancy

Use rufinamide with caution in pregnancy.

At the time of writing, there is highly limited data on exposed pregnancies available. Animal studies have not revealed any teratogenic effects, but foetotoxicity occurred in the presence of maternal toxicity. The potential risk for humans is unknown.

Due to the lack of data and experience, use of rufinamide during pregnancy is not recommended unless absolutely necessary. However, adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Rufinamide is contraindicated during breastfeeding.

It is not known whether rufinamide is excreted in human breast milk. Its low molecular weight, lipophilic nature and long plasma half-life suggest that it will (Briggs 2015). The manufacturer advises that breastfeeding should be avoided during maternal treatment with rufinamide.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Accidental injury
Acne
Anorexia
Anxiety
Back pain
Blurred vision
Constipation
Contusion
Convulsions
Decreased appetite
Diarrhoea
Diplopia
Dizziness
Drowsiness
Dyspepsia
Ear infection
Epistaxis
Fatigue
Fever
Gait abnormality
Haematuria
Headache
Hypersensitivity reactions
Impaired co-ordination
Increases in hepatic enzymes
Influenza
Insomnia
Lymphadenopathy
Nasopharyngitis
Nausea
Nystagmus
Oligomenorrhoea
Pneumonia
Precipitation of status epilepticus
Psychomotor hyperactivity
Rash
Rhinitis
Sinusitis
Somnolence
Tremor
Vertigo
Vomiting
Weight loss

Presentation

Oral formulations containing rufinamide.

Drugs List

Therapeutic Indications

Uses

Seizures linked with Lennox-Gastaut Syndrome: adjunct (with valproate)
Seizures linked with Lennox-Gastaut Syndrome: adjunct (without valproate)

Dosage

Treatment should be initiated by a specialist in paediatrics or neurology and with experience in the treatment of epilepsy.

Adults

Children

Additional Dosage Information

Administration

If the patients has difficulty in swallowing, the tablets may be crushed and added to water.

Contraindications

Children under 1 year
Breastfeeding
Severe hepatic impairment

Precautions and Warnings

Females of childbearing potential
Suicidal ideation
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Lactose intolerance
Pregnancy
Shortened QT interval

Patients at risk of suicide should be closely supervised
Advise patient blurred vision may affect ability to drive/operate machinery
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Consider prescribing by manufacturer to ensure seizure control maintenance
Folic acid 5mg daily required pre-conception to end of 1st trimester
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
May cause an increase in seizure frequency or onset of new seizure types
Advise patients/carers to seek medical advice if suicidal intent develops
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if drug-related rash or other hypersensitivity reactions occur
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient of increased risk of falls
Advise patients to report skin rash

Assess benefits and risk on continued therapy if patients develop new seizure types and/or an increased frequency of status epilepticus that is different from the baseline condition.

Dizziness, somnolence, ataxia and gait disturbances have been associated with rufinamide therapy. These effects could increase the risk of falls. Patients and their carers should be advised to exercise caution until they are aware of how they respond to rufinamide therapy.

Antiepileptic drug hypersensitivity syndrome is a rare but potentially fatal syndrome associated with some antiepileptic drugs. Patients usually present with fever, rash, lymphadenopathy and other organ system involvement. Other possible symptoms include liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure. If signs or symptoms of hypersensitivity syndrome occur, the drug should be withdrawn immediately and expert advice sought. Patients must be closely monitored if they develop a rash during therapy.

Pregnancy and Lactation

Pregnancy

Use rufinamide with caution in pregnancy.

At the time of writing, there is highly limited data on exposed pregnancies available. Animal studies have not revealed any teratogenic effects, but foetotoxicity occurred in the presence of maternal toxicity. The potential risk for humans is unknown.

Due to the lack of data and experience, use of rufinamide during pregnancy is not recommended unless absolutely necessary. However, adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Rufinamide is contraindicated during breastfeeding.

It is not known whether rufinamide is excreted in human breast milk. Its low molecular weight, lipophilic nature and long plasma half-life suggest that it will (Briggs 2015). The manufacturer advises that breastfeeding should be avoided during maternal treatment with rufinamide.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Rufinamide may cause dizziness, somnolence and blurred vision, which may affect an individual's ability to drive and operate machinery.

Patients and their carers should be advised to exercise caution until they are aware of how they respond to rufinamide therapy.

Women of child bearing potential should be advised to maintain adequate contraception during and for one month after treatment.

Patients should be advised to consult their physician if they are planning a pregnancy, and consider taking folic acid 5mg daily before conception.

Patients and caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour, and the need to seek medical advice immediately if they present.

Advise patient not to use products containing St John's Wort with rufinamide.

Side Effects

Abdominal pain
Accidental injury
Acne
Anorexia
Anxiety
Back pain
Blurred vision
Constipation
Contusion
Convulsions
Decreased appetite
Diarrhoea
Diplopia
Dizziness
Drowsiness
Dyspepsia
Ear infection
Epistaxis
Fatigue
Fever
Gait abnormality
Haematuria
Headache
Hypersensitivity reactions
Impaired co-ordination
Increases in hepatic enzymes
Influenza
Insomnia
Lymphadenopathy
Nasopharyngitis
Nausea
Nystagmus
Oligomenorrhoea
Pneumonia
Precipitation of status epilepticus
Psychomotor hyperactivity
Rash
Rhinitis
Sinusitis
Somnolence
Tremor
Vertigo
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Inovelon tablets. Eisai Ltd. Revised August 2018

Summary of Product Characteristics: Inovelon oral suspension. Eisai Ltd. Revised August 2018

Clinical Knowledge Summaries - Epilepsy
Scenario: Women of childbearing age
Available at: https://cks.nice.org.uk/epilepsy
Last accessed: June 2015

MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: https://webarchive.nationalarchives.gov.uk/20141205150130/https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: 09 December 2016

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 October 2018