Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures with/without secondary generalisation-adjunctive

Cenobamate is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in patients with epilepsy who have not been adequately controlled despite treatment with at least two anti-epileptic medicinal products.

Contraindications

Children under 18 years
Breastfeeding
End stage renal disease
Galactosaemia
Haemodialysis
Severe hepatic impairment
Shortened QT interval

Precautions and Warnings

Elderly
Females of childbearing potential
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Mild renal impairment
Pregnancy

Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Monitor closely for skin reactions
Monitor for signs of suicide ideation or behaviour
Discontinue treatment if DRESS is suspected
Gradually withdraw over 2 weeks
Consider reducing dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Contraception required during and for 1 month after treatment
Female: Non-hormonal contraception advised in addition to hormonal
Advise patient/carers to report signs of suicide ideation or behaviour

A dose-dependent shortening of the QTcF interval has been observed with cenobamate. Reductions of the QTcF interval below 340msec were not observed. There was no evidence from clinical trials that the combination of cenobamate with other antiepileptic medicines led to further QT-shortening. Clinicians should use caution when prescribing cenobamate in combination with other medicinal products that are known to shorten the QT.

Drug reaction with eosinophilia and systemic symptoms (DRESS), has been reported in association with cenobamate when started at higher doses and titrated rapidly (weekly or faster titration). When initiated as 12.5mg/day and titrated every two weeks, no cases of DRESS where reported. Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.

Pregnancy and Lactation

Pregnancy

Use cenobamate with caution during pregnancy.

The manufacturer recommends that cenobamate should not be used during pregnancy and by women of childbearing potential not using contraception unless the clinical condition of the women requires treatment with cenobamate. At the time of writing, there is no adequate data regarding the use of cenobamate in pregnant women. Animal studies have shown that cenobamate can cross the placenta of rates. They have also shown reproductive toxicity at levels below clinical exposure.

Lactation

Cenobamate is contraindicated during breastfeeding.

The manufacturer recommends that as a precautionary measure, breastfeeding should be discontinued during treatment with cenobamate. It is unknown if cenobamate or its metabolites are excreted in human milk. Animal studies have shown excretion of cenobamate in the maternal milk of rats. A risk to the suckling child cannot be excluded.

LactMed (2020) indicates that if cenobamate is required by a nursing mother, it is not a reason to discontinue breastfeeding, but until more data becomes available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Infant should be monitored for excessive drowsiness.

Side Effects

Aphasia
Ataxia
Blurred vision
Confusion
Constipation
Diarrhoea
Diplopia
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dysarthria
Fatigue
Gait abnormality
Headache
Hypersensitivity reactions
Hypersomnia
Impaired memory
Impaired vision
Increases in hepatic enzymes
Irritability
Movement disturbances
Nausea
Nystagmus
Rash
Somnolence
Speech disturbances
Suicidal ideation
Suicidal tendencies
Vertigo
Vomiting

Presentation

Oral formulations of cenobamate.

Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures with/without secondary generalisation-adjunctive

Cenobamate is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in patients with epilepsy who have not been adequately controlled despite treatment with at least two anti-epileptic medicinal products.

Dosage

Cenobamate should always be initiated at 12.5mg once daily and titrated not faster than once every two weeks.

Adults

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
End stage renal disease
Galactosaemia
Haemodialysis
Severe hepatic impairment
Shortened QT interval

Precautions and Warnings

Elderly
Females of childbearing potential
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Mild renal impairment
Pregnancy

Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Monitor closely for skin reactions
Monitor for signs of suicide ideation or behaviour
Discontinue treatment if DRESS is suspected
Gradually withdraw over 2 weeks
Consider reducing dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Contraception required during and for 1 month after treatment
Female: Non-hormonal contraception advised in addition to hormonal
Advise patient/carers to report signs of suicide ideation or behaviour

A dose-dependent shortening of the QTcF interval has been observed with cenobamate. Reductions of the QTcF interval below 340msec were not observed. There was no evidence from clinical trials that the combination of cenobamate with other antiepileptic medicines led to further QT-shortening. Clinicians should use caution when prescribing cenobamate in combination with other medicinal products that are known to shorten the QT.

Drug reaction with eosinophilia and systemic symptoms (DRESS), has been reported in association with cenobamate when started at higher doses and titrated rapidly (weekly or faster titration). When initiated as 12.5mg/day and titrated every two weeks, no cases of DRESS where reported. Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.

Pregnancy and Lactation

Pregnancy

Use cenobamate with caution during pregnancy.

The manufacturer recommends that cenobamate should not be used during pregnancy and by women of childbearing potential not using contraception unless the clinical condition of the women requires treatment with cenobamate. At the time of writing, there is no adequate data regarding the use of cenobamate in pregnant women. Animal studies have shown that cenobamate can cross the placenta of rates. They have also shown reproductive toxicity at levels below clinical exposure.

Lactation

Cenobamate is contraindicated during breastfeeding.

The manufacturer recommends that as a precautionary measure, breastfeeding should be discontinued during treatment with cenobamate. It is unknown if cenobamate or its metabolites are excreted in human milk. Animal studies have shown excretion of cenobamate in the maternal milk of rats. A risk to the suckling child cannot be excluded.

LactMed (2020) indicates that if cenobamate is required by a nursing mother, it is not a reason to discontinue breastfeeding, but until more data becomes available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Infant should be monitored for excessive drowsiness.

Side Effects

Aphasia
Ataxia
Blurred vision
Confusion
Constipation
Diarrhoea
Diplopia
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dysarthria
Fatigue
Gait abnormality
Headache
Hypersensitivity reactions
Hypersomnia
Impaired memory
Impaired vision
Increases in hepatic enzymes
Irritability
Movement disturbances
Nausea
Nystagmus
Rash
Somnolence
Speech disturbances
Suicidal ideation
Suicidal tendencies
Vertigo
Vomiting

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 2021

Reference Sources

Summary of Product Characteristics: Ontozry 12.5mg tablets and 25mg film-coated tablets. Arvelle Therapeutics UK. Revised July 2021.
Summary of Product Characteristics: Ontozry 50mg film-coated tablets. Arvelle Therapeutics UK. Revised July 2021.
Summary of Product Characteristics: Ontozry 100mg film-coated tablets. Arvelle Therapeutics UK. Revised July 2021.
Summary of Product Characteristics: Ontozry 150mg film-coated tablets. Arvelle Therapeutics UK. Revised July 2021.
Summary of Product Characteristics: Ontozry 200mg film-coated tablets. Arvelle Therapeutics UK. Revised July 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 December 2021

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Cenobamate Last revised: 21 September 2020
Last accessed: 21 December 2021