| System organ class | frequency | Adverse reactions from clinical TRIALS |
|---|---|---|
| Immune system disorders | Uncommon | Hypersensitivity* |
| Psychiatric disorders | Common | Confusional state, irritability |
| Nervous system disorders | Very Common | Somnolence,* coordination and gait abnormalities,* headache |
| Common | Dysarthria, nystagmus, aphasia, memory impairment | |
| Eye disorders | Common | Diplopia, vision blurred |
| Gastrointestinal disorders | Common | Constipation, diarrhoea, nausea, vomiting, dry mouth |
| Skin and subcutaneous tissue disorder | Common | Rash* |
| Rare | Drug reaction with eosinophilia and systemic symptoms (DRESS) | |
| Investigations | Common | Hepatic enzyme increased* |
*Grouped terms: somnolence: somnolence, fatigue, sedation and hypersomnia; coordination and gait abnormalities: dizziness, vertigo, balance disorder, ataxia, gait disturbance and abnormal coordination; hypersensitivity: hypersensitivity, drug hypersensitivity, eyelid oedema; rash: rash, rash erythematous, rash generalised, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic; hepatic enzyme increased: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hepatic function abnormal, transaminases increased.
See the Summary of Product Characteristics for more information on adverse reactions and full prescribing information, including special warnings and precautions for use, and use in selected patient populations.1
Drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, has been reported in association with cenobamate when started at higher doses and titrated rapidly (weekly or faster titration). When cenobamate was initiated at 12.5 mg/day and titrated every 2 weeks, in an open-label safety study of 1,340 epilepsy patients (study C021), no cases of DRESS were reported.1
At the time of prescription, patients should be advised of the signs and symptoms of DRESS and monitored closely for skin reactions. Symptoms of DRESS typically, although not exclusively, include fever, rash associated with other organ system involvement, lymphadenopathy, liver function test abnormalities and eosinophilia. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If signs and symptoms suggestive of these reactions appear, cenobamate should be withdrawn immediately and an alternative treatment considered (as appropriate).1
A dose-dependent shortening of the QTcF interval has been observed with ONTOZRY®. Reductions of the QTcF interval below 340 milliseconds were not observed. In clinical trials there was no evidence that the combination of cenobamate with other antiepileptic medicines led to further QT-shortening. Use caution when prescribing ONTOZRY® in combination with other medicinal products that are known to shorten the QT.1
Familial Short QT syndrome is a rare genetic syndrome, which is associated with an increased risk of sudden death and ventricular arrhythmias, particularly ventricular fibrillation. ONTOZRY® must not be used in patients with Familial Short-QT syndrome.1
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known, and the available data do not exclude the possibility of an increased risk for ONTOZRY®. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.1
Women of childbearing potential and contraception in males
and females
ONTOZRY® is not recommended in women of childbearing
potential not using contraception. Women of reproductive
potential concomitantly using oral contraceptives should
practice additional or alternative non-hormonal measures of
birth control during treatment with ONTOZRY® and
until 4 weeks after treatment discontinuation.1
Pregnancy
Risk related to epilepsy and antiepileptic medicinal
products in general
It has been shown that in the offspring of treated women with
epilepsy, the prevalence of malformations is two to three times
greater than the rate of approximately 3% in the general
population. In the treated population, an increase in
malformations has been noted with polytherapy; however, the
extent to which the treatment and/or the underlying condition is
responsible has not been elucidated. Discontinuation of
anti-epileptic treatments may result in exacerbation of the
disease which could be harmful to the mother and the foetus.1
Risk related to cenobamate
There are no adequate data from the use of ONTOZRY®
in pregnant women.
Animal studies have shown that cenobamate crosses the placenta
of rats. Studies in animals have shown reproductive toxicity at
levels below clinical exposure. ONTOZRY® should not
be used during pregnancy unless the clinical condition of the
woman requires treatment with cenobamate. Women of childbearing
potential must use effective contraception during use of
cenobamate and until 4 weeks after treatment
discontinuation.1
Breast-feeding
It is unknown whether cenobamate or its metabolites are excreted
in human milk.
Studies in rats showed excretion of cenobamate in the maternal
milk. A risk to the suckling child cannot be excluded. As a
precautionary measure, breast-feeding should be discontinued
during treatment with ONTOZRY®.1
Fertility
The effects of cenobamate on human fertility are unknown. Animal
data are insufficient due to exposure below clinical levels.1
ONTOZRY® contains lactose. Patients with rare hereditary problems such as galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.1
DRESS = drug reaction with eosinophilia and systematic symptoms
Reference:
1. ONTOZRY® Summary of product characteristics.
UK11421P | April 2022
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should be reported to Arvelle Therapeutics UK on 02034889643 or at UKIReporting@angelinipharma.com.
This site is published and funded by Arvelle Therapeutics UK which is solely responsible for its content. This site is intended exclusively for UK healthcare professionals.
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should be reported to Arvelle Therapeutics UK on 02034889643 or at UKIReporting@angelinipharma.com.
This site is published and funded by Arvelle Therapeutics UK which is solely responsible for its content. This site is intended exclusively for UK healthcare professionals.
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