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ONTOZRY® is generally well tolerated1

  • The most commonly reported adverse reactions were somnolence, dizziness, fatigue and headache1

Adverse reactions reported in clinical studies, listed per system organ class and then per frequency (ranked in decreasing order of severity): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000).1

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

Special warnings and precautions for use

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

Learn about the ONTOZRY® dosing and titration schedule

Read More

DRESS = drug reaction with eosinophilia and systematic symptoms

Reference:

1. ONTOZRY® Summary of product characteristics.

UK11421P | April 2022

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