Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Angelini Pharma S.p.A, Viale Amelia 70, 00181, Rome – Italy
Ontozry is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least 2 anti-epileptic medicinal products.
The recommended starting dose of cenobamate is 12.5 mg per day, titrated gradually to the recommended target dose of 200 mg per day. Based on clinical response, dose may be increased to a maximum of 400 mg per day.
The recommended titration schedule is provided in table 1, which should not be exceeded because of the potential for serious adverse reactions (see section 4.8).
Table 1. Recommended dosage in adults with focal-onset seizures in epilepsy:
| Treatment phase | Dose (per day, oral) | Duration |
|---|---|---|
| Treatment initiation | 12,5 mg | Weeks 1 and 2 |
| 25 mg | Weeks 3 and 4 | |
| Titration | 50 mg | Weeks 5 and 6 |
| 100 mg | Weeks 7 and 8 | |
| 150 mg | Weeks 9 and 10 | |
| Target dose | 200 mg | Weeks 11 and 12 and onwards |
| Dose optimisation δόσης | Some patients, who do not reach optimal seizure control, may benefit from doses above 200 mg (increased by increments of 50 mg/day every two weeks) up to a maximum of 400 mg daily. | |
If patients miss one dose, it is recommended that they take a single dose as soon as they remember, unless it is less than 12 hours until their next regularly scheduled dose.
It is recommended that discontinuation be undertaken gradually to minimise the potential for rebound seizures (i.e. over at least 2 weeks), unless safety concerns require abrupt withdrawal.
Clinical studies of cenobamate did not include sufficient numbers of subjects aged 65 and over, to determine whether they responded differently from younger patients. It has been reported that elderly subjects on antiepileptic medicinal products have higher incidence of adverse reactions such as fatigue, gait disturbance, fall, ataxia, balance disorder, dizziness and somnolence. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function and of concomitant disease as well as the potential interactions in polymedicated patients (see section 4.4).
Cenobamate should be used with caution and reduction of the target dose may be considered in patients with mild to moderate (creatinine clearance 30 to <90 ml/min) or severe (creatinine clearance <30 ml/min) renal impairment. The maximum recommended dose for patients with mild, moderate, or severe renal impairment is 300 mg/day. Cenobamate should not be used in patients with end-stage renal disease or patients undergoing haemodialysis.
Exposure to cenobamate was increased in patients with chronic hepatic disease. A change in the starting dose is not required; however, a decrease in target doses of up to 50% may need to be considered. The maximum recommended dose in patients with mild and moderate hepatic impairment is 200 mg/day. Cenobamate should not be used in patients with severe hepatic impairment.
The safety and efficacy of Ontozry in children aged 0 months to 18 years have not yet been established. No data are available.
Oral use.
Cenobamate should typically be taken once daily as single oral dose at any time. However, it should preferably be taken at the same time each day. It may be taken with or without food (see section 5.2). The tablet should be swallowed with a glass of water. The tablets cannot be split accurately as there is no break line and the accuracy of the dose cannot be ensured.
Symptoms of overdose are expected to be consistent with the known adverse reactions of Ontozry and include somnolence, fatigue, dizziness. There is no available specific antidote to the effects of cenobamate. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient.
12.5 mg tablets; 25 mg film-coated tablets; 50 mg film-coated tablets; 100 mg film-coated tablets:
4 years.
150 mg film-coated tablets; 200 mg film-coated tablets:
3 years.
This medicinal product does not require any special storage conditions.
PVC/aluminium blisters.
Ontozry Treatment Initiation pack 12.5 mg tablets and 25 mg film-coated tablets:
Pack of 14 tablets of 12.5 mg and 14 film-coated tablets of 25 mg.
Ontozry 50 mg film-coated tablets:
50 mg – packs of 14, 28 or 84.
Ontozry 100 mg film-coated tablets:
100 mg – packs of 14, 28 or 84.
Ontozry 150 mg film-coated tablets:
150 mg – packs of 14, 28 or 84.
Ontozry 200 mg film-coated tablets:
200 mg – packs of 14, 28 or 84.
Not all pack sizes may be marketed.
Cenobamate is very persistent (vP) in aquatic systems. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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