Harmonia MentisHarmonia Mentis

ONTOZRY®▼ (cenobamate) Dosing + Titration

  1. Home
  2. UK HCP
  3. Clinical Practicalities

  4. You are here: ONTOZRY®▼ (cenobamate) Dosing + Titration

Article

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events and product complaint should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard for the UK or www.hpra.ie for Ireland. Adverse events and product complaint should also be reported to Angelini Pharma on (UK) +44 2034889643, (IRE) +353 1 584 4671 or UKIReporting@angelinipharma.com

ⓘ Click here for Prescribing Information and Adverse Event Reporting

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 treatment with at least 2 anti-epileptic medicinal products.1

How is ONTOZRY® indicated and titrated?

Dosing and titration of ONTOZRY®

How should the drug be taken?

ONTOZRY® is taken orally ONCE DAILY, preferably at the same time each day.1

What is the starting dose?

The recommended starting dose of ONTOZRY® is 12.5 mg per day, titrated gradually to the recommended target dose of 200 mg per day.1

What are the benefits of a slow titration schedule?

The titration schedule shown below reduces the number and severity of treatment-emergent adverse events (TEAEs), including the rate of DRESS*, compared to a faster titration rate.2,3

What is the maximum dose?

Based on clinical response, the dose may be increased to a maximum of 400 mg per day.1

Recommended titration schedule for the adjunctive treatment of focal onset seizures in adult patients with epilepsy1

This schedule should not be exceeded because of the potential for serious adverse reactions1

Dose optimisation

Some patients who do not reach optimal seizure control may benefit from doses above 200 mg (increased by increments of 50 mg per day every 2 weeks) up to a maximum of 400 mg daily.1

Missed dose

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.1 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.1

Paediatric patients: ONTOZRY® is not indicated for children aged 0 months to 18 years.1

See the Summary of Product Characteristics for full prescribing information.1

Footnotes

*The interim results of a large safety study support the concept that initiating ONTOZRY® at a lower dose and slowing the initial titration rate may lower the rate of DRESS. No cases of DRESS were identified in 1339 patients initiating cenobamate using a start-low, go-slow approach of 12.5 mg/d and titrating every 2 weeks to a maximum of 400 mg/d.2

Oral once daily administration is convenient for patients and could increase adherence4

Cenobamate should typically be taken once daily as a single oral dose at any time¹

The tablet should be swallowed with a glass if water¹

It may be taken with or without food¹

It should preferably be taken at the same time each day¹

No dose adjustments are needed with many concomitant ASMs1

Reducing doses of concomitant ASMs, across a range of drugs with multiple mechanisms of action, led to fewer patients discontinuing ONTOZRY®.†5

See the Summary of Product Characteristics for full prescribing information.1

Footnotes

*Post hoc analysis of data from 240 adult patients enrolled in the ongoing safety study C021. 177 patients (73.8%) remained on ONTOZRY®. For the majority of concomitant ASMs, ongoing ONTOZRY® patients had greater decreases in mean concomitant ASM dose (first vs last dose) vs those who discontinued. Dose decreases were mostly due to adverse events, mainly during titration/early maintenance phases during ONTOZRY® dose escalation. Phenytoin, clobazam, and lacosamide were decreased early and resulted in better retention. Among ongoing ONTOZRY® patients, 98/395 (24.8%) concomitant baseline ASMs were discontinued completely, including carbamazepine in 31.3% of patients, oxcarbazepine in 26.7%, clobazam in 26.7%, lacosamide in 23.4%, eslicarbazepine in 23.1%, levetiracetam in 20.3%, and lamotrigine in 14.5%.5

Cenobamate and interactions with contraceptives and enzyme substrates1

See the Summary of Product Characteristics for full prescribing information.1

  1. Ontozry Summary of Product Characteristics. 
  2. Sperling MR, et al. Epilepsia. 2020 Jun;61(6):1099–1108.
  3. Steinhoff BJ, et al. Acta Neurol Scand. 2022 Sep;146(3):265–275.
  4. NICE Technology Appraisal Guidance [TA753]. Cenobomate for treating focal onset seizures in epilepsy. Published 15 December 2021. Available at: https://www.nice.org.uk/guidance/ta753/chapter/3-Committee-discussion (last accessed December 2022).
  5. Rosenfeld W, et al. Epilepsia. 2021 Dec;62(12):3016–3028.

UKxxxxP | July 2023

;