Cenobamate (XCOPRI) visual mnemonics

Excerpt from Cafer's Mood Stabilizers and Antiepileptics, available on Amazon

Cenobamate (XCOPRI)

“Cinnabon Ex-couple”
Pronunciation: sen oh BAM ate / EX cop ree

❖ Antiepileptic ❖ GABAA modulator ❖ DEA Schedule V

FDA approved for:   ❖ Partial-onset seizures (adults)

Cenobamate (Xcopri) is the newest antiepileptic drug (AED), released in 2020. There are some serious risks, side effects and kinetic drug/drug interactions. 

Dosing is similar to lamotrigine (Lamictal), with a slow titration to a recommended dose of 200 mg over 11 weeks. As with lamotrigine, maximum dose is 400 mg. The slow titration is necessary to avoid Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity. There were no cases of DRESS among over 1,000 patients with adherence to the slow titration schedule.

Cenobamate shortens QT interval and is contraindicated with Familial Short QT Syndrome. QTc interval under 300 is dangerous. 

Dose-dependent side effects are common (36% at 200 mg; 57% at 400 mg) including somnolence/fatigue, dizziness, diplopia/blurred vision, cognitive impairment, and headaches. Dropout rates were 11%, 9%, and 21% respectively for patients randomized to receive Cenobamate 100 mg/day, 200 mg/day, and 400 mg/day (versus 4% for placebo).

Cenobamate is a Schedule V (five) controlled substance (least restrictive) because euphoric feelings are possible at high doses. The risk of psychiatric adverse effects appears to be about 1 in 333. All antiepileptics have a risk of suicidal ideation. In the clinical trial there were 4 suicides among over 25,000 patients, versus none for 16,000 patients on placebo. Causation was not established. A withdrawal syndrome was observed with sudden discontinuation, including tremor, mood disturbance, and insomnia. 

At 400 mg (maximum dose), liver enzymes were elevated with ALT greater than 3x upper limit of normal in almost 3% of patients. Cenobamate may also elevate serum potassium. 

Dosing: The initial dose is 12.5 mg QD, to be titrated over 11 weeks to the recommended maintenance dose of 200 mg QD; May take with or without food, at any (consistent) time of day; The recommended titration schedule should not be exceeded; Maximum dose is 400 mg QD (200 if mild/moderate hepatic impairment); To discontinue, taper over at least 2 weeks. 

Dynamic interactions:  ❖ Sedation/CNS depression  ❖ QT shortening  ❖ Hypokalemia  ❖ Liver enzyme elevation

Kinetic interactions: ❖ 2C19 inHibitor ⁃ Increases levels of phenytoin (Dilantin) by 75%, requiring dose adjustment ⁃ Increases levels of phenobarbital (Luminal) and active metabolite of clobazam (Onfi) ❖ 3A4 inDucer ⁃ Decreases levels of hormonal contraceptives and carbamazepine (Tegretol) ❖ UGT inDucer ⁃ Decreases levels of lamotrigine (Lamictal)

Compare pharmacy prices for Xcopri Titration pack of 12.5mg/25mg package (1 qty) Costco 97.18 Medicine Shoppe 100.31 Rite Aid 102.10 See prices near you: Compare prices for Xcopri & other drugs at GoodRx

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