Clobazamdosage

For doses above 5 mg/day administer in two divided doses Patients ≤30 kg body weight: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily Patients >30 kg body weight: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily Dosage adjustment needed in following groups: Geriatric patients Known CYP2C19 poor metabolizers Mild or moderate hepatic impairment; no information for severe hepatic impairment Tablets: Administer whole, broken in half along the score, or crush and mix in applesauce Measure prescribed amount of oral suspension using provided adapter and dosing syringe Tablets and Oral suspension: Can be taken with or without food 2.1 Dosing Information A daily dose of ONFI greater than 5 mg should be administered in divided doses twice daily; a 5 mg daily dose can be administered as a single dose. Dose patients according to body weight. Individualize dosing within each body weight group, based on clinical efficacy and tolerability. Each dose in Table 1 (e.g., 5 to 20 mg in ≤30 kg weight group) has been shown to be effective, although effectiveness increases with increasing dose. Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state. Table 1. Recommended Total Daily Dosing by Weight Group ≤30 kg Body Weight >30 kg Body Weight Starting Dose 5 mg 10 mg Starting Day 7 10 mg 20 mg Starting Day 14 20 mg 40 mg

2.2 Discontinuation or

Dosage Reduction of ONFI To reduce the risk of withdrawal reactions, increased seizure frequency, and status epilepticus, use a gradual taper to discontinue ONFI or reduce the dosage. Taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly.

2.3 Important

Administration Instructions Instruct patients to read the "Instructions for Use" carefully for complete directions on how to properly dose and administer ONFI oral suspension. ONFI Tablet Oral Administration ONFI tablets can be taken with or without food. ONFI tablets can be administered whole, broken in half along the score, or crushed and mixed in applesauce. ONFI Oral Suspension Oral Administration ONFI oral suspension can be taken with or without food. Shake ONFI Oral Suspension well before every administration. When administering the oral suspension, use only the oral dosing syringe provided with the product. Each carton includes two syringes, but only one syringe should be used for dosing. The second oral syringe is reserved as a replacement in case the first syringe is damaged or lost. Insert the provided adapter firmly into the neck of the bottle before first use and keep the adapter in place for the duration of the usage of the bottle. To withdraw the dose, insert the dosing syringe into the adapter and invert the bottle then slowly pull back the plunger to prescribed dose. After removing the syringe from the bottle adapter, slowly squirt ONFI Oral Suspension into the corner of the patient's mouth. Replace the cap after each use. The cap fits over the adapter when the adapter is properly placed. See ONFI Oral Suspension "Instructions for Use" for complete instruction on how to properly dose and administer the ONFI Oral Suspension.

2.4 Dosage Adjustments in

Geriatric Patients Plasma concentrations at any given dose are generally higher in the elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients. Then titrate elderly patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21.

2.5 Dosage Adjustments in CYP2C19

Poor Metabolizers In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21.

2.6 Patients with

Renal Impairment No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with ONFI in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if clobazam or its active metabolite, N-desmethylclobazam, is dialyzable.

2.7 Dosage Adjustments in

Patients with Hepatic Impairment ONFI is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of ONFI. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), the starting dose should be 5 mg/day in both weight groups. Then titrate patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, start an additional titration on day 21 to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group). There is inadequate information about metabolism of ONFI in patients with severe hepatic impairment. Therefore no dosing recommendation in those patients can be given.