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ONFI® (clobazam) is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.
DOSAGE AND ADMINISTRATION
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 [see Clinical Studies]. 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
|≤ 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|
As with all antiepileptic drugs and benzodiazepines, withdraw ONFI gradually. Taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued [see WARNINGS AND PRECAUTIONS].
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 [see CLINICAL PHARMACOLOGY].
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.
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 [see Use In Specific Populations].
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 [see Use In Specific Populations, CLINICAL PHARMACOLOGY].
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 [see Use in Specific Populations, CLINICAL PHARMACOLOGY].
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 [see Use in Specific Populations, CLINICAL PHARMACOLOGY].
Dosage Forms And Strengths
Tablets: 10 mg and 20 mg with a functional score for oral administration.
Each ONFI tablet is a white to off-white, oval tablet with a functional score on one side and either a “1” and “0” or a “2” and “0” debossed on the other side.
Oral Suspension: 2.5 mg/mL for oral administration. Each bottle contains 120 mL of an off-white suspension.
Storage And Handling
Each ONFI tablet contains 10 mg or 20 mg of clobazam and is a white to offwhite, oval tablet with a functional score on one side and either a “1” and “0” or a “2” and “0” debossed on the other side.
NDC 67386-311-01: 10 mg scored tablet, Bottles of 100
NDC 67386-312-01: 20 mg scored tablet, Bottles of 100
ONFI oral suspension is a berry flavored off-white liquid supplied in a bottle with child-resistant closure. The oral suspension is packaged with a dispenser set which contains two calibrated oral dosing syringes and bottle adapter. Store the oral suspension in an upright position. Use within 90 days of first opening the bottle, then discard any remainder.
NDC 67386-313-21: Bottle containing 120 mL of suspension
Store tablets and oral suspension at 20°C to 25°C (68°F to 77°F). See USP controlled room temperature.
Tablets manufactured by: Catalent Pharma Solutions, LLC Winchester, KY 40391, U.S.A. Oral suspension manufactured by: Rosemont Pharmaceuticals, Ltd. Leeds, West Yorkshire LS11 9XE, U.K. Marketed by: Lundbeck, Deerfield, IL 60015, U.S.A. Revised: 11/2013
Last reviewed on RxList: 12/4/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Onfi Information
Report Problems to the Food and Drug Administration
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