Clobazam

CLOBAZAM — clobazam suspension
NorthStar RxLLC

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions ( 5.1), Drug Interactions ( 7.1)].
• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required. • Follow patients for signs and symptoms of respiratory depression and sedation.

1 INDICATIONS AND USAGE

Clobazam oral suspension is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

A daily dose of clobazam oral suspension 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 mg to 20 mg in ≤30 kg weight group) has been shown to be effective, although effectiveness increases with increasing dose [see Clinical Studies (14)]. 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 Gradual Withdrawal

As with all antiepileptic drugs and benzodiazepines, withdraw clobazam oral suspension gradually. Taper by decreasing the total daily dose by 5 mg to 10 mg/day on a weekly basis until discontinued [see Warnings and Precautions (5.4)].

2.3 Important Administration Instructions

Instruct patients to read the “Instructions for Use” carefully for complete directions on how to properly dose and administer clobazam oral suspension.
Clobazam Oral Suspension Oral Administration
Clobazam oral suspension can be taken with or without food [see Clinical Pharmacology (12.3)]. Shake Clobazam 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 clobazam 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 clobazam oral suspension “Instructions for Use” for complete instruction on how to properly dose and administer the clobazam 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 [see Use in Specific Populations (8.5)].

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 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.5)].

2.6 Patients with Renal Impairment

No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with clobazam oral suspension 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 (8.7), Clinical Pharmacology (12.3)].

2.7 Dosage Adjustments in Patients with Hepatic Impairment

Clobazam oral suspension is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of clobazam oral suspension. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 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 clobazam oral suspension in patients with severe hepatic impairment. Therefore no dosing recommendation in those patients can be given [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Oral Suspension: 2.5 mg/mL for oral administration. Each bottle contains 120 mL of an off-white suspension.

4 CONTRAINDICATIONS

Clobazam oral suspension is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions [see Warnings and Precautions (5.5)].

5 WARNINGS AND PRECAUTIONS

5.1 Risks from Concomitant Use with Opioids

Concomitant use of benzodiazepines, including clobazam oral suspension, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe clobazam oral suspension concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when clobazam oral suspension is used with opioids [see Drug Interactions (7.1)].

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