Sympazan Dosage

2.1 Dosing Information

A daily dose of SYMPAZANTM 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 or less 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.

2.2 Gradual Withdrawal

Avoid abrupt withdrawal from SYMPAZANTM in order to minimize the risk of increased seizure frequency, status epilepticus, and other adverse reactions [see Warnings and Precautions (5.4)]. Taper by decreasing the total daily dosage by 5-10 mg/day on a weekly basis until discontinued.

2.3 Important Administration Instructions

Instruct patients and/or caregivers to read the “Instruction for Use” carefully for complete directions on how to properly dose and administer SYMPAZANTM oral films.

Apply SYMPAZANTM on top of the tongue where it adheres and dissolves.

SYMPAZANTM oral film can be taken with or without food [see Clinical Pharmacology (12.3)]. Do not administer with liquids. As the film dissolves, saliva should be swallowed in a normal manner, but the patient should refrain from chewing, spitting or talking.

Only one oral film should be taken at a time; if a second film is needed to complete the dosage, it should not be taken until the first film has completely dissolved.

2.4 Dosage Adjustments in Geriatric Patients

Plasma concentrations at any given dose are generally higher in geriatric patients [see Clinical Pharmacology (12.3)]. Therefore, the starting dosage should generally be 5 mg/day for all geriatric patients. Then proceed slowly with dose escalation; titrate according to weight, but to half the dosage presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dosage (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 [see Clinical Pharmacology (12.4)]. Therefore, the starting dosage should be 5 mg/day in patients known to be CYP2C19 poor metabolizers. Then proceed slowly with dose escalation; titrate according to weight, but to half the dosage presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dosage (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 [see Use in Specific Populations (8.6)].

2.6 Dosage Adjustments in Patients with Hepatic Impairment

SYMPAZANTM is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of SYMPAZANTM. For patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), the starting dosage should be 5 mg/day (regardless of weight). Then proceed slowly with dosing escalations; titrate patients according to weight, but to half the dosage presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dosage (20 mg/day or 40 mg/day, depending on weight) may be started on day 21. There is inadequate information about metabolism of clobazam in patients with severe hepatic impairment. Therefore, no dosing recommendation can be given for those patients [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].