SYMPAZAN Dosage & Rx Info | Uses, Side Effects

Sympazan Generic Name & Formulations

Legal Class

CIV

General Description

Clobazam 5mg, 10mg, 20mg; oral films; raspberry-type flavor.

Pharmacological Class

Benzodiazepine.

How Supplied

Oral films—60

Manufacturer

Aquestive Therapeutics

Generic Availability

Mechanism of Action

The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA_A receptor.

Sympazan Indications

Indications

Adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome.

Sympazan Dosage and Administration

Adults and Children

<2yrs: not established. Allow each film to dissolve completely before administering the next film; do not give with liquids. Individualize. ≥2yrs: Give in divided doses twice daily (except for 5mg dose). ≤30kg: initially 5mg, then increase to 10mg on Day 7, then increase to 20mg on Day 14. >30kg: initially 10mg, then increase to 20mg on Day 7, then increase to 40mg on Day 14. Do not increase dose sooner than weekly. Elderly, CYP2C19 poor metabolizers, mild to moderate hepatic impairment (Child-Pugh score 5–9): initially 5mg/day; titrate according to weight (as shown above) but to half the dose, an additional titration to max dose (20mg/day or 40mg/day, depending on weight) may be started at Day 21.

Sympazan Contraindications

Not Applicable

Sympazan Boxed Warnings

Boxed Warning

Risks from concomitant use with opioids. Abuse, misuse, and addiction. Dependence and withdrawal reactions.

Sympazan Warnings/Precautions

Warnings/Precautions

Increased risk of drug-related mortality from concomitant use with opioids. Monitor for somnolence or sedation. Monitor for signs/symptoms of serious skin reactions (eg, SJS, TEN), esp. during the first 8 weeks of initiation or when re-introducing therapy; discontinue at the first sign of rash unless it's not drug-related. Evaluate immediately if signs or symptoms of drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity develop; discontinue if alternative etiology cannot be established. Monitor for the emergence or worsening of depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior. Assess patient's risk for abuse, misuse, addiction prior to and during therapy. Avoid abrupt cessation; taper by decreasing total daily dose by 5–10mg/day on a weekly basis. Drug or alcohol abusers. Severe renal or hepatic impairment or ESRD. Elderly. Neonatal sedation and withdrawal syndrome; monitor neonates exposed during pregnancy or labor. Pregnancy (esp. late stage). Nursing mothers: monitor infants.

Sympazan Pharmacokinetics

Absorption

After single-dose administration, the time to peak concentrations (T_max) of clobazam oral film under fasted conditions ranged from 0.33 to 4.0 hours.

Distribution

The volume of distribution at steady state was ~100 L. The in vitro plasma protein binding of clobazam and N-desmethylclobazam is ~80-90% and 70%, respectively.

Metabolism

Hepatic (CYP3A4, CYP2C19, CYP2B6).

Elimination

Renal (82%), fecal (11%).

Sympazan Interactions

Interactions

Increased risk of profound sedation, respiratory depression, coma, and death with opioids; reserve concomitant use in those for whom alternative options are inadequate; limit dosages/durations to minimum required; monitor. May increase risk of sedation/somnolence with concomitant other CNS depressants, alcohol. May diminish effect of hormonal contraceptives (use non-hormonal forms). May need to adjust dose of drugs metabolized by CYP2D6. May be potentiated by CYP2C19 inhibitors (eg, fluconazole, fluvoxamine, ticlopidine, omeprazole); may need dose adjustment. Concomitant cannabidiol may increase risk of clobazam-related reactions; consider dose reduction of either drug if occur.

Sympazan Adverse Reactions

Adverse Reactions

Constipation, somnolence, sedation, pyrexia, lethargy, drooling; withdrawal reactions.

Sympazan Clinical Trials

See Literature

Sympazan Note

Notes

To register pregnant patients in the North American Antiepileptic Drug (NAAED) Pregnancy Registry, call (888) 233-2334.

Sympazan Patient Counseling