ONFI ORAL SUSPENSION Dosage & Rx Info

Onfi Oral Suspension Generic Name & Formulations

Legal Class

CIV

General Description

Clobazam 2.5mg/mL; berry flavor.

Pharmacological Class

Benzodiazepine.

How Supplied

Tabs—100; Susp—120mL (w. 2 dosing syringes)

Manufacturer

Lundbeck Inc.

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.

Onfi Oral Suspension Indications

Indications

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS).

Onfi Oral Suspension Dosage and Administration

Adults and Children

<2yrs: not established. Tabs may be swallowed whole, scored, or crushed and mixed in applesauce. ≥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. 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.

Onfi Oral Suspension Contraindications

Not Applicable

Onfi Oral Suspension Boxed Warnings

Boxed Warning

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

Onfi Oral Suspension Warnings/Precautions

Warnings/Precautions

Increased risk of drug-related mortality from concomitant use with opioids. Monitor for the emergence or worsening of depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior. 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. 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.

Onfi Oral Suspension Pharmacokinetics

Absorption

Relative bioavailability of clobazam tablets vs oral solution is approximately 100%. Time to peak concentration: ranged from 0.5 to 4 hours (clobazam tablets); ranged from 0.5 to 2 hours (oral susp).

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%).

Onfi Oral Suspension 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 be potentiated by CYP2C19 inhibitors (eg, fluconazole, fluvoxamine, ticlopidine, omeprazole). May diminish effect of hormonal contraceptives (use non-hormonal forms). May need to adjust dose of drugs metabolized by CYP2D6.

Onfi Oral Suspension Adverse Reactions

Adverse Reactions

Somnolence, sedation, drooling, constipation, pyrexia, lethargy, cough, UTI, aggression, insomnia, dysarthria, fatigue; hypersensitivity, withdrawal reactions.

Onfi Oral Suspension Clinical Trials

See Literature

Onfi Oral Suspension Note