Clobazam

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. Clobazam oral suspension is a benzodiazepine indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older ( 1 )

• For doses above 5 mg/day administer in two divided doses Patients ≤30 kg body weight: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily Patients greater than 30 kg body weight: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily Dosage adjustment needed in following groups: o Geriatric patients o Known CYP2C19 poor metabolizers o Mild or moderate hepatic impairment; no information for severe hepatic impairment Measure prescribed amount of oral suspension using provided adapter and dosing syringe Oral suspension: Can be taken with or without food 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 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. …

Oral Suspension: 2.5 mg/mL for oral administration. Each bottle contains 120 mL of an off-white suspension. Oral Suspension: 2.5 mg/mL in 120 mL bottles ( 3 )

• Safety and effectiveness in patients less than 2 years of age have not been established
• In a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose
• The effect on bone density, but not on behavior, was reversible when drug was discontinued. …

Clinical studies of clobazam oral suspension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, elderly subjects appear to eliminate clobazam more slowly than younger subjects based on population pharmacokinetic analysis. For these reasons, the initial dose in elderly patients should be 5 mg/day. Patients should be titrated initially to 10 to 20 mg/day. …

• Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use)
• Risks from Concomitant Use with Opioids Inform patients and caregivers that potentially fatal additive effects may occur if clobazam oral suspension is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider [see Warnings and Precautions , Drug Interactions ]. …

• 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 ]
• History of hypersensitivity to the drug or its ingredients

Alcohol: Increases blood levels of clobazam by about 50% ( 7.2 ) Drugs metabolized by CYP2D6: Lower doses of these drugs may be required when used concomitantly with clobazam oral suspension ( 7.3 ) Strong or Moderate CYP2C19 Inhibitors: Dosage adjustment of clobazam oral suspension may be necessary ( 7.4 ) 7.1 Opioids The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites, and opioids interact primarily at mu receptors. …

Somnolence or Sedation: Monitor for central nervous system (CNS) depression. Risk may be increased with concomitant use of other CNS depressants ( 5.4 , 5.5 ) Serious Dermatological Reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis): Discontinue clobazam oral suspension at first sign of rash unless the rash is clearly not drug-related ( 5.6 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: Discontinue if no alternative etiology ( 5.7 ) Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behaviors ( 5.8 ) Neonatal Sedation and Withdrawal Syndrome: Clobazam use during pregnancy can result in neonatal sedation an …

Clinically significant adverse reactions that appear in other sections of the labeling include the following: Risks from Concomitant Use with Opioids [see Warnings and Precautions ( 5.1 )] Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2)] Dependence and Withdrawal Reactions [see Warnings and Precautions ( 5.3 )] Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants [see Warnings and Precautions ( 5.4 )] Somnolence or Sedation [see Warnings and Precautions ( 5 .5 )] Serious Dermatological Reactions [see Contraindications ( 4 ), Warnings and Precautions ( 5.6 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensiti …

8.1 Pregnancy Pregnancy Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as clobazam, during pregnancy. Healthcare providers are encouraged to recommend that pregnant women taking clobazam enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/. …

Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. …

9.1 Controlled Substance Clobazam oral suspension contains clobazam, a Schedule IV controlled substance. 9.2 Abuse Clobazam oral suspension is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.