鎮靜安眠、癲癇治療 Panic disorder: Treatment of panic disorder, with or without agoraphobia Seizure disorders: Treatment of the Lennox-Gastaut syndrome, akinetic, and myoclonic seizures; absence seizures unresponsive to succinimides
藥理
Antiseizure Agent; Benzodiazepine The exact mechanism is unknown, but believed to be related to its ability to enhance the activity of GABA; suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in the motor cortex.
藥動學
Absorption: 1. Rapidly and completely absorbed. 2. Onset of action: ~20 to 40 minutes. 3. Duration: (Infants and young children) 6 to 8 hours; (Adults) ≤12 hours 4. Bioavailability: ~90% 5. Time to peak, serum: 1 to 4 hours Distribution: 1. Vd: (Children) 1.5 to 3 L/kg; (Adults) 1.5 to 6.4 L/kg 2. Protein binding: ~85% Metabolism: 1. Extensively hepatic via glucuronide and sulfate conjugation; undergoes nitroreduction to 7-aminoclonazepam, followed by acetylation to 7-acetamidoclonazepam; nitroreduction and acetylation are via CYP3A4; metabolites undergo glucuronide and sulfate conjugation 2. Half-life elimination: (Neonates) 22 to 81 hours; (Children) 22 to 33 hours; (Adults) 17 to 60 hours Excretion: Urine (<2% as unchanged drug); metabolites excreted as glucuronide or sulfate conjugates
禁忌症
1. Hypersensitivity to benzodiazepines 2. Patients with significant liver disease 3. Patients with acute narrow angle glaucoma
懷孕分類
D
哺乳分類
1. According to the manufacturer, the decision to breastfeed during therapy should consider the risk and benefits. 2. If chronic use of a benzodiazepine is needed in breastfeeding females, use of shorter acting agents is preferred.
Anxiety disorder: 1. Initial: 0.25 to 1 mg/day in 1 to 2 divided doses; may be given as needed or scheduled 2. Adjustment: May increase daily dose in increments of 0.25 to 0.5 mg every few days (eg, ≥3 days); usual target range: 1 to 3 mg/day in 1 to 4 divided doses; maximum: 4 mg/day 3. Administration: To minimize daytime motor impairment and drowsiness, may be taken as a single dose at bedtime Seizure disorders: 1. Monotherapy: Initial 0.5 to 1.5 mg/day in 1 to 3 divided doses 2. Adjunctive therapy: Initial 0.5 to 1 mg/day in 1 to 3 divided doses 3. Dosage adjustment: May increase dose based on response and tolerability in increments of 0.5 to 1 mg every 3 to 7 days to usual maintenance dose of 2 to 8 mg/day in 1 to 2 divided doses; maximum dose: 20 mg/day
小兒調整劑量
Anxiety disorder: (for Adolescents ≥18 years) 1. Initial: 0.25 mg twice dailiy; increase in increments of 0.125 to 0.25 mg twice daily every 3 days; target 1 mg/day in divided doses; maximum 4 mg/day 2. To discontinue, treatment should be withdrawn gradually; decrease dose by 0.125 mg twice daily every 3 days until medication is completely withdrawn. Seizure disorders: (In Infants and Children <10 years or ≤30 kg) 1. Initial: 0.01 to 0.03 mg/kg/day in 2 to 3 divided doses; maximum 0.05 mg/kg/day; increase by ≤0.25 to 0.5 mg every third day until seizures are controlled or adverse effects observed 2. Maintenance: 0.1 to 0.2 mg/kg/day in 3 divided doses; maximum 0.2 mg/kg/day Seizure disorders: (In Children ≥10 years or >30 kg and Adolescents) 1. Initial: 0.01 to 0.05 mg/kg/day in 2 or 3 divided doses; maximum 0.5 mg/dose 3 times daily; may increase dose by 25% or by 0.5 to 1 mg every 3 to 7 days until seizures are controlled or adverse effects observed 2. Maintenance: 0.05 to 0.2 mg/kg/day in 2 to 3 divided doses; maximum 20 mg/day
腎功能調整劑量
1. Altered kidney function: Initial: No dosage adjustment necessary for any degree of kidney impairment 2. Hemodialysis, Peritoneal dialysis: Unlikely to be substantially dialyzed (highly protein bound, large Vd); Titrate based on tolerability and response 3. CRRT, PIRRT: No dosage adjustment necessary; Titrate based on tolerability and response
肝功能調整劑量
1. There are no dosage adjustments provided in the manufacturer's labeling; use with caution. 2. Contraindicated in patients with significant hepatic impairment.