Clobazam

Indications

Clobazam is used for: Anxiety, tension, irritability, restlessness, epilepsy.

Adult Dose

Seizures Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years or older >30 kg: Initiate at 5 mg PO q12hr; may titrate as tolerated up to 40 mg/day divided q12hr Dose escalation should not proceed more rapidly than once weekly Hepatic impairment Limited data to characterize the effect of hepatic impairment on the pharmacokinetics; proceed with low and slow titration Mild-to-moderate (Child-Pugh 5-9): Starting dose should be 5 mg/day and titrated according to weight, but to half the typical adult dose; additional titration to the maximum dose (20 mg/day or 40 mg/day), depending on the weight group may be started on day 21 Severe hepatic impairment: Not recommended

Child Dose

Seizures Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years or older <30 kg Starting dose: 5 mg PO qDay; titrate as tolerated up to 20 mg PO daily After 7 days, may increase to 5 mg PO q12hr; if needed, may increase to 10 mg PO q12hr after an additional 7 days >30 kg Starting dose: 5 mg PO q12hr; titrate as tolerated up to 40 mg PO daily After 7 days, may increase to 10 mg PO q12hr; if needed, may increase to 20 mg PO q12hr after an additional 7 days

Renal Dose

Renal impairment Mild or moderate renal impairment: No dose adjustment required Severe renal impairment or ESRD: No experience

Administration

May be taken with or without food. Individualize weight-based dose according to clinical efficacy and tolerability Doses above 5 mg/day should be administered in divided doses twice daily (5 mg dose can be administered as a single daily dose) May be administered whole, or crushed and mixed in applesauce When discontinuing, withdraw gradually; taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued

Contra Indications

Hypersensitivity; history of drug dependence; myasthaenia gravis; pregnancy (1st trimester), lactation; serious liver damage; sleep apnoea syndrome; impaired respiratory function.

Precautions

May impair ability to perform skilled tasks and hazardous activities; elderly; renal or hepatic impairment; alcoholics; obesity; withdrawal should be gradual. Lactation: Excreted in breast milk; effects of exposure on infants unknown

Pregnancy-Lactation

Interactions

Increased hepatic clearance of clobazam when administered with phenytoin, phenobarbital or carbamazepine. Cimetidine may increase levels of clobazam. Potentially Fatal: Concurrent alcohol, hypnotics and sedative antidepressants can potentiate CNS side effects of clobazam

Adverse Effects

Side effects of Clobazam : >10% Somnolence or sedation (26%),Somnolence (22%),Pyrexia (13%),Upper respiratory tract infection (12%) 1-10% Drooling (9%),Aggression (8%),Irritability (7%),Vomiting (7%),Insomnia (5%),Ataxia (5%),Sedation (5%),Constipation (5%),Fatigue (5%),Cough (5%),Psychomotor hyperactivity (4%),Pneumonia (4%),Urinary tract infection (4%),Dysarthria (3%),Decreased appetite (3%),Increased appetite (3%),Bronchitis (2%),Dysphagia (2%) Potentially Fatal: Respiratory depression.

Mechanism of Action

Clobazam binds to one or more specific GABA receptors at several sites within the CNS including the limbic system and reticular formation. Increased permeability of neuronal membrane to chloride ions results in GABA's inhibitory effect leading to hyperpolarisation and stabilisation.