Adults

For epilepsy: Initial 0.5 mg, three times daily. Gradually increase by 0.5-1 mg every 3 days until seizure control or side effects preclude further increase. Maximum daily dose: 20 mg. For panic disorder: Initial 0.25 mg, twice daily. After 3 days, may increase to 0.5 mg twice daily. Maximum daily dose: 4 mg.

Elderly

Lower initial doses (e.g., 0.25 mg once daily at bedtime) and slower titration are recommended due to increased sensitivity and slower metabolism. Monitor carefully for adverse effects.

Renal_impairment

No specific dosage adjustment is usually required for mild to moderate renal impairment, but caution is advised. For severe renal impairment, lower doses may be considered.

Onset

Oral: 20-60 minutes

Excretion

Excreted mainly in the urine as metabolites (50-70%), with a small amount in feces (10-30%). Less than 2% is excreted unchanged.

Half life

18-50 hours (average 30 hours)

Absorption

Rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are achieved within 1-4 hours.

Metabolism

Extensively metabolized in the liver, primarily via nitroreduction to 7-amino-clonazepam, followed by N-acetylation and hydroxylation.

Opioids

Increased risk of profound sedation, respiratory depression, coma, and death. Avoid concomitant use or use with extreme caution and reduced dosages of both.

CYP3A4 Inducers (e.g., Rifampicin)

May decrease clonazepam plasma levels, reducing its efficacy.

CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole)

May increase clonazepam plasma levels, potentially increasing side effects.

Antiepileptics (e.g., Phenytoin, Carbamazepine, Phenobarbital)

May alter plasma concentrations of both clonazepam and the co-administered antiepileptic drug, requiring dosage adjustments.

Alcohol and other CNS Depressants (e.g., barbiturates, antidepressants, antihistamines)

Potentiation of CNS depressant effects, leading to increased sedation, dizziness, and respiratory depression.