Generic Name

Clonazepam

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Classification

FDA Approved Indications

• Seizure disorders (absence seizures, myoclonic seizures, Lennox-Gastaut syndrome)
• Epilepsy
• Panic disorder with or without agoraphobia

Mechanism of Action

Enhances the effect of gamma-aminobutyric acid (GABA) at GABA-A receptor sites, leading to sedative, anticonvulsant, and muscle-relaxant effects.

Dosage and Administration

Adult: Typically 0.25 mg twice daily, titrated up as needed and tolerated; maximum dose varies based on condition.

Pediatric: Dosing varies by age and condition; usually starting at 0.01-0.03 mg/kg/day in divided doses.

Geriatric: Start low, e.g., 0.25 mg at bedtime, titrate cautiously due to increased sensitivity.

Renal Impairment: Use with caution, dose adjustments may be necessary.

Hepatic Impairment: Use with caution; dose adjustment may be needed.

Pharmacokinetics

Absorption: Well absorbed with oral administration.

Distribution: Widely distributed, crosses the blood-brain barrier.

Metabolism: Primarily hepatic via CYP3A4 to inactive metabolites.

Excretion: Renal excretion of metabolites.

Half Life: 18-50 hours, duration varies depending on individual metabolism.

Contraindications

• Hypersensitivity to benzodiazepines.
• Acute narrow-angle glaucoma.

Precautions

• History of substance abuse, depression, or suicidal ideation; use cautiously in older adults.
• Pregnancy Category D; risks in pregnancy, especially for congenital malformations, should be considered.

Adverse Reactions - Common

• Drowsiness (Very common)
• Dizziness (Common)
• Fatigue (Common)
• Ataxia (Uncommon)

Adverse Reactions - Serious

• Respiratory depression (Rare)
• Dependence and withdrawal syndrome (Varies with duration and dose)
• Paradoxical reactions (agitation, aggression) (Rare)

Drug-Drug Interactions

• CNS depressants (opioids, alcohol, other benzodiazepines) — may enhance sedation and respiratory depression.
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) — may increase clonazepam levels.
• CYP3A4 inducers (e.g., carbamazepine) — may decrease effectiveness.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Do not operate heavy machinery or drive until effect is known.
• Avoid alcohol and other CNS depressants.
• Take medication exactly as prescribed; do not discontinue abruptly.
• Report worsening depression or suicidal thoughts.

Special Considerations

Black Box Warnings:

• Potential for abuse, misuse, and dependence.
• Risks in pregnancy, including congenital malformations.

Genetic Factors: Metabolism varies with CYP3A4 activity, which can be affected by genetic polymorphisms.

Lab Test Interference: May alter liver function tests or CBC.

Overdose Management

Signs/Symptoms: Excess sedation, respiratory depression, coma.

Treatment: Supportive care, airway management, activated charcoal if ingestion was recent, and flumazenil (benzodiazepine antagonist) under careful monitoring.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable within the expiration date on the package.