Clozapine

Class

    • Tricylic dibenzodiazepine atypical antipsychotic

Indications

Administration/Absorption

    • Oral

Dosage

Distribution

    • 97% protein bound

Mechanism

    • Selective monoaminergic antagonist with high affinity for:

      • serotonin Type 2 (5HT2)

      • dopamine Type 2 (D2)

    • Clozapine acts as an antagonist at other receptors, but with lower potency, explaining side effects

      • Antagonism of histamine H1 receptors may explain somnolence

      • Antagonism of adrenergic a1 receptors may explain orthostatic hypotension

    • Antipsychotic action is likely mediated through a combination of antogistic effects at:

      • D2 receptors in the mesolimbic pathway

        • Relieves positive symptoms

      • 5-HT2A receptors in the frontal cortex

        • Alleviates negative symptoms.

Excretion

    • Half-life 8 hours (range 4-12 hours)

    • Approximately 50% of the administered dose is excreted in the urine and 30% in the feces

Side effects

      • other adverse cardiovascular and respiratory effects

      • increased mortality in elderly patients with dementia-related psychosis

      • weight gain

      • GI hypomotility

      • sialorrhoea

Interactions

    • Fluvoxamine inhibits the metabolism of clozapine leading to significantly increased blood levels of clozapine

    • Alcohol

    • Caffeine

Contraindications