Clozapine

Clozapine is a prescription medicine used in the treatment of schizophrenia (a mental disorder that can result in hallucinations or delusions and also adversely affects a person's ability to think and behave). Clozapine may be taken with or without food. However, it is advised to take it at the same time each day as this helps to maintain a consistent level of medicine in the body. Take this medicine in the dose and duration as advised by your doctor and if you have missed a dose, take it as soon as you remember. Do not skip any doses and finish the full course of treatment even if you feel better. It is important that this medication is not stopped suddenly without talking to your doctor as it may worsen your symptoms.

Clozapine is an atypical antipsychotics. It works by modulating the action of certain chemical messengers in the brain that affects thoughts.

• Schizophrenia (in patients unresponsive to or intolerant of conventional antipsychotic drugs)
• Psychosis in Parkinson's disease

Clozapine is classified as an 'atypical' antipsychotic drug because of its profile of binding to dopamine receptors and its effects on various dopamine-mediated behaviors differ from those exhibited by other typical antipsychotic drug products. In particular, although Clozapine does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor. This evidence, consistent with the view that Clozapine is preferentially more active at limbic than at striatal dopamine receptors. This may explain the relative freedom of Clozapine from extrapyramidal side effects. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.

Clozapine has relatively weak dopamine receptor-blocking activity at D1, D2, D3 and D5 receptors but has high affinity for the D4 receptor. It has also blocking effects on serotonin, α-adrenergic, histamine H1 and cholinergic receptors.

Adult Dose (Schizophrenia - Oral): Initial: 12.5 mg once or twice daily; Day 2: 25-50 mg; increase by 25-50 mg daily (if well tolerated) to 300-450 mg/day by 2 weeks; may increase to 600-900 mg/day if needed. Maintenance: Continue effective dose.

Adult Dose (Psychosis in Parkinson's disease): Initial: 12.5 mg at night; increase by 12.5 mg up to twice weekly based on response; usual dose: 25-37.5 mg at night; max: 100 mg/day in 1-2 divided doses.

Elderly: Lower initial dose of 12.5-25 mg/day; titrate more slowly.

Renal Dose: Severe renal impairment: Contraindicated (CrCl <10 mL/min).

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Clozapine may be taken with or without food, but it is better to take it at a fixed time.

If you miss a dose of Clozapine, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Common Side Effects:

• Increased sweating
• Visual impairment
• Decreased blood pressure
• Constipation
• Dizziness or lightheadedness
• Drowsiness
• Headache
• Increased watering of mouth
• Nausea or vomiting
• Unusual weight gain

Serious Side Effects: Agranulocytosis (life-threatening), myocarditis, seizures, neuroleptic malignant syndrome, hyperglycemia, orthostatic hypotension.

• [UNSAFE] Clozapine may cause side effects which could affect your ability to drive. You may feel tired, drowsy, dizzy or faint, especially during early treatment.
• Do not stop abruptly (taper over 1-2 weeks).
• WBC monitoring: Weekly for first 6 months, then every other week.
• Inform your doctor immediately if you notice signs of infection (fever, sore throat, rash).
• May cause dizziness and sleepiness; avoid driving or activities requiring concentration.
• Monitor weight, blood sugar and cholesterol.
• Caution during pregnancy and contraindicated during lactation.

• History of bone marrow disorders (including agranulocytosis)
• Circulatory collapse
• Alcoholic or toxic psychosis
• Drug intoxication
• Uncontrolled epilepsy
• Severe renal, hepatic or cardiac disease
• Paralytic ileus
• Pregnancy and lactation

Increased risk/severity of bone marrow suppression with bone marrow suppressants. Concomitant use with benzodiazepines may increase risk of circulatory collapse. Additive CNS depression with MAOIs and CNS depressants. May potentiate effects of anticholinergics or antihypertensives. Increased plasma concentration of highly protein bound substances (warfarin, digoxin). Decreased plasma concentrations with phenytoin. Concomitant use with lithium can increase risk of neuroleptic malignant syndrome. Decreased clozapine levels with CYP1A2 inducers (omeprazole). Increased clozapine levels with CYP1A2 inhibitors (fluvoxamine, caffeine, ciprofloxacin).

[UNSAFE] It is unsafe to consume alcohol with Clozapine.

[SAFE IF PRESCRIBED] Clozapine is generally considered safe to use during pregnancy. Animal studies have shown low or no adverse effects to the developing baby; however, there are limited human studies. Pregnancy Category B.

[CONSULT YOUR DOCTOR] Clozapine is probably unsafe to use during breastfeeding. Limited human data suggests that the drug may pass into the breastmilk and harm the baby. If used, monitor the baby for excessive sedation and periodically check the baby's white blood cell count.

Limited information is available regarding use in children.

Elderly patients are more susceptible to adverse effects (agranulocytosis, cardiovascular, anticholinergic, and tardive dyskinesia).

[CAUTION] Use with caution in patients with kidney disease. Dose adjustment may be needed. Severe renal impairment (CrCl <10 mL/min): Contraindicated.

[CAUTION] Use with caution in patients with liver disease. Dose adjustment may be needed. Regular monitoring of liver function tests is advisable. Avoid in symptomatic or progressive liver disease or hepatic failure.

Overdose symptoms: Altered states of consciousness (drowsiness, delirium, coma), tachycardia, hypotension, respiratory depression/failure, hypersalivation, aspiration pneumonia, cardiac arrhythmias, seizures. Treatment: Establish and maintain airway; ensure adequate oxygenation and ventilation; activated charcoal; cardiac and vital signs monitoring; general symptomatic and supportive measures. Avoid epinephrine and derivatives; avoid quinidine and procainamide. No specific antidotes.

Do not store above 30°C. Keep away from light and out of reach of children.

Clozapine