Clozapine: Dosage, Contraindications, Precautions, Adverse Reactions and Interactions

It belongs to a group of medicines called antipsychotics. These drugs work on the balance of chemicals in the brain.

A specialist doctor will prescribe clozapine and will closely monitor your progress. Clozapine is prescribed to alleviate the symptoms of psychosis; this is the name used by doctors to describe a disordered mood.

Clozapine is prescribed in particular for people with schizophrenia. Schizophrenia is a mental health problem that causes disordered ideas, beliefs, and experiences. People with schizophrenia may have a hard time knowing which thoughts and experiences are genuine and authentic and which are not.

Symptoms similar to these can sometimes occur in people with Parkinson’s disease.

Clozapine dosage

Adult: schizophrenia PO 12.5 mg 1-2 times on day 1 followed by 25 mg 1-2 times on day 2, gradually increased in 25-50 mg increments up to 300 mg / day with 14-21 days. Subsequent increases of 50-100 mg can be done 1-2 times per week. Usual dose: 200-450 mg / day. Max: 900 mg / day.

Psychosis in initial Parkinson’s disease: 12.5 mg at bedtime. It can be increased in 12.5 mg increments up to two weeks, not> 50 mg/day at the end of the second week. Usual dose: 25-37.5 mg / day. Max: 100 mg / day.

Elderly: ≥60 years initially, 12.5 mg on day 1, subsequently increase in increments of 25 mg daily.



It can be taken with or without food.


  • Patient with paralytic ileus.
  • Uncontrolled epilepsy
  • History of circulatory collapse.
  • Alcoholic or toxic psychosis.
  • Drug intoxication.
  • Coma or severe CNS depression.
  • Severe heart disease (e.g., myocarditis).
  • Bone marrow suppression.
  • Myeloproliferative disorders or differential blood or white cell abnormality, history of drug-induced neutropenia, or agranulocytosis.
  • Renal failure is severe.

Special precautions

  • Patient with risk factors for stroke, history of long QT syndrome.
  • History of seizures or conditions that lower the seizure threshold.
  • History of heart failure or abnormal heart findings on examination.
  • Benign prostatic hyperplasia.
  • Angle-closure glaucoma.
  • History of colonic disease or lower abdominal surgery.
  • Avoid abrupt withdrawal.
  • Elderly with dementia-related psychosis.
  • Hepatic or mild to moderate kidney failure.
  • Pregnancy and breastfeeding.

Adverse drug reactions

  • Sedation.
  • Weight gain.
  • Neutropenia is reversible.
  • Eosinophilia.
  • Tachycardia.
  • Orthostatic hypotension.
  • Dizziness
  • Nocturnal hypersalivation.
  • Headache.
  • Sickness.
  • Vomiting
  • Constipation.
  • Urinary incontinence and retention.
  • Fatigue.
  • Transient fever.
  • Glucose homeostasis abnormalities and the onset of DM.
  • Obsessive-compulsive symptoms.


  • Anemia.
  • Thrombocytopenia
  • Extrapyramidal disorders, including tardive dyskinesia.
  • Circulatory collapse with cardiac arrest and respirator.
  • HA.
  • Dysphagia.
  • Enlargement of the parotid gland.
  • Confusion.
  • Delirium.
  • Thromboembolism.
  • Acute pancreatitis.
  • Hepatitis and cholestatic jaundice.


Animal reproduction studies have not shown a fetal risk.

However, no controlled studies in pregnant women or animal reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of risk in subsequent quarters).

Counseling the patient

This drug can cause sedation and lowers the seizure threshold. If you are affected, avoid driving or operating machinery.

Avoid smoking cigarettes.

Monitoring parameters

Monitor cardiac and vital signs, white blood cells, and differential blood count every week for 18 weeks and then at least every two weeks; clinical monitoring of hyperglycemia.



  • Drowsiness.
  • Lethargy.
  • Reflection.
  • Coma.
  • Confusion.
  • Hallucinations
  • Agitation.
  • Delirium.
  • Hyperreflexia.
  • Seizures
  • Hypersalivation
  • Mydriasis
  • Blurry vision.
  • Termolabilidad.
  • Hypotension
  • Collapse.
  • Tachycardia.
  • Cardiac arrhythmias.
  • Aspiration pneumonia.
  • Dyspnoea.
  • Depression or respiratory failure.

Management: symptomatic and supportive treatment. Establish and maintain airways and ensure adequate ventilation and oxygenation.

Gastric lavage and administration of activated charcoal in the first 6 hours after ingestion. Close medical supervision is needed for at least five days due to the possibility of late reactions.


With other medications

Increased risk and severity of bone marrow suppression with bone marrow suppressants (e.g., Carbamazepine, chloramphenicol), sulfonamides (e.g., Cotrimoxazole), pyrazolone pain relievers (e.g., phenylbutazone), penicillamine, cytotoxic agents or long-acting inhibitors of antipsychotics.

Concomitant use of benzodiazepines may increase the risk of circulatory collapse, leading to cardiac and respiratory arrest.

Additive CNS depression and cognitive and motor performance interference with MAOIs and CNS depressants, including antihistamines, benzodiazepines, and opioid analgesics.

It can potentiate the effects of anticholinergic or antihypertensive drugs—increased plasma concentration of highly protein-bound substances (e.g., Warfarin, Digoxin).

It decreased plasma concentrations with phenytoin.

Mechanism of action

Description: Clozapine is a derivative of dibenzodiazepine and a prototype of atypical antipsychotics. It is proposed that its therapeutic efficacy is mediated by antagonism of the D 2 and 5-HT 2A receptors.

It also acts as an antagonist at α-adrenergic, histamine H 1, cholinergic, and other dopamine and serotonergic receptors.


Absorption: Well absorbed from the gastrointestinal tract.

Bioavailability: approximately 50%.

Time to reach maximum plasma concentration: approximately 2.5 hours.

Plasma protein binding: approximately 95%.

Metabolism: almost completely metabolized through N-demethylation, hydroxylation, and N-oxidation mainly mediated by the isoenzyme CYP1A2.

Excretion: through urine (approximately 50%) and feces (30%) as metabolites and traces of drug unchanged.

Terminal elimination half-life: approximately 12 hours.


Store between 15-30 ° C.