Clozapine

Antipsychotic Drug

Drug class: Atypical Antipsychotic

Clozapine (CLOZARIL)（中文：氯氮平）

Common Strengths of Clozapine Tablet

Clozapine are available in the following strengths:

• 25 mg and 100 mg tablets

Drug Trade Names of Clozapine Tablet

Clozaril

Drug Usage

Clozapine is used for:

• Treatment-resistant schizophrenia.
• Reducing risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.

Mechanism of Action

Partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at serotonin 5-HT2A receptors.

Route of ADministration

Oral

Dosages

• Initial dose: 12.5 mg once or twice daily
• Target dose: 300 - 450 mg/day in divided doses
• Maximum dose: 900 mg/day

Side Effects

Frequency	Adverse reactions
Common	Drowsiness and sedation: Many patients experience significant drowsiness or sedation, which can impact daily activities
	Weight gain: Clozapine can lead to substantial weight gain, which may increase the risk of metabolic syndrome
	Increased salivation
	Constipation
	Dizziness and lightheadedness: Espeically when standing up quickly, due to orthostatic hypotension
Uncommon	Agranlocytosis: Clozapine can cause a significant decrease in white blood cells, leading to a higher risk of infections. Regular blood monitoring is required
	Seizures: The risk of seizures increase with higher doses of clozapine
	Myocarditis and cardiomyopathy
	Neuroleptic Malignant Syndrome (NMS): This is a rare but potentially fatal condition characterized by high fever, muscle stiffness, and altered mental status
	Tardive dyskinesia: This is a movement disorder that may become irreversible with prolonged use, particularly in older adults
	QT prolongation
	Liver issues: Symptoms may include jaundice, dark urine, and abdominal pain

Pharmacokinetics

• Pharmacologic effects (e.g. sedation) are apparent within 15 minutes
• Peak plasma concentrations are typically attained within 1.5 to 2.5 hours after single or multiple doses of clozapine tablets
• Elimination half-life: 8 hours (single dose), 12 hours (multiples doses)
• Approximately 50% excreted in urine, 30% in feces

Drug Precautions

Pregnancy

Use caution; potential risks to the fetus should be considered

Breastfeeding

Contraindicated during lactation

Children & Elderly

• Contraindicated in children before puberty
• Use caution in elderly patients

Monitoring Requirements

Patients on clozapine require regular monitoring, including:

• Frequent blood test to monitor white blood cell counts.
• Cardiac monitoring to detect any changes in heart rhythm.
• Regular metabolic assessments to check for weight gain, blood sugar levels, and lipid profiles.

Drug Interactions

Interactions with strong CYP1A2 inhibitors, CYP2D6 inhibitors, and CYP3A4 inducers

• CYP1A2 Inhibitors
  • Drugs such as fluvoxamine, ciprofloxacin, and hormonal contraceptives can increase clozapine levels, raising the risk of adverse effects
• CYP1A2 inducers
  • Substances like omeprazole can decrease clozapine levels, potentially reducing its efficacy
• Lamotrigine
  • THis anticonvulsant can increase clozapine levels, requiring close monitoring
• Caffeine
  • Can increase clozapine levels due to CYP1A2 inhibition
• Grapefruit Juice
  • May increase clozapine levels bhy inhibiting CYP3A4
• Smoking
  • Can decrease clozapine levels; cessation can lead to increase plasma levles and potential toxicity

FAQ

How Should I Take the Tablet?

Take with or without food.

What should I avoid while taking?

Avoid activities requiring mental alertness until you know how the medication affects you.

What Happens if I Miss a Dose?

Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not double doses.