Common uses of Clozapine
Clozapine is an atypical antipsychotic reserved for situations where two or more other antipsychotics have not provided adequate symptom control or have caused intolerable side effects. Its FDA-approved indications include: treatment-resistant schizophrenia and reducing the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder. Clozapine’s ability to address persistent positive symptoms (such as hallucinations and delusions), mitigate aggressive behavior, and decrease suicidality makes it an essential option in difficult-to-treat cases.
Clinically, clozapine often improves both positive and negative symptoms and may reduce relapse risk when maintained appropriately with monitoring. It does not cure schizophrenia; rather, it helps manage symptoms, supports functioning, and can lower hospitalization rates in treatment-resistant populations when adherence and safety labs are maintained.
Dosage and directions (overview, not medical advice)
Clozapine dosing is highly individualized and must be supervised by a qualified prescriber enrolled in the Clozapine REMS program. A typical approach starts low and goes slow to minimize risks of orthostatic hypotension, seizures, and myocarditis. Many patients begin at 12.5 mg once or twice on day one, then titrate upward gradually as tolerated. Common maintenance doses range from 300–600 mg per day, divided, though some patients may need lower or higher amounts. The FDA-labeled maximum is 900 mg daily. Never start, stop, or change your dose without medical supervision.
Clozapine requires regular absolute neutrophil count (ANC) monitoring to detect neutropenia early. In the U.S., the typical schedule is weekly ANC for the first 6 months, then every 2 weeks for the next 6 months, and monthly thereafter if counts remain acceptable. If therapy is interrupted for 48 hours or longer, re-titration from a low dose is usually required to reduce the risk of severe hypotension, respiratory or cardiac collapse, and seizures.
Food does not meaningfully affect clozapine efficacy, but consistency in caffeine and tobacco use matters because both can alter clozapine levels. Patients should keep the same pattern of smoking and caffeine intake if possible and promptly inform their prescriber of any changes.
Precautions before and during therapy
Clozapine carries boxed warnings for severe neutropenia, orthostatic hypotension/bradycardia/syncope, seizures, myocarditis and cardiomyopathy, and increased mortality in elderly patients with dementia-related psychosis (it is not approved for this population). Rigorous baseline assessment and ongoing monitoring are essential for safety.
Tell your clinician about all medical conditions, especially prior low white blood cell counts, heart disease, myocarditis, cardiomyopathy, seizures or epilepsy, bowel disorders (including chronic constipation), diabetes, liver or kidney impairment, Parkinson’s disease, and glaucoma or urinary retention. Clozapine can worsen constipation and, rarely, cause bowel obstruction or ileus; a proactive bowel regimen is often necessary. Report any signs of infection (fever, sore throat), chest pain, shortness of breath, palpitations, fainting, new or worsening constipation, or seizure activity immediately.
Clozapine commonly causes sedation and orthostatic hypotension; use caution when driving or operating machinery, especially during initiation and dose increases. Alcohol and other CNS depressants can amplify sedation and respiratory risks. Smoking changes (starting, stopping, or altering amount) can shift clozapine blood levels via CYP1A2 induction; inform your provider in advance so dosing and monitoring can be adjusted. Caffeine also raises levels; keep intake steady.
Contraindications to Clozapine
Clozapine is contraindicated in patients with: a history of serious hypersensitivity to clozapine or any component of the formulation; a history of clozapine-induced severe neutropenia or agranulocytosis (unless the benefits outweigh the risks and careful hematologic oversight is arranged); uncontrolled paralytic ileus; and in situations where required ANC monitoring cannot be reliably performed. Patients with baseline ANC below program thresholds generally should not start clozapine unless under hematology-guided protocols.
Agents that significantly depress bone marrow (for example, carbamazepine) are typically avoided with clozapine due to additive risk of agranulocytosis. Many other conditions warrant caution rather than absolute avoidance; decisions should be individualized by your prescriber with full risk–benefit discussion.
Possible side effects
Common clozapine side effects include sedation, dizziness, tachycardia, orthostatic hypotension, increased salivation (sialorrhea), dry mouth, constipation, nausea, weight gain, increased appetite, and fever. Metabolic changes such as elevated blood sugar and lipids can occur, so monitoring of weight, glucose, and lipids is recommended. Some patients experience blurred vision, tremor, or sweating.
Serious adverse effects can include severe neutropenia or agranulocytosis, myocarditis and cardiomyopathy, seizures (dose-related risk increases above 600 mg/day), severe constipation leading to ileus or bowel obstruction, aspiration pneumonia, QT prolongation and arrhythmias (usually modest but clinically relevant in susceptible individuals), venous thromboembolism, and neuroleptic malignant syndrome. Seek urgent care for chest pain, shortness of breath, palpitations, fainting, confusion, severe abdominal pain, inability to pass stool, fever with sore throat, or any seizure.
Elderly patients with dementia-related psychosis treated with antipsychotics have increased mortality; clozapine is not approved for these patients. Pregnant or breastfeeding individuals should discuss potential risks and benefits with their clinician; decisions should be individualized with obstetric and psychiatric input.
Drug interactions to know
Clozapine is metabolized by CYP1A2, CYP3A4, and CYP2D6. Strong CYP1A2 inhibitors can markedly raise clozapine levels and toxicity risk. Notable inhibitors include fluvoxamine, ciprofloxacin, and, to a lesser extent, high caffeine intake. CYP1A2 inducers reduce levels and efficacy; tobacco smoke (polycyclic aromatic hydrocarbons), carbamazepine, phenytoin, and rifampin are examples. Inform your prescriber before starting or stopping any of these substances.
Avoid combining clozapine with other medications that cause bone marrow suppression (for example, carbamazepine) due to additive risk of neutropenia. Concurrent benzodiazepines at initiation or rapid dose escalation may increase the risk of severe hypotension or respiratory depression; careful clinical judgment is required. Additive anticholinergic effects from other agents (e.g., certain antihistamines, tricyclics, oxybutynin) can worsen constipation or urinary retention. Alcohol and other CNS depressants amplify sedation. Lithium coadministration requires caution for potential neurotoxicity; valproate may increase sedation and has been associated in some reports with myocarditis risk during clozapine initiation—coordinate closely with your prescriber.
Always provide a complete, up-to-date medication and supplement list (including nicotine products and caffeine habits) to your healthcare team so they can anticipate interactions and adjust your plan safely.
Missed dose guidance
If you miss a dose of clozapine, take it as soon as you remember the same day. If it is almost time for the next dose, skip the missed dose and resume your regular schedule. Do not double up to catch up. If you have missed taking clozapine for 48 hours or longer, contact your prescriber before resuming; you will typically need to restart at a low dose and re-titrate to reduce the risk of severe hypotension, syncope, or seizures.
Overdose information
Clozapine overdose can be life-threatening. Symptoms may include profound sedation, confusion or delirium, agitation, seizures, drooling, dilated pupils, fast heart rate, low blood pressure, breathing difficulty, and cardiac arrhythmias. There is no specific antidote. Emergency management focuses on airway and breathing support, cardiac monitoring, seizure control, and symptomatic care. If an overdose is suspected, call emergency services immediately and contact Poison Control (U.S. 1-800-222-1222). Do not delay seeking care.
Storage and handling
Store clozapine tablets at controlled room temperature (generally 20–25°C/68–77°F), protected from moisture and light. Keep in the original container with the child-resistant cap firmly closed. Do not store in bathrooms. Keep out of reach of children and pets. If using orally disintegrating tablets, follow the package instructions: open the blister with dry hands and use immediately after opening. Dispose of expired or unused medication via take-back programs when available.
Monitoring while on Clozapine
Regular ANC monitoring is mandatory through the REMS program to detect neutropenia early. Your prescriber may also check CRP/troponin during the first weeks if there are cardiac concerns, and periodically monitor weight, A1C or fasting glucose, lipids, blood pressure, and signs of constipation or ileus. Report infections or fevers promptly—do not wait for a routine appointment. Shared decision-making and adherence to lab schedules are key to keeping clozapine both effective and safe.
U.S. sale and prescription policy for Clozapine (REMS, safety, and access)
In the United States, clozapine is an Rx-only medication dispensed exclusively through the Clozapine REMS program. A valid prescription from a licensed prescriber and up-to-date ANC results are required for every dispense. Pharmacies, prescribers, and patients must be REMS-enrolled, and pharmacies must verify lab values and dispense authorization before filling. Buying clozapine without a prescription is not permitted and may be unsafe or illegal. Be cautious of online vendors that claim to sell clozapine without prescription or REMS verification.
HealthSouth Rehabilitation Hospital of Las Vegas supports safe, legal, and structured access to clozapine by: participating in REMS-compliant workflows; coordinating prescription transfers; helping patients and caregivers understand monitoring schedules; and, when appropriate, connecting patients to licensed prescribers or telehealth partners for evaluation. We do not dispense clozapine without a valid prescription, but we make lawful access as straightforward as possible, with transparent communication about labs, refills, and follow-up. Contact our team to discuss how we can coordinate with your clinician, manage reminders for ANC testing, and streamline REMS documentation.
If you are switching pharmacies, relocating, or re-establishing care, HealthSouth Rehabilitation Hospital of Las Vegas can help ensure a seamless transition by verifying your REMS status, confirming recent labs, and working with your provider to prevent gaps in therapy. Our goal is to keep treatment continuous, safe, and compliant with federal and state requirements.
