Common use
Clozaril (clozapine) is an atypical antipsychotic approved for two main indications: treatment-resistant schizophrenia (TRS) and reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. “Treatment-resistant” generally means persistent, significant symptoms despite adequate trials of at least two other antipsychotics. For many individuals with TRS, Clozaril can reduce hallucinations, delusions, aggression, and disorganization where standard agents have fallen short. Additionally, in appropriate patients with persistent suicidality, Clozaril has been shown to lower the risk of suicidal behavior.
Clozaril’s clinical benefits often extend beyond symptom reduction. Patients and families frequently report improved emotional responsiveness, social engagement, and overall functioning. However, because clozapine affects multiple neurotransmitter systems (including dopamine and serotonin) and carries unique risks—particularly severe neutropenia—it is reserved for carefully selected patients and requires structured monitoring, consistent follow-up, and education on side effects. When introduced thoughtfully, Clozaril can be a pivotal therapeutic option in a comprehensive, person-centered treatment plan that may also include psychotherapy, skills training, and social supports.
Dosage and direction
Clozaril dosing must be individualized and titrated slowly to minimize risks such as orthostatic hypotension, seizures, and myocarditis. A common adult initiation is 12.5 mg once or twice daily, with gradual increases by 25–50 mg/day as tolerated. Many patients reach 300–450 mg/day by the end of week two, taken in divided doses, with subsequent adjustments based on clinical response and side effects. Some may require higher doses; the U.S. maximum is typically 900 mg/day. Older adults and those with comorbidities require slower titration and lower targets. Never start, stop, or change a dose without prescriber guidance.
Clozaril can be taken with or without food. Because dizziness and drowsiness are common early on, many clinicians recommend taking a larger portion of the dose at bedtime. Avoid alcohol and other sedatives unless your prescriber approves. Stay hydrated, rise slowly from sitting or lying positions to reduce fainting risk, and do not drive or operate machinery until you know how Clozaril affects you. Smoking status matters: tobacco smoke induces CYP1A2, lowering clozapine levels. Abruptly quitting smoking can significantly raise levels and side-effect risk, so coordinate any smoking changes with your care team.
Precautions
Clozaril carries boxed warnings for severe neutropenia, seizures, orthostatic hypotension with syncope, myocarditis/cardiomyopathy, and increased mortality in older adults with dementia-related psychosis (Clozaril is not approved for this population). In the U.S., Clozaril is dispensed only through the Clozapine REMS Program, which requires regular Absolute Neutrophil Count (ANC) monitoring: typically weekly for 6 months, every 2 weeks for months 7–12, then monthly if counts remain within acceptable ranges. Patients must promptly report signs of infection (fever, sore throat, mouth ulcers), chest pain, shortness of breath, palpitations, or fainting.
Constipation is common and can become severe (ileus). Preventive measures—adequate fluids, fiber, activity, and, when advised, bowel regimens—are important. Excess saliva (sialorrhea), sedation, weight gain, and metabolic changes (glucose and lipids) are also frequent; routine metabolic monitoring is recommended. Use caution in patients with a history of seizures, heart disease, gastrointestinal motility disorders, or those at risk for aspiration. Pregnancy and breastfeeding require individualized risk–benefit discussions. Because clozapine can impair thermoregulation and cause drowsiness, avoid overheating and alcohol. Ensure all clinicians and pharmacists involved in your care know you take Clozaril.
Contraindications
Clozaril is contraindicated in patients with known serious hypersensitivity to clozapine or formulation components (including reactions such as DRESS), and in those with paralytic ileus. It should generally not be used in individuals with a history of clozapine-induced agranulocytosis or severe neutropenia unless benefits clearly outweigh risks and a specialist agrees to close oversight. Patients unable to comply with required blood monitoring are not candidates.
Use is typically avoided or requires extreme caution in uncontrolled epilepsy, active myocarditis or cardiomyopathy, severe orthostatic hypotension, significant conduction abnormalities, and in those taking other potent myelosuppressive drugs. Clozaril is not approved for dementia-related psychosis in older adults because of increased mortality risk in this population.
Possible side effects
Common side effects include drowsiness, dizziness, constipation, sialorrhea (excess saliva), dry mouth, blurred vision, increased heart rate, weight gain, and metabolic changes (elevated blood sugar and lipids). Many improve over time or with dose adjustments and supportive measures. Orthostatic hypotension—lightheadedness or fainting upon standing—is most likely during early titration or rapid increases. Sexual dysfunction, sweating, and mild tremor can occur.
Serious adverse effects require urgent attention. These include severe neutropenia/agranulocytosis (signs: fever, sore throat, infections), myocarditis or cardiomyopathy (chest pain, shortness of breath, rapid heartbeat, fatigue), seizures (risk increases with higher doses and rapid titration), severe constipation/ileus (abdominal pain, bloating, no bowel movement), aspiration pneumonia, and severe orthostatic hypotension or syncope. Other rare but critical risks: neuroleptic malignant syndrome (high fever, muscle rigidity, confusion), venous thromboembolism, hepatotoxicity (yellowing of eyes/skin, dark urine), and severe cutaneous reactions (e.g., DRESS, Stevens–Johnson syndrome). Any sudden change in mental status, high fever, chest symptoms, or signs of infection warrants immediate medical evaluation.
Drug interactions
Clozaril is metabolized primarily by CYP1A2 and to a lesser extent by CYP3A4 and CYP2D6. Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) can markedly increase clozapine levels—dose reductions and close monitoring are typically required. CYP1A2 inducers (notably tobacco smoke; also carbamazepine) can lower levels and efficacy; abrupt smoking cessation raises levels and side-effect risk. Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) may increase levels; strong inducers (rifampin) may decrease levels.
Avoid combining Clozaril with bone marrow–suppressing agents (e.g., carbamazepine, chloramphenicol, certain chemotherapy) due to compounded neutropenia risk. Early in treatment, concurrent benzodiazepines or other CNS depressants can increase the risk of profound sedation, respiratory depression, and circulatory collapse—use only if clinically justified and carefully monitored. Additive anticholinergic effects with agents like tricyclic antidepressants, oxybutynin, or antihistamines can worsen constipation and ileus risk. Caffeine can raise clozapine concentrations; maintain consistent intake. Caution with QT-prolonging drugs, hypotensive agents, lithium (neurotoxicity risk), and valproate (sedation; rare neutropenia). Always review your full medication and supplement list with your prescriber and pharmacist.
Missed dose
If you miss a dose, take it when you remember unless it is close to the next scheduled dose; do not double up. If you miss Clozaril for 48 hours or more, do not restart at your previous dose—contact your prescriber. Retitration (often beginning at 12.5 mg) is required to reduce risks like orthostatic hypotension and seizures. Maintaining consistent dosing and attending scheduled lab draws are essential to safe, effective therapy.
Overdose
Overdose may lead to profound sedation or coma, delirium, seizures, severe hypotension, tachycardia, arrhythmias, respiratory depression, hypersalivation, and aspiration. This is a medical emergency. Call emergency services and seek immediate care. Management is supportive: secure the airway, monitor ECG and vital signs, treat seizures (commonly with benzodiazepines), and correct hypotension with IV fluids and, if needed, vasopressors (avoid epinephrine due to paradoxical hypotension; norepinephrine is generally preferred). Activated charcoal may be considered if the patient presents shortly after ingestion and airway is protected. Continuous monitoring is warranted until clinically stable.
Storage
Store Clozaril at room temperature (typically 20–25°C/68–77°F), away from moisture and direct light. Keep tablets in their original container, tightly closed, and out of reach of children and pets. For orally disintegrating tablets, keep blisters sealed until use to protect from humidity. Do not use after the expiration date, and dispose of unused medication per pharmacist guidance or community take-back programs.
U.S. Sale and Prescription Policy
In the United States, Clozaril cannot be legally dispensed without a valid prescription and compliance with the Clozapine REMS Program. This REMS requires patient, prescriber, and pharmacy enrollment and ongoing ANC monitoring before refills can be released. While people may search for “buy Clozaril without prescription,” doing so is unsafe and unlawful. HealthSouth Rehabilitation Hospital of Tallahassee does not bypass prescription requirements; instead, it provides a legal, structured pathway by connecting you with licensed clinicians for evaluation, coordinating necessary lab work and REMS enrollment, and working with certified pharmacies. If Clozaril is appropriate for you, the team can help you access it safely, within all regulatory standards.
