Clozaril (Clozapine): Important Warnings

Black Box Warnings:

• Clozaril carries five serious warnings about possible severe side effects and drug interactions.
• Due to these warnings, Clozaril can only be prescribed through a special program called the Clozapine Risk Evaluation and Mitigation Strategies (REMS) Program.
• The REMS program ensures monitoring of white blood cell (WBC) count and absolute neutrophil count (ANC) as per the schedule below before delivering the next medication supply.
• Your doctor and pharmacist must be registered with this program to prescribe and dispense Clozaril.

Agranulocytosis:

• Agranulocytosis is an abnormally low WBC count, which is necessary to fight diseases and can be potentially fatal.
• Baseline WBC count and ANC are required before starting Clozaril, along with regular counts during treatment and for 4 weeks after discontinuation.
• Less than 1% of patients taking Clozaril may develop agranulocytosis, a life-threatening adverse event.

Seizures:

• Seizures have been associated with Clozaril use, with higher doses increasing the likelihood.
• Patients should avoid activities where sudden loss of consciousness could pose risks.
• Caution is advised for patients with a history of seizures or predisposing factors.

Myocarditis and Cardiomyopathy:

• Myocarditis is inflammation of the heart muscle, and cardiomyopathy is an enlarged heart.
• Seek immediate medical attention if you experience shortness of breath, fever, extreme tiredness, or chest pain while taking Clozaril.

Orthostatic Hypotension:

• Orthostatic hypotension is a sudden decrease in blood pressure upon standing, causing lightheadedness or dizziness.
• Syncope, or fainting, can also occur.
• This can happen when starting Clozaril or changing the dosage.
• Consult your doctor if you have severe diarrhea, vomiting, or dehydration or accidentally skip two or more Clozaril doses.

Increased Mortality in Elderly Patients With Dementia:

• Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs, including Clozaril, have an increased risk of death compared to placebo.
• Causes of death were varied, mostly cardiovascular (heart failure or sudden death) or infectious in nature.
• Clozaril is not approved for treating dementia-related psychosis.