Clozapine

DEA Class;  Rx

Common Brand Names; Clozaril, Versacloz

Hypersensitivity (eg, photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome)

• Hypersalivation (13-48%)
• Sedation/somnolence (21-46%)
• Weight gain (4-31%)
• Dizziness (14-27%)
• Tachycardia (17-25%)
• Constipation (14-25%)
• Insomnia (2-20%)
• Dizziness/vertigo (19%)
• Nausea (17%)
• Vomiting (17%)
• Dyspepsia (14%)
• Hypotension (9-13%)
• Fever (5-13%)
• Headache (7-10%)
• Tremor (6%)
• Syncope (6%)
• Sweating (6%)
• Dry mouth (5-6%)
• Visual disturbances (5%)
• Disturbed sleep/nightmares (4%)
• Restlessness (4%)
• Hypokinesia/akinesia (4%)
• Agitation (4%)
• Hypertension (4%)
• Abdominal discomfort/heartburn (4%)
• Seizures (3%)
• Rigidity (3%)
• Akathisia (3%)
• Confusion (3%)
• Leukopenia/neutropenia (3%)
• Fatigue (2%)
• Diarrhea (2%)

Increased risk of dose-related seizures

Eosinophilia (blood eosinophil count >700/mm³) reported; associated in some patients with myocarditis, pancreatitis, hepatitis, colitis, and nephritis; organ involvement could be consistent with a drug reaction with eosinophilia and systemic symptoms syndrome (DRESS)

Increased risk of cerebrovascular adverse events reported with some atypical antipsychotics (mechanism unknown)

FDA warning regarding off-label use for dementia-related psychosis in elderly patients; increased risk of death

Antipsychotic drugs can cause the potentially fatal symptom complex referred to as neuroleptic malignant syndrome (NMS); if NMS occurs, immediately discontinue antipsychotic drug, and other drugs not essential to therapy; implement intensive symptomatic treatment and medical monitoring

Possible QT prolongation; use with caution in patients with history of long QT syndrome or other conditions that may increase risk (eg, hypokalemia, hypomagnesemia)

Severe, life threatening, and in some cases fatal hepatotoxicity including hepatic failure, hepatic necrosis, and hepatitis reported in post marketing studies; monitor for appearance of signs and symptoms of hepatotoxicity such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, coagulopathy, and hepatic encephalopathy; perform serum tests for liver injury and consider permanently discontinuing treatment if hepatitis or transaminase elevations combined with other systemic symptoms are due to clozapine

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including clozapine, during pregnancy; 

Clozapine is present in human milk; there are reports of sedation and a report of agranulocytosis in an infant exposed to clozapine through human milk; there is no information on effects of clozapine on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed-child from drug or from underlying maternal condition

Infants exposed to drug should be monitored for excess sedation