• Monitor mental status (orientation, mood, behavior) before and periodically during therapy. Titrate slowly and monitor closely; may cause orthostatic hypotension, bradycardia, syncope, and cardiac arrest.
• Monitor BP (sitting, standing, lying) and HR before and frequently during initial dose titration.
• Assess weight and body mass index initially and periodically during therapy. Refer as appropriate for nutritional/weight management and medical management.
• Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
• Monitor for signs of myocarditis (unexplained fatigue, dyspnea, tachypnea, fever, chest pain, palpitations, other signs and symptoms of HF). Monitor ECG changes (ST-T wave abnormalities, arrhythmias, or tachycardia during 1st mo of therapy). If these occur, permanently discontinue clozapine.
• Monitor for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill-rolling motion of hands, mask-like face, shuffling gait, rigidity, tremors and dystonic muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Notify health care professional if these symptoms occur; ↓ in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benzotropine may be used to control these symptoms.
• Monitor for possible tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Report these symptoms immediately; may be irreversible.
• Monitor frequency and consistency of bowel movements and assess for symptoms of hypomotility (nausea, vomiting, abdominal distension, abdominal pain). Symptoms range from constipation to paralytic ileus; ↑ risk with use of other anticholinergic medications. ↑ fiber and fluids in the diet and laxatives may help to minimize constipation. Prophylactic laxatives may be used for high-risk patients.
• Clozapine lowers the seizure threshold. Institute seizure precautions for patients with history of seizure disorder.
• Transient fevers may occur, especially during 1st 3 wk of therapy. Fever is usually self-limiting but may require discontinuation of medication. Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
• Assess respiratory status during therapy. If DVT, acute dyspnea, chest pain, or other respiratory signs and symptoms occur, consider PE.
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability ↑ risk. Institute prevention if indicated.
• Monitor for signs and symptoms of hepatotoxicity (fatigue, malaise, anorexia, nausea, jaundice, hyperbilirubinemia, coagulopathy, hepatic encephalopathy). May require permanent discontinuation if combined with ↑ transaminases.

Lab Test Considerations:

• Verify negative pregnancy status before starting theory. Monitor CBC with differential before starting therapy. ANC must be ≥1500/mm³ for the general population and ≥1000/mm³ for patients with documented benign ethnic neutropenia (BEN) for patient to begin therapy. Monitor ANC once for the 1st 6 mo; then biweekly for the next 6 mo; then, if maintained within acceptable parameters, monthly after 12 mo. If mild neutropenia (ANC 1000–1499/mm³) occurs, continue therapy and monitor ANC 3 times/wk until ANC ≥1500/mm³. Once ANC ≥1500/mm³, return to patient's last ANC monitoring interval. If moderate neutropenia (ANC 500–999/mm³) occurs, recommend hematology consultation. Interrupt therapy for suspected clozapine-induced neutropenia. Resume therapy once ANC ≥1000/mm³. Monitor ANC daily until ANC ≥1000/mm³ and then 3 times/wk until ANC ≥1500/mm³. Once ANC ≥1500/mm³, check ANC once weekly for 4 wk; then return to patient's last ANC monitoring interval. If severe neutropenia (<500/mm³) occurs, recommend hematology consultation. Interrupt therapy for suspected clozapine-induced neutropenia. Do not rechallenge unless benefit outweighs risk. Monitor ANC daily until ANC ≥1000/mm³ and then 3 times/wk until ANC ≥1500/mm³. If patient rechallenged, resume therapy as a new patient using normal monitoring once ANC ≥1500/mm³. For patients with BEN, obtain ≥2 baseline ANC levels before starting therapy. Monitor ANC once weekly for the 1st 6 mo; then biweekly for the next 6 mo; then, if maintained within acceptable parameters, monthly after 12 mo. If neutropenia (ANC 500–999/mm³) occurs, recommend hematology consultation and continue therapy. Monitor ANC 3 times/wk until ANC ≥1000/mm³ or at patient's known baseline. Once ANC ≥1000/mm³, check ANC once weekly for 4 wk; then return to patient's last ANC monitoring interval. If severe neutropenia (<500/mm³) occurs, recommend hematology consultation. Interrupt therapy for suspected clozapine-induced neutropenia. Do not rechallenge. Monitor ANC daily until ANC ≥500/mm³ and then 3 times/wk until ANC ≥patient's baseline. If patient rechallenged, resume therapy as a new patient using normal monitoring once ANC ≥1000/mm³ or at patient's baseline.
  • Assess fasting blood glucose and cholesterol levels initially and throughout therapy.
  • Monitor liver function tests periodically during therapy or if clinical signs of hepatotoxicity occur.

Toxicity and Overdose:

• Overdose is treated with activated charcoal and supportive therapy. Monitor patient for several days because of risk of delayed effects.
  • Avoid use of epinephrine and its derivatives when treating hypotension, and avoid quinidine and procainamide when treating arrhythmias.