• Monitor mental status (orientation, mood, behavior) before and periodically during therapy.

• Assess orthostatic vitals (HR and BP lying, sitting, standing) frequently during initial dosage adjustment and periodically throughout therapy. Titrate slowly and monitor closely; may cause orthostatic hypotension, bradycardia, syncope, and cardiac arrest.

• 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 and symptoms of myocarditis (unexplained fatigue, dyspnea, tachypnea, fever, chest pain, palpitations), pericarditis (pericardial friction rub, chest pain relieved by leaning forward), or HF (dyspnea, peripheral edema, rales/crackles, jugular venous distension, fluid weight gain). Monitor ECG changes (ST-T wave abnormalities, arrhythmias, or tachycardia during 1st months 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, masklike 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 provider if these symptoms occur; ↓ in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benztropine 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 ↓ 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 signs and symptoms of NMS (hyperpyrexia, muscle rigidity, seizures, altered mental status, evidence of autonomic instability [irregular HR or BP, tachycardia, diaphoresis, cardiac arrhythmia]). Notify health care provider immediately if these symptoms occur.
• Assess respiratory status during therapy. Monitor for signs and symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema).

• 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. For the general population (patients without BEN), ANC must be ≥1500 cells/mm³ to begin 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 mild neutropenia (ANC 1000–1499 cells/mm³) occurs, continue therapy and monitor ANC 3 times/wk until ANC ≥1500 cells/mm³; then return to patient's last ANC monitoring interval. If moderate neutropenia (ANC 500–999 cells/mm³) occurs, hold clozapine and obtain hematology consultation. Resume therapy once ANC ≥1000 cells/mm³. Monitor ANC daily until ANC ≥1000 cells/mm³, and then 3 times/wk until ANC ≥1500 cells/mm³. Once ANC ≥1500 cells/mm³, check ANC once weekly for 4 wk; then return to patient's last ANC monitoring interval. If severe neutropenia (<500 cells/mm³) occurs, discontinue clozapine and obtain hematology consultation. Monitor ANC daily until ANC ≥1000 cells/mm³ and then 3 times/wk until ANC ≥1500 cells/mm³. If benefits of treatment outweigh risks, resume clozapine and monitor ANC as if newly initiating therapy. For patients with BEN, obtain ≥2 baseline ANC levels before starting therapy. ANC must be ≥1000 cells/mm³ to begin 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 cells/mm³) occurs, obtain hematology consultation and continue therapy. Monitor ANC 3 times/wk until ANC ≥1000 cells/mm³ and at least at patient's known baseline. Once ANC ≥1000 cells/mm³, check ANC once weekly for 4 wk; then return to patient's last ANC monitoring interval. If severe neutropenia (<500/mm³) occurs, discontinue clozapine and obtain hematology consultation. Monitor ANC daily until ANC ≥500 cells/mm³ and then 3 times/wk until ANC ≥1000 cells/mm³ and at least at patient's known baseline. If benefits of treatment outweigh risks, resume clozapine and monitor ANC as if newly initiating therapy.

  • Assess renal function, serum electrolytes, and magnesium prior to initiating and periodically during therapy.
  • Assess fasting lipid profile at baseline, Wk 12, and every 5 yr thereafter.
  • Monitor fasting blood glucose at baseline, Wk 12, and annually; patients with diabetes should be monitored more frequently.
  • Monitor liver function tests periodically during therapy or if clinical signs of hepatotoxicity occur.