• Assess patient’s mental status (orientation, mood, behavior) prior to and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of behavior or depression, especially during early therapy.
• Observe patient carefully when administering medication to ensure medication is actually taken and not hoarded or cheeked.
• Assess orthostatic vitals (HR and BP lying, sitting, standing) during initial dosage adjustment and periodically throughout therapy. May be associated with dizziness, tachycardia, and syncope.
• Assess cardiac history and ECG at baseline; avoid use in patients with long QT syndrome or cardiac arrhythmias associated with prolonged QT interval.
• Assess weight and BMI at baseline, at Wk 4, at Wk 8, at Wk 12, following initiation or change in therapy, and quarterly thereafter. Measure waist circumference at baseline and annually. Refer as appropriate for nutritional/weight and medical management.
• Monitor patient 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 of hands, masklike face, shuffling gait, rigidity, tremors; dystonia: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs). Immediately report the onset of these symptoms. Parkinsonian effects are more common in older adults, may occur during the 1st few days of therapy, and ↑ with dose ↑. Akathisia and dystonias are more common in younger and male patients and may occur within 24–48 hr of initiation of therapy. Notify health care provider if these symptoms occur, because ↓ dosage or discontinuation of medication may be necessary. Trihexyphenidyl, diphenhydramine, or benztropine may be used to control these symptoms.
• Monitor for 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; excessive eye blinking). Notify health care provider immediately if these symptoms occur because these side effects may be irreversible. Use lowest effective dose and consider discontinuation.
• May lower seizure threshold. Institute seizure precautions for patients with a history of a seizure disorder.
• Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, delirium, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, cardiac arrhythmia, pallor, fatigue). Discontinue and notify health care provider immediately if these symptoms occur.
• Ocular examinations may be required periodically during high-dose or prolonged therapy to monitor for deposition of particulate matter on the lens or cornea. Intraoperative floppy iris syndrome may occur.
• Monitor for signs/symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction, changes in libido, erectile or ejaculatory dysfunction).
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability ↑ risk. Institute prevention if indicated.

Lab Test Considerations:

• Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. If ANC <1000/mm³) occurs, discontinue milsaperidone and follow WBC until recovery.
• Prior to dosing, consider CYP2D6 genetic testing to determine the patient’s CYP2D6 metabolizer status; if patient is a poor metabolizer, follow modified titration and dosing schedule.
• Measure fasting plasma glucose at baseline, Wk 12, and then annually thereafter. Patients with diabetes or prediabetes should be regularly monitored for worsening of glucose control.
• Measure fasting lipid profile at baseline, Wk 12, and then every 5 yr thereafter. Repeat testing more frequently as clinically indicated.
• Liver function tests should be monitored periodically during therapy.
• Monitor serum potassium and magnesium levels at baseline and periodically in patients prone to electrolyte disturbance.
• Monitor serum prolactin prior to and periodically during therapy. May ↑ serum prolactin levels.

Toxicity and Overdose:

• The antipsychotic therapeutic reference range for iloperidone is 5–10 ng/mL, with a laboratory alert level of 20 ng/mL.