Sudden, large increases in clozapine dosage have led to cardiovascular collapse and death, particularly in patients who are also taking respiratory depressant medication. This is a particular issue when clozapine has been stopped, when a patient has been non-adherent, or when a patient has taken substantially less clozapine than prescribed. Consistent adherence to clozapine is important. If the patient has not taken clozapine or has taken less clozapine than prescribed for more than two days, the prescribed dosage should be reduced. When determining this reduced clozapine dosage, the clinician should consider the duration of not taking clozapine or taking less clozapine, and the potential risks and benefits for the patient. The clinician should consider the patient’s likely effective clozapine level, and what dosage to reduce to, which can be as low as 12.5 mg once or twice a day. After dose reduction, the dose may be increased to the previously therapeutic dose more quickly than recommended for initial treatment. With regard to monitoring of neutrophils, if treatment is interrupted for less than 30 days, continue monitoring as before. If treatment is interrupted for 30 days or more, monitor as if it was a patient newly on clozapine. See the clozapine REMS for further information.