There are no absolute contraindications to clozapine beyond those in the clozapine REMS that pertain to provider and pharmacy registration, and patient baseline neutrophil count. Complete information regarding REMS requirements for starting clozapine is found here. The decision regarding whether to offer a patient clozapine involves consideration of the individual’s potential risks and benefits. Patients are considered a high-risk clozapine start if they have a relevant concurrent serious medical illness, concurrent problematic medications that cannot be discontinued, or they previously experienced a serious clozapine side effect, such as myocarditis, severe neutropenia, or poorly controlled seizures. These side effects can recur, but do not recur in all patients. When considering rechallenging these patients with clozapine, one should consider whether clozapine caused the side effect, and whether the patient and caregivers believe that the benefits of clozapine outweigh the risks. A rechallenge can pose substantial risks, since the side effect may recur. With regard to re-challenging after severe neutropenia, neutropenia has been found to occur in about 30 to 40% of rechallenged patients. The risk may be higher in patients who had neutropenia earlier in the course of clozapine treatment. Neutropenia can be more rapid and longer lasting the second time around. With regard to re-challenging after myocarditis, the rate of success is unknown, though there have been case reports of successful rechallenge. When re-challenging patients, the re-challenge should be considered a high-risk start with intensive monitoring and supports, and done at the appropriate level of care in consultation with hematology or cardiology.