In March 2020, the FDA offered the following guidance for the REMS program:
- “FDA recognizes that during the COVID-19 PHE, completion of REMS-required laboratory testing or imaging studies may be difficult because patients may need to avoid public places and patients suspected of having COVID-19 may be self-isolating and/or subject to quarantine. Under these circumstances, undergoing laboratory testing or imaging studies in order to obtain a drug subject to a REMS can put patients and others at risk for transmission of the coronavirus.”
- “For drugs subject to these REMS with laboratory testing or imaging requirements, health care providers prescribing and/or dispensing these drugs should consider whether there are compelling reasons not to complete these tests or studies during the PHE, and use their best medical judgment in weighing the benefits and risks of continuing treatment in the absence of laboratory testing and imaging studies. Health care providers should also communicate with their patients regarding these judgments, including the risks associated with it.”
- “Although all REMS requirements remain in effect, FDA does not intend to take enforcement action against sponsors or others for accommodations made regarding laboratory testing or imaging study requirements imposed under sections 505-1(f)(3)(d) or (e) of the FD&C Act (21 U.S.C. 355-1 (f)(3)(d) or (e)) during the PHE declared by the Secretary of HHS on January 31, 2020, provided that such accommodations were made based on the judgment of a health care professional.”
Since there is not specific guidance from REMS or FDA, clinicians prescribing clozapine should weigh the potential risks and benefits of Absolute Neutrophil Count (ANC) in individual patients. These should be discussed with patients, and there should be an informed consent discussion with any changes in testing. There are likely to be patients for whom risks related to contracting COVID while getting blood drawn are higher than the risk of not having an ANC test. In evaluating risks, clinicians can include consideration of the following: About two thirds of cases of severe neutropenia occur during the first three months of exposure to clozapine. About one tenth occur between four and six months. The rest occur at a low rate after that period. While risk factors for serious COVID related complications are not yet fully defined, risk appears increased with older age, concurrent medical problems, immunosuppression, and pulmonary problems. With regard to serious mental illness, note that this population may be at increased risk for chronic obstructive pulmonary disease, asthma, obesity and diabetes; and rates of smoking are very high.