Call for Revisions and Updates to the PAMI Pain Management and Dosing Guide

The early use of intravenous remdesivir and new oral antiviral medications molnupiravir and Paxlovid have been evaluated in controlled clinical trials among non-hospitalized, high-risk individuals with mild to moderate COVID-19 and have been found to improve COVID-19 outcomes including disease progression, hospitalization, and death. Current NIH recommendations favor the use of Paxlovid followed by sotrovimab and remdesivir for mild to moderate COVID-19 in outpatients. Molnupiravir should only be considered in those over 18 if the three options are not available or clinically cannot be used. The EUA authorizes the use of remdesivir IV in children weighing at least 3.5 kg and with laboratoryconfirmed COVID-19, who are within 7 days of symptom onset, at high risk for progression to severe COVID-19, and not hospitalized for COVID-19. However this requires daily infusions on three consultative days, which can be difficult to coordinate in the outpatient setting.

The FDA issued an EUA for the use of oral antiviral therapy for the treatment of mild to moderate COVID-19 at the end of December on the basis of results of a Phase 2/3 randomized, double-blind, placebo-controlled trial in high-risk individuals ≥18 years of age. There is no pharmacokinectic or pharmacodynamic data on anyone under the age of 18. Furthermore, there is no safety or efficacy date on this population as well. The EUA authorizes the use of Paxlovid in: children ≥12 years of age and weighing ≥40 kg, with laboratory-confirmed CVOID-19, are within 5 days of symptom onset, and who are at high risk for progression to severe COVID-19 and not hospitalized for COVID-19. Paxlovid should not be used in individuals with severe hepatic or renal impairment, and there is a potential for severe drug-drug interactions if given concurrently with other medications that rely on or induce CYP3A enzymes for metabolism and clearance, which include antiarrhythmics, oral anticoagulants, immunosuppressants, anticonvulsants, antineoplastics, and neuropsychiatric drugs. The EUA authorizes the use of molnupiravir in: individuals ≥18 years of age with laboratory-confirmed SARS-CoV-2, who are within 5 days of symptom onset and at high risk for progression to severe COVID-19, and for whom other, FDA-authorized COVID-19 treatment options are not readily accessible, available, or clinically appropriate. Children were not eligible to participate in the study because of concerns about effects on bone and cartilage growth. No dosage adjustments are needed in patients with renal or hepatic impairment of any degree. Molnupiravir is not recommended for use in pregnancy given the potential of fetal harm. Current NIH guidelines recommend the use of molnupiravir in eligible patients only when monoclonal antibody, Paxlovid, or remdesivir cannot be used.

There will be varying access to monoclonal antibodies and antivirals geographically, requiring additional triage for patients at highest risk for COVID-19. State and local health departments will allocate therapies to healthcare facilities prioritizing the treatment of COVID-19 in patients at highest risk for COVID-19 complications and hospitalizations. This means supplies may be scarce for pediatric treatment and must only be given to those who truly meet the criteria put forth by the FDA. Other than supportive care, therapeutic interventions for children and adolescents with mild to moderate COVID-19 will be limited. Parents/ caretakers will be concerned and scared when their child is diagnosed with COVID-19 and will want some therapeutic intervention. Many people have heard of these treatments for COVID-19 and may ask about the option. With the limited safety and efficacy data supporting their use in children and adolescents under 18, a serious discussion about the risks, benefits, and shared decision-making with the parents/caretakers may be the best path forward. ■

REFERENCES

1. FDA Takes Actions to Expand Use of Treatment for Outpatients with

Mild-to-Moderate COVID-19. Jan. 21, 2022. Access at fda.gov/newsevents/press-announcements/ fda-takes-actions-expand-usetreatment-outpatients-mildmoderate-covid-19

The Pain Assessment and Management Initiative (PAMI) at the University of Florida College of Medicine – Jacksonville is preparing to make updates to the 2020 Pain Management and Dosing Guide. The Guide is a comprehensive tool for managing adult and pediatric pain in the emergency department and other health care settings.

The PAMI team welcomes your clinical review and feedback to assist us in revising the current version to ensure we are providing the latest evidence based information in a concise resource. We are requesting your suggestions for information to add, remove or rearrange content. The Guide contains six distinct panels of information, including oral, nasal, parenteral and topical medications for acute and chronic pain and procedural sedation, as well as patient safety, discharge planning and nonpharmacologic management information.

Please contact the PAMI team at pami@ jax.ufl.edu to share your input and be part of this year’s revisions. The Guide will also undergo revision by the PAMI multidisciplinary stakeholder team based on review of current medical literature and practice guidelines. Once finalized, it will be available online as a free access resource with an option to print or download.

To contact PAMI, email us at pami@jax.ufl.edu or call (904) 244-4986. Stay connected with us on Facebook and LinkedIn for our latest updates. ■