General Evusheld Announcement: The FDA announced on January 26, 2023, that the Emergency Use Authorization (EUA) for Evusheld has been revised. Evusheld is currently not authorized for use in the US. Please see the information regarding this decision here: https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us. Please notify providers to discontinue use of Evusheld and retain any leftover product in accordance with ASPR recommendations: https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us. Any orders submitted this week will not be placed. “The U.S. Government recommends that facilities and providers with Evusheld retain all product in the event that SARS-CoV-2 variants which are neutralized by Evusheld become more prevalent in the U.S. in the future. Retained product must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers and the Letter of Authorization.” This is guidance we recently received from CDPH with respect to the destruction of unauthorized/expired therapeutics: Licensed provider locations with destruction procedures in place that follow all federal, state, and local regulations may destroy therapeutics on site only if: Guidelines are followed on what product can be destroyed Only expired product or unauthorized product that can no longer be stored No unexpired product that is currently authorized for use can be destroyed Sites are to follow established protocols for destruction and attest in HPOP to following all regulations Quantities of any product destroyed is recorded in HPOP

• HHS Assistant Secretary for Preparedness & Response Important Updates
• HHS COVID-19 Therapeutics Decision Aid (updated 12/2022)
• NIH Treatment Guidelines (updated 12/06/22)

• • When there are no logistical constraints, therapies are to be prescribed for any eligible individual.
  • If logistical constraints are faced, Providers should follow the NIH Prioritization.

• CDC Interim Clinical Considerations for COVID-19 Treatment in Outpatients (updated 12/05/2022)
• CDC Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals (updated 12/05/2022)
• CDPH HEALTH ADVISORY: Reminder to Lower Barriers to Prescribing COVID-19 Therapeutics to Mitigate Impact of COVID-19 (12/02/2022)

• Do you have a clinical question about therapeutics? Email COVIDRxProviders@cdph.ca.gov.
• Receive frequent updates!
  • Register to attend CDPH weekly Provider webinars occurring Fridays at 9:00 am. Click here to view webinar recordings.
  • Sign up to receive frequent email updates from CDPH.
• COVID-19 Treatments Toolkit (ca.gov)
• CDPH Therapeutics Best Practices
• CDPH COVID-19 Test-to-Treat Playbook
• CDPH COVID-19 Treatments Webpage for Providers
• HHS Therapeutics Clinical Implementation Guide
• Pharmacists Resources
  • Electronic Data Transmission Prescriptions – Frequently Asked Questions – California State Board of Pharmacy
  • September 2021 Edition of The Script (ca.gov)
  • Pharmacist-Prescribed Paxlovid Guide (CPESN, 9/15/22)
  • The Emergency Use Authorization (EUA) for Paxlovid allows pharmacists to prescribe Paxlovid under specific circumstances. Please see the California Board of Pharmacy Order Waiving Restrictions on Pharmacists Independently Initiating and Furnishing Paxlovid to Individual Patients for more details. The Department of Healthcare Services (DHCS) will reimburse pharmacists for prescribing and/or dispensing Paxlovid when in accordance with California Board of Pharmacy Waiver and the Food and Drug Administration’s EUA.
• Billing Instructions
  • DHCS will reimburse pharmacists for prescribing (consultation and assessment)
  • Providers will be reimbursed professional dispensing fee only, not the ingredient cost
  • Claims for reimbursement of the dispensing fee must be submitted to Medi-Cal Rx for processing
  • Claims for consultation and assessment must be billed to DHCS as a Pharmacist Service
  • Reimbursement claims for consultation & assessment (CPT codes 99202 & 99212) must be submitted on a CMS 1500 medical claim form
  • Eligible claims must have an ICD-10-CM diagnosis code, U07.1 (COVID-19)
  • Effective through the end of the declared public health emergency

• • The Ventura County Variants report provides aggregate whole genome sequencing results for local COVID-19 cases.  This report updates every Wednesday with the most current local data.
    • For help navigating this report, watch this video.
  • The California COVID Assessment Tool (CalCAT) website includes nowcasts, forecasts, scenarios, and variants
  • The Centers for Disease Control (CDC) Variant Proportions webpage reflects up-to-date variant monitoring, links to nowcasts, and breaks down variant proportion by region
  • The National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCAT) Open Data Portal on variant therapeutics offers a summary of findings from recent studies, with table allowing for comparison of resistance profiles of different variants
  • Variant Therapeutic in vitro Activity Visualization (nih.gov)

• • CDPH Variant Tracking
  • Therapeutic Efficacy Status as of 12/14/2022:

• • • Paxlovid /Lagevrio (Molnupiravir) /Veklury (Remdesivir) expected to retain activity against all circulating variants based on preliminary data and sequence analysis; additional data pending.
    • mAbs currently not authorized for use (Regen-COV, Bamlanivimab/Etesevimab, Sotrovimab, Bebtelovimab) are routinely tested against emerging variants.

In most cases, the packaging labels do not represent the most current expiration date for that product. Be sure to always check the relevant webpages for current product specific expiration dates.

• Expiration Dating Extension | FDA
• Paxlovid Product Extension
  • Extension from 9 months to 12 months (4/5/22)
  • Extension from 12 months to 18 months (9/6/22)
• Lagevrio (Molnupiravir) Product Extension from 24 months to 30 months (10/21/22 )
• Bebtelovimab Product Extension from 18 months to 24 months (10/26/22)

Monoclonal Treatment

Bebtelovimab

• FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region | Important Update | HHS/ASPR (11/30/2022)

Paxlovid

Pfizer’s Paxlovid
Type: Oral antiviral – protease inhibitor.
Administration Route: By mouth (PO) – twice daily for 5 days.
Timing: As soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.
Target Population: COVID-19 patients 12 years of age and older weighing at least 40 kg who are at high risk for progression to severe COVID-19 symptoms. Many drug-drug interactions.

• Paxlovid EUA Letter
• Paxlovid Fact Sheets
  • Provider Fact Sheet
  • Fact Sheet for Patient/Caregivers
  • Fact Sheet for Patient/Caregivers (Spanish)
• Paxlovid Resources
  • Sample Prescription
  • Sample Standing Order
  • Information Sheet: Paxlovid Eligibility and Effectiveness (hhs.gov)
  • FAQs on the EUA for Paxlovid 07062022 (fda.gov)
  • PAXLOVID Patient Eligibility Screening Checklist and Drug Interaction Tool 08262022 (fda.gov)
  • Information on Viral Rebound

• • • Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19 | medRxiv
    • Recurrence of Symptoms Following a 2-Day Symptom Free Period in Patients With COVID-19 | Infectious Diseases | JAMA Network Open | JAMA Network
    • Nirmatrelvir–Ritonavir and Viral Load Rebound in Covid-19 | NEJM
    • Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study | medRxiv
    • Game Changer: Paxlovid Reduces Hospitalizations and Saves Lives  l  Epic Research
    • CDC Morbidity and Mortality Weekly Report (MMWR):

• • • • Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment (06/24/2022)
      • Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022 (12/02/2022) 

• • • COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 | medRxiv
    • Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons – PMC (nih.gov)
    • CDC Health Advisory: COVID-19 Rebound After Paxlovid Treatment

• Pharmacists Resources
  • Electronic Data Transmission Prescriptions – Frequently Asked Questions – California State Board of Pharmacy
  • September 2021 Edition of The Script (ca.gov)
  • Pharmacist-Prescribed Paxlovid Guide (CPESN, 9/15/22)

Lagevrio (Molnupiravir)

Merck and Ridgeback’s Molnupiravir
Type: Oral antiviral – nucleoside analogue.
Administration Route: By mouth (PO) – every 12 hours for 5 days
Timing: As soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.
Target Population: COVID-19 patients 18 years of age and older who are at high risk for progression to severe COVID-19 symptoms. NOT recommended in pregnancy.

• Molnupiravir EUA Letter
• Molnupiravir Fact Sheets
  • Provider Fact Sheet (updated 08/05/2022)
    • Updated Section Microbiology (Section 12.4)
    • Addition of viral RNA rebound: Viral RNA Rebound Post treatment increases in SARS CoV 2 RNA shedding levels (i.e., viral RNA rebound) in nasopharyngeal samples were observed on Day 10, Day15, and/or Day 29 in a subset of LAGEVRIO and placebo recipients in the Phase 3MOVe OUT trial. Approximately 1% of both LAGEVRIO and placebo recipientshad evidence of recurrent COVID 19 symptoms coinciding with a rebound in viral RNA levels in nasopharyngeal samples. Post treatment viral RNA rebound wasnot associated with the primary clinical outcome of hospitalization or death through Day 29 following the single 5 day course of LAGEVRIO treatment. Posttreatment viral RNA rebound also was not associated with the detection of cell culture infectious virus in nasopharyngeal swab samples.
  • Fact Sheet for Patient/Caregivers
  • Fact Sheet for Patient/Caregivers (Spanish)
• Molnupiravir Resources
  • FAQs on the EUA
  • Information Sheet: Lagevrio Eligibility and Effectiveness (hhs.gov)
  • Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic | SpringerLink
  • Effectiveness of Molnupiravir in High-Risk Patients: A Propensity Score Matched Analysis | Clinical Infectious Diseases | Oxford Academic

Remdesivir

Gilead’s Veklury (Remdesivir)
Type: nucleotide analog RNA polymerase inhibitor
Administration Route: intravenous (IV) infusion over 30 to 120 minutes
Timing: For non-hospitalized patients, as soon as possible after diagnosis of COVID-19 and within 7 days of symptom onset. See Patient Information for initiation of treatment in hospitalized patients as well as the duration of treatment for hospitalized and non-hospitalized patients.
Target Population: Adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing, who are hospitalized or not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.

• Dear Healthcare Provider Letter
• Prescribing Information
• Patient Information
• Veklury Resources
  • https://www.veklury.com/
  • Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients | NEJM

• COVID-19 Convalescent Plasma EUA Letter
• COVID-19 Convalescent Plasma Provider Fact Sheet
• Recommendations for Investigational COVID-19 Convalescent Plasma | FDA

• • FDA issued an EUA to permit the emergency use of the unapproved product, COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies, for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting. COVID-19 convalescent plasma is not authorized to treat immunocompetent patients with COVID-19.
  • Given that the clinical evidence in patients with immunosuppressive disease or receiving immunosuppressive treatment remains limited, data from additional randomized, controlled trials are needed.
  • FDA has authorized other treatments for emergency use for the treatment of COVID-19 in adults and pediatric patients in the outpatient setting. These products have more consistently demonstrated clinical benefit in this population, and do not carry some of the risks associated with transfusion of blood components.

• COVID-19 Treatment Guidelines: Convalescent Plasma and Immune Globulins | NIH

• • Based on the available data, the Panel revised the recommendation language for the use of CCP in patients who are immunocompromised. There is currently insufficient evidence for the Panel to recommend either for or against the use of high titer CCP for the treatment of COVID 19 in hospitalized or nonhospitalized patients who are immunocompromised. Some Panel members would use CCP to treat an immunocompromised patient with significant symptoms attributable to COVID 19 and with signs of active SARS-CoV-2 replication and who is having an inadequate response to available therapies. In these cases, clinicians should attempt to obtain high titer CCP from a vaccinated donor who recently recovered from COVID 19 likely caused by a SARS-CoV-2 variant similar to the variant causing the patient’s illness.

• CCP Resources

• • Convalescent Plasma l CDC & IDSA

• Telehealth Resources (HHS)
• Health Equity in Telehealth
• California Telehealth Resource Center

Paxlovid and Molnupiravir: When prescribing these medications to your patients, providers should visit the HHS Therapeutics Locator to find pharmacies with current supply of these products. Patients may also be advised of the HHS Test to Treat (T2T) program and the HHS T2T Locator map.

Remdesivir: Veklury (Remdesivir) is commercially available through Gilead Pharmaceuticals and multiple distributors. For additional purchasing information or how to access Remdesivir, Providers may email remdesivir@amerisourcebergen.com, call 1-800-746-6273, or reach out directly to your AmerisourceBergen , Cardinal, or McKesson representative.

• COVID-19 Uninsured Group Program (ca.gov)
• Frequently Asked Questions (FAQs) Presumptive Eligibility (PE) for Coronavirus (COVID-19) (ca.gov)
• Billing and Cost Sharing Overview for COVID-19 Vaccination, Testing, and Treatment | Bureau of Primary Health Care (hrsa.gov)
• Medi-Cal NewsFlash: Reminder: COVID-19 Oral Antivirals for Uninsured Group
• CMS COVID-19 Vaccines and Monoclonal Antibodies

Click here to view the CDPH HPoP Reporting and Transfer instructions.

General inquiries: COVIDTherapeutics@ventura.org
Clinical questions: COVIDRxProviders@cdph.ca.gov
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