Warm Springs Health and Wellness Center Interim Guidelines for Outpatient Treatment of Mild to Moderate CoVID-19 via the Test to Treat Approach

Purpose

To provide the Medical clinic and Pharmacy with guidelines for treatment of mild to moderate CoVID-19 with currently available oral antiviral therapies under Emergency Use Authorizations (EAU) via the Test to Treat method

Scope

All Medical Clinic Staff (MD, ANP, and PA) and Pharmacists

Policy

Patients testing positive for CoVID-19 need to be evaluated regarding risk for progression to severe disease or hospitalization in a timely fashion. Prompt provider notification of positive CoVID-19 test results will increase access to same day treatment with oral antiviral medications and decrease disease progression to hospitalization or death

1. Notification of positive results
   1. Laboratory staff will notify the designated provider or the ordering provider of positive results of a CoVID-19 Abbot –ID now or Cepheid PCR test as a critical value
   2. Nursing or Dental staff completing Binax Point of Care testing will notify the designated provider or the ordering provider of positive results verbally
   3. Nurse Case Managers, CoVID-19 Nurse, and/or ER and hospitalization admissions Reviewer will notify the designated provider or ordering provider of positive CoVID-19 tests
   4. Contact Investigator or Tracers will notify designated provider or the ordering provider by phone call and EHR note of positive home test and date of symptoms onset
2. The provider will evaluate the patient’s qualifications for treatment with Paxlovid or molnupiravir. Evaluation will be documented using the CoVID Therapeutics Evaluation Note Template
   1. 1st level criteria
      1. Must be minimum of 12yo and weigh >40kg for Paxlovid and 18yo for molnupiravir
      2. Must have a positive test for COVID-19 (no presumptive or post exposure prophylaxis)
      3. Must be symptomatic of CoVID-19
      4. Must be considered high risk for progression of severe disease or hospitalization by at least one of the following criteria. Each criteria can be considered 1 point
         1. Body Mass index ≥25
         2. Pregnant
         3. Chronic Kidney Disease
         4. Diabetes
         5. Immunosuppressive disease or immunosuppressive treatment
         6. Cardiovascular Disease or hypertension
         7. Age ≥65yo
         8. Chronic lung disease
         9. Sickle Cell Disease
         10. Neurodevelopmental Disorder or congenital anomalies
         11. Any medical related technological dependence (gastrostomy or CPAP)
      5. An unvaccinated status should be considered as one point in those meeting one or more of the above criteria in triaging of multiple cases for treatment
      6. Patients meeting at least one criteria (point) will be contacted to discuss and offer treatment options
      7. In the event of multiple cases of CoVID-19 qualifying for treatment, providers may need to discuss and prioritize those most critical to treat first based on risk factors, symptoms, therapeutic window, and supply availability
   2. Available treatment options: local treatment options may change based on nationwide supply, current variants of the CoVID-19 virus, new Emergency Use Authorizations, or FDA approvals. These guidelines will be updated as needed to reflect available outpatient treatment options. As much as possible, treatments are provided on the same day of positive CoVID-19 test identification.
   1. Paxlovid: Nirmatrelvir 300mg (2 x 150mg tablets) with ritonavir 100mg (1 tablet)
      1. Clinical Considerations
         1. Must be >12yo and weigh >40kg
         2. Must be started within 5 days of symptom onset and as soon as possible after diagnosis
         3. Can be used in patient requiring supplemental oxygen
         4. Not authorized for use in patients requiring hospitalization
         5. No human data is available regarding use n pregnancy or lactation
      2. Contraindications
         1. History of severe hypersensitivity reaction to nirmatrelvir or ritonavir or any other components
         2. Chronic kidney or liver disease
            1. eGFR <30 mL/min
            2. Severe hepatic impairment (Child-Pugh Class C)
         3. Co-administration with drugs dependent on CYP3A for clearance where elevated concentrations are associated with serious and/or life-threatening reactions

            Alfuzosin, pethidine, propoxyphene, anolazine, amiodarone, dronedarone, flecainide, propafenone, quinidine, colchicine, lurasidone, pimozide, clozapine, dihydroergotamine, ergotamine, methylergonovine, lovastatin, simvastatin, sildenafil, triazolam, oral midazolam

         4. Co-administration with potent CYP3A inducers may decrease the potential for loss of virologic response and possible resistance.

            Apalutamide, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort

      3. Precautions:
         1. Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice. Use caution in patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis
         2. HIV-1 Drug Resistance: may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection
         3. Ritonavir can decrease the efficacy of combined hormonal contraceptives
      4. Adverse reactions: commonly seen (1-2%) side effects in clinical trials include dysgeusia diarrhea, hypertension, myalgia
      5. Dosing
         1. For eGFR >60 mL/min: Nirmatrelvir 300mg (2 tablets) with ritonavir 100mg (1 tablet) PO BID for 5 days
         2. For eGFR >30 to <60 mL/min: Nirmatrelvir 150mg (1 tablet) with ritonavir 100mg (1 tablet) PO BID for 5 days
         3. Order can be found under “CoVID Symptom treatment” menu in EHR
      6. The provider is responsible reporting of all serious adverse events and medication errors potentially related to Paxlovid within 7 calendar days via MedWatch Exit Disclaimer: You Are Leaving www.ihs.gov 
      and VAERS.
      7. EAU fact sheet for providers Exit Disclaimer: You Are Leaving www.ihs.gov 
   2. Molnupiravir 800mg (4 x 200mg capsules)
      1. Clinical Considerations
         1. Must be age >18yo as it may affect bone and cartilage growth
         2. Must be started within 5 days of symptom onset and as soon as possible after diagnosis
         3. Not authorized for use in patients requiring hospitalization
         4. Use when alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate
      2. Contraindications: no absolute contraindications
      3. Precautions:
         1. Not recommended for use in pregnancy
            1. Advise sexually active males of childbearing age with female partners to use contraception during and for 3 months after treatment completed
            2. Advise sexually active females of childbearing potential to use contraception during treatment and for 4 days after the last molnupiravir dose
            3. Breastfeeding is not recommended during and for 4 days after treatment completed
         2. Adverse reactions: diarrhea, nausea, dizziness
         3. Dose: 800mg molnupiravir PO BID for 5 days
            1. No dose adjustment for renal impairment
            2. Order can be found under “CoVID Symptom treatment” menu in EHR
         4. The Provider is responsible for reporting of all serious adverse events and medication errors potentially related to molnupiravir within 7 calendar days via MedWatch Exit Disclaimer: You Are Leaving www.ihs.gov  and VAERS
      4. EAU fact sheet for providers Exit Disclaimer: You Are Leaving www.ihs.gov 
   1. The provider will document each evaluation in EHR
      1. The Provider will document the evaluation and medication prescribing via the CoVID Therapeutics Evaluation Note Template
      2. The Provider will include a comment in the EHR evaluation note stating: This prescription must be dispensed [and started] by ________. This date is 5 days from symptom onset and complies with the patient eligibility criteria under the EUA
   2. The Pharmacist will process each CoVID-19 treatment prescription as an expedited order
      1. The pharmacist will review the dispense/start by date to ensure prescription is valid
      2. Review patient charts for drug/drug interactions, contraindications, pregnancy/breastfeeding status
      3. Review prescribed dosing for any required renal adjustments
      4. Contact provider with questions or clarifications
      5. A copy of the associated EUA Fact Sheet will be included with each prescription
      6. Same day dispensing of prescribed medication
         1. If patient is still in room with provider, pharmacy will deliver medication to the patient room in medical clinic
         2. If patient is not in clinic, the prescription will be stored in will-call ready to dispense to the patient or proxy via delivery to vehicle or other designated area
   3. All components of the oral antiviral EUA, HHS, and IHS policies will be adhered to including proper storage, handling, inventory management, reporting requirements, and HPoP use
   4. If neither oral antiviral medication is an option, but the patient meets criteria and concerns in item II. iv., the provider will evaluate whether the patient qualifies for monoclonal antibody therapy and process referral and/or schedule appointment as soon as possible including same day if determines necessary