Guidance for healthcare providers May 2023 Recently, various novel agents have become available in BC for the treatment of COVID-19 in mild-moderately ill patients. These therapies include a direct-acting oral combination antiviral nirmatrelvir/ritonavir (Paxlovid), an IV antiviral remdesivir (Veklury) and an anti-spike protein monoclonal antibody (mAb) sotrovimab (Xevudy) Please see the full guide developed by the B.C. COVID Therapeutics Committee for more information: Clinical Practice Guide for the Use of Therapeutics in Mild-Moderate COVID-19 Who is the treatment currently being considered for? Refer to: Practice Tool #1-Assessment Steps and Practice Tool #2-CEV Definitions Patients who test positive for COVID-19 via a Polymerase Chain Reaction (PCR) or Rapid Antigen Test (RAT) test AND have been identified as being at increased risk for needing to go to the hospital for COVID-19: o Individuals who are immunocompromised or have high-risk conditions identified as Clinically Extremely Vulnerable (CEV) regardless of vaccine status or previous infection (Not all children ages 12-17 who are CEV will benefit from treatment. Those with multiple co-morbidities would have the highest potential benefit)# 
- Individuals with TWO of the following three risk factors: o 70 years (60 years if they are Indigenous) o Are unvaccinated or under-vaccinated as per Strong Recommendations by NACI^ o Have at least one serious chronic medical condition- ^ National Advisory Committee on Immunization: i.e., lack of a primary two-dose series PLUS a "Fall Booster" (or a booster in the last year), which may be delayed up to 6 months post COVID-19 infection *Serious chronic medical conditions may include stroke, heart failure, heart disease, diabetes, kidney or liver disease, chronic lung disease like COPD or interstitial lung disease, neurological conditions. Some discretion can be used

# Therapy recommendations:
Patients offered treatment should be appreciably symptomatic from COVID 19.  Nirmatrelvir/ritonavir is also contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.

# Significant drug-drug interactions:
(See Practice Tool 3: Drug Interactions and Contraindications for more details).
- Most common contraindications include amiodarone, DOACs, some antipsychotics, statins, midazolam and triazolam, fentanyl and antiepileptics  Some drug-drug interactions can be managed
The most comprehensive drug-drug interaction checker with nirmatrelvir/ritonavir was developed by the University of Liverpool and is found here: . This tool should be consulted when considering modifying therapy due to drug-drug interactions. Use multiple resources (e.g. LexiComp) as some information may be conflicting or incomplete.

# THERAPY: remdesivir (Veklury)direct acting antiviral administered by intravenous injection
When to start: IV x 3 daily doses is recommended within 7 days of symptom onset as an alternative to nirmatrelvir/ritonavir in cases where IV administration is feasible. Patients with a risk of hospitalization of  5% are currently being prioritized and offered treatment with remdesivir.
Remdesivir infusions are currently being delivered through Health Authority based clinics.

# Contraindications and Cautions
Drug-to-Drug Interactions  Hypersensitivity reactions and infusion reactions are rare.  ALT > 5X ULN  Patients with an eGFR of < 30ml/min require dose adjustments and monitoring.
Possesses no significant drug-drug interactions.

# THERAPY: sotrovimab (Xevudy)monoclonal antibody administered by intravenous injection
When to start: IV x 1 dose within 7 days of symptom onset in extenuating circumstances when remdesivir cannot be given. Sotrovimab has demonstrated reduced neutralization against the BA.2 variant although it may retain some activity. If sotrovimab is used as a last line agent where potential of benefit outweighs the risk, disclosure to patients of risks and benefits in consideration of individual circumstances (clinical status, patient values, logistics) is necessary. Sotrovimab should not be chosen solely for convenience reasons.
Sotrovimab infusions are currently being delivered through Health Authority based clinics.

# Contraindications and Cautions Drug-to-Drug Interactions
Hypersensitivity reactions and infusion reactions are rare. If reactions develop during the 1-hour infusion, the infusion should be stopped.
Possesses no significant drug-drug interactions.