Mild to moderate disease refers to patients with COVID-19 symptoms such as cough, nasal congestion, headache, sore throat, taste disturbance, muscle aches, fever and/or malaise who do not require supplemental oxygen support (i.e., have oxygen saturations of ≥ 94% on room air) for COVID-19 illness.
Patients are usually ambulatory and recovering at home; however, patients with mild-moderate COVID-19 may also reside in Long-Term-Care or Assisted Living or be hospitalized for reasons other than to receive respiratory/organ support for COVID-19.
Various novel agents have become available in B.C. for the treatment of COVID-19 in mild-moderately ill patients. These therapies include a direct-acting oral combination antiviral nirmatrelvir/ritonavir (Paxlovid) and an IV direct acting antiviral remdesivir (Veklury). A monoclonal antibody, sotrovimab (Xevudy) is no longer in routinely use due to potential loss of activity against the BA.2 variant of concern. It likely retains some activity but it is reserved as a last-line agent.
Read: Health Care Provider Information on Paxlovid, remdesivir and sotrovimab - updated April 12, 2022
Clinical Practice Guide: Recommendations and Evidence -updated January 12, 2023
- This document provides general guidance on the use of four therapeutic agents for clinicians and supporting evidence. It includes information on:
- sotrovimab (Xevudy)
- nirmatrelvir/ritonavir (Paxlovid).
- remdesivir (Veklury)
- molnupiravir (Lagevrio)
Practice Tool #4: Pharmacist Counselling Checklist -
updated June 21, 2022
- This checklist is intended for use by pharmacists as a quick reference guide and should not be regarded as a substitute for clinical judgement and patient-specific counselling.
Practice Brief: Crushing Nirmatrelvir/ritonavir (Paxlovid) - new July 4, 2022
- Both ritonavir and nirmatrelvir can be split or crushed and mixed with apple sauce, pudding or any common food or liquid including dairy-containing products based on Phase I studies demonstrating that suspensions achieve similar pharmacokinetics to whole tablets.
- Both ritonavir and nirmatrelvir can be crushed and mixed with water to the desired consistency and considered for administration via feeding tubes; the tube should be flushed with water after administration. There are currently no precise recipes available; standard practices for administering regular powered tablets via feeding tubes should be applied. It may not be appropriate to administer crushed medications through smaller bore feeding tubes where obstruction is a concern (e.g., jejunal or naso-jejunal); consultation with an expert dietician or nursing staff may be required.
- Due to lack of information pertaining to stability and storage of nirmatrelvir suspension, it is recommended that any suspension made with crushed nirmatrelvir and ritonavir be extemporaneously compounded as single-dose preparation and not as multi-dose liquid.
COVID-19 Action Plan - Updated November 4, 2022
- This Action Plan can be used with high-risk patients who are candidates for COVID-19 therapy before they get sick.
- Patients can follow testing, treatment and public health recommendations contained in the Green, Yellow and Red zones.
Health Canada approved a monoclonal antibody cocktail tixagevimab/cilgavimab (Evusheld) for the prevention of COVID-19 in those who are severely immune compromised and unlikely to mount an adequate immune response to COVID‐19 vaccination or for whom COVID-19 vaccination is not recommended.
However, due to the prevalence of the BA 4/5 Variants of Concern, the activity of tixagevimab/cilgavimab (Evusheld) is greatly reduced and the clinical evidence for its use has been non-reassuring. The updated Practice Guide includes a summary of this evidence and updated recommendations.
Nirmatrelvir/ritonavir 300/100mg PO BID x 5 days (or 150/100mg PO BID x 5 days for eGFR 30-60 ml/min) is recommended within 5 days* of symptom onset for patients without contraindications** deemed at high risk# for disease progression/hospitalization from COVID-19 and who are appreciably symptomatic. (Conditional recommendation pending peer-reviewed publication)
*It is appropriate to allow the addition of adequate time for delivery of medication for those living in remote and rural communities.
#Patients at high-risk for disease progression and hospitalization from COVID-19 are those who are:
- Immunocompromised individuals and those with high-risk conditions identified asidentified as Clinically Extremely Vulnerable Group 1, Group 2, and Group 3
(CEV 1, CEV 2 and CEV 3),
regardless of vaccine status or previous infection (See also
Practice Tool 2 CEV Definitions).
Unvaccinated individuals without previous infection
who are EITHER:
≥50 years OR
- have three or more chronic conditions/co-morbidities
Individuals ≥ 50 years with 1-2 vaccine doses or previous infection alone, with three or more chronic conditions/co-morbidities
Individuals aged ≥70 years with 1-2 vaccine doses or previous infection alone, with one or more chronic condition/co-morbidity
≥ 70 years
with three or more chronic conditions/co-morbidities,
regardless of vaccine status or previous infection
Indigenous individuals (if not captured above) who are EITHER:
unvaccinated without previous infection OR
≥ 50 years with 1-2 vaccine doses or with previous infection alone OR
≥ 70 years regardless of
vaccine status or previous infection
Remdesivir 200mg IV on day 1, followed by 100mg IV on days 2 and 3 (200mg IV on day 1, followed by 100mg IV 48-72 hours later in eGFR <30ml/min)
is recommended within 7 days of symptom onset as an alternative to nirmatrelvir/ritonavir. Patients at the highest risk# of progression to severe disease (≥ 5%) are currently being prioritized for treatment with remdesivir.
#Patients at highest risk (≥ 5%) for disease progression and hospitalization from COVID-19 are those who are:
- Severely immunocompromised individuals identified as Clinically Extremely Vulnerable Group 1 (CEV 1), regardless of vaccine status or previous infection (See also Practice Tool 2 CEV Definitions).
- Moderately immunocompromised individuals and those with high-risk conditions identified as Clinically Extremely Vulnerable Group 2 and 3 (CEV 2 and CEV 3)
(See also Practice Tool 2 CEV Definitions), who are either:
- ≥ 50 regardless of vaccine status or previous infection OR
- < 50 with 0-2 doses of vaccine or previous infection alone
- Individuals who have a combination of age, under-vaccination, and risk factors such as co-morbidities or Indigenous status who are shown to have a risk of ≥ 5%. (To assess risk, see the point system or thermal maps in the
Clinical Practice Guide)
Sotrovimab 500mg IV X 1 dose has reduced efficacy against the BA. 5.1, BA. 5.2 and 5.2.1 variants, although it may retain some activity. Real-world evidence shows limited efficacy against the BA 1. and BA. 2 variants of concern (VoCs) in immunocompromised or non-immune individuals, which may predict its performance against most BA. 5 VoCs. Sotrovimab has unknown clinical efficacy against many currently circulating VoCs (e.g., BA. 4.6, BQ. 1, BQ 1.1, XBB and BF. 7) where a reduction in binding, but not complete resistance, is seen.
If sotrovimab is used in cases where remdesivir or nirmatrelvir/ritonavir cannot be used, patient disclosure to risks and benefits in consideration of individual circumstances (clinical and immune status, patient values, logistics) is necessary. The convenience of single dose sotrovimab should not be the primary indication for use.
Tixagevimab/cilgavimab 600mg IM x 1 dose has demonstrated a 50.5% relative risk reduction (RRR) in COVID-19 hospitalization and death in unvaccinated, non-hospitalized adults with mild- moderate COVID-19 (TACKLE), which is lower than the RRR seen with other COVID-19treatments in similar trials. Tixagevimab/cilgavimab is likely ineffective against many currently circulating VoCs including BA. 4.6, BF. 7, BA. 2.75.2, BQ 1, BQ 1.1 and XBB where 300-1000-fold reductions in binding are seen.
If tixagevimab/cilgavimab is used as a last line treatment in cases where nirmatrelvir/ritonavir, IV remdesivir or sotrovimab cannot be used, disclosure to patients of risks, including cardiovascular serious adverse events (SAEs), and benefits and consideration of individual circumstances (clinical and immune status, patient values, logistics) is necessary. The convenience of the IM route of administration of tixagevimab/cilgavimab should not be the primary indication for use.
Colchicine was evaluated at 0.6 mg PO BID x 3 days, then 0.6 mg daily x 27 days in a large Canadian RCT (COLCORONA) and demonstrated a reduction in progression of COVID-19 and hospitalization in a sub-group of patients with PCR confirmed COVID-19. The trial’s primary endpoint was not statistically significant and impact of colchicine against hospitalizations from Omicron is unclear.
The trial was stopped early; due to decreased power leading to the low certainty of its results, as well as a higher risk of adverse events (diarrhea and blood clots) guidelines (WHO, NIH) do not recommend colchicine.
If colchicine is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values are necessary.
Fluvoxamine was evaluated at 100 mg PO BID x 14 days in a Brazilian RCT (TOGETHER) and shown to reduce emergency room visits lasting > 6 hours, a surrogate endpoint for hospitalizations. It did not demonstrate reductions in actual hospitalizations from COVID-19, length of stay or mortality. For every 12 trial participants, one additional patient stopped fluvoxamine prematurely.
Due to low generalizability from a very high event rate during the Delta wave, as well as lack of robust safety data considering that the maximum daily dose was used in the trial, guidelines (e.g., IDSA, NIH) do not recommend the use of fluvoxamine. A Canadian fluvoxamine study (STOP COVID 2) stopped enrollment due to futility.
If fluvoxamine is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values are necessary.
Inhaled corticosteroids budesonide 800 µg twice daily OR ciclesonide 320 µg twice daily for 14 days may be considered within 14 days of symptom onset in adults with mild-moderate lower respiratory track symptoms of COVID-19 (e.g., cough, increased work of breathing or pneumonia) aged ≥65 OR aged ≥50 with underlying health conditions (e.g., heart disease, chronic lung disease, diabetes, stroke or other neurological conditions) who are not candidates for nirmatrelvir/ritonavir, sotrovimab or remdesivir.
Patients should be informed of uncertainty in the benefit of treatment in decreasing symptom severity or progression, and the risks and potential adverse effects.
Based on the current scientific evidence and best practice guidelines, inclusive of considering retracted publications, the College of Physicians and Surgeons of BC, the College of Pharmacists of BC, the BC College of Nurses and Midwives and the CTC do not approve of the use of ivermectin for either treatment or prophylaxis for COVID-19 and
BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials.
Various therapies have been evaluated to be ineffective and/or unsafe in treatment of mild-moderate COVID-19 and are not recommended outside of clinical trials. These include:
- Lopinavir/ritonavir (Kaletra)
- Oseltamivir (Tamiflu)
- Chloroquine or hydroxychloroquine
- Ribavirin and interferon
- Antivirals used for Hepatitis C (e.g., sofosbuvir/ledipasvir)
- Oral corticosteroids (e.g., dexamethasone)
- Intravenous Immunoglobulin G (IVIg)
- Convalescent Plasma
- Vitamins D and C
- Acetylsalicylic Acid (ASA, Aspirin)