FINAL-COVID-19 treatment Flashcards
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What are the treatment recommendations for non-severe, severe and critical Covid-19?
How should outpatients with covid-19 symptoms be managed?
Outpatients with COVID-19 symptoms should be offered standard care for influenza-like illness such as antipyretics and cough and cold products where appropriate, adequate nutrition, and appropriate hydration. There is no evidence to suggest that NSAIDs should be avoided based solely on a COVID-19 diagnosis. Individuals and their caretakers should be counselled on signs of deterioration such as light headedness, difficulty breathing, chest pain, dehydration, etc. which may prompt further assessment by a healthcare provider. Isolation to contain viral spread should be practiced whenever feasible.
SHould NSAIDS be avoided in patients with covid-19?
Nope!
When should nirmatrelvir/ritonavir be offered to patients who have covid-19 symptoms?
Outpatient COVID-19 treatment consists primarily of nirmatrelvir/ritonavir (Paxlovid®) for eligible patients who are at high (strong evidence) or moderate (weak evidence) risk of hospitalization. Evidence comes primarily from the EPIC-HR study, which looked at patients with at least one risk factor for severe disease.
RISK FACTORS ARE:
a. Severe immunosupression - Recipient of solid organ transplant, treatment for a malignant hematologic condition, bone marrow, stemcell transplant, or transplant related immunosuppressant use, receipt of an anti-CD20 drug or B-cell depleting drugs such as rituximab, in the past 2 years, severe primary immunodeficiencies
b: Moderate immunosuppression
- Cancer treatment, including solid tumors
- Treatment with sfnificantly immunosuppressing drugs (eg. A Biologic in the past 3 months, oral immune-suppressing medication in the past month, oral steroid (20mg/day of prednisone equivalent taken on an ongoing basis), in the past month, or immune-suppressing infusion or injection in the past 3 months
- Advanced HIV infection
- Moderate primary immunodeficienies
- renal conditions (dialysis, peritoneal dialysis, glomerulonephritis.
REVIEW THE COVID-19 medications used to treat table from notes!
Go to notes.
What is recommended regarding drug interactions and Paxlovid?
Due to the high potential for drug interactions with nirmatrelvir/ritonavir – see table below – it is recommended to consult with a specialized drug interaction database (e.g. University of Liverpool COVID-19 interactive drug interaction checker: https://www.covid19-druginteractions.org/) to screen for clinically important interactions before prescribing and/or dispensing to patients receiving other medication.
What treatments may hospitalized patients receive?
Hospitalized patients may receive treatment with corticosteroids (dexamethasone preferred), IL-6 blockers (tocilizumab or sarilumab), a Janus Kinus inhibitor (baricitinib), or a combination of these treatments. Evidence for dexamethasone and baricitinib comes from the RECOVERY trial, which was the largest RCT of therapeutic options for the treatment of COVID-19. This trial was responsible for providing evidence for the lack of efficacy for many investigational agents as well.
What did the recovery trial determine?
The RECOVERY trial demonstrated a reduce mortality and reduced progression to needing mechanical ventilation or death in patients who received tocilizumab.
What is the evidence regarding remdesivir?
Remdesivir has weak evidence favouring its use in both outpatient and inpatient settings. The PINETREE RCT looked at ambulatory patients who received a 3-day course of remdesivir within 7 days or symptoms and 4 days of positive PCR test, and found a lower rate of COVID-related hospitalizations and death by day 28 [HR 0.13, (0.03-0.59)] compared to placebo. Evidence for remdesivir in hospitalized patients came from the ACTT-1 and SOLIDARITY studies, as summarized below.
Answer the following questions regarding paxlovid?
a. Classification
b. Mechanism of action
c. Dosage >60mls/min or 30-59 mls/min, <30mls/min
d. What is its clinical use
e. What are side effects?
f. Drug interactions
PAXLOVID
1. Classification - Protease inhibitor
2. MOA - Prevents viral replication
3. >60mls/min - nirmatrelvir/ritonavir - 300/100mg BID for 7 days 30-59mls/min - 150mg/100mg BID for 5 days, <30mls/min contraindicated
4. For the treatment of mild-moderate Covid-19 in those at high risk for hospitalization - MUST BE USED within 5 days of symptom onset following a positive test of covid-19
5. Side effects - Altered taste, elevated BP, diarrhea, vomiting, headache, muscle pain, rebound covid-19 symptoms, hepatotoxicity
6. Nirmatrelvir and ritonavir are CYP3A4 substrates. Ritonavir is a strong CYP3A4 inhibitor
Careful consideration to clinical implications of adjustment (ie. dose reductions, holding/changing current medications) should be taken when managing drug interactions with Paxlovid. Think: Does the clinical benefit outweigh the risks of altering current therapy
*Ritonavir is an HIV-1 protease inhibitor but is not active against the SARS-CoV-2 3CL protease. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir
Answer the following questions regarding Dexamethasone?
a. Classification
b. Mechanism of action
c. Dosage and alternatives
d. What is its clinical use
e. What are side effects?
f. Drug interactions
Dexamethasone
a. Classification - Corticosteroid
b. Mechanism of action - Exert anti-inflammatory effects by stimulating the synthesis and release of anti-inflammatory proteins and by inhibiting that of pro-inflammatory cytokines
c. PREFERRED is DEX: Dosage 6mg po/IV for 7 to 10 days. Alternatives would be hydrocortisone 50mg IV q8h for 7 to 10 days, and methylprednisolone 10mg every 6 hours for 7 days, prednisone 40mg daily for 7 days
d. What is its clinical use - For patients with severe or critical COVID to decrease risk for mortality and progression to mechanical ventilation
- May be combined with an IL-6 receptor blockers and baricitinib
e. What are side effects? Neuropsychiatric effects, increased appetite, hyperglycaemia, GI irritation, ulceration, fluid retention, weight gain, may mask signs of infection.
f. Drug interactions: Dexamethasone is a CYP3A4 substrate. CYP3A4 inhibitors (such as ritonavir) may decrease its metabolism. Antacids and CYP3A4 inducers may increase its metabolis
Answer the following questions regarding tocilizumab or sarilumab?
a. Classification
b. Mechanism of action -
c. Dosage
d. What is its clinical use
e. What are side effects?
f. Drug interactions
Answer the following questions regarding tocilizumab or sarilumab?
a. Classification - monoclonal antibody
b. Mechanism of action - monoclonal antibodies blocking IL-6. Elevated IL-6 concentrations are associated with severe outcomes in COVID-19, including respiratory failure and death
c. Dosage - Tocilizumab 8mg/kg IV (max 800mg)
or
Sarilumab 400mg IV
*initial dose administered over 1 hour
Second dose may be administered after 12-48 hour
d. What is its clinical use - For patients with severe or critical COVID to decrease risk for mortality and progression to mechanical ventilation
May be combined with a corticosteroid and baricitinib
*Both marketed for RA
e. What are side effects? - Tocilizumab: infusion reactions, serious infections, GI perforation, increased neutrophils, decreased platelets, neutropenia, elevated ALT, increased lipids
Sarilumab: infusion-site reactions, upper respiratory infections, neutropenia, elevated ALT levels.
f. Drug interactions - May enhance the immunosuppressive effect of other immunosuppressants and diminish the therapeutic effect of vaccines
Answer the following questions regarding Baricitinib/Ruxolitinib/Tofacitinib
1. Classification
2. MOA
3. Dosage
4. Indication
5. Adverse effects
6. Drug interactions
Answer the following questions regarding Baricitinib/Ruxolitinib/Tofacitinib
1. Classification - Janus Kinase (JAK) inhibitor
2. MOA - JAK inhibitors inhibit intracellular signalling in response to numerous interleukins, interferons, colony stimulating factors, and hormones. As a consequence, they interfere with many cellular responses, including antiviral responses, angiotensin-converting enzyme 2 (ACE2) expression, T cell function and differentiation, and macrophage activation
3. Dosage - Baricitinib - 4mg daily for 14 days or until hospital discharge - PREFERRED AGENT. Ruxolitinib 5mg BID for 14 days or until hospital discharge OR Tofacitinib 10mg BID for 14 days
4. Indication - For patients with severe or critical COVID to decrease risk for mortality and progression to mechanical ventilation
Baricitinib is preferred due to uncertain benefits and possibility of serious adverse effects of the other JAK inhibitors
5. Adverse effects - Infections (including TB, herpes zoster and pneumonia); GI perforation, neutropenia, increased lipids., increased risk of VTE and PE, as well as cases of arterial thrombosis.
Elevated liver enzymes and cases of hepatotoxicity have been reported.
6. Drug interactions - Monitor for drug interactions mediated by CYP3A4
