Paxlovid™ Updates

It is important to note that our understanding of the best treatment option(s) as well as the course of the COVID-19 virus and resulting disease continues to change at a rapid pace. Ensure you are consulting the most up-to-date version of these prescribing guidelines and documents.                  

Note: Prescribing of oral antiviral agents is authorized ONLY during a COVID-19 pandemic declared by the Chief Medical Health Officer for Saskatchewan.

These guidelines have been developed according to Saskatchewan pharmacy prescribing standards. Please reference your own province's guidelines when prescribing and billing.

Paxlovid™ Resources and Documents

PAR/Prescription

Algorithm

Drug Interactions Table

Renal Dosing Stickers

paxlovid^Tm Patient Handout

At Home with COVID-19? Handout

Paxlovid^Tm Patient Handout

Paxlovid for COVID - Eligibility Overview

Immuno -suppressive Medications

Mild COVID-19 Infection: Guidelines for Prescribing Paxlovid™

The medSask Guidelines for Prescribing for Minor Ailments and Patient Self-Care (the “Guidelines”) are intended to be used as a tool to aid decision-making when prescribing for certain minor ailments or self-care conditions. The Guidelines are intended solely for educational and informational purposes and are not to be used for diagnostic purposes, and do not replace personal skill, professional judgment, and care of a pharmacist or other healthcare professionals.

Description

• An acute viral respiratory tract infection caused by the SARS-CoV-2 coronavirus, resulting in COVID-19 disease.
• Other viruses may cause similar symptoms, making it impossible to differentiate clinically between the COVID-19 virus and other viruses. Some clinical features (for example, smell or taste disorders) are more common with COVID-19, but these cannot be used as reliable distinguishing signs or symptoms.
• The virus first started circulating at the end of 2019, causing outbreaks and a worldwide pandemic.
• The COVID-19 pandemic continues due to the emergence of novel strains for which there is/may be little to no pre-existing immunity. 
• Transmission of the COVID-19 virus occurs via respiratory droplets or aerosols (e.g. coughing, sneezing, singing, talking, etc.), by direct or indirect contact, or both.
  • Incubation period is usually within 14 days of exposure, with most cases occurring within 4 to 5 days after exposure.
  • The patient is considered infective 2 days prior to symptom onset or date of initial positive test, and for 10 days following symptom onset or date of initial positive test. However, in some patients (particularly in patients severely ill from COVID-19 and immunocompromised patients) the viral shedding may occur for 20 days or longer from symptom onset. 
• Patient groups at higher risk of symptomatic disease and progression to critical illness from COVID-19 include:
  • Older age (risk increases incrementally with each increase in decade of life)
    • In Saskatchewan, patients age ≥ 55 are considered high risk
  • Obesity: BMI ≥ 30 kg/m²
  • Pregnancy (all stages and 4 weeks post-pregnancy)
  • Indigenous peoples
  • Residents of long-term care and other chronic care facilities
  • Asthma, COPD, other chronic pulmonary diseases
  • Chronic kidney disease
  • Cardiovascular disease
  • Hypertension
  • Cancer
  • Diabetes mellitus
  • Immunocompromised due to disease or medication
  • Compromised handling of respiratory secretions – may occur in cognitive dysfunction, spinal cord injury, seizure disorders, neuromuscular disorders, cerebral palsy, etc.

**Note: Eligibility criteria varies based on different health authorities. For the purposes of this prescribing guideline, community prescribers will be expected to align with the Saskatchewan Health Authority (SHA). See the “Treatment” section for current eligibility. **

• Spectrum of illness ranges from asymptomatic infection, to mild symptoms, to severe pneumonia with acute respiratory distress (ARDS) and multiorgan dysfunction.
• Potential complications:
  • Respiratory failure: acute respiratory distress syndrome (ARDS)
  • Thromboembolic complications or thrombosis (VTE, PE), acute stroke and limb ischemia
  • Inflammatory complications: persistent fever, auto-anti-body mediated conditions such as Guillain-Barre syndrome and MIS-C (more common in children)
  • Neurological complications: encephalopathy, stroke, ataxia, delirium, movement disorders and sensory and motor deficits, neuropathy, and less commonly seizures.
  • Dehydration, hypovolemia
  • Acute kidney injury and renal insufficiency (low urine output)
  • Worsening of underlying medical conditions (e.g. heart failure, diabetes, COPD)
• Recovery time is highly variable and takes into consideration the patient’s age, comorbidities as well as severity of illness. Patients with mild illness generally recover within 2 weeks, while patients with more severe illness may take several months to recover.
• Many patients report long-term health effects that may persist for months after recovery from acute illness. Early reports estimate that approximately 10% of patients with mild illness (no hospitalization required) have symptoms persisting beyond four weeks, while a small percentage of patients have symptoms persisting beyond 12 weeks, and in some cases, up to 6 months.
  • Note: A case-control study found that patients who were vaccinated prior to infection with COVID-19 were less likely to develop “long-COVID” or “post-COVID” symptoms compared to unvaccinated patients.
• Most commonly reported “long-COVID” or “post-COVID” symptoms:
  • Fatigue
  • Cough
  • Shortness of breath
  • Chest pain or tightness
• Less commonly reported “long-COVID” or “post-COVID” symptoms:
  • Anosmia, dysgeusia, poor appetite
  • Arthralgia or myalgia
  • Headache
  • Memory loss, cognitive difficulty
  • Dizziness, palpitations
  • Depression, insomnia
  • Physical limitations of normal activity

As the information continues to evolve at a rapid rate, for more information and to access the most up to date information, see the following websites:

• Public Health Agency of Canada (PHAC)
• Centers for Disease Control and Prevention (CDC)
• World Health Organization (WHO)

LAST UPDATED: 09 May 2022

Signs and Symptoms

• Other viruses may cause similar symptoms, making it impossible to differentiate clinically between the COVID-19 virus and other viruses.  Some clinical features (for example, smell or taste disorders) are more common with COVID-19, but these cannot be used as reliable distinguishing signs or symptoms.
• When COVID-19 is known to be circulating in the community, diagnosis can be made based on a positive PCR or rapid antigen test (RAT).
• Presenting symptoms of mild COVID-19 vary, and may include: 
  • Cough
  • Sore throat
  • Rhinitis or congestion
  • Anosmia (loss of smell), dysgeusia (taste disturbance) or ageusia (loss of taste)
  • Myalgia (muscle pain) or arthralgia (joint pain)
  • Headache
  • Conjunctivitis
  • Dyspnea (shortness of breath); new or worsening over baseline, or change in activities that cause breathlessness
  • Fatigue, malaise, confusion
  • Fever ≥ 38.5°C (lasting < 72 hours)
  • Chills or rigors
  • Gastrointestinal (GI) symptoms (nausea, diarrhea, vomiting, anorexia, abdominal pain)
  • Anxiety, depression, insomnia
    • New or worsening 

Severity classification:                  
 ** Classification of symptom severity varies based on different references, health authorities, etc. For the purposes of this prescribing guideline, community prescribers will be expected to align with the Saskatchewan Health Authority (SHA).**

Mild Illness

• Signs and symptoms of mild illness.
• Non-hospitalized adults, not requiring supplemental oxygen (or increase in supplemental oxygen from baseline) with SpO₂ greater than 92% at rest, and have no increased work of breathing.

Moderate Illness

• Hospitalized patients requiring low-flow supplemental oxygen.

Severe Illness

• Hospitalized patients requiring additional interventions such as ventilatory or circulatory support.
  • Note: Patients may progress from one severity category to another relatively quickly. The rapidity of symptom progression does not appear to predict a worse outcome. Ensure patients are educated on signs and symptoms that indicate worsening of their condition and when to seek emergency medical attention. Provide the patient with the medSask document "Managing COVID-19 or Flu at Home."

LAST UPDATED: 09 May 2022

Differential Assessments

Many different bacterial and viral infections of the upper respiratory tract may present with similar symptoms as COVID-19, making it difficult to distinguish. The only way to rule out the following conditions that may present with similar symptoms is with a confirmatory PCR test or RAT.

• Influenza – symptoms may be very similar, however, gastrointestinal symptoms are generally uncommon in adults with influenza. Presentation varies, but in general includes signs and symptoms of upper and/or lower respiratory tract involvement in addition to systemic symptoms usually lasting 4 to 7 days but may last up to 10 days. Initial symptoms tend to be systemic progressing to more respiratory symptoms as systemic symptoms improve. 
  • Children: may present with a non-specific fever, or respiratory illness such as bronchitis or croup.
  • Healthy adolescents and adults: abrupt onset of fever and dry cough is highly predictable.
  • Older adults: ≥ 2 symptoms of cough, sore throat, myalgia and extreme weakness or exhaustion. 
• Common cold – less severe symptoms than influenza which resolve in a few days. Initial complaints are usually related to the throat (dry, scratchy, sore), nasal congestion and rhinorrhea. May experience cough that starts dry, progressing to productive.
• Allergic rhinitis – persistent upper respiratory tract symptoms such as rhinitis, sneezing, conjunctivitis, and absence of fever. Suspect if history of allergic rhinitis or exposure to allergen. See the Allergic Rhinitis prescribing guidelines.
• Pneumonia
  • Primary: persistent symptoms which worsen instead of resolving - high fever, dyspnea, coughing purulent sputum
  • Secondary bacterial pneumonia: exacerbation of fever, respiratory symptoms after initial improvement
  • Mixed: concurrent viral and bacterial infections. Patients may experience gradual worsening of symptoms or may experience some improvement followed by worsening. 
• Acute exacerbation of COPD or asthma – characterized by change in baseline symptoms beyond normal daily variations that requires change in therapy.
• Sinusitis – persistent purulent nasal secretions, nasal congestion, facial tenderness or pain, and headache are common. May also experience fever. 
• Streptococcal pharyngitis – acute onset of sore throat, fever, tender lymph nodes and pain upon swallowing. Unlikely to present with cough, runny nose or other common symptoms of upper respiratory infection.
• Croup – non-productive, barking cough, inspiratory stridor (whistling wheeze), hoarseness, most common in children less than 3 years of age. Symptoms often worsen at night. 
• Mononucleosis – classical presentation triad: fever, pharyngitis, and swollen glands. Additional symptoms may include fatigue, headache and lack of appetite.  
• Heart failure – cough, shortness of breath, history of heart failure.

LAST UPDATED: 09 May 2022

 

When to Refer

Patients with mild COVID-19 signs/symptoms and positive PCR test or RAT usually do not require further investigation, however, an assessment by the patient's primary care provider, referral to 811 or emergency referral may be required in the following situations.

Ineligible Patients

These patients should be advised to manage their symptoms at home, unless their symptoms progress from mild to moderate or severe disease. Patients should then be referred to emergency.

• Age < 18 years
• Patient is asymptomatic
  • Patients must present with symptom(s) to be eligible.
• Patient does not have a confirmed positive PCR or RAT result.
  • Patients may be directed to Saskatchewan.ca for information on where to obtain RAT.
• Pregnant patients
• Breastfeeding patients
• All patients (all sexes) unwilling to use contraception or abstain from heterosexual intercourse for the duration of treatment and 4 days after completion of treatment.
• Patients on dialysis or CrCl < 30mL/min
• Patients with active liver disease
• Un- or under- vaccinated patients age ≥ 18 to < 55 without ≥ 1 high risk factor or immunocompromised.
  • High risk factors include:
    • BMI ≥ 30 kg/m²
    • Chronic kidney disease (≥ 30 to < 60 mL/min)
      • Patients must have stable values within the last 6 months with no change in their clinical condition. If patients do not have recent kidney function values, complete the patient assessment as fully as possible. If they meet all other eligibility criteria, refer the patient to the SHA Early COVID Therapeutics Team. 
    • Cardiovascular or cerebrovascular disease (Hypertension, Coronary Artery Disease, Congestive Heart Failure, Congenital Heart Disease, Cardiomyopathy, Atrial Fibrillation, Hyperlipidemia, Stroke)
    • Diabetes (Type 1 or 2)
    • Chronic lung disease (COPD, Moderate to Severe Asthma, Cystic Fibrosis, Pulmonary Fibrosis, Pulmonary Hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorder (e.g. Cerebral Palsy, Down’s Syndrome) or other conditions that confer medical complexity (e.g. genetic or metabolic syndromes and severe congenital abnormalities)
  • Fully vaccinated^* patients (that are not immunocompromised) age ≥ 70 without either:
    • ≥ 3 high risk factors or
    • ≥ 2 high risk factors if the patient is Indigenous or resides in the  North [NE1, NE2, NW1, AHA]

*Fully vaccinated is defined by the SHA as the patient having received two doses of a two-dose vaccine or one dose of Janssen Jcovden™.

• Previous COVID-19 infection in which it has been fewer than 90 days since symptoms have resolved. 90-day timeframe is to ensure that the current infection is a distinct and new infection. Clinical discretion should be used in determining symptom resolution.
• Previous treatment with 2 courses of early COVID-19 antiviral (i.e. Paxlovid and/or remdesivir). Record of previous treatment can be obtained from patient history, PIP profile (Paxlovid™), and eHR viewer (Paxlovid™, remdesivir).
• Unable to confirm patient’s self diagnosis and/or self-care is not appropriate. Refer to the patient’s primary care provider, 811, or emergency department, as appropriate, for further investigation and/or supervised therapy. 

Emergency Referral

Considered complex cases. Some patients may be eligible for Paxlovid™ or in some cases, remdesivir.

Refer the patient to the appropriate specialist- SHA Early COVID Therapeutics Team, Cancer Specialist or Transplant Specialist.

Note: If Transplant or Cancer patients are unable to reach their specialist, advise them to call 811. 

• > day 5 since symptom onset; patient may be eligible for remdesivir up to day 7 after symptom onset.
  • Note: According to SHA, day of symptom onset = Day 0
• Patients with HIV infection not currently on antiretroviral therapy, HIV infection with recent detectable viral load, AIDS-defining illness, CD4 count less than 200, or suspicion of uncontrolled HIV.
• Patients with drug interaction(s) that have been deemed non-manageable by the community prescriber, but may be manageable by the specialists, such as transplant and cancer medications.
• Immunocompromised by complex disease state: 
  • Active treatment for cancer
  • Hematopoietic stem cell transplant recipient
  • Solid organ transplant recipient
  • Moderate to severe primary immunodeficiency

LAST UPDATED: 30 Aug 2022

Treatment

NOTE: Community practitioner prescribing of oral antiviral agents is authorized ONLY during a COVID-19 pandemic declared by the Chief Medical Health Officer for Saskatchewan.

Goals of Therapy

• Relieve symptoms of COVID-19
• Reduce severity and duration of symptoms and infection
• Decrease and/or prevent the risk of complications such as worsening of co-morbid conditions, hospitalization, or death 
• Prevent the spread of infection

A thorough patient history is pertinent in determining the most appropriate treatment option. Particular attention must be paid to the following:

• Time since symptom onset
• Signs and symptom(s) and their severity
• Presence of risk factors
• Level of circulating COVID-19 in the community
• Whether patient has a positive PCR test or RAT
• Vaccination status
• Previous COVID-19 infection
• Previous treatment with an early COVID-19 antiviral

Non-pharmacologic Treatment

• Recommend plenty of fluids, rest, and increased humidity.
• Reduce spread of the virus by:
  • Handwashing with soap and water or using an alcohol-based hand rub after contact with eyes, mouth, nose, or respiratory secretions.
  • Covering the mouth and nose when coughing or sneezing.
  • Staying at home when feeling unwell.
  • Wearing a mask.

Pharmacologic Treatment

Over-the-Counter Options

• Supportive or symptomatic management in addition to non-pharmacologic treatment for mild COVID-19 symptoms may be all that is required.
• Analgesics such as acetaminophen or NSAIDs (e.g. ibuprofen) can be used for fever relief, headache and myalgia.
  • Usual dosing as per the product label is recommended.
• ASA should not be used in children or adolescents due to a risk of Reye syndrome.
• Saline sprays, solutions and gels may provide symptomatic relief of nasal irritation.
• Cough and cold remedies may provide relief of upper respiratory symptoms.
  • Avoid in children < 6 years of age
• The CPhA has developed a simple  infographic that can be provided to patients. 

Prescription Options

Antiviral: Nirmatrelvir/ Ritonavir (Paxlovid ™)

• Mechanism of Action:
  • Nirmatrelvir: a SARS-CoV-2-3CL protease inhibitor
    • Inhibits the replication of SARS-CoV-2; the virus requires this enzyme to replicate.
  • Ritonavir: an HIV-1 protease inhibitor and CYP3A inhibitor
    • Helps to slow down nirmatrelvir’s metabolism; allows it to remain active in the body and at higher concentrations for longer.
  • Supporting Evidence:
    • EPIC-HR trial:
      • Consistent efficacy for previously identified variants (i.e., alpha, beta, delta, gamma, lambda, and mu).
      • In vitro data confirms efficacy against the Omicron 3CL protease.
• Eligibility Criteria:                  
  **Only specific patients that meet all inclusion criteria and do not meet exclusion criteria are eligible**
  • Positive PCR test or RAT
  • ≤ day 5 since symptom onset; Day of symptom onset = Day 0
    • Patients may be eligible for remdesivir up to day 7 after symptom onset.
  • Mild COVID-19 signs and symptoms
  • At least 90 days have elapsed since symptoms from previous infection (if applicable) have resolved.
    • 90-day timeframe is to ensure that the current infection is a distinct and new infection. Clinical discretion should be used in determining symptom resolution.
  • No more than one previous treatment course with an early COVID-19 antiviral (i.e. Paxlovid™ and/or remdesivir)
    • Individuals are eligible for a maximum of 2 courses of early COVID-19 antiviral treatment.
    • COVID-19 antiviral therapy can be provided to those who have received previous treatment with monoclonal antibodies (e.g., sotrovimab). Monoclonal antibodies are not antiviral agents.
  • Immunocompromised by complex disease state or medication regardless of COVID-19 vaccination status (see below to define immunocompromised)
  • Unvaccinated or under-vaccinated
    • Age ≥ 18 to < 55 with ≥ 1 high risk factor (defined below)
    • Age ≥ 55
  • Fully vaccinated*                  
     *Fully vaccinated is defined by the SHA as the patient having received two doses of a two-dose vaccine or one dose of Janssen Jcovden™.
    • Age ≥ 70 years with ≥ 3 high risk factors (defined below)
    • Age ≥ 70 years and Indigenous [regardless of geographic location] with ≥ 2 high risk factors (defined below)
      • Note: patients can self-identify as Indigenous.
    • Age ≥ 70 years and living in the north [NE1, NE2, NW1, AHA] with ≥ 2 high risk factors (defined below)
  • Specific high-risk factors for severe disease progression that determine eligibility include:
    • Body mass index ≥ 30 kg/m²
    • Chronic kidney disease with a decreased CrCl (≥ 30 mL/min to < 60 mL/min) (Reminder: < 30mL/min is a contraindication to treatment)
      • Patients must have stable values within the last 6 months with no change in their clinical condition. If patients do not have recent kidney function values, complete the patient assessment as fully as possible. If they meet all other eligibility criteria, refer the patient to the SHA Early COVID Therapeutics Team. 
    • Cardiovascular or cerebrovascular disease (Hypertension, Coronary Artery Disease, Congestive Heart Failure, Congenital Heart Disease, Cardiomyopathy, Atrial Fibrillation, Hyperlipidemia, Stroke)
    • Diabetes mellitus (Type 1 and 2)
    • Chronic lung disease (COPD, Moderate to Severe Asthma, Cystic Fibrosis, Pulmonary Fibrosis, Pulmonary Hypertension)
    • Neurodevelopmental disorders (e.g. Cerebral Palsy, Down’s Syndrome) or other conditions that confer medical complexity (e.g. genetic or metabolic syndromes and severe congenital abnormalities)
    • Sickle cell disease

Note: If a patient has several conditions within a listed category, it is still only considered 1 high risk factor. For example, under cardiovascular or cerebrovascular disease, if the patient has hypertension and atrial fibrillation, this would only be considered 1 high risk factor. 

Definition of Immunocompromised

• Active treatment for cancer including cancer chemotherapeutic agents classified as immunosuppressive or chimeric antigen receptor (CAR)-T-cell therapy 
• Hematopoietic stem cell transplant recipient
• Moderate or severe primary immunodeficiency (e.g. DiGeorge syndrome, Wiskott-Aldrich syndrome, etc.)
• Solid organ transplant recipient
• Immunocompromised due to medication such as active treatment with high-dose corticosteroids (e.g. greater than or equal to 20 mg prednisone or equivalent per day when administered for greater than or equal to 2 weeks), alkylating agents and anti-metabolites, tumor-necrosis factor (TNF) blockers, other biologic agents that are significantly immunosuppressive.
  • Refer to the medSask document “ Immunosuppressive Potential of Medications NOT Including Oncological Agents”

Reminder: Patients receiving active treatment for cancer should be referred directly to their Cancer Specialist, and any patients that have received any type of transplant should be directly referred to their Transplant Specialist. If Transplant or Cancer patients are unable to reach their specialist, advise them to call 811. For patients that are consider complex cases, such as those with moderate to severe primary immunodeficiency, complete the assessment as fully as possible, and if the patient is eligible, refer the patient to the SHA Early COVID Therapeutics Team.

• Treatment initiation:
  • Indicated for the treatment of mild COVID-19 in adults who are at high risk for progression to severe disease. 
    • (See the Eligibility Criteria section immediately above for patients considered to be high risk for the purpose of this prescribing guideline.)
  • Initiate within ≤ day 5 of symptom onset: ideally as soon as possible after confirmation of a positive PCR test or RAT.
    • May reduce complications of COVID-19 such as hospitalization, exacerbation of comorbidities and death.
  • Initiation > day 5 after symptom onset: not applicable. Patients presenting with symptoms up to ≤ day 7 after symptom onset may be eligible for remdesivir therapy and should be referred if they are eligible.
  • Paxlovid™ should not be routinely used for asymptomatic patients, or in patients < 18 years of age that are otherwise healthy and do not have any risk factors for severe disease progression. 
  • Paxlovid™ is not indicated for COVID-19 prophylaxis (in patients that are considered close household contacts).
• Dosage: Nirmatrelvir/ Ritonavir (Paxlovid ™)
  • Recommended dose in adults ≥ 18 years of age:
    • 300 mg (TWO x 150 mg tablets) of nirmatrelvir with 100 mg (ONE x 100 mg tablet) of ritonavir, every 12 hours for FIVE days.
    • All tablets in a dose must be taken together; if doses are separated the ritonavir is unable to “boost” the nirmatrelvir, possibly making it ineffective.
    • Take with or without food with adequate fluid.
    • Do not chew, cut, or crush the tablets
  • Adjustments required in renal impairment:
    • CrCl < 30 mL/min or on dialysis: contraindicated
    • CrCl ≥ 30 to < 60 mL/min: dose adjustment required
      • Dose: 150 mg (ONE x 150 mg tablets) of nirmatrelvir with 100 mg (ONE x 100 mg tablet) of ritonavir, every 12 hours for FIVE days.
      • Important note: Paxlovid ™ is available in packaging specific for this dosing (DIN 02527804): cartons contain 5 blister cards that include 2x 150 mg nirmatrelvir and 2x 100 mg tablets of ritonavir (ONE tablet each to be taken for each dose of the day).
      • The original packaging containing blisters of 4x 150 mg nirmatrelvir tablets and 2x 100 mg ritonavir tablets (DIN 02524031) can be used if the renal dose packaging is not available. However, the five blister cards must be manipulated. Pharmacy must:
        • Remove and dispose of the unneeded doses from the package. (TWO nirmatrelvir tablets per blister)
        • Inform the patient that packaging has been modified.
        • Ensure the prescription label instructions match the appropriate dosing.
        • Apply a  sticker indicating the dose has been manipulated. 
• Adjustments required in hepatic impairment:
  • No adjustment in mild to moderate impairment Child-Pugh Class A or B
  • Contraindicated in severe impairment- Child-Pugh Class C
    • Note: at this time, according to SHA eligibility criteria, any patients with any medical history of active liver disease (or suspicion of such) are not eligible.
• Missed doses:
  • If within ≤ 8 hours of the usual time it is taken, the patient should take the dose as soon as possible and resume normal dosing schedule.
  • If > 8 hours, the patient should skip the dose and resume normal dosing schedule. The dose should not be doubled and should be properly discarded.
• Pediatrics:
  • The safety and efficacy have not been established in patients below 18 years of age.
• Pregnancy:
  • Pregnancy is not a risk factor for COVID-19 infection, however, pregnancy (any stage) is a risk factor for severe disease and complications due to COVID-19. This is especially true in patients with asthma, diabetes, obesity, advanced maternal age, hypertension, or heart disease.
    • The use of Paxlovid™ is contraindicated in this population.
    • Precaution: all patients (all sexes) are required to use contraception or abstain from intercourse for the duration of treatment and 4 days after completion of treatment.
• Breastfeeding:
  • Unknown whether nirmatrelvir or any components:
    • are present in human milk
    • affect milk production
    • have an effect on a breastfed infant
  • HIV studies have shown ritonavir to be present in breast milk.
  • The use of Paxlovid™ is contraindicated in this population.
• Adverse Effects:
  • From the EPIC-HR study: mild to moderate grade and are comparable to placebo
    • Dysgeusia (altered sense of taste) (6%)
      • This is the most frequent adverse effect being seen in “real-world” use. Tell patients to expect it so that they are prepared. 
      • Remind patients that taste will return to normal.
    • Diarrhea (3%)
    • Hypertension (1%)
    • Myalgia (1%)
    • Vomiting
      • If a patient vomits, they should not retake that dose and should continue on with therapy until completion of the course. If a patient misses more than one dose, they should discontinue the therapy.
    • Headache
• Drug Interactions
  • For guidance on drug interactions, and management by the community prescriber, see the next drop-down tab. 

LAST UPDATED: 30 Aug 2022

Drug Interactions

• Many potential drug interactions.
  • Some are absolute contraindications.
  • Some are not manageable by a community prescriber.
  • Some interactions require intervention and/ or modification to treatment and are manageable by a community prescriber.
  • Some require monitoring by the patient. 
• For the purpose of this prescribing guideline, see Paxlovid Drug Interactions to determine whether an interaction is manageable by the community prescriber, as well as guidance on how to manage the interaction.
• All patients that are cancer patients or transplants patients are not manageable at the community level or by the usual prescribers. All patients must be referred directly to their specialist. 
• Remember: Just because a drug in the table is deemed “manageable”, it does not necessarily mean it is manageable for every patient. Do not forget to consider additional patient factors that affect their ability to properly manage the drug interaction, such as:
  • Do they understand which medication to hold or to split in half?
  • Can they actually split the tablet themselves?
  • Do they receive compliance packs which require manipulating?
  • Do they comprehend when to restart their medication? 

CYP 3A Drug Interactions

Ritonavir is a CYP 3A inhibitor:

• Ritonavir may decrease the metabolism of medications dependent on CYP 3A.
  • In those medications that require CYP 3A for clearance, elevated concentrations may occur. This could result in a serious or life-threatening reaction.
  • In those medications that require CYP 3A for activation, such as prodrugs, reduced concentrations may occur. This could result in a decreased therapeutic effect of the medication.

Nirmatrelvir and Ritonavir are both CYP 3A substrates:

• CYP 3A inducers may increase metabolism of Paxlovid™
• Potential for loss of virologic response and/or resistance. Treatment failure!

 Natural Medicines and Herbal Products

• Many products contain multiple ingredients; ensure each ingredient is assessed for a potential drug interaction. 
• Pay particular attention to any that involve the CYP pathway.
• Prescribers will have to decide on whether the interaction is significant and/or manageable.
• Natural Medicines (available through SHIRP) is a suggested resource. 

LAST UPDATED: 09 May 2022

General Advice/Monitoring

Advice

• Remind patients of measures to prevent spreading by:
  • Handwashing with soap and water or using an alcohol-based hand rub after contact with eyes, mouth, nose, or respiratory secretions.
  • Covering the mouth and nose when coughing or sneezing.
  • Staying at home when feeling unwell.
  • Wearing a mask.
  • Following all public health recommendations.
• In most cases, individuals are infectious for 2 days prior to symptom development or positive PCR test or RAT and continue for up to 10 days after presentation of symptoms.
  • Note: patients with severe COVID-19 infection and immunocompromised patients may shed the virus for a longer duration. 
• Recommend non-pharmacologic measures and OTC treatments.
• Educate patients on signs and symptoms that would indicate worsening of condition and need for medical attention; patients may progress from one severity category to another relatively quickly. Provide the patient with the medSask document Managing COVID-19 or Flu at Home.       
• If the patient receives a prescription for Paxlovid™:
  • Provide the patient with the medSask Paxlovid™ Patient Handout.
• Remind the patient of the importance of:
  • Taking all tablets per dose together
  • Taking all doses
• Advise the patient how to manage missed doses.
• Remind all patients (all sexes) that they are required to use contraception or abstain from heterosexual intercourse for the duration of treatment and 4 days after completion of treatment with Paxlovid™.
• If the patient has not received a complete primary vaccination series or is eligible for a booster dose, encourage them to get vaccinated in the future. The patient does not need to wait for vaccination.
  • Patients with acute illness may receive the vaccine as soon as the acute illness has resolved. See the medSask COVID-19 Vaccine Doses, Eligibility, and Intervals guidance. 

Assess Benefit

• Follow-up in 2 days.
• Refer to emergency department if symptoms have progressed to more severe or patient is deteriorating.
• If an antiviral is prescribed:
  • Improvement in symptoms varies amongst patients. Some patients are seeing improvements within 1 day, while others are not seeing improvement until the course is completed.
  • If patient is improving or not worsening, and still has mild symptoms, advise patient to continue with the medication until the course is completed and to continue symptomatic treatment as needed.
  • Remind patients that signs and symptoms may wax and wane, however, it is important to complete the entire course of therapy even if they are feeling better.
• If the patient had a “manageable” drug interaction, ensure they are managing the drug as advised, such as holding the drug, monitoring, etc.
  • If the patient was required to hold a drug or reduce the dose, ensure the patient understands when to restart their previous dose.

Assess Adverse Effects

• Patient expectation is key! Remind patients to push through the adverse effects if they are mild as stated below and it is reasonable to do so.
• Paxlovid ™ is well tolerated. Side effects are comparable to placebo.
  • Dysgeusia (altered sense of taste)
    • This is the most frequently experienced side effect. Tell patients ahead of time to expect it. Remind patients that taste will return to normal once the medication is completed.
  • Diarrhea
  • Hypertension
  • Myalgia
  • Vomiting
    • If a patient vomits, they should skip that dose and continue on with therapy until completion of the course. If a patient misses more than one dose, they should discontinue the therapy.
  • Headache
• If a patient discontinues due to adverse effects, ensure it is documented on the patient follow-up.

Reporting Adverse Events

• Any serious or unexpected side effects should be reported to either:
• Pfizer Canada ULC                  
  17300 Trans-Canada Highway Kirkland, QC H9J 2M5                  
  pfizersafetyreporting.com                  
  Telephone: 1-866-723-7111 Fax: 1-855-242-5652
• Health Canada                  
  Toll-free at 1-866-234-2345                  
  For information on how to report online, by mail or by fax, see MedEffect Canada's Web page

LAST UPDATED: 09 May 2022

Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in eCPS, Lexi-Comp, or other reliable drug monograph references. This information should be routinely consulted before prescribing.

Generic Name	Strength/ Formulation
Nirmatrelvir/ Ritonavir (Paxlovid ™)	150 mg / 100 mg tablet

Available in two package formats:

• The original dose carton (DIN 02524031) contains 5 blister cards of 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and is to be used for patients with CrCl ≥ 60 mL/min (or manipulated as described in Treatment if needed for patients with CrCl  ≥ 30 mL/min to < 60 mL/min).
• The renal dose carton (DIN 02527804) contains 5 blister cards of 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and is to be used for patients with CrCl ≥ 30 mL/min to < 60 mL/min.

LAST UPDATED: 24 Aug 2022

Prescribing and Billing Details

Prescribing of oral antiviral agents is authorized ONLY during a COVID-19 pandemic declared by the Chief Medical Health Officer for Saskatchewan.

• May prescribe sufficient quantity to treat ONE episode of pandemic COVID-19.
  • Treatment for symptomatic patients is 5 days. No refills. 
• Patients are only eligible for a maximum of TWO courses of treatment with COVID-19 early antiviral agents (i.e. Paxlovid™ and/or remdesivir).                  
  * For example, if a patient has already received a previous course of Paxlovid™ or remdesivir, they are eligible for a second course of Paxlovid™ provided the current infection is new and distinct from the previous infection and it has been longer than 90 days since resolution of symptoms from the previous infection.
• Only products with an official indication from Health Canada for COVID-19 infection are considered for these guidelines. Only the active ingredients in the "products" section are approved for pharmacist prescribing.

For Pharmacy Use Only

Service	pseudoDIN/DIN	Claim Thresholds
Minor Ailment Fee: COVID-19 (Paxlovid™)	00951375	Maximum of TWO (2) claims
*Paxlovid™ Ineligibility / Referral Assessment Fee: Pharmacist Prescriber	00951376	Maximum of FOUR (4) claims
*Paxlovid™ Ineligibility / Referral Assessment Fee: Other Prescribers	00951377	Maximum of FOUR (4) claims
*Paxlovid™ Distribution Fee Original Packaging	02524031	Maximum of TWO (2) claims ^
*Paxlovid™ Distribution Fee Renal Dose Packaging	02527804

^{* These fees are unique to Paxlovid™ and are not eligible in conjunction with any other DPEBB professional service programs.                  
^ Maximum two claims for Paxlovid™ total, not two claims per DIN.}

LAST UPDATED: 30 Aug 2022

Treatment Algorithms

Document

paxlovid-for-covid-algorithm.pdf124.52 KB

Document

paxlovid-for-covid-eligibility-overview.pdf162.93 KB

_{No part of this work may be reproduced, distributed, or transmitted in any form outside Saskatchewan, or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the copyright holder. For copyright permission requests, please contact druginfo@usask.ca.}

Prescriber Assessment Record (PAR) / Prescription

Document

paxlovid-for-covid-par.pdf2.75 MB

LAST UPDATED: 30 Aug 2022

_{No part of this work may be reproduced, distributed, or transmitted in any form outside Saskatchewan, or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the copyright holder. For copyright permission requests, please contact druginfo@usask.ca.}

Additional Resources

Accessibility

• Pharmacies Dispensing and/or Prescribing Paxlovid™ in Saskatchewan: interactive map

Pharmacy Process

• Saskatchewan Drug Plan: Important Information and Standard Forms

General Information

• Paxlovid™ Product Monograph
• Science Table (Ontario) -  Nirmatrelvir/Ritonavir (Paxlovid™): What Prescribers and Pharmacists Need to Know 
• CPhA -  Treatment of COVID-19 with Paxlovid™

Drug Interactions

• University of Liverpool - COVID-19 Drug Interactions
• Science Table (Ontario) -  Nirmatrelvir/Ritonavir (Paxlovid™): What Prescribers and Pharmacists Need to Know

Adverse Reaction Reporting (report to either)

• Pfizer Canada ULC – Reporting online or Call 1-866-723-7111 
• Health Canada – Report a Side Effect  

Medication Error/Incident Reporting

• COMPASS (SK pharmacies)
• ISMP Canada – Individual Practitioner Reporting (other healthcare providers)

Summary and Updates

30 Aug 2022

• Eligibility criteria for Paxlovid™ prescribing have been updated. Individuals that have previously been infected and have recovered from the infection are now potentially eligible to receive Paxlovid™.  In addition, individuals who previously received an early COVID-19 therapeutic agent are now potentially eligible to receive an additional course of an early COVID-19 antiviral (Paxlovid™, remdesivir). The Guideline, Prescriber Assessment Record, and algorithms have been updated to reflect the changes.

24 Aug 2022

• New dose packaging of Paxlovid™ (DIN 02527804) became available August 2022 for patients with moderate renal impairment (CrCl ≥ 30 to < 60 mL/min). The carton contains 5 blister cards of 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each).
• Information has been added to the "Treatment", "Products", and "Precribing and Billing Details" sections.

References

1. Dresser L. Covid-19. In: Therapeutics [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2022 [updated 28 Mar 2022]. Available from: http://www.myrxtx.ca. Also available in paper copy from the publisher
2. Public Health Agency of Canada. COVID-19: Prevention and risks. Ottawa: Government of Canada; [Updated 22 Apr 2022] Available from: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/prevention-risks.html
3. Cohen P, Gebo K. COVID-19: Outpatient evaluation and management of acute illness in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (updated 15 Apr 2022; accessed 12 May 2022) Subscription required
4. McIntosh K. COVID-19: Clinical features. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (updated 14 Apr 2022; accessed 12 May 2022) Subscription required
5. Anesi G. COVID-19: Epidemiology, clinical features, and prognosis of the critically ill adult. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (updated 30 Mar 2022; accessed 12 May 2022) Subscription required
6. Hammond J, Leister-Tebbe H, Gardner A, et al; EPIC-HR Investigators. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397-1408. doi: 10.1056/NEJMoa2118542. Epub 2022 Feb 16. PMID: 35172054; PMCID: PMC8908851.
7. Infectious Diseases Association of America. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. [document on the Internet]. Updated 10 May 2022. Available from https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/# 
8. BC COVID THERAPEUTICS COMMITTEE (CTC). Practice Tool #3 – Drug-Drug Interactions and Contraindications. Feb 11, 2022. Available from:  http://www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/PracticeTool3_DrugInteractionsContraindications.pdf
9. University of Liverpool. Covid-19 Drug Interactions; Interaction checker. c2022. Available from: https://www.covid19-druginteractions.org/checker
10. Lexi-Comp Online^TM, Interactions, Hudson, Ohio: Lexi-Comp, Inc.; 2022; Available from: http://online.lexi.com. Subscription required
11. Centers for Disease Control and Prevention. Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals. [updated 15 Feb 2022]. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
12. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Special Considerations in Pregnancy. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/special-populations/pregnancy/
13. UK Health Security Agency 2022. Patient information for Paxlovid. GOV.UK. Updated 04 May 2022. Available from: https://www.gov.uk/government/publications/covid-19-antiviral-treatment-paxlovid/patient-information-for-paxlovid#information-for-people-who-are-breastfeeding

Full list of references available upon request. 

LAST UPDATED: 12 May 2022

Evusheld™ (tixagevimab / cilgavimab)

Clinical Practice Guidelines - Pre-Exposure Prophylaxis

Considerations for HCPs - Infographic

Evusheld^Tm Expiry Date Extension

Prepared by: K Bazylak BSP

Reviewed by: Satchan Takaya (MD FRCPC, Associate Professor, Division of Infectious Diseases, University of Saskatchewan, Medical Co-Lead, Early COVID-19 Therapeutics, SHA), Stephen Lee (MD FRCPC, Assistant Professor, Division of Infectious Diseases, University of Saskatchewan, Medical Co-lead, Early COVID-19 Therapeutics, SHA)

Funded by: The Government of Saskatchewan and the Saskatchewan College of Pharmacy Professionals (SCPP)