Nirmatrelvir/Ritonavir(PAXLOVID) is available only in limited supplies, prioritizing access to treatment using eligibility criteria remains necessary.
Treatment: Within 5 days of symptom onset
Before prescribing nirmatrelvir/ritonavir, clinicians should carefully review concomitant medications for drug interactions to reduce the risk of harm.
Drug interaction tools and resources:
Drug classes of particular concern are:
Questions to consider:
Potential management strategies:
Potential management strategies to facilitate the use of nirmatrelvir/ritonavir may differ depending on the magnitude and significance of the interaction. Options include:
These strategies should be considered for the 5-day duration of nirmatrelvir/ritonavir treatment and for at least 2 to 5 days after treatment completion (and for potentially longer if nirmatrelvir/ritonavir is administered with an interacting concomitant medication that has a long half-life).
Please note, the onset of inhibition is RAPID and clinically significant drug-drug interactions may occur despite the short treatment course.
The following medications should be avoided in combination with nirmatrelvir/ritonavir, they are either:
For more information please use the following tools & resources:
***Caution - the list below is only intended as a quick reference guide, and may not be complete.
|Antiarrhythmics||amiodarone, disopyramide, dronedarone, flecainide, propafenone, quinidine|
|Anticancer||apalutamide, enzalutamide, neratinib, venetoclax|
|Anticoagulant/ antiplatelet||apixaban, rivaroxaban, ticagrelor, clopidogrel (significant reduction in antiplatelet activity, avoid if at very high-risk of thrombosis - review in interaction checker for more details)|
|Anticonvulsants||carbamazepine, clonazepam, eslicarbazepine, oxcarbamazepine phenobarbital, phenytoin, primidone|
|Antipsychotics||clozapine, lurasidone, pimozide, quetiapine|
|Anxiolytics/hypnotics/ sedatives||alprazolam, diazepam, flurazepam, midazolam (oral), triazolam|
|Ergot derivatives||dihydroergotamine, ergonovine, ergotamine|
|HCV DAAs||elbasvir/grazoprevir, glecaprevir/pibrentasvir|
|Hypotension/Heart Failure Agents||aliskiren, bosentan, eplerenone, ivabradine, ranolazine|
|Immunosuppressants||cyclosporine, sirolimus, tacrolimus, everolimus|
|Lipid lowering agents||lovastatin, simvastatin, lomitapide|
|PDE5 Inhibitors||sildenafil (PAH), tadalafil (PAH), vardenafil (PAH)|
|Herbal/Natural Health Products||St John’s Wort|
-PAH - Pulmonary arterial hypertension
***There are limited clinical data and serious/unexpected adverse events may occur that have not been previously reported.***
Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering to patients with preexisting liver diseases, liver enzyme abnormalities, or hepatitis.
Reproductive Health: Female and Male Potential
Women of childbearing potential should use effective contraception during treatment. Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment.
Risk of HIV-1 Resistance Development
Because nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
(See product monograph for more detail)
(See product monograph for more detail)
Adverse events (incidence ≥1% and ≥5 patient difference):
(studies are limited - possible that all adverse effects, including those that are rare but serious, are not known)
GNB Public Health recommends the use of nirmatrelvir/ritonavir for symptomatic patient meeting eligibility criteria at high-risk of progression to severe disease
Patients must meet ALL the applicable eligibility criteria and NONE of the exclusion criteria.
Clinical Assessment Process - what to consider?
(Click here for more details on assessment steps)
1 Mild-to-moderate illness:
2 Moderately to Severely Immunocompromised:
Usual Dosing (eGFR ≥ 60 mL/min):
Moderate renal impairment (eGFR ≥30 to <60 mL/min):
(consider removing extra tablets prior to dispensing and advise patient of adjustment to blister package)
Severe renal impairment (eGFR <30 mL/min):
Health Canada Resources:
Drug Interaction Tools and Resources
Evidence Reviews and Summaries
Other Useful Practice Tools