Interactions between ritonavir-boosted nirmatrelvir and chemotherapeutic agents should also be managed in consultation with the patient’s specialist providers. For guidance on managing these interactions, refer to the FDA prescribing information for ritonavir-boosted nirmatrelvir and the prescribing information for the chemotherapeutic agent. The University Health Network/Kingston Health Sciences Centre provides an additional resource for evaluating drug-drug interactions between ritonavir-boosted nirmatrelvir and chemotherapeutic agents.
Patients should be counseled about ritonavir-boosted nirmatrelvir’s drug-drug interaction potential and the signs and symptoms of potential adverse effects. If ritonavir-boosted nirmatrelvir is prescribed to patients who take certain recreational drugs, those patients will require counseling and careful monitoring for adverse effects.
The guidance in Box 2 is based on the drug-drug interaction potential of the FDA-approved, 5-day course of ritonavir-boosted nirmatrelvir.
Not all medications that may interact with ritonavir-boosted nirmatrelvir are included in Box 2. Deviation from the recommended strategies may be appropriate in certain clinical scenarios.
| Prescribe Alternative COVID-19 Therapy | ||
|---|---|---|
| For these medications, management strategies are not possible or feasible, or the risks outweigh the potential benefits. | ||
Anticonvulsants
| Cardiovascular
| Pulmonary Hypertensionc
|
| Temporarily Withhold Concomitant Medication, if Clinically Appropriate | ||
| Withhold these medications during ritonavir-boosted nirmatrelvir (Paxlovid) treatment and for at least 2–3 days after treatment completion. They may need to be withheld for longer if the patient is an adult of advanced age or if the interacting medication has a long half-life. If withholding is not clinically appropriate, use an alternative concomitant medication or COVID-19 therapy. | ||
Anticoagulants
| Immunosuppressantsf
| Neuropsychiatric
|
| Adjust Concomitant Medication Dose and Monitor for Adverse Effects | ||
| Reduce the dose and/or extend the dosing interval of the concomitant medication. Consult the Liverpool COVID-19 Drug Interactions website or the University of Waterloo/University of Toronto drug interaction guide for specific dosing recommendations.j If the dose of the concomitant medication cannot be adjusted, withhold the medication (if clinically appropriate) or use an alternative concomitant medication or COVID-19 therapy. | ||
Anticoagulants
| Immunosuppressants
| Pain
|
| Continue Concomitant Medication and Monitor for Adverse Effects | ||
| There is no need to pre-emptively adjust the doses of these drugs, but dose adjustments may be considered in patients with a high risk of AEs. Educate patients about potential AEs. Consult the Liverpool COVID-19 Drug Interactions website or the University of Waterloo/University of Toronto drug interaction guide for monitoring guidance and dose adjustment information.j | ||
Anticoagulants
| Cardiovascular
| Pain
|
a Reduced effectiveness of clopidogrel is likely. It may be acceptable to continue using clopidogrel if the benefits of using ritonavir-boosted nirmatrelvir outweigh the risk of reduced clopidogrel effectiveness. b For patients with a very high risk of thrombosis (e.g., those who received a coronary stent within the past 6 weeks), consider prescribing an alternative antiplatelet (e.g., prasugrel, if clinically appropriate) or an alternative COVID-19 therapy. c Some PDE5 inhibitors are used to treat both PAH and erectile dysfunction; however, the doses used to treat PAH are higher than those used for erectile dysfunction. Because of this, and because PDE5 inhibitors are used chronically in patients with PAH, coadministration with ritonavir-boosted nirmatrelvir is contraindicated in these patients. PDE5 inhibitors can be coadministered with ritonavir-boosted nirmatrelvir in patients with erectile dysfunction, though the dose of the PDE5 inhibitor should be adjusted. d Ritonavir-boosted nirmatrelvir may increase concentrations of some chemotherapeutic agents, leading to an increased potential for drug toxicities. Some chemotherapeutic agents may decrease the effectiveness of ritonavir-boosted nirmatrelvir. Please refer to the FDA prescribing information for ritonavir-boosted nirmatrelvir and the prescribing information for the chemotherapeutic agent and consult the patient’s specialist provider. The University Health Network/Kingston Health Sciences Centre is an additional resource for evaluating drug-drug interactions for chemotherapeutic agents. e For patients with a high risk of arterial or venous thrombosis (e.g., those who had a stroke within the past 3 months with a CHA2DS2-VASc score of 7–9 or a pulmonary embolism within the past month), consult the patient’s primary or specialty provider and consider using an alternative anticoagulant (e.g., LMWH) or an alternative COVID-19 therapy. For patients with a lower risk of arterial or venous thrombosis, clinicians may consider administering low-dose aspirin while rivaroxaban is being withheld. f The use of another COVID-19 therapy may need to be considered. These immunosuppressants have significant drug-drug interaction potential with ritonavir, and they should not be used if close monitoring, including therapeutic drug monitoring (i.e., measuring drug concentrations), is not feasible. Consult the patient’s specialist providers before coadministering these immunosuppressants with ritonavir-boosted nirmatrelvir. See the American Society of Transplantation statement for more information. g Withhold lovastatin and simvastatin for at least 12 hours before initiating ritonavir-boosted nirmatrelvir, during treatment, and for 5 days after treatment completion. Withhold atorvastatin and rosuvastatin at the beginning of treatment with ritonavir-boosted nirmatrelvir and resume after completing the 5-day course. If withholding a statin is not clinically appropriate (e.g., because the patient recently had a myocardial infarction), clinicians can reduce the doses of atorvastatin and rosuvastatin and continue treatment. However, lovastatin and simvastatin should be switched to an alternative statin. h The guidance on managing drug-drug interactions between certain benzodiazepines and ritonavir-boosted nirmatrelvir can vary significantly between product information resources. Note that abrupt discontinuation or rapid dose reduction of benzodiazepines may precipitate an acute withdrawal reaction.4 The risk is greatest for patients who have been using high doses of benzodiazepines over an extended period. i Do not coadminister this medication with ritonavir-boosted nirmatrelvir in patients with hepatic or renal impairment. j For medications that are not included on the Liverpool COVID-19 Drug Interactions website or in the University of Waterloo/University of Toronto drug interaction guide, refer to the FDA labels for information on coadministering these medications with ritonavir or other strong CYP3A4 and/or P-gp inhibitors (e.g., ketoconazole). k Dexamethasone exposure is expected to increase 2.60-fold when dexamethasone is coadministered with ritonavir-boosted nirmatrelvir.5 Clinicians should weigh the risks and benefits of continuing the patient’s normal dose of dexamethasone (while monitoring for AEs) against the risks and benefits of decreasing the dose. Patients who are receiving higher doses of dexamethasone will be at a greater risk of AEs. l Patients should take ritonavir-boosted nirmatrelvir at least 3 hours after taking brincidofovir. m Ritonavir-boosted nirmatrelvir interacts with certain conjugated mAbs, such as ado-trastuzumab emtansine, mirvetuximab soravtansine, brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin. Before coadministering ritonavir-boosted nirmatrelvir and any of these conjugated mAbs, refer to the drug’s FDA prescribing information and consult the patient’s specialist providers as needed.
Key: AE = adverse effect; ARV = antiretroviral; BPH = benign prostatic hyperplasia; CHA2DS2-VASc = congestive heart failure, hypertension, age, diabetes, stroke, vascular disease; CYP = cytochrome P450; FDA = Food and Drug Administration; LMWH = low-molecular-weight heparin; mAb = monoclonal antibody; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase 5; P-gp = P-glycoprotein; PO = oral | ||
The guidance in this document is based on the drug-drug interaction potential of the FDA-approved, 5-day course of ritonavir-boosted nirmatrelvir. Longer treatment courses may be utilized in certain cases (see Special Considerations in People Who Are Immunocompromised). Clinicians should be aware that the drug-drug interaction potential of ritonavir may change based on the duration of treatment. Clinicians should also be aware that:
Clinicians should consult with experts (e.g., pharmacists and physicians with HIV expertise) when using extended courses of ritonavir-boosted nirmatrelvir. The Liverpool COVID-19 Drug Interactions website also provides guidance for managing drug-drug interactions during extended courses (i.e., ≥10 days) of ritonavir-boosted nirmatrelvir.