tadalafil Coadministration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system [see Contraindications (4)]. Eligible patients were randomized within 5 days of symptom onset, were not vaccinated against COVID-19, and had at least 1 risk factor for progression to severe disease.8 Patients were excluded if they used medications that were either highly dependent upon CYP3A4 for clearance or strong inducers of CYP3A4. Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. The emergency use of Paxlovid is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID- 19 pandemic under Section 564 (b) (1) of the Act, 21 U.S.C. vardenafil. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. The most common adverse effects of ritonavir-boosted nirmatrelvir are dysgeusia, diarrhea, hypertension, and myalgia. hyperglycemia. In some cases, the recommendation is to avoid co-administration. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PAXLOVID for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death. 2022. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. PAXLOVID TM (nirmatrelvir tablets; ritonavir tablets) has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including . Key:AE = adverse effect; BPH = benign prostatic hyperplasia; CHA2DS2-VASc = congestive heart failure, hypertension, age, diabetes, stroke, vascular disease; CYP = cytochrome P450; EUA = Emergency Use Authorization; FDA = Food and Drug Administration; LMWH = low-molecular-weight heparin; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase 5; P-gp = P-glycoprotein, Ritonavir-Boosted Nirmatrelvir (Paxlovid), Table: Characteristics of Antiviral Agents, Including Antibody Products, Table: Characteristics of Immunomodulators, Table: Characteristics of Miscellaneous Drugs, Liverpool COVID-19 Drug Interactions website, University of Waterloo/University of Toronto drug interaction guide, Therapeutic Management of Nonhospitalized Adults With COVID-19, American Society of Transplantation statement, University Health Network/Kingston Health Sciences Centre, https://www.ncbi.nlm.nih.gov/pubmed/21937987, https://www.ncbi.nlm.nih.gov/pubmed/32556272, https://covid19-druginteractions.org/prescribing_resources, https://www.fda.gov/media/142368/download, https://www.ncbi.nlm.nih.gov/pubmed/30843777. Published studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage. Ritonavir-boosted nirmatrelvir is contraindicated in this setting because the delayed offset of enzyme induction may reduce the concentrations of nirmatrelvir and ritonavir, rendering the treatment ineffective against SARS-CoV-2. 2022. By clicking this link, you will be redirected to Pfizer Medical Information. Emergency Use Authorization (EUA) for Paxlovid (nirmatrelvir tablets co-packaged with ritonavir tablets): Center for Drug Evaluation and Research (CDER) review. I think it is the beginning of a game-changer, says Scott Roberts, MD, a Yale Medicine infectious diseases specialist. For General Product Inquiries call 1877C19PACK (18772197225). (The FDA has provided a fact sheet on Paxlovid with a full list of known side effects.). Refer to the bedaquiline product label for further information. The most common side effects of Paxlovid treatment tend to be mild and include diarrhea, muscle aches, high blood pressure, and an altered sense of taste, Roberts says. Coadministration contraindicated due to potential loss of virologic response and possible resistance. But in order to qualify for a prescription, you must also have had a positive COVID-19 test result and be at high risk for developing severe COVID-19. Surveillance for the emergence of significant resistance to nirmatrelvir is critical. hydrocodone . The healthcare provider should consult other appropriate Deo R, Choudhary MC, Moser C, et al. There are no available human data on the use of nirmatrelvir during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Severely immunocompromised patients can experience prolonged periods of SARS-CoV-2 replication, which may lead to rapid viral evolution. Fish Oil (omega-3 polyunsaturated fatty acids), Email this report to a friend, doctor, or patient. Dosage adjustment of saxagliptin is recommended. 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. cariprazine vorapaxar The safety and effectiveness of PAXLOVID have not been established in pediatric patients. The EUA states that ritonavir-boosted nirmatrelvir is not recommended for patients with an eGFR of <30 mL/min until more data are available to establish appropriate dosing.3 Additional information is available in the initial FDA Center for Drug Evaluation and Research review for the EUA of ritonavir-boosted nirmatrelvir.16 Clinical experience on the use of ritonavir-boosted nirmatrelvir in patients who require hemodialysis is limited.25 Based on limited data, some groups have proposed dosing adjustments for ritonavir-boosted nirmatrelvir in patients with an eGFR of <30 mL/min and in those who require hemodialysis.26-28 A clinical trial (ClinicalTrials.gov Identifier NCT05487040) that will evaluate the use of ritonavir-boosted nirmatrelvir in patients with COVID-19 and severe renal impairment is currently underway. The proportions of subjects who discontinued treatment due to an adverse event were 2% in the PAXLOVID group and 4% in the placebo group.The following adverse reactions have been identified during post-authorization use of PAXLOVID. hyperlipidemia. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy.Lactation: There are no available data on the presence of nirmatrelvir in human or animal milk, the effects on the breastfed infant, or the effects on milk production. It's really our first efficacious oral antiviral pill for this virus. The University Health Network/Kingston Health Sciences Centre is an additional resource for evaluating drug-drug interactions for chemotherapeutic agents. Required Reporting for Serious Adverse Events and Medication Errors: The prescribing healthcare provider and/or the providers designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to PAXLOVID within 7 calendar days from the healthcare provider's awareness of the event.Submit adverse event and medication error reports to FDA MedWatch using one of the following methods: In addition, please provide a copy of all FDA MedWatch forms to: www.pfizersafetyreporting.com, or by fax (18666358337) or phone (18004381985).PAXLOVID is a strong inhibitor of CYP3Aand may increase plasma concentrations of drugs that are primarily metabolized by CYP3A. There are no available data on the presence of nirmatrelvir in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Otherwise, an alternative therapy for COVID-19 should be considered. m Ritonavir-boosted nirmatrelvir interacts with certain conjugated monoclonal antibodies, such as ado-trastuzumab emtansine, brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin. Clinicians should be aware that, in some cases, drug-drug interactions with ritonavir-boosted nirmatrelvir may lead to serious or life-threatening drug toxicities. Nirmatrelvir/Ritonavir (Paxlovid): What Prescribers and Pharmacists Need to Know. Pulmonary hypertension agents (PDE5 inhibitors) Tamiflu is taken twice a day for five days, and it must be started within 48 hours of flu onset. For anyone who experiences a rebound, the CDC advises people restart isolation for five days, following its isolation guidance. brexpiprazole Microsomal triglyceride transfer protein (MTTP) inhibitor. Information provided in Yale Medicine articles is for general informational purposes only. ritonavir is the boosting agent in Paxlovid. Consult the. Available at: Dryden-Peterson S, Kim A, Kim AY, et al. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. For guidance on managing these interactions, refer to the FDA EUA fact sheet and the prescribing information for the chemotherapeutic agent. nicardipine, Viral rebound and the recurrence of COVID-19 symptoms can also occur in the absence of treatment with ritonavir-boosted nirmatrelvir.20,21, The EPIC-HR trial demonstrated a clinical benefit of ritonavir-boosted nirmatrelvir in patients who were not vaccinated and who were at high risk of progressing to severe COVID-19. The following medicines have established and potentially significant interactions with Paxlovid and may cause serious or life-threatening side effects or affect how the medicine works. A dose decrease may be needed for these drugs when coadministered with PAXLOVID. Drug-Drug Interactions Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir 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. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. Avoid concomitant use of tadalafil with PAXLOVID. Refer to the tofacitinib product label for more information. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19., Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. elexacaftor/tezacaftor/ivacaftor Patients should complete the 5-day treatment course of ritonavir-boosted nirmatrelvir, because there are concerns that a shorter treatment course may be less effective or lead to resistance. Observational studies and the EPIC-HR trial have described SARS-CoV-2 viral rebound and the recurrence of COVID-19 symptoms in some patients who have completed treatment with ritonavir-boosted nirmatrelvir.16-19 The frequency, mechanism, and clinical implications of these events are unclear. Stopping lopinavir/ritonavir in COVID-19 patients: duration of the drug interacting effect. To be used for longer than 5 days in a row. have been reported with PAXLOVID. Providers should counsel patients about renal dosing instructions. Educate patients about potential adverse effects. To prevent COVID-19. (eg, toxic epidermal necrolysis [TEN] or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product. (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Param Patel is a pharmacist. 239 are major, 364 are moderate, and 40 are minor. Pfizer launched a clinical trial in March to study the safety and efficacy of Paxlovid in children and teenagers ages 6 to 17 who have COVID-19 symptoms and test positive for the virus, and who are neither hospitalized nor at risk for severe disease. PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min based on CKD-EPI formula) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined. Refer to the sofosbuvir/velpatasvir/voxilaprevir product label for further information. University of Liverpool. Ritonavir, a strong cytochrome P450 (CYP) 3A4 inhibitor and a P-glycoprotein inhibitor, is coadministered with nirmatrelvir to increase the blood concentration of nirmatrelvir, thereby making it effective against SARS-CoV-2. The trial demonstrated that starting ritonavir-boosted nirmatrelvir within 5 days of symptom onset in these patients reduced the risk of hospitalization or death through Day 28 by 89% compared to placebo.3,8 This efficacy is comparable to remdesivir (87% relative reduction)9 and greater than the efficacy reported for molnupiravir (31% relative reduction).10 However, these agents have not been directly compared in clinical trials. But in many cases, patients can talk to their doctors about taking a temporary break from some of those drugs while taking Paxlovid, he adds. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. , ombitasvir/paritaprevir/ Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4)]. For information on using ritonavir-boosted nirmatrelvir in pediatric patients, see Special Considerations in Children, Therapeutic Management of Nonhospitalized Children With COVID-19, and Therapeutic Management of Hospitalized Children With COVID-19. Reduce the dose and/or extend the dosing interval of the concomitant medication. In the EPIC-SR study of PAXLOVID (nirmatrelvir [PF-07321332] tablets and ritonavir tablets), the novel primary endpoint of self-reported, . Available at: BC COVID Therapeutics Committee (CTC) COVID Therapy Review and Advisory Working Group (CTRAWG). The hope is that the restrictions on who can take Paxlovid will be relaxed over time. Evaluating the interaction risk of COVID-19 therapies. Sufficient information is available, such as through access to health records less than 12 months old or consultation with a health care provider in an established provider-patient relationship with the individual patient, to assess renal and hepatic function; and. Paxlovid associated with decreased hospitalization rate among adults with COVID-19United States, April-September 2022. that have not been previously reported with PAXLOVID use. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.Contraception: Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. However, lovastatin and simvastatin should be switched to an alternative statin. 2022. Refer to the quetiapine prescribing information for recommendations. (See also Liverpool's Quick Guide on Interactions with Outpatient Medicines and Paxlovid ) The list of drugs that Paxlovid interacts with includes some organ anti-rejection drugs that transplant patients take, as well as more common drugs like some used to treat heart arrhythmias. Clinical trials are needed to determine whether combination therapy has a role in the treatment of COVID-19. If you suspect the product you have received may be counterfeit, contact us at 18004381985or visit www.pfizersafetyreporting.com. Additional resources include NIH recommendations for drug-drug interactions between PAXLOVID and UpToDate PAXLOVID drug information. Sufficient information is not available to assess renal and hepatic function. oxycodone Paxlovid (nirmatrelvir/ritonavir), along with tezacaftor/ivacaftor, ivacaftor When it applied for FDA authorization, Pfizer presented data from a clinical trial conducted between mid-July and early Decemberin 2021. Pfizer. PAXLOVID may be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs. National Institute of Health website said, Trazodone dose should be adjusted while taking Paxlovid (antiviral med for Covid) and then patients be monitored for adverse effect. University of Liverpool. Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Dosage adjustment of tofacitinib is recommended. Bottom line, a glass won't kill you.. immediately. diltiazem, Data sources include IBM Watson Micromedex (updated 2 Apr 2023), Cerner Multum (updated 17 Apr 2023), ASHP (updated 10 Apr 2023) and others. Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception.Pediatrics: PAXLOVID is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40 kg. The CDC says a rebound does not mean a person was resistant to Paxlovid, nor does it mean they were reinfected with the virus. Deviation from the recommended strategies may be appropriate in certain clinical scenarios. You can use the site to search for the places near you where you can fill a COVID-19 prescription, or identify sites that provide testing, medical care, and COVID-19 medications. Drugs listed in Table 1 are a guide and not considered a comprehensive list of all possible drugs that may interact with PAXLOVID. Paxlovidan antiviral medicationis a tool we still have left. The EUA advises against crushing nirmatrelvir and ritonavir tablets. Available at: Hiremath S, McGuinty M, Argyropoulos C, et al. FDA advisers voted 16-1 on Thursday in support of approval of Paxlovid, stating that the benefits outweigh the risks of the drug for treatment of mild-to-moderate Covid-19 in adult high risk for . Paxlovid (nirmatrelvir and ritonavir) is a combination antiviral agent that has been shown to significantly reduce the risk of hospitalization or death from COVID in high-risk adults when administered within 5 days of symptom onset. 2021. At the same time, nirmatrelvir and ritonavir are CYP3A substrates; therefore . If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. co-administration of colchicine with PAXLOVID is contraindicated (see. brexpiprazole, Avoid use of PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. (While the recommendation is to take Paxlovid within five days of symptom onset, participants in the clinical trial took the drug within three days.). hydrocodone, IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing. Drug-drug interactions are an important when considering whether to prescribe Paxlovid. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. Refer to the upadacitinib product label for more information. Refer to the apixaban product label for more information. Avoid concomitant use Teens Are in a Mental Health Crisis: How Can We Help? Updated: Feb. 3, 2023]. e For patients who are at 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 79 or a pulmonary embolism within the past month), consult the primary or specialty provider and consider using an alternative anticoagulant (e.g., LMWH) or an alternative COVID-19 therapy. Dosing recommendations for co-administration of apixaban with Paxlovid depend on the apixaban dose. To view PAXLOVID dispensing information for patients with moderate renal impairment, see theFact Sheet for Healthcare Providers. g Withhold lovastatin and simvastatin for at least 12 hours before initiating ritonavir-boosted nirmatrelvir, during treatment, and for 5 days after treatment completion. Boucau J, Uddin R, Marino C, et al. But this enzyme directly interacts with alcohol. View all available interactions with Nirmatrelvir/ritonavir (5 days) [Please read the interaction details as management of these interactions may be complex.] This document allows users see at-a-glance the risk and management of drug-drug interactions between Paxlovid and selected drugs that may be used in the outpatient . For patients at high risk of venous/arterial thromboembolism (VTE/ATE), consider switching from apixaban to low molecular weight heparin (LMWH); patients with a lower risk of VTE/ATE could be switched to aspirin on a case-by-case basis. Pharmacists can be a valuable resource for assessing and helping manage these interactions. Not all medications that may interact with ritonavir-boosted nirmatrelvir are included in Box 2. ticagrelor, This is the drug that inhibits the enzyme cytochrome P450, among another. The hypothesis is that the immune system didnt have a chance to see the full extent of the virus, since Paxlovid suppressed replication early in disease, Dr. Roberts says. Coadministration of ritonavir is required to increase nirmatrelvir concentrations to the target therapeutic range. All rights reserved. Paxlovid associated with decreased hospitalization rate among adults with COVID-19United States, AprilSeptember 2022. Enter other medications to view a detailed report. Coadministration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4)]. Nirmatrelvir use and severe COVID-19 outcomes during the Omicron surge. We are actively monitoring for fraudulent offers of illegitimate PAXLOVIDto protect patients from products that might be dangerous and lead to serious and life-threatening harm. Refer to the midazolam product label for further information. Consult Table 1 of the Fact Sheet for Healthcare Providers for clinically significant drug interactions, including contraindicated drugs. Abemaciclib: Ethinylestradiol: The products discussed in this site may have different product labeling in different countries. The decision to prescribe ritonavir-boosted nirmatrelvir to patients who are receiving calcineurin and mammalian target of rapamycin inhibitors should always be made in consultation with the patients specialist providers. emtricitabine Nirmatrelvir and ritonavir is an inhibitor of CYP3A and may increase drugs primarily metabolized by CYP3A Individual doses are not for sale. Vangeel L, Chiu W, De Jonghe S, et al. verapamil. Below are their responses. Interactions between ritonavir-boosted nirmatrelvir and chemotherapeutic agents should also be managed in consultation with the patients specialist providers. amlodipine, The EPIC-SR trial, which included both of these populations, found that ritonavir-boosted nirmatrelvir did not reduce the duration of symptoms and did not have a statistically significant effect on the risk of hospitalization or death compared to placebo, although the event rates were low.11 Some observational studies have shown a benefit of ritonavir-boosted nirmatrelvir in vaccinated individuals who were at high risk of progressing to severe COVID-19.12-15 However, observational studies have inherent limitations. These medications may be coadministered without dose adjustment and without increased monitoring. There is a full list of potential drug interactions on the Emergency Use Authorization fact sheet for providers on Paxlovid. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Co-administration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Prescription et dispensation du Paxlovid en ville There were no deaths in the ritonavir-boosted nirmatrelvir arm and 13 deaths in the placebo arm. Apixaban is a substrate of P-gp and is metabolized by CYP3A4. Therefore, caution should be exercised when administering PAXLOVID to patients with, Because nirmatrelvir is co-administered with ritonavir, there may be a. in individuals with uncontrolled or undiagnosed HIV-1 infection. Efficacy of antiviral agents against Omicron subvariants BQ.1.1 and XBB. buspirone, Potential Drug Interactions. Paxlovid Summary of Product Characteristics, Pfizer Ltd, August 2022. Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using a limited sampling strategy. No dosage adjustment is needed in patients with mild renal impairment. Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported with ritonavir, a component of PAXLOVID (refer to NORVIR prescribing information). Early remdesivir to prevent progression to severe COVID-19 in outpatients. By selecting continue, you acknowledge you have a medical question regarding a potential drug interaction. cariprazine, In patients with moderate renal impairment (eGFR 30 to <60 mL/min), reduce the dose of PAXLOVID to 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Many drug-drug interactions between ritonavir-boosted nirmatrelvir and concomitant medications can be safely managed (e.g., with certain statins, calcium channel blockers, or direct oral anticoagulants). Paxlovid update: Effectiveness, rebounding, drug interactions. estazolam, Paxlovid's primary side effect is a metallic taste in the mouth during the five days of treatment. Viral load rebound in placebo and nirmatrelvir-ritonavir treated COVID-19 patients is not associated with recurrence of severe disease or mutations. Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. An overview of severe acute respiratory syndrome-coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy. Patients who are receiving higher doses of dexamethasone will be at a greater risk of AEs. Alternative treatment for COVID-19 should be prescribed. Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer: There are limited clinical data available for PAXLOVID. Other drugs such as dexamethasone, chloroquine, and monoclonals such as sarilumab and tocilizumab provide moderate interaction with cardioprotective drugs that need caution and monitoring. clopidogrel active metabolite. Refer to the digoxin product label for further information. As a COVID-19 treatment, ritonavir essentially shuts down nirmatrelvirs metabolism in the liver, so that it doesnt move out of your body as quickly, which means itcan work longergiving it a boost to help fight the infection. Using alternative COVID-19 therapies (see, Cobicistat- or ritonavir-boosted antiretrovirals. Coadministration of ritonavir is required to . lumateperone, Systemic exposure of nirmatrelvir increases in renally impaired patients with increase in the severity of renal impairment. h The guidance on managing drug-drug interactions between certain benzodiazepines and ritonavir-boosted nirmatrelvir can vary significantly between product information resources. Risk of Serious Adverse Reactions Due to Drug Interactions: Initiation of PAXLOVID, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized . Longer treatment courses of ritonavir-boosted nirmatrelvir are not authorized by the current FDA Emergency Use Authorization (EUA), and there are insufficient data on the efficacy of administering a second treatment course in cases where SARS-CoV-2 viral rebound is suspected. Consult a patients specialist providers before coadministering these immunosuppressants with ritonavir-boosted nirmatrelvir. The usual apixaban treatment should be resumed 3 days after the last dose of nirmatrelvir/ritonavir. There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on milk production. methylprednisolone, . Coadministration has not been studied. zolpidem clorazepate, Concentrations of apixaban are expected to increase due to CYP3A4 and P-gp inhibition by ritonavir. It may be acceptable to continue clopidogrel if the benefits of using ritonavir-boosted nirmatrelvir outweigh the risk of reduced clopidogrel effectiveness. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered. an altered or impaired sense of taste. This is not a comprehensive list of all the medications that are not expected to have clinically relevant interactions with ritonavir-boosted nirmatrelvir.a. An additional, nonhormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID. 4 3CL PRO is responsible for cleaving polyproteins 1a and 1ab of SARS-CoV-2.
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