If coadministered, refer to individual product label for calcium channel blocker for further information. The authorized adult dosing regimen is expected to result in comparable serum exposures of nirmatrelvir and ritonavir in patients 12 years of age and older and weighing at least 40 kg as observed in adults, and adults with similar body weight were included in the trial EPIC-HR. Avoid concomitant use of tadalafil with PAXLOVID. 7 common Paxlovid interactions to know about Paxlovid is made up of two antiviral medications, nirmatrelvir and ritonavir. PAXLOVID is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40 kg. of Health and Human Services (HHS), 1: Established and Other Potentially Significant Drug Interactions, Copyright 2023 Pfizer Inc. All rights reserved. Concentrations of apixaban are expected to increase due to CYP3A4 and P-gp inhibition by ritonavir. In June, the CDC releasedguidance for clinicians, saying a brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some people, independent of treatment with Paxlovid, adding that there is no evidence additional treatment is needed. No dosage adjustment is needed in patients with mild renal impairment. Refer to the upadacitinib product label for more information. 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. emtricitabine Before coadministering ritonavir-boosted nirmatrelvir and any of these conjugated monoclonal antibodies, refer to the drugs FDA prescribing information and consult with the patients specialist providers as needed. These medications may be coadministered without dose adjustment and without increased monitoring. The darifenacin daily dose should not exceed 7.5 mg when coadministered with 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. Hammond J, Leister-Tebbe H, Gardner A, et al. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Immune System Disorders:Anaphylaxis, hypersensitivity reactionsGastrointestinal Disorders: Abdominal pain, nauseaGeneral Disorders and Administration Site Conditions: Malaise. Paxlovid disease interactions. Nirmatrelvir/ritonavir ( Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new . 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: and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A. In cases where the risks of the drug interaction outweigh the potential benefits, alternative COVID-19 therapy must be prescribed. 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. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use [see Dosage and Administration (2.4)]. Serious and unexpected adverse events may occur that have not been previously reported with PAXLOVID use.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 by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A. d Ritonavir-boosted nirmatrelvir may increase concentrations of some chemotherapeutic agents, leading to an increased potential for drug toxicities. Refer to individual product label for more information. More than 120 medications have been flagged for interactions, and each case needs to be evaluated, taking into account an individual's conditions, as well as kidney and liver function. dihydroergotamine,ergotamine,methylergonovine, dihydroergotamine ergotamine methylergonovine. Symptom and viral reboundin untreated SARS-CoV-2 infection. If you suspect the product you have received may be counterfeit, contact us at 18004381985or visit www.pfizersafetyreporting.com. Ritonavir-boosted nirmatrelvir is not recommended for patients with known or suspected severe hepatic impairment (i.e., Child-Pugh Class C), and it should be used with caution in patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. These studies have not yet been published in peer-reviewed medical journals. Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Secure .gov websites use HTTPSA lock (LockA locked padlock) or https:// means youve safely connected to the .gov website. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. One of our biggest public health challenges is to decrease the rate of severe COVID-19 disease in the face of pandemic fatigue, dried up funding, misinformation, and a changing virus. The cartonhas a colorless, glossy coating that contains a repeated pattern of the Pfizer name and logo all over, and these repeating features are seen in a contrasting matte finish. The recommended treatment course of ritonavir-boosted nirmatrelvir for COVID-19 is 5 days. Nirmatrelvir plus ritonavir for early COVID-19 in a large U.S. health system: a population-based cohort study. Nirmatrelvir-ritonavir and viral load rebound in COVID-19. In some cases, the recommendation is to avoid co-administration. Paxlovidan antiviral medicationis a tool we still have left. No dosage adjustment is needed in patients with mild renal impairment. It also interacts with common medications, including cholesterol-lowering statins like Lipitor. Erectile dysfunction agents (PDE5 inhibitors), sildenafil Coadministration may increase apixaban concentrations. Refer to individual product label for more information. View all available interactions with Nirmatrelvir/ritonavir (5 days) [Please read the interaction details as management of these interactions may be complex.] For more information on ritonavir-boosted nirmatrelvir, see. 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. Refer to the bosentan product label for further information. These interactions may lead to: Consult Table 1 of the Fact Sheet for Healthcare Providers for clinically significant drug interactions, including contraindicated drugs. 2022. Early testing is key to making these drugs work, he says. The National Institutes of Health (NIH) has a more comprehensive list of medications that are expected to have drug-drug interactions with Paxlovid. Drug-Drug Interactions Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring.Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.Pregnancy: 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. 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. Refer to the tofacitinib product label for more information. But this enzyme directly interacts with alcohol. zolpidem Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect. Additional resources include NIH recommendations for drug-drug interactions between PAXLOVID and UpToDate PAXLOVID drug information. Pfizer Paxlovid Drug Interaction Checker, or ; the TGA-approved Product Information for more detailed information. Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications. triamcinolone. Refer to rifabutin product label for further information on rifabutin dose reduction. FDA has provided a fact sheet on Paxlovid. But, in general, "Paxlovid will have a slew of drug-drug interactions . a This list is primarily based on the most common medication searches by U.S. users on the Liverpool COVID-19 Drug Interactions website between January 1 and December 31, 2022 (internal communication, January 2023). Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications, Loss of therapeutic effect of PAXLOVID and possible development of resistance. (administered parenterally). This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. vorapaxar Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.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.Adverse events in the PAXLOVID group (1%) that occurred at a greater frequency (5 subject difference) than in the placebo group were dysgeusia (6% and <1%, respectively), diarrhea (3% and 2%), hypertension (1% and <1%), and myalgia (1% and <1%). If it is clinically appropriate, the medication you're taking . Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)]. The information provided is for educational purposes only. Nirmatrelvir (PF-07321332) is an orally bioavailable 3C-like protease (3CL PRO) inhibitor that is the subject of clinical trial NCT04756531. 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. At the same time, nirmatrelvir and ritonavir are CYP3A substrates; therefore . Pfizer Inc.; September 26, 2022. Refer to the digoxin product label for further information. Public Health Patient Stories Facts About ID Guidelines Practice Guidelines Search Practice Guidelines App . Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir component of the combination. By clicking this link, you will be redirected to Pfizer Medical Information. [Originally published: March 10, 2022. All rights reserved. Scientists are still studying the Paxlovid rebound. Based on the pharmacokinetics of the drugs in Paxlovid, the differences in metabolism and excretionliver and kidney function specificallyof these drugs in this age group are thought to be similar to that of adults, Dr. Topal says. There have been reports of a rebound of COVID-19 symptoms in some people within 2 to 8 days after completing the five-day course of Paxlovid; in those cases, some have tested positive again but have no symptoms; others have a recurrence of symptoms. Ontario COVID-19 Drugs and Biologics Clinical Practice Guidelines Working Group on behalf of the Ontario COVID-19 Science Advisory Table and University of Waterloo School of Pharmacy. PAXLOVID will be packaged in a rectangular carton. vardenafil. The Food and Drug Administration's fact sheet on Paxlovid notes an extensive list of drug-drug interactions for health care providers, noting "caution is warranted" with Amlodipine, that "clinical . The FDA also granted an EUA in December to a pill from Merck called molnupiravir (Lagevrio), but some studies suggest that molnupiravir has only a 30% reduction in the risk for hospitalization and death from COVID-19. The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor such as ritonavir.PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions: PAXLOVID is contraindicated with drugs that are potent CYP3A inducerswhere significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. However, recent data shows . Ritonavir-boosted nirmatrelvir should not be given within 2 weeks of administering a strong CYP3A4 inducer (e.g., St. Johns wort, rifampin). The release of Paxlovid is still a game-changer in the fight against COVID-19, but because of the risk for serious medication interactions, taking the antiviral is a decision your entire care team needs to make together. COVID-19 rebound after Paxlovid treatment. 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. Serious interactions with other medicines: Many medicines interact with PAXLOVID. The products discussed in this site may have different product labeling in different countries. 2.4 Important Drug Interactions with PAXLOVID Refer to other sections of the Fact Sheet for important drug interactions with PAXLOVID. The University Health Network/Kingston Health Sciences Centre provides an additional resource for evaluating drug-drug interactions between ritonavir-boosted nirmatrelvir and chemotherapeutic agents. There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on milk production. clopidogrel, aliskiren Scientists are studying the effects of longer treatment durations, longer periods of isolation, and other ways of managing the problem, he adds. 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. Its worth noting that because Paxlovid is still being monitored in the real world, it is possible that all of the risks are not yet known. Paxlovid is an oral antiviral pill that can be taken at home to help keep high-risk patients from getting so sick that they need to be hospitalized. Boucau J, Uddin R, Marino C, et al. c Ritonavir-boosted nirmatrelvir interacts with certain conjugated monoclonal antibodies, such as ado-trastuzumab emtansine, brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin. oxycodone, Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease 2019. The usual apixaban treatment should be resumed 3 days after the last dose of nirmatrelvir/ritonavir. 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. Examples of risk factors include living in residential aged care, having certain medical conditions such as asthma, diabetes or obesity. For the Panels recommendations on preferred and alternative antiviral therapies for outpatients with COVID-19, see Therapeutic Management of Nonhospitalized Adults With COVID-19. Dosage adjustment of tofacitinib is recommended. Pfizer had said that in the clinical trial for Paxlovid, several participants appeared to have a rebound in virus levels, although this also occurred in some people who were given a placebo. 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. Studies outside of the laboratory have since confirmed Paxlovids effectivenessamong people who have been vaccinated. While Paxlovid is authorized for use in adolescents and teenagers ages 12 and up, and weighing at least 88 pounds, that age group wasnt tested in the original clinical trial. Paxlovids clinical trials took place before Omicron and later subvariants like BA.5 became predominant, but Pfizer says the drug works against the highly contagious variant. Coadministration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushings syndrome and adrenal suppression. vorapaxar COVID-19 supplemental clinical guidance #4: nirmatrelvir/ritonavir (Paxlovid) use in patients with advanced chronic kidney disease and patients on dialysis with COVID-19. Share sensitive information only on official, secure websites. of glecaprevir/pibrentasvir with PAXLOVID. diltiazem, Note: Information in this article was accurate at the time of original publication. 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 . Systemic exposure of nirmatrelvir increases in renally impaired patients with increase in the severity of renal impairment.