Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Coadministration contraindicated due to potential loss of virologic response and possible resistance. Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Pfizer reports additional data on PAXLOVID supporting upcoming new drug application submission to U.S. FDA. PAXLOVID will be packaged in a rectangular carton. Studies outside of the laboratory have since confirmed Paxlovids effectivenessamong people who have been vaccinated. Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported with ritonavir, a component of PAXLOVID (refer to NORVIR prescribing information). Available at: Charness ME, Gupta K, Stack G, et al. (The FDA has provided a fact sheet on Paxlovid with a full list of known side effects.). 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. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. If you are pregnant or breastfeeding, the FDA recommends discussing your options and specific situation with your health care provider, since there is no experience using the drug in these populations. Trazodone and Paxlovid interaction. Because ritonavir-boosted nirmatrelvir is the only highly effective oral antiviral for the treatment of COVID-19, drug interactions that can be safely managed should not preclude the use of this medication. The EUA advises against crushing nirmatrelvir and ritonavir tablets. Coadministration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia [see Contraindications (4)]. 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. Published studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage. Fewer ritonavir-boosted nirmatrelvir recipients discontinued the study drug due to an adverse event than placebo recipients (2% vs. 4%). 2022. Shah MM, Joyce B, Plumb ID, et al. If coadministered, dose adjustment of the immunosuppressant and monitoring for immunosuppressant concentrations and immunosuppressant-associated adverse reactions is recommended. 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). Avoid combinations; the risk of the interaction outweighs the benefit. Consider the potential for drug interactions prior to and during PAXLOVID therapy; review concomitant medications during PAXLOVID therapy and monitor for the adverse reactions associated with the concomitant medications.Anaphylaxis and other hypersensitivity reactionshave been reported with PAXLOVID. He encourages taking a test even if you think you only have a cold or allergiesand if you can get one. Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4)]. Early testing is key to making these drugs work, he says. Avoid concomitant use of tadalafil with PAXLOVID. For patients with a lower risk of arterial or venous thrombosis, clinicians may consider administering low-dose aspirin while rivaroxaban is being withheld. There are theoretical concerns that using a single antiviral agent in these patients may produce antiviral-resistant viruses. Caution is warranted and clinical monitoring of patients is recommended. 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. oxycodone Paxlovid is usually very well-tolerated, he says. You have to take Paxlovid within five days of developing symptoms. Refer to apixaban Summary of Product Characteristics for further information. iloperidone Coadministration of midazolam Pfizer recommends reporting it to them on its portal for adverse events associated with Paxlovid. **Tip: If you use CONTROL + F, you can type the name of the drug you are looking to find on the list. Pulmonary hypertension agents (PDE5 inhibitors). Viral load rebound in placebo and nirmatrelvir-ritonavir treated COVID-19 patients is not associated with recurrence of severe disease or mutations. An oral SARS-CoV-2 M. Food and Drug Administration. After looking closely at the drug-drug interactions listed for the new oral COVID-19 drug, Paxlovid, I realized that a large percentage of my patients are taking medications on the list.. 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. Like all antivirals, Paxlovid works best early in the course of an illnessin this case, within the first five days of symptom onset, says Jeffrey Topal, MD, a Yale Medicine infectious diseases specialist who is involved in determining COVID-19 treatment protocols for Yale New Haven Hospital patients. 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. Because of the potential for significant drug-drug interactions with concomitant medications, this regimen may not be the optimal choice for all patients. There are limited clinical data available for PAXLOVID. The strategy may need to continue for a longer duration if ritonavir-boosted nirmatrelvir is initiated in an adult of advanced age or if the interacting medication has a long half-life. No dosage adjustment is needed in patients with mild renal impairment. l Patients should take ritonavir-boosted nirmatrelvir at least 3 hours after receipt of brincidofovir. A total of 2,246 patients enrolled in the trial. The role of combination antiviral therapy or a longer treatment duration in treating patients who are severely immunocompromised is not yet known. This is not a comprehensive list of all the medications that are not expected to have clinically relevant interactions with ritonavir-boosted nirmatrelvir.a. The information provided is for educational purposes only. There were no deaths in the ritonavir-boosted nirmatrelvir arm and 13 deaths in the placebo arm. diltiazem, And as far as convenience, this medication is considered an improvement over treatments like remdesivir (approved by the FDAin October 2020), which is administered by intravenous (IV) injection. If ritonavir-boosted nirmatrelvir is prescribed to patients who take certain recreational drugs, those patients will require counseling and careful monitoring for adverse effects. Erectile dysfunction agents (PDE5 inhibitors), sildenafil 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. meperidine, fentanyl It helps that the pills are packaged in a dose card, basically a medication blister pack that allows you to punch out the pills as needed. Concentrations of apixaban are expected to increase due to CYP3A4 and P-gp inhibition by ritonavir. Key: EUA = Emergency Use Authorization; FDA = Food and Drug Administration. Coadministration with eplerenone is contraindicated due to potential for hyperkalemia [see Contraindications (4)]. Forty-seven percent of the patients tested negative for SARS-CoV-2 antibodies, and 66% started study treatment within 3 days of symptom onset. oxycodone, Interactions between Paxlovid and common heart medications are well known, said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in . Corticosteroids primarily metabolized by CYP3A, betamethasone, nifedipine, Additional resources include NIH recommendations for drug-drug interactions between PAXLOVID and UpToDate PAXLOVID drug information. budesonide, Sufficient information is available, such as through access to health records, patient reporting of medical history, or consultation with a health care provider in an established provider-patient relationship with the individual patient, to obtain a comprehensive list of medications (prescribed and non-prescribed) that the patient is taking to assess for potential drug interaction. For information on treatment considerations for vaccinated individuals, see Therapeutic Management of Nonhospitalized Adults With COVID-19. View all available interactions with Nirmatrelvir/ritonavir (5 days) [Please read the interaction details as management of these interactions may be complex.] Paxlovid associated with decreased hospitalization rate among adults with COVID-19United States, AprilSeptember 2022. View interaction reports for Paxlovid (nirmatrelvir / ritonavir) and the medicines listed below. Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease 2019. 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. For patients with severe kidney diseaseor who are on dialysisor those with severe liver disease, Paxlovid is not recommended; the levels of the drug can become too high and could cause increased side effects, he says. Avoid concomitant use of suvorexant with PAXLOVID. PharmaCare previously paid a fee (PAX-F) to pharmacists for following up and monitoring patients for adverse drug events. fluticasone, Providers should counsel patients about renal dosing instructions. However, recent data shows . Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. The purpose is to make people aware there is a drug/drug interaction." Paxlovid is a combination of two drugs, nirmatrelvir and ritonavir , and experts say the main concerns for drug . These immunosuppressants have significant drug-drug interaction potential with ritonavir, and they should not be used if close monitoring, including therapeutic drug monitoring, is not feasible. molnupiravir, remdesivir, Actemra, Lagevrio, Olumiant, nirmatrelvir / ritonavir. lovastatin simvastatin. An overview of severe acute respiratory syndrome-coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy. 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 . . For the Panels recommendations on preferred and alternative antiviral therapies for outpatients with COVID-19, see Therapeutic Management of Nonhospitalized Adults With COVID-19. Ritonavir-boosted nirmatrelvir should not be given within 2 weeks of administering a strong CYP3A4 inducer (e.g., St. Johns wort, rifampin). Pfizer Inc.; February 2023. LIMITATIONS OF AUTHORIZED USE, PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of Learn about interactions between Xarelto and other medications, supplements, foods, alcohol, and more. The more underlying medical conditions a person has, the higher their risk for developing a severe case of COVID-19, according to the CDC. Drug-Drug Interactions Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir Bottom line, a glass won't kill you.. immediately. High doses of ketoconazole or itraconazole (>200 mg/day) are not recommended. For patients with renal and/or hepatic impairment. Drug-Drug Interactions with Nirmatrelvir/Ritonavir (Paxlovid) and Select Cardiovascular Medications NOTE: Holding or reducing the dose of select cardiovascular medications and/or other special monitoring requirements are recommended during treatment with nirmaltrelvir/ritonavir (Paxlovid) and for 3 days thereafter (for a total of 8 days from the 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. 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 . Dosage adjustment of saxagliptin is recommended. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Before prescribing ritonavir-boosted nirmatrelvir, clinicians should carefully review the patients concomitant medications, including over-the-counter medications, herbal supplements, and recreational drugs, to evaluate potential drug-drug interactions. Ritonavir-boosted nirmatrelvir has not been studied in patients who were hospitalized for mild to moderate COVID-19. Comprehensive, up-to-date, evidence-based COVID19 drug-drug interaction resource, freely available to healthcare workers, patients and researchers. For anyone who experiences a rebound, the CDC advises people restart isolation for five days, following its isolation guidance. . Vangeel L, Chiu W, De Jonghe S, et al. Paxlovid update: Effectiveness, rebounding, drug interactions. I think it's a good comparison, says Dr. Roberts. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. In cases where the risks of the drug interaction outweigh the potential benefits, alternative COVID-19 therapy must be prescribed. tezacaftor/ivacaftor, ivacaftor 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). 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. Share sensitive information only on official, secure websites. Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported with ritonavir, a component of PAXLOVID (refer to NORVIR prescribing information). 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. 239 are major, 364 are moderate, and 40 are minor. Public Health Patient Stories Facts About ID Guidelines Practice Guidelines Search Practice Guidelines App . Increased grazoprevir concentrations can result in ALT elevations. 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%). (While the recommendation is to take Paxlovid within five days of symptom onset, participants in the clinical trial took the drug within three days.). Ritonavir-boosted nirmatrelvir may be prescribed safely to select patients if an expert in managing the interaction is available and close therapeutic drug monitoring is logistically feasible. Anderson AS, Caubel P, Rusnak JM, EPIC-HR Trial Investigators. midazolam There are maternal and fetal risks associated with untreated COVID-19 in pregnancy. 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. Temporarily withholding the concomitant medication. Owen DR, Allerton CMN, Anderson AS, et al. Both are prescription-only oral antiviral pills given early in illness. Coadministration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances [see Contraindications (4)]. Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Fish Oil (omega-3 polyunsaturated fatty acids), Email this report to a friend, doctor, or patient. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAXLOVID and any potential adverse effects on the breastfed infant from PAXLOVID or from the underlying maternal condition. Vaccination, testing, and mitigation efforts such as masking, remaina key part of prevention, even as more drugs become available, says Dr. Topal. reference. Box 2 below lists select outpatient medications that have clinically relevant drug-drug interactions with ritonavir-boosted nirmatrelvir. 2023. If you could become pregnant, its recommended that you use effective barrier contraception or do not have sexual activity while taking Paxlovid. However, the lower ethinyl estradiol concentrations are not expected to be clinically significant during the 5 days of therapy. Otherwise, an alternative therapy for COVID-19 should be considered. PAXLOVID IS NOT approved for any of the following: To treat patients who are hospitalized due to severe or critical COVID-19. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information. Its cheaper than many other COVID-19 drugs (its provided for free by the U.S. government while there is a public health emergency), and, perhaps most reassuring, it is expected to work against the Omicron variant. The drug was granted an emergency use authorization (EUA) by the Food and Drug Administration (FDA) in December for anyone ages 12 and older who weighs at least 88 pounds, and is at high risk for severe disease. Patients with moderate renal impairment may receive a carton that has been opened and modified by the pharmacist to indicate a dose adjustment. Before prescribing ritonavir-boosted nirmatrelvir (Paxlovid) to treat patients with mild to moderate COVID-19, carefully review the patients concomitant medications, including over-the-counter medicines, herbal supplements, and recreational drugs. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. 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. hepatotoxicity. Ritonavir-Boosted Nirmatrelvir (Paxlovid), Table: Characteristics of Antiviral Agents, Including Antibody Products, Table: Characteristics of Immunomodulators, Table: Characteristics of Miscellaneous Drugs, Therapeutic Management of Nonhospitalized Children With COVID-19, Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications, Liverpool COVID-19 Drug Interactions website, University of Waterloo/University of Toronto drug interaction guide, Therapeutic Management of Nonhospitalized Adults With COVID-19, Pregnancy, Lactation, and COVID-19 Therapeutics, Therapeutic Management of Hospitalized Children With COVID-19, https://www.ncbi.nlm.nih.gov/pubmed/26878082, https://www.ncbi.nlm.nih.gov/pubmed/34726479, https://www.fda.gov/media/155050/download, https://www.ncbi.nlm.nih.gov/pubmed/35263535, https://www.ncbi.nlm.nih.gov/pubmed/35085683, https://www.ncbi.nlm.nih.gov/pubmed/35461811, https://www.ncbi.nlm.nih.gov/pubmed/36476720, https://www.ncbi.nlm.nih.gov/pubmed/35172054, https://www.ncbi.nlm.nih.gov/pubmed/34937145, https://www.ncbi.nlm.nih.gov/pubmed/34914868, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting, https://www.ncbi.nlm.nih.gov/pubmed/36508742, https://www.ncbi.nlm.nih.gov/pubmed/36001529, https://www.ncbi.nlm.nih.gov/pubmed/36454693, https://www.fda.gov/media/155194/download, https://www.ncbi.nlm.nih.gov/pubmed/36069968, https://www.ncbi.nlm.nih.gov/pubmed/35737946, https://www.ncbi.nlm.nih.gov/pubmed/36069818, https://www.researchsquare.com/article/rs-1720472/v1, https://pubmed.ncbi.nlm.nih.gov/36802755/, https://www.ncbi.nlm.nih.gov/pubmed/35698452, https://emergency.cdc.gov/han/2022/han00467.asp, http://www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/Crushing_Paxlovid.pdf, https://www.ncbi.nlm.nih.gov/pubmed/36723285, https://covid19-druginteractions.org/prescribing_resources, https://www.ontariohealth.ca/sites/ontariohealth/files/2022-04/PaxlovidClinicalGuide.pdf, https://www.ncbi.nlm.nih.gov/pubmed/35680135, The COVID-19 Treatment Guidelines Panel (the Panel) recommends using, For recommendations on using ritonavir-boosted nirmatrelvir in nonhospitalized children with COVID-19, see. If it is clinically appropriate, the medication you're taking . Coadministration contraindicated due to potential for postural hypotension [see Contraindications (4)]. COVID-19 rebound after Paxlovid treatment. i Do not coadminister this medication with ritonavir-boosted nirmatrelvir in patients with hepatic or renal impairment. Potential Drug Interactions. Coadministration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4)]. Serious interactions with other medicines: Many medicines interact with PAXLOVID. In patients with suspected renal impairment, clinicians may consider checking the patients renal function to inform the dosing of ritonavir-boosted nirmatrelvir. Data sources include IBM Watson Micromedex (updated 2 Apr 2023), Cerner Multum (updated 17 Apr 2023), ASHP (updated 10 Apr 2023) and others. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. Researchers showed that Paxlovid can prevent hospitalization and death. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. Withhold atorvastatin and rosuvastatin at the beginning of treatment with ritonavir-boosted nirmatrelvir and resume after completion of the 5-day course. University of Liverpool. These are some of the commonly used medications that interact with Paxlovid and management strategies. Below are their responses. ciclesonide, PAXLOVID must be prescribed by a licensed healthcare provider and supplied by a government-approved pharmacy or medical facility. (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., Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment, Important Prescribing & Dispensing Letter to Healthcare Professionals (Aug. 2022), Fact Sheet for Patients, Parents, and Caregivers, PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19, 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 providerpatient relationship with the individual patient, to assess renal and hepatic function; and. Tamiflu is taken twice a day for five days, and it must be started within 48 hours of flu onset. 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. Dosing recommendations for co-administration of apixaban with Paxlovid depend on the apixaban dose. aripiprazole, 2020. Nirmatrelvir use and severe COVID-19 outcomes during the Omicron surge. In some cases, the recommendation is to avoid co-administration. Paxlovid disease interactions. Pfizer is committed to patient safety and ensuring that people have accurate information about the investigationaldrug PAXLOVID, including how it is accessed and administered. The EPIC-HR study was a multinational randomized trial that compared the use of ritonavir-boosted nirmatrelvir PO twice daily for 5 days to placebo in nonhospitalized patients aged 18 years with mild to moderate COVID-19 who were at high risk of clinical progression. Most people who take Paxlovid should not experience serious side effects, explains Dr. Roberts. elexacaftor/tezacaftor/ivacaftor Tables with guidance on managing specific drug-drug interactions: Increasing monitoring for potential adverse events to the concomitant medication.