Management of Drug Interactions With Nirmatrelvir/Ritonavir (Paxlovid): Resource for Clinicians Facebook Twitter LinkedIn Email. g Withhold lovastatin and simvastatin for at least 12 hours before initiating ritonavir-boosted nirmatrelvir, during treatment, and for 5 days after treatment completion. Once youve been ill with the virus for more than a week, the damage done to the body in a severe case cant be undone by the antiviral, he says. Ritonavir-Boosted Nirmatrelvir (Paxlovid) Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring. Early remdesivir to prevent progression to severe COVID-19 in outpatients. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and ritonavir. . 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. Other drugs such as dexamethasone, chloroquine, and monoclonals such as sarilumab and tocilizumab provide moderate interaction with cardioprotective drugs that need caution and monitoring. FDA has provided a fact sheet on Paxlovid. FDA Updates on Paxlovid for Health Care Providers | FDA 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 . 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%). Refer to the digoxin product label for further information. PAXLOVID is not an appropriate therapeutic option based on the authorized Fact Sheet for Healthcare Providers or due to potential drug interactions for which recommended monitoring would not be feasible. In November 2022, the CDC reported on a real-world study that showed adults who took Paxlovid within five days of a COVID-19 diagnosis had a 51% lower hospitalization rate within the next 30 days than those who were not given the drug. 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. pimavanserin, aripiprazole Download . vardenafil. 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. Nirmatrelvir is an oral protease inhibitor that is active against MPRO, a viral protease that plays an essential role in viral replication by cleaving the 2 viral polyproteins.1 It has demonstrated antiviral activity against all coronaviruses that are known to infect humans.2 Nirmatrelvir is packaged with ritonavir (as Paxlovid), a strong cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent that has been used to boost HIV protease inhibitors. 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. These medications may be coadministered without dose adjustment and without increased monitoring. . The following adverse reactions have been identified during post-authorization use of PAXLOVID. For patients with a lower risk of arterial or venous thrombosis, clinicians may consider administering low-dose aspirin while rivaroxaban is being withheld. 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. For more information on ritonavir-boosted nirmatrelvir, see. Its important to note that although health care providers can write a prescription, pharmacists may also provide Paxlovid (with certain limitations) if theyve opted to do so, provided you can share your electronic or printed medical records, including a list of medications you are already taking, and blood test results from the last 12 months. Will some people still be hospitalized? budesonide, clopidogrel active metabolite. He encourages taking a test even if you think you only have a cold or allergiesand if you can get one. Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. nifedipine, Vangeel L, Chiu W, De Jonghe S, et al. Before taking Paxlovid, consider these drug interactions - KevinMD.com Copyright 2023 The University of Liverpool. PAXLOVID 9 Drug Interactions - Pfizer Medical Information Avoid use of PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. CYP3A4 inhibition occurs rapidly, with maximum inhibition occurring within 48 hours of ritonavir initiation.1 After treatment is completed and ritonavir is discontinued, 70% to 90% of CYP3A4 inhibition resolves within 2 to 3 days.2 The time to resolution of inhibition varies based on factors such as the patients age; therefore, resolution may take longer in some individuals, such as in adults of advanced age. Moderately clinically significant. 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. These interactions may lead to: Consult Table 1 of the Fact Sheet for Healthcare Providers for clinically significant drug interactions, including contraindicated drugs. i Do not coadminister this medication with ritonavir-boosted nirmatrelvir in patients with hepatic or renal impairment. Refer to the individual product label for more information. Because of the potential for significant drug-drug interactions with concomitant medications, this regimen may not be the optimal choice for all patients. Pulmonary hypertension agents (PDE5 inhibitors) 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 providerpatient 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 Medical Information visit www.pfizermedicalinformation.com or call 18004381985 Nirmatrelvir/ritonavir (5 days) [Please read the interaction details as management of these interactions may be complex.]. FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. Yesno medication is perfect, he says. A total of 2,224 patients who received at least 1 dose of either ritonavir-boosted nirmatrelvir or placebo were included in the EPIC-HR safety analysis set. Ritonavir-boosted nirmatrelvir may be used in patients who are hospitalized for a diagnosis other than COVID-19, provided they have mild to moderate COVID-19 (i.e., those who do not require supplemental oxygen), are at high risk of progressing to severe disease, and are within 5 days of symptom onset. pimavanserin. 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. The healthcare provider should consult other appropriate Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)]. Refer to individual product label for more information. ritonavir (as Paxlovid), a strong cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent that has been used to boost HIV protease inhibitors. 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. If it is clinically appropriate, the medication you're taking . Key: EUA = Emergency Use Authorization; FDA = Food and Drug Administration. Comprehensive, up-to-date, evidence-based COVID19 drug-drug interaction resource, freely available to healthcare workers, patients and researchers. If coadministration is necessary, consider reducing the clozapine dose and monitor for adverse reactions. Available at: Dryden-Peterson S, Kim A, Kim AY, et al. Coadministration of sildenafil with PAXLOVID is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope [see Contraindications (4)]. Withhold these medications during ritonavir-boosted nirmatrelvir treatment and for at least 23 days after treatment completion. molnupiravir, remdesivir, Actemra, Lagevrio, Olumiant, nirmatrelvir / ritonavir. 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. Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir component of the combination. Available at: Hiremath S, Blake PG, Yeung A, et al. Everything You Need to Know If You're Prescribed Paxlovid - CreakyJoints midazolam You have to take Paxlovid within five days of developing symptoms. University of Liverpool. 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. 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. Microsomal triglyceride transfer protein (MTTP) inhibitor. LIMITATIONS OF AUTHORIZED USE, PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of fluticasone, Prescription et dispensation du Paxlovid en ville This is the drug that inhibits the enzyme cytochrome P450, among another. Available at: Li M, Zhu L, Chen L, Li N, Qi F. Assessment of drug-drug interactions between voriconazole and glucocorticoids. Potentially increased apixaban concentrations which may lead to an increased bleeding risk. Consult the, Pre-emptive dose adjustment is not required but may be considered based on an individualized assessment of the patients risk for adverse reactions. 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 . dihydroergotamine,ergotamine,methylergonovine, dihydroergotamine ergotamine methylergonovine. To be used for longer than 5 days in a row. Management of Drug Interactions With Nirmatrelvir/Ritonavir (Paxlovid Xarelto Interactions: Other Medications, Alcohol, and More - Healthline 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. Refer to the bedaquiline product label for further information. Potential clinically significant interaction that is likely to require additional monitoring, alteration of drug dosage or timing of administration. Studies outside of the laboratory have since confirmed Paxlovids effectivenessamong people who have been vaccinated. View all available interactions with Nirmatrelvir/ritonavir (5 days) [Please read the interaction details as management of these interactions may be complex.] For treatment of atrial fibrillation with standard apixaban dose (i.e., 5 mg twice daily), reduce apixaban to 2.5 mg twice daily. It's used when there are contraindications for Paxlovid, such as liver/kidney issues, allergies, or medication interactions. When you give a patient Tamiflu beyond that, it doesnt really change the course of their flu, Dr. Roberts says. Emergency Use Authorization (EUA) for Paxlovid (nirmatrelvir tablets co-packaged with ritonavir tablets): Center for Drug Evaluation and Research (CDER) review. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. An official website of the United States government. High doses of ketoconazole or itraconazole (>200 mg/day) are not recommended. 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. Drug-Drug Interactions. Ritonavir-Boosted Nirmatrelvir (Paxlovid) | COVID-19 Treatment Guidelines Coadministration contraindicated due to potential loss of virologic response and possible resistance. Coadministration may increase apixaban concentrations. 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 . Coadministration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4)]. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy. Consider consulting with an expert (e.g., a pharmacist or the patients specialist providers) when treating patients who are receiving highly specialized therapies or drugs that are prone to concentration-dependent toxicities, such as certain anticonvulsant, anticoagulant, antiarrhythmic, chemotherapeutic, neuropsychiatric, and immunosuppressant drugs. Fact sheet for healthcare providers: Emergency Use Authorization for Paxlovid. 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. 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 . This guide to COVID-19 medications and drug-drug interactions contains a helpful interaction checker, which provides a recommendation for management of DDIs in addition to a description of the primary data.