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nirmatrelvir–ritonavir

Paxlovid

Pharmaceutical company: Pfizer

Pharmacologic classification: Protease inhibitors

Therapeutic classification: Antivirals
 

AVAILABLE FORMS

Tablets: 150 mg nirmatrelvir copackaged with 100 mg ritonavir
 

INDICATIONS AND DOSAGES

Mild-to-moderate coronavirus disease 2019 (COVID-19) in patients at high risk for progression to severe COVID-19, including hospitalization or death

Adults: 300 mg nirmatrelvir PO with 100 mg ritonavir PO taken together b.i.d. for 5 days.
 

Adjust-a-dose: For eGFR of 30 to less than 60 mL/minute, 150 mg nirmatrelvir PO with 100 mg ritonavir PO taken together b.i.d. for 5 days.

CONTRAINDICATIONS AND CAUTIONS

• Contraindicated with drugs primarily metabolized by CYP3A and for which elevated levels are associated with serious or life-threatening reactions, and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir levels may be associated with loss of virologic response and possible resistance.
• Boxed Warning: Consider the benefit of PAXLOVID treatment in reducing hospitalization and death, and whether the risk of drug-to-drug interactions for the patient can be appropriately managed.
• Nirmatrelvir–ritonavir isn't approved for preexposure or postexposure prevention of COVID-19.
• Contraindicated in patients with a history of significant hypersensitivity reactions (toxic epidermal necrolysis or Stevens-Johnson syndrome) to nirmatrelvir or ritonavir or any other components of the product. Anaphylaxis, severe cutaneous adverse reactions, and other hypersensitivity reactions have been reported.
• Transaminase elevations, hepatitis, and jaundice have occurred in patients receiving ritonavir. Use cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. This drug isn't recommended in patients with Child-Pugh class C liver impairment.
• This drug isn't recommended in patients with GFR less than 30 mL/minute or patients on kidney replacement therapy.
• There may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
• Use cautiously in older adults.
• Safety and effectiveness in children haven't been established.
• Dialyzable drug: Unknown.

 

PREGNANCY-LACTATION-REPRODUCTION

• Studies on use of nirmatrelvir or ritonavir during pregnancy are inadequate. Use cautiously during pregnancy.
• There are patient and fetal risks associated with untreated COVID-19.
• It's unknown if nirmatrelvir is excreted in human milk. Ritonavir is present in human milk. Use cautiously during pregnancy.
• Patients with COVID-19 who are breastfeeding should follow clinical guidelines to avoid exposing their infants to COVID-19.
• Ritonavir may reduce the efficacy of combined hormonal contraceptives. Use an effective alternative contraceptive or an additional barrier method of contraception during treatment.

 

INTERACTIONS

Alert: Nirmatrelvir with ritonavir has the potential for significant interactions with many drugs. Consult a drug interaction resource or pharmacist for additional information.

Drug-drug. 
Alpha 1-adrenoreceptor antagonists (alfuzosin, tamsulosin): May increase levels of the antagonist and risk of hypotension. Avoid use together. Coadministration with alfuzosin is contraindicated.
Antiarrhythmics (amiodarone, disopyramide, dronedarone, flecainide, lidocaine [systemic], propafenone, quinidine): May increase antiarrhythmic level. Use together with disopyramide or lidocaine cautiously with therapeutic level monitoring, if available. Use with amiodarone, dronedarone, flecainide, propafenone, or quinidine is contraindicated.
Antibacterials (clarithromycin, erythromycin): May increase level of antibacterial. Refer to antibacterial prescribing information.
Anticancer drugs (abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine):May increase level of the anticancer drug. Avoid coadministration of encorafenib or ivosidenib due to risk of serious adverse events, including QT interval prolongation. Avoid use with neratinib, venetoclax or ibrutinib. Coadministration of vincristine and vinblastine may lead to significant hematologic or GI adverse effects.
Anticoagulants (apixaban, dabigatran and rivaroxaban, warfarin): May increase risk of bleeding and anticoagulant level. May increase or decrease warfarin level. Closely monitor INR when used with warfarin. Avoid use with rivaroxaban. Reduce dose of dabigatran and apixaban or avoid concomitant use. Refer to anticoagulant prescribing information.
Anticonvulsants (carbamazepine, phenobarbital, primidone, phenytoin): May cause loss of virologic response and possible resistance. Use together is contraindicated.
Antifungals (isavuconazonium, itraconazole azole, ketoconazole, voriconazole): May increase isavuconazonium, itraconazole, ketoconazole, and nirmatrelvir–ritonavir levels. May decrease voriconazole level. Avoid use with voriconazole. Refer to antifungal prescribing information.
Anti-HIV agents (bictegravir–emtricitabine–tenofovir, efavirenz, maraviroc, nevirapine, zidovudine): May alter anti-HIV agent level. Refer to anti-HIV agent prescribing information.
Anti-HIV protease inhibitors (atazanavir, darunavir, tipranavir):  May increase protease inhibitor level. Refer to protease inhibitor prescribing information. Patients on ritonavir- or cobicistat-containing HIV regimens should continue treatment as indicated. Monitor for increased adverse events.
Antimigraine medications (eletriptan, rimegepant, ubrogepant): May increase level of antimigraine medication. Use of eletriptan within 72 hours of Paxlovid is contraindicated due to risk for serious adverse reactions, including CV and cerebrovascular events. Coadministration of ubrogepant is contraindicated because of the risk for serious adverse reactions. Avoid use with rimegepant.
Antimycobacterial (bedaquiline, rifabutin):  May increase level of antimycobacterial. Refer to antimycobacterial prescribing information.
Antipsychotics (clozapine, lurasidone, pimozide, quetiapine): May increase level of antipsychotic. Refer to antipsychotic prescribing information.
Apalutamide:  May decrease nirmatrelvir or ritonavir levels. Coadministration is contraindicated.
Atorvastatin, rosuvastatin: May increase statin level. Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment. Atorvastatin and rosuvastatin don't need to be withheld prior to or after completing Paxlovid.
Bosentan: May increase bosentan level and decrease nirmatrelvir or ritonavir level. Discontinue bosentan at least 36 hours prior to initiation of Paxlovid.
Bupropion: May decrease level of bupropion. Monitor for adequate antidepressant response.
Calcium channel blockers (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil): May increase level of calcium channel blocker. Monitor closely and consider decreasing the calcium channel dose.
Cardiovascular agents (aliskiren, ticagrelor, vorapaxar): May increase level of CV agent. Avoid use together.
Cilostazol: May increase cilostazol level. Decrease dose of cilostazol.
Clonazepam: May increase clonazepam level. Decrease clonazepam dosage as indicated, and monitor therapy.
Clopidogrel: May decrease level of clopidogrel active metabolite. Use together cautiously.
Colchicine: May increase colchicine level and risk of serious reactions. Use together is contraindicated in patients with kidney or liver impairment.
Corticosteroids metabolized by CYP3A (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone):  May increase level of corticosteroid. Consider alternative corticosteroid (beclomethasone, prednisone, prednisolone).
Cystic fibrosis transmembrane conductance regulator potentiators (ivacaftor, elexacaftor–tezacaftor–ivacaftor, tezacaftor–ivacaftor): May increase level of cystic fibrosis drug. Refer to prescribing information for dosage adjustment.
Darifenacin: May increase darifenacin level. The darifenacin dose should not exceed 7.5 mg daily. Refer to darifenacin prescribing information.
Digoxin: May increase digoxin level. Monitor digoxin level.
Eplerenone, ivabradine: May increase level of these drugs. Use together is contraindicated.
Ergot derivatives (dihydroergotamine, ergotamine, methylergonovine): May increase level of ergot derivative and risk for toxicity. Use together is contraindicated.
Ethinyl estradiol: May decrease hormone level. Consider using an additional, nonhormonal method of contraception during the 5 days of treatment and until one menstrual cycle after stopping Paxlovid.
Finerenone: May increase finerenone level. Use together is contraindicated.
Flibanserin: May increase flibanserin level and risk of hypotension, syncope, and CNS depression. Use together is contraindicated.
Hepatitis C direct acting antivirals (elbasvir–grazoprevir, glecaprevir–pibrentasvir, ombitasvir–paritaprevir–ritonavir–dasabuvir, sofosbuvir–velpatasvir–voxilaprevir): May increase level of antiviral. Avoid concomitant use with glecaprevir–pibrentasvir. Patients on ritonavir-containing hepatitis C virus (HCV) regimens should continue treatment as indicated. Monitor for increased drug adverse events with use together. Refer to HCV antiviral prescribing information.
Immunosuppressants (cyclosporine, tacrolimus): May increase immunosuppressant level. Avoid concomitant use when close monitoring of immunosuppressant level is not feasible. If coadministered, adjust immunosuppressant dose and closely monitor immunosuppressant level and assess for adverse reactions.
Immunosuppressant (voclosporin): May increase voclosporin level. Coadministration contraindicated due to potential for kidney toxicity.
Ivabradine: May increase ivabradine level and risk for bradycardia or conduction disturbances. Use together is contraindicated.
Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib): May increase JAK inhibitor level. Adjust dose of tofacitinib. Dose adjustment for coadministration of upadacitinib depends on the upadacitinib indication. Refer to the JAK inhibitor prescribing information.
Lomitapide: May increase risk for liver toxicity and GI adverse reactions. Use together is contraindicated.
Lovastatin, simvastatin: May increase statin level and risk for myopathy. Use together is contraindicated.
Lumacaftor–ivacaftor: May decrease levels of nirmatrelvir or ritonavir. Use together is contraindicated.
Methadone: May decrease methadone level. Monitor methadone-maintained patients closely for evidence of withdrawal and adjust methadone dose accordingly.
mTOR inhibitors (everolimus, sirolimus): May increase mTOR inhibitor level. Avoid use together.
Neuropsychiatric agents (aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin, suvorexant): May increase level of neuropsychiatric agent. Avoid use of suvorexant. Adjust dose of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin.
Opioid analgesics (fentanyl, hydrocodone, oxycodone, meperidine): May increase opioid level. Closely monitor for therapeutic and adverse opioid effects including potentially fatal respiratory depression. Consider decreasing opioid dosage.
Opioid antagonists (naloxegol): May increase naloxegol level. Use together is contraindicated due to the potential for opioid withdrawal.
PDE5 inhibitors for erectile dysfunction (avanafil, sildenafil, tadalafil, vardenafil): May increase PDE5 inhibitor level. Don't use with avanafil. Adjust dose of sildenafil, tadalafil, and vardenafil. Refer to inhibitor prescribing information.
PDE5 inhibitors (sildenafil, tadalafil): May increase PDE5 inhibitor level. Use of sildenafil is contraindicated for pulmonary hypertension because of potential for sildenafil-associated adverse events. Avoid use with tadalafil for pulmonary hypertension.
sGC stimulator (riociguat): May increase riociguat level. Dosage adjustment of riociguat recommended when used for pulmonary hypertension.
Ranolazine: May increase ranolazine level. Use is contraindicated because of the potential for serious or life-threatening reactions.
Salmeterol: May increase salmeterol level and risk of CV adverse events (QT prolongation, palpitations, sinus tachycardia). Avoid use together.
Saxagliptin: May increase saxagliptin level. Decrease dose of saxagliptin. Refer to saxagliptin prescribing information.
Silodosin: May increase silodosin level and risk of postural hypotention. Use together is contraindicated.
Sedative-hypnotics (oral midazolam, triazolam): May increase benzodiazepine level. Use together is contraindicated.
Sedative-hypnotics (buspirone, clorazepate, diazepam, flurazepam, parenteral midazolam, zolpidem): May increase sedative-hypnotic level. Consider dose decrease and monitor for adverse events. Coadministration of parenteral midazolam should be done in a setting with monitoring and appropriate medical management in case of respiratory depression or prolonged sedation.
Trazodone: May increase trazodone level and its adverse reactions (nausea, dizziness, hypotension, syncope). Consider decreasing trazodone dose.
Tolvaptan: May increase tolvaptan level and risk for dehydration, hypovolemia, and hyperkalemia. Use together is contraindicated.
Drug-herb. St. John's wort:  May decrease drug level. Use together is contraindicated due to potential loss of virologic response and possible resistance.

ADVERSE REACTIONS

CNS: altered taste, headache, malaise.
CV: hypertension.
GI: diarrhea, abdominal pain, nausea, vomiting.
Hepatic: transaminase elevations, hepatitis, jaundice.
Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome. .
Other: hypersensitivity reactions, anaphylaxis.

Reactions in bold italics are life-threatening.
 

Released: October 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

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