Viral infections:

Indications for: PAXLOVID

Mild to moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.

Limitations of Use:

Not for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

Adult Dosage:

Swallow whole. 300mg nirmatrelvir (2 × 150mg tabs) with 100mg ritonavir (1 × 100mg tab) twice daily for 5 days. Initiate 5-day treatment course as soon as possible after a diagnosis of COVID-19, and within 5 days of symptom onset. Moderate renal impairment (eGFR 30–<60mL/min): 150mg nirmatrevir with 100mg ritonavir twice daily for 5 days. 

Children Dosage:

Not established.

PAXLOVID Contraindications:

Concomitant alfuzosin HCl, ranolazine, amiodarone, dronedarone, flecainide, propafenone, quinidine, colchicine (in renal and/or hepatic impairment), lurasidone, pimozide, silodosin,  eplerenone, ivabradine, ergots, lovastatin, simvastatin, voclosporin, lomitapide, eletriptan (within at least 72hrs of Paxlovid), ubrogepant, finerenone, naloxegol, sildenafil (as Revatio for PAH), oral midazolam, triazolam, flibanserin, tolvaptan, apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, lumacaftor/ivacaftor, St. John's Wort.

Boxed Warning:

Significant drug interactions with Paxlovid.

PAXLOVID Warnings/Precautions:

Potentially life-threatening drug-drug interactions (see Contraindications).  Review all medications to assess potential drug-drug interactions and determine whether dose adjustment, interruption, and/or additional monitoring is required. Discontinue immediately and initiate appropriate medications and/or supportive care if signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur. Pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. Severe renal (eGFR) <30mL/min), ESRD (eGFR <15mL/min), or severe hepatic (Child-Pugh Class C) impairment: not recommended. Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception. Pregnancy. Nursing mothers. 

PAXLOVID Classification:

SARS-CoV-2 main protease inhibitor + HIV-1 protease inhibitor/CYP3A inhibitor.

PAXLOVID Interactions:

See Contraindications. See full labeling. Potentiates tamsulosin, aliskiren, ticagrelor, vorapaxar, glecaprevir/pibrentasvir, calcineurin inhibitors (eg, cyclosporine, tacrolimus), mTOR inhibitors (eg, everolimus, sirolimus), salmeterol, rimegepant, suvorexant, tadalafil (as Adcirca), avanafil; avoid. Potentiates anticancer agents (eg, abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine), antifungals (eg, ketoconazole, isavuconazonium sulfate, itraconazole), antipsychotics (eg, quetiapine, clozapine), clarithromycin, erythromycin, rifabutin, bedaquiline; avoid or reduce doses (see full labeling). Potentiates disopyramide, lidocaine, digoxin, anti-HIV protease inhibitors (eg, atazanavir, darunavir, tipranavir), anti-HIV (eg, efavirenz, maraviroc, nevirapine, bictegravir, tenofovir), elbasvir/grazoprevir, ombitasvir/paritaprevir/ ritonavir and dasabuvir, sofosbuvir/velpatasvir/voxilaprevir, glucocorticoids (eg, dexamethasone, betamethasone, fluticasone, budesonide, ciclesonide, methyprednisolone, mometasone, triamcinolone; consider alternatives), narcotic analgesics (eg, fentanyl, hydrocodone, oxycodone, meperidine); monitor. Potentiates trazodone, clonazepam (monitor), cilostazol, CCBs (eg, amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil), cystic fibrosis transmembrane conductance regulator potentiators (eg, ivacaftor, elexacaftor/tezacaftor/ivacaftor, tezacaftor/ivacaftor), saxagliptin, JAK inhibitors (eg, tofacitinib, upadacitinib), darifenacin (max 7.5mg/day), neuropsychiatric agents (eg, aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin), riociguat, sildenafil, tadalafil, vardenafil, sedative/hypnotics (eg, buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, parenteral midazolam); may need dose reductions. Increased bleeding risk with rivaroxaban (avoid), dabigatran, apixaban; see full product labeling. Consider temporarily stopping atorvastatin and rosuvastatin during Paxlovid treatment. Antagonizes voriconazole, clopidogrel; avoid. Antagonizes oral contraceptives (eg, ethinyl estradiol); consider additional non-hormonal contraception during 5-day treatment course and until 1 menstrual cycle after stopping Paxlovid. Discontinue bosentan at least 36hrs prior to initiating Paxlovid. Monitor methadone, warfarin. 

Adverse Reactions:

Dysgeusia, diarrhea.

Metabolism:

  • Nirmatrelvir is a CYP3A substrate but when dosed with ritonavir, metabolic clearance is minimal. Ritonair is metabolized primarily by CYP3A (minor CYP2D6).

Drug Elimination:

  • Nirmatrelvir: Renal (49.6%), fecal (35.3%). Ritonavir: Renal (11.3%), fecal (86.4%). 

  • Mean half-life: 6.05 hours for nirmatrelvir; 6.15 hours for ritonavir.

  • Mean apparent clearance: 8.99 L/hr for nirmatrelvir; 13.92 L/hr for ritonavir.

Generic Drug Availability:

NO

How Supplied:

Blister packs—30 (150mg × 20 tabs + 100mg × 10 tabs); 20 (150mg × 10 tabs + 100mg × 10 tabs)