• Treatment of mild-to-moderate COVID-19 infection in patients who are at high risk for progression to severe COVID-19, including hospitalization or death.

Contraindicated in:

• Hypersensitivity
• Concurrent use of alfuzosin, amiodarone, apalutamide, carbamazepine, clozapine, colchicine, dihydroergotamine, dronedarone, ergotamine, flecainide, lovastatin, lurasidone, methylergonovine, midazolam (PO), phenobarbital, phenytoin, piroxicam, pimozide, propafenone, quinidine, ranolazine, rifampin, simvastatin, sildenafil (Revatio), St. John's wort, or triazolam
• Severe renal impairment (CCr <30 mL/min)
• Severe hepatic impairment.

Use Cautiously in:

• Moderate renal impairment (↓ dose)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Safety not established in breastfeeding
• Pedi: Safety and effectiveness not established in children.

CV: hypertension.

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

GI: ↑ liver enzymes, abdominal pain, diarrhea, nausea, vomiting.

MS: myalgia.

Neuro: dysgeusia, headache.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS).

Drug-Drug:

• May ↑ levels and risk of toxicity of some antiarrhythmics (amiodarone, dronedarone, flecainide, propafenone, quinidine), some antipsychotics (clozapine, pimozide, lurasidone), alfuzosin, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), colchicine, piroxicam, ranolazine, sildenafil (Revatio), midazolam (oral), and triazolam; concurrent use contraindicated.
• May ↑ levels and risk of toxicity of lovastatin and simvastatin; concurrent use contraindicated; discontinue lovastatin and simvastatin ≥12 hr before starting nirmatrelvir/ritonavir,
• Apalutamide, carbamazepine, phenobarbital, phenytoin, rifampin may ↓ levels and effectiveness and promote resistance; concurrent use contraindicated.
• May ↑ levels and risk of toxicity of lidocaine; monitor lidocaine levels closely.
• May ↑ levels and risk of toxicity of digoxin; monitor digoxin levels closely.
• May ↑ levels and risk of toxicity of cyclosporine, sirolimus, and tacrolimus; avoid concurrent use with sirolimus; monitor cyclosporine and tacrolimus levels closely.
• May ↑ levels and risk of toxicity of abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, and vincristine; avoid concurrent use with encorafenib ibrutinib, ivosidenib, neratinib, and venetoclax.
• May ↑ or ↓ warfarin levels; closely monitor INR.
• May ↑ levels of and risk of bleeding with rivaroxaban; avoid concurrent use.
• May ↓ levels and effectiveness of bupropion.
• May ↑ levels and risk of toxicity of trazodone; consider ↓ trazodone dose.
• May ↑ levels and risk of toxicity of quetiapine; consider ↓ quetiapine dose.
• May ↑ levels and risk of toxicity of amlodipine, diltiazem, felodipine, nicardipine, and nifedipine; consider ↓ calcium channel blocker dose.
• May ↓ levels and effectiveness of voriconazole; avoid concurrent use.
• May ↑ levels and risk of toxicity of atazanavir, bedaquiline, bictegravir, clarithromycin, darunavir, efavirenz, erythromycin, fentanyl, fosamprenavir, isavuconazonium, itraconazole, ketoconazole, maraviroc, midazolam (parenteral)nelfinavir, nevirapine, rifabutin, tenofovir, and tipranavir.
• Isavuconazonium, itraconazole, and ketoconazole may ↑ levels and risk of toxicity.
• May ↓ levels and effects of raltegravir and zidovudine.
• May ↑ levels and risk of toxicity of bosentan; discontinue bosentan ≥36 hr prior to starting nirmatrelvir/ritonavir.
• May ↑ levels and risk of toxicity of elbasvir/grazoprevir, glecaprevir/pibrentasvir, ombitasvir/partiaprevir/ritonavir/dasabuvir, and sofosbuvir/velpatasvir/voxilaprevir; avoid concurrent use with glecaprevir/pibrentasvir.
• May ↑ levels and risk of toxicity of atorvastatin and rosuvastatin; consider temporarily discontinuing atorvastatin and rosuvastatin during treatment.
• May ↓ levels and effectiveness of oral contraceptives containing ethinyl estradiol; use an additional non-hormonal contraceptive during treatment.
• May ↑ levels and risk of toxicity of salmeterol; concurrent use not recommended.
• May ↓ levels and effectiveness of methadone; monitor patients closely for signs/symptoms of withdrawal.
• May ↑ levels and risk of toxicity of betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, or triamcinolone; consider alternative corticosteroid such as beclomethasone or prednisolone.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness and promote resistance; concurrent use contraindicated.

• Tablets: nirmatrelvir 150 mg + ritonavir 100 mg (separate tablets);

• PO (Adults): Two nirmatrelvir 150–mg tablets and one ritonavir 100–mg tablet twice daily for 5 days. Should be started as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.

Paxlovid

• Nirmatrelvir acts as an inhibitor of the SARS-CoV-2 main protease (Mpro) which ultimately prevents viral replication. While ritonavir is also a protease inhibitor, this drug has no activity against Mpro. Ritonavir inhibits the CYP3A4-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.

• Reduction in COVID-19 related hospitalization or death from any cause.

Therapeutic Classification: antivirals

Pharmacologic Classification: protease inhibitors

Nirmatrelvir

Absorption: Well absorbed.

Distribution: Extensively distributed to extravascular tissues.

Metabolism/Excretion: CYP3A4 substrate; minimal metabolism by this isoenzyme when coadministered with ritonavir. Excreted in feces (49.6%) and urine (35.3%);.

Half-life: 6 hr.

Ritonavir

Absorption: Well absorbed.

Distribution: Extensively distributed to extravascular tissues.

Protein Binding: 98–99%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A isoenzyme, and to a lesser extent by the CYP2D6 isoenzyme. Primarily excreted in feces (86.4%), with 11.3% excreted in urine.

Half-life: 6 hr.

(plasma concentrations)

• Instruct patient to take Paxlovidas directed. If a dose is missed within 8 hr of the time it is usually taken, patient should take it as soon as possible and resume the normal dosing schedule. If the dose is missed by >8 hrs, omit dose and take next dose at regularly scheduled time. Do not double dose to make up for a missed dose. Advise patient to read Patient Information before starting therapy.
• Advise patient to notify health care professional if signs and symptoms of hypersensitivity reactions (skin rash, hives or other skin reactions, difficulty in swallowing or breathing, swelling of the lips, tongue, face, tightness of the throat, hoarseness, or other symptoms of an allergic reaction) occur. Advise patient to immediately discontinue Paxlovid and to notify health care professional at the first sign of a reaction.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• Rep: Advise females of reproductive potential to notify health care professional is pregnancy is planned or suspected or if breastfeeding. Ritonavir may reduce the efficacy of hormonal contraceptives. Advise patients using hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception.

nur-maTREL-veer/ri-TOE-na-veer