Paxlovid

COVID-19 in adults who do not require supplemental O₂ & at increased risk for progressing to severe COVID-19.

Nirmatrelvir 300 mg (two 150 mg tab) w/ ritonavir 100 mg (one 100 mg tab) every 12 hr for 5 days. Moderate renal impairment (eGFR ≥30-<60 mL/min) Reduce dose to 150 mg/100 mg every 12 hr for 5 days.

May be taken with or without food: Swallow whole, do not chew/break/crush.

Hypersensitivity. Concomitant use w/ medicinal products highly dependent on CYP3A for clearance & for which elevated plasma conc are associated w/ serious &/or life-threatening reactions eg, alfuzosin, ranolazine, dronedarone, propafenone, quinidine, neratinib, venetoclax, colchicine, terfenadine, lurasidone, pimozide, quetiapine, silodosin, eplerenone, ivabradine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, voclosporin, lovastatin, simvastatin, lomitapide, eletriptan, finerenone, naloxegol, avanafil, sildenafil, tadalafil, vardenafil, clorazepate, diazepam, estazolam, flurazepam, oral midazolam & triazolam, tolvaptan; potent CYP3A inducers where significantly reduced nirmatrelvir/ritonavir plasma conc may be associated w/ potential for loss of virologic response & possible resistance eg, rifampicin, rifapentine, apalutamide, carbamazepine, phenobarb, phenytoin, primidone, lumacaftor/ivacaftor, St. John's wort.

Immediately discontinue use if signs & symptoms of clinically significant hypersensitivity reaction or anaphylaxis occur. Risk of serious adverse reactions due to interactions w/ other medicinal products; HIV-1 developing resistance to HIV PIs in individuals w/ uncontrolled or undiagnosed HIV-1 infection. HTN. Patients w/ pre-existing liver diseases, liver enzyme abnormalities or hepatitis. Concomitant use w/ CYP3A inhibitors or inducers; calcineurin & mTOR inhibitors. Not to be taken by patients w/ galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Not to be used in patients w/ severe renal (eGFR <30 mL/min, including patients w/ ESRD under hemodialysis) & hepatic (Child-Pugh class C) impairment. Women of childbearing potential should avoid becoming pregnant during & for 7 days after treatment. Patients using combined hormonal contraceptives should use effective alternative contraception or additional barrier method of contraception during treatment & until 1 menstrual cycle after treatment. Not recommended during pregnancy & in women of childbearing potential not using contraception unless clinical condition requires treatment. Discontinue breastfeeding during & for 7 days after treatment. Safety & efficacy have not been established in childn <18 yr. Regularly monitor BP in the elderly due to higher risk of experiencing serious HTN complications.

Dysgeusia, headache; diarrhea, vomiting, nausea.

Plasma conc may be decreased & therapeutic effect reduced w/ CYP3A inducers. Plasma conc may be increased w/ CYP3A4 inhibitors. Increased plasma conc of CYP3A substrates. May increase conc of CYP2D6 substrates. Concomitant use w/ P-gp substrates. May induce glucuronidation & oxidation by CYP1A2, CYP2C8, CYP2C9 & CYP2C19 thereby increasing biotransformation of some medicinal products metabolized by these pathways & may result in decreased systemic exposure which could decrease or shorten their therapeutic effect. Increased plasma conc of alfuzosin, tamsulosin; amphetamine; buprenorphine, fentanyl, oxycodone, pethidine; ranolazine; amiodarone, flecainide, digoxin, disopyramide, dronedarone, propafenone, quinidine; abemaciclib, afatinib, apalutamide, ceritinib, dasatinib, nilotinib, vinblastine, vincristine, encorafenib, ivosidenib, fostamatinib, ibrutinib, neratinib, venetoclax; apixaban, dabigatran, rivaroxaban; clonazepam; ketoconazole; amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline; colchicine; glecaprevir/pibrentasvir, sofosbuvir/velpatasvir/voxilaprevir; fexofenadine, loratadine, terfenadine; bictegravir/tenofovir, efavirenz, maraviroc; bedaquiline, clarithromycin, erythromycin, itraconazole, fusidic acid (systemic route), rifabutin; clozapine, haloperidol, risperidone, thioridazine, lurasidone, pimozide, quetiapine; silodosin; salmeterol; amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil, lercanidipine; aliskiren, cilostazol, eplerenone, ivabradine, ticagrelor; elexacaftor/tezacaftor/ivacaftor, ivacaftor, tezacaftor/ivacaftor; saxagliptin; bosentan, riociguat; dihydroergotamine, ergonovine, ergotamine, methylergonovine; cisapride; atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin; voclosporin; calcineurin inhibitors (cyclosporine, tacrolimus) & mTOR inhibitors (everolimus, sirolimus); tofacitinib, upadacitinib; lomitapide; eletriptan, rimegepant; finerenone; darifenacin, solifenacine; aripiprazole, brexpiprazole, cariprazine; naloxegol; avanafil, sildenafil, tadalafil, vardenafil; alprazolam, buspirone, clorazepate, diazepam, estazolam, flurazepam, oral & parenteral midazolam, triazolam; zolpidem; dexamethasone, prednisolone; tolvaptan. Decreased plasma conc of methadone, morphine, piroxicam; theophylline; R-warfarin; divalproex, lamotrigine; raltegravir, zidovudine; atovaquone; voriconazole; clopidogrel; ethinyl estradiol; bupropion. Decreased plasma conc w/ carbamazepine, phenobarb, phenytoin, primidone; rifampicin, rifapentine; St. John's wort. Potential loss of virologic response & possible resistance w/ lumacaftor/ivacaftor. Frequent ECG monitoring throughout full treatment period is recommended in co-administration w/ delamanid. Systemic corticosteroid effects including Cushing's syndrome & adrenal suppression w/ inhaled or intranasal fluticasone propionate; other corticosteroids metabolized by CYP3A eg, budesonide & triamcinolone. Potential interaction w/ levothyroxine.

Antivirals

J05AE30 - nirmatrelvir and ritonavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.

Rx