Paxlovid

COVID-19 patients w/ ≥18 yr not requiring supplemental O₂ & at high risk for progression to severe COVID-19.

300 mg nirmatrelvir (two 150 mg tab) + 100 mg ritonavir (one 100 mg tab) bid for 5 days given as soon as possible after +ve results of direct SARS-CoV-2 viral testing & w/in 5 days of onset of symptoms. Missed dose: Take as soon as possible & w/in 8 hr of scheduled time & resume normal dosing schedule. If >8 hr has elapsed, do not take missed dose & resume according to normal dosing schedule. Moderate renal impairment (eGFR ≥30 to <60 mL/min) Reduce dose to 150 mg/100 mg bid for 5 days.

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

Patients w/ history of clinically significant hypersensitivity. Medicinal products that are highly dependent on CYP3A & potent CYP3A inducers. Severe hepatic & renal impairment.

Immediately discontinue treatment if signs & symptoms of clinically significant hypersensitivity reaction or anaphylaxis occur. Not to be taken >5 consecutive days. Not to be used before or after exposure for prevention of COVID-19; in another indication that is not for COVID-19 treatment. 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. Patients w/ pre-existing liver diseases, liver enzyme abnormalities or hepatitis. Anaphylaxis, hypersensitivity reactions & serious skin reactions including TEN & SJS. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Closely & regularly monitor serum conc of immunosuppressants in co-administration w/ calcineurin & mTOR inhibitors. May increase or decrease conc w/ CYP3A inhibitor or inducer medicinal products. Patients w/ severe renal impairment (eGFR <30 mL/min) or renal failure; severe (Child-Pugh Class C) hepatic impairment. Women of childbearing potential should avoid becoming pregnant during treatment. Patients using combined hormonal contraceptives should use effective alternative contraceptive method or additional barrier method of contraception during treatment & until after 1 complete menstrual cycle after stopping of treatment. Discontinue breastfeeding during treatment & for 7 days after last dose of treatment. Ped patient <18 yr.

Dysgeusia, diarrhoea, vomiting & headache.

Decreased exposure w/ apalutamide; carbamazepine; rifampicin; rifapentine. Decreased plasma conc w/ lumacaftor/ivacaftor. Nirmatrelvir: May induce CYP3A4, CYP2B6, CYP2C8, CYP2C9 (w/ low potential to inhibit BCRP, MATE2K, OAT1, OAT3, OATP1B3 & OCT2) & inhibit MDR1, MATE1, OCT1 & OATP1B1 at clinically relevant conc. Ritonavir: Increased plasma conc of alfuzosin; fentanyl, hydrocodone, oxycodone, meperidine; amiodarone, dronedarone, flecainide, propafenone, quinidine; loratadine; itraconazole, erythromycin; salmeterol; Ca channel antagonists (eg, amlodipine, diltiazem, nifedipine, verapamil); ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine); HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin, pravastatin); lomitapide; cyclosporine, tacrolimus, everolimus, sirolimus; buspirone, clonazepam, clorazepate, diazepam, estazolam & flurazepam; silodosin; eplerenone, ivabradine. Increased plasma conc of triazolam & oral midazolam; dexamethasone; both fusidic acid & ritonavir. Increased conc of amphetamine & its derivatives; ranolazine; imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine, or sertraline; colchicine; fexofenadine; haloperidol, risperidone, thioridazine; lurasidone, pimozide, quetiapine. Increased plasma levels of buprenorphine & its active metabolites. May increase methadone dose. May decrease morphine levels. Modification of P-gp mediated digoxin efflux. Increased dose of theophylline. Increased serum conc w/ BCRP. Increased serum conc of abemaciclib, ceritinib; dasatinib, nilotinib, vincristine, vinblastine, encorafenib, ibrutinib, neratinib, venetoclax; vorapaxar; glecaprevir/pibrentasvir. Increased AUC & C_max of afatinib; alprazolam. Increased fostamatinib metabolite R406 exposure. Increased bleeding risk w/ apixaban & dabigatran. Increased plasma levels & pharmacodynamic effects of rivaroxaban. Decreased R-warfarin levels. Decreased plasma conc of anticonvulsants; atovaquone. Decreased serum levels w/ phenytoin. Decreased AUC & C_max of 2-hydroxy metabolite of desipramine. Large increased in rifabutin AUC. Avoid co-administration w/ tamsulosin; voriconazole; bedaquiline; clarithromycin. Increased incidence of GI & hepatic adverse reactions of ketoconazole. Increased serum levels of atazanavir, darunavir; maraviroc. Higher frequency of adverse reactions & lab abnormalities w/ efavirenz. Slightly decreased levels of zidovudine. Increased steady-state of bosentan C_max & AUC. Reduced effectiveness of estradiol-containing contraceptives. Concomitant use of aliskiren, ticagrelor, vorapaxar; avanafil, sildenafil, tadalafil, vardenafil; voclosporin; eletriptan w/in at least 72 hr of treatment, ubrogepant, rimegepant; finerenone; suvorexant; flibanserin; tolvaptan. Excessive sedative effects w/ zolpidem. Decreased bupropion levels. Increased risk of Cushing's syndrome & adrenal suppression w/ corticosteroids (all routes of administration) primarily metabolized by CYP3A. Decreased plasma conc of clopidogrel. Increased AUC of metabolite prednisolone. Potential interaction w/ levothyroxine. Dosage adjustment w/ clozapine; cilostazol; saxagliptin; tofacitinib; aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, & pimavanserin; riociguat; naloxegol. Not to exceed 7.5 mg daily dose of darifenacin when co-administered.

Antivirals

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

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