Interactions Finder | paxlovid-hcp.ca

Established and Other Potentially Significant Drug Interactions

Concomitant Drug Class	Drug Name	Effect on Concentration of PAXLOVID or Concomitant Drug	Clinical Comment

Alpha₁-adrenoreceptor Antagonist:	alfuzosin	↑ alfuzosin	Based on results of a drug interaction study with ketoconazole, another potent inhibitor of CYP3A4, a significant increase in alfuzosin exposure is expected in the presence of ritonavir (600 mg twice daily). Therefore, alfuzosin is contraindicated with PAXLOVID (see the CONTRAINDICATIONS section of the Product Monograph).
Alpha₁-adrenoreceptor Antagonist:	tamsulosin	↑ tamsulosin	Avoid concomitant use with PAXLOVID.
Analgesics, Narcotic:	fentanyl, hydrocodone, oxycodone, meperidine	↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine	Ritonavir inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of fentanyl. Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. Refer to the individual product label for more information.
Analgesics, Narcotic:	tramadol, propoxyphene^a	↑ tramadol ↑ propoxyphene	Ritonavir inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of tramadol and propoxyphene. Use tramadol and propoxyphene with caution, dose reduction of these drugs may be needed.
Analgesics, Narcotic:	methadone	↓ methadone	Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly. Dosage increase of methadone may be considered.
Anesthetic:	meperdine	↓ meperidine ↑ normeperidine (metabolite)	Dosage increase and long-term use of meperidine with ritonavir are not recommended due to the increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (e.g., seizures).
Antianginal:	ranolazine	↑ ranolazine	Co-administration contraindicated due to potential for serious and/or life-threatening reactions (see the CONTRAINDICATIONS section of the Product Monograph).
Antiarrhythmics:	disopyramide, lidocaine (systemic), mexiletine	↑ antiarrhythmic	Plasma concentrations of these drugs are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Antiarrhythmics:	amiodarone, bepridil^a, dronedarone, flecainide, propafenone, quinidine^a	↑ antiarrhythmic	Co-administration may lead to serious and/or life-threatening reactions, such as cardiac arrhythmias. Therefore, use of these antiarrhythmics with PAXLOVID is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph).
Antibacterial:	fusidic acid	↑ fusidic acid ↑ ritonavir	Co-administration of protease inhibitors, including ritonavir with fusidic acid is expected to increase fusidic acid, as well as the protease inhibitor concentration in plasma (see the CONTRAINDICATIONS section of the Product Monograph).
Anticancer agents:	apalutamide	↓ nirmatrelvir/ritonavir	Co-administration is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph).
Anticancer agents:	abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, vincristine, vinblastine	↑ anticancer agents	Serum concentrations increase when co-administered with ritonavir resulting in the potential for increased incidence of adverse events, some of which may be serious. Co-administration of ritonavir with ibrutinib is not recommended due to expected increase in ibrutinib exposure that could potentially result in a risk of tumor lysis syndrome. Co-administration of ritonavir with dasatinib should be avoided due to expected increase in dasatinib exposure. If the co-administration is unavoidable, close monitoring for toxicity and a dasatinib dose reduction should be considered (see SPRYCEL Product Monograph). Co-administration of encorafenib or evosidenib with ritonavir should be avoided due to potential risk of serious adverse events such as QT interval prolongation. If co-administration cannot be avoided, modify encorafenib dose as recommended in the encorafenib Product Monograph. Co-administration of ritonavir with nilotinib should be avoided due to expected increase in nilotinib exposure. If the co-administration is unavoidable, close monitoring for the QT interval prolongation is recommended (see TASIGNA Product Monograph). Co-administration of ritonavir with abemaciclib should be avoided due to expected increase in abemaciclib exposure. If the co-administration is unavoidable, close monitoring for toxicity and abemaciclib dose reduction should be considered (see VERZENIO Product Monograph). Co-administration of ritonavir with neratinib is contraindicated due to expected increase in neratinib exposure (see the CONTRAINDICATIONS section of the Product Monograph). Co-administration of vincristine and vinblastine may lead to significant hematological or gastrointestinal side effects.
Anticancer agents:	venetoclax	↑ venetoclax	Concomitant use of strong CYP3A inhibitors, such as ritonavir, and venetoclax may increase the risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase (see the CONTRAINDICATIONS section of the Product Monograph). For patients who have completed the ramp-up phase and are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75% when used with strong CYP3A inhibitors (see VENCLEXTA Product Monograph).
Anticoagulants:	apixaban	↑ apixaban	Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for co-administration of apixaban with PAXLOID depend on the apixaban dose. Refer to the apixaban product label for more information.
Anticoagulants:	dabigatran	↑ dabigatran	Co-administration with PAXLOVID results in increasing dabigatran exposure and an increased risk of bleeding. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information.
Anticoagulants:	rivaroxaban	↑ rivaroxaban	A study has shown that co-administration of ritonavir and rivaroxaban resulted in increased exposure of rivaroxaban which may lead to risk of increased bleeding. Co-administration of PAXLOVID and rivaroxaban is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph).
Anticoagulants:	warfarin	↓ R-warfarin ↓ ↑ S-warfarin	Initial frequent monitoring of the INR (International Normalized Ratio) during ritonavir and warfarin co-administration is indicated.
Anticonvulsants:	clonazepam, ethosuximide, divalproex, lamotrigine	↑ clonazepam ↑ ethosuximide ↓ divalproex ↓ lamotrigine	Plasma concentrations of clonazepam and ethosuximide are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed and clinical monitoring is recommended. Plasma concentrations of divalproex and lamotrigine are expected to decrease by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose increase of these drugs may be needed.
Anticonvulsants:	carbamazepine, phenobarbital, phenytoin, primidone	↑ carbamazepine ↓ phenytoin ↓ ritonavir ↓ nirmatrelvir	Co-administration of PAXLOVID with carbamazepine, phenobarbital, phenytoin or primidone is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph).
Antidepressants:	amitriptyline, clomipramine, fluoxetine, imipramine, maprotiline^a, nefazodone^a, nortriptyline, paroxetine, sertraline, trimipramine, venlafaxine	↑ antidepressants	Ritonavir dosed as a pharmacokinetic enhancer is not expected to result in any clinically meaningful increases in CYP2D6 substrates. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Antidepressants:	bupropion	↓ bupropion and active metabolite hydroxy bupropion	Bupropion is primarily metabolized by CYP2B6. Concurrent administration of bupropion with repeated doses of ritonavir decreases bupropion levels. Monitor for an adequate clinical response to bupropion.
Antidepressants:	desipramine	↑ desipramine	A study has shown that co-administration of ritonavir and desipramine resulted in increased exposure of desipramine. Dosage reduction and concentration monitoring of desipramine is recommended.
Antidepressants:	trazodone	↑ trazodone	Concomitant use of ritonavir and trazodone increases concentrations of trazodone. Adverse events of nausea, dizziness, hypertension, and syncope have been observed. If trazodone is used with a CYP3A4 inhibitor, such as ritonavir, the combination should be used with caution and a lower dose of trazodone should be considered.
Antiemetics:	dronabinol^a	↑ dronabinol	Plasma concentrations of dronabinol are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of dronabinol may be needed.
Antifungal:	ketoconazole, isavuconazonium sulfate, itraconazole	↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole ↑ nirmatrelvir/ritonavir	High doses of ketoconazole or itraconazole (>200 mg/day) are not recommended. Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information.
Antifungal:	voriconazole	↓ voriconazole	Avoid concomitant use of voriconazole.
Antigout:	colchicine	↑ colchicine	For patients with renal and/or hepatic impairment: - Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and ritonavir. For patients with renal and/or hepatic impairment co-administration of colchicine with PAXLOVID is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph). For patients with normal renal and/or hepatic function: - Treatment of gout flares: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days. - Prophylaxis of gout flares: If the original colchicine regimen was 0.6 mg twice daily, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.3 mg twice daily, the regimen should be adjusted to 0.3 mg once every other day. - Treatment of Familial Mediterranean fever (FMF): Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Anti-infective:	clarithromycin, erythromycin	↑ clarithromycin ↑ erythromycin	For patients with renal impairment, the following dosage adjustments should be considered: - For patients with CL_CR 30 to 60 mL/min, the dose of clarithromycin should be reduced by 50%. - For patients with CL_CR < 30 mL/min, the dose of clarithromycin should be reduced by 75%. No dose adjustment for patients with normal renal function is necessary. Refer to the prescribing information for anti-infective dose adjustment.
Antimycobacterial:	rifabutin	↑ rifabutin and rifabutin metabolite ↓ ritonavir	Dosage reduction of rifabutin by at least three- quarters of the usual dose of 300 mg/day is recommended (e.g., 150 mg every other day or 3 times a week). Further dosage reduction may be necessary.
Antimycobacterial:	rifampin	↓ ritonavir ↓ nirmatrelvir	Co-administration of PAXLOVID with rifampin is contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered (see the CONTRAINDICATIONS section of the Product Monograph).
Antiparasitics:	atovaquone	↓ atovaquone	Plasma concentrations of atovaquone are expected to decrease by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose increase of atovaquone may be needed.
Antiparasitics:	quinine	↑ quinine	Plasma concentrations of quinine are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of quinine may be needed.
Anxiolytics/Sedative/Hypnotics:	triazolam, midazolam, oral^a	↑ triazolam ↑ midazolam	Midazolam is extensively metabolized by CYP3A4. Increases in the concentration of midazolam are expected to be significantly higher with oral than parenteral administration. Co-administration is contraindicated due to potential for extreme sedation and respiratory depression (see the CONTRAINDICATIONS section of the Product Monograph).
Anxiolytics/Sedative/Hypnotics:	midazolam, parenteral	↑ midazolam	Concomitant use of parenteral midazolam with ritonavir may increase plasma concentrations of midazolam. Coadministration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Anxiolytics/Sedative/Hypnotics:	buspirone, clorazepate, diazepam, estazolam^a, flurazepam, zolpidem	↑ Anxiolytics/ Sedatives/ Hypnotics	Plasma concentrations of these drugs are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Benign prostatic hyperplasia agents:	silodosin	↑ silodosin	Co-administration is contraindicated due to potential for postural hypotension (see the CONTRAINDICATIONS section of the Product Monograph).
Beta-blockers:	metoprolol, timolol	↑ beta-blockers	Plasma concentrations of these drugs are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Bronchodilator:	theophylline	↓ theophylline	Increased dosage of theophylline may be required; therapeutic monitoring should be considered.
Calcium channel blockers:	amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil	↑ calcium channel blocker	Plasma concentrations of these drugs are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Cardiovascular agents:	eplerenone	↑ eplerenone	Co-administration with eplerenone is conraindicated due to potential for hyperkalemia (see the CONTRAINDICATIONS section of the Product Monograph).
Cardiovascular agents:	ivabradine	↑ ivabradine	Co-administration with ivabradine is conraindicated due to potential for bradycardia or conduction disturbances (see the CONTRAINDICATIONS section of the Product Monograph).
Cardiovascular agents:	aliskiren, ticagrelor, vorapraxar, clopidogrel	↑ aliskiren ↑ ticagrelor ↑ vorapraxar ↓ clopidogrel active metabolite	Avoid concomitant use with PAXLOVID.
Corticosteroids:	budesonide, fluticasone propionate, triamcinolone	↑ fluticasone ↑ budesonide ↑ triamcinolone	Concomitant use of ritonavir and inhaled, injectable, or intranasal fluticasone propionate, budesonide, triamcinolone, or other glucocorticoids that are metabolized by CYP3A4 are not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid side effects, including Cushing’s syndrome and adrenal suppression. Concomitant use of ritonavir and fluticasone propionate, budesonide or triamcinolone can significantly increase fluticasone propionate, budesonide or triamcinolone plasma concentrations and reduce serum cortisol concentrations. Consider alternatives to fluticasone propionate, budesonide, or triamcinolone particularly for long-term use.
Corticosteroids:	dexamethasone	↑ dexamethasone ↓ ritonavir	Dexamethasone, which increases CYP3A activity, would be expected to increase the clearance of ritonavir resulting in decreased ritonavir plasma concentrations.
Corticosteroids:	prednisone	↑ prednisone	Plasma concentrations of dexamethasone and prednisone are expected to increase by co-administration with ritonavir. Therefore, PAXLOVID should be used with caution, dose adjustment of these drugs may be needed.
Corticosteroids:	digoxin	↑ digoxin	A literature report has shown that co-administration of ritonavir (300 mg every 12 hours) and digoxin resulted in significantly increased digoxin levels. Caution should be exercised when co-administrating ritonavir and digoxin, with appropriate monitoring of serum levels.
Cystic fibrosis transmembrane conductance regulator potentiators:	lumacaftor/ivacaftor	↓ nirmatrelvir/ritonavir	Co-administration is contraindicated due to potential loss of virologic response and possible resistance (see the CONTRAINDICATIONS section of the Product Monograph).
Cystic fibrosis transmembrane conductance regulator potentiators:	ivacaftor	↑ ivacaftor	Reduce dosage when co-administered with PAXLOVID.
Cystic fibrosis transmembrane conductance regulator potentiators:	elexacaftor/tezacaftor/ivacaftor, tezacaftor/ivacaftor	↑elexacaftor/tezacaftor/ivacaftor ↑ tezacaftor/ivacaftor	Refer to individual product labels for more information.
Dipeptidyl peptidase 4 (DPP4) inhibitors:	saxagliptin	↑ saxagliptin	Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information.
Endothelin receptor antagonist:	bosentan	↑ bosentan	Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Refer to the bosentan product monograph for further information.
Ergot derivatives:	dihydroergotamine, ergotamine, methylergonovine^a	↑ dihydroergotamine ↑ ergotamine ↑ methylergonivine	Co-administration is contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see the CONTRAINDICATIONS section of the Product Monograph).
Gonadotropin releasing hormone (GnRH) receptor antagonist:	elagolix	↑ elagolix	Coadministration of elagolix with ritonavir could increase elagolix exposure due to inhibition of CYP3A and P-gp. Known serious adverse events for elagolix include suicidal ideation and hepatic transaminase elevations. In addition, elagolix is a weak/moderate inducer of CYP3A, which may decrease exposure of ritonavir. Refer to the elagolix label for dosing information with strong CYP3A4 inhibitors.
HCV-Antiviral Agents HCV Combination Drug:	elbasvir/grazoprevir, glecaprevir/pibrentasvir, ombitasvir/paritaprevir/ritonavir with or without dasabuvir^a, sofosbuvir/velpatasvir/voxilaprevir	↑ antiviral	Increased grazoprevir concentrations can result in ALT elevations. Co-administration with ritonavir is not recommended due to an increased risk of ALT elevations associated with increased glecaprevir exposure. Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID. Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information. Refer to the sofosbuvir/velpatasvir/voxilaprevir product label for further information. Patients on ritonavir-containing HCP regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use.
*HCV-Antiviral Agents* HCV Protease Inhibitors:	simeprevir^a	↑ simeprevir	A pharmacokinetic study demonstrated that concomitant administration of simeprevir 200 mg once daily with ritonavir 100 mg twice daily resulted in an increase in simeprevir concentrations. It is not recommended to co-administer PAXLOVID with simeprevir.
Herbal products:	St. John's Wort (hypericum perforatum)	↓ nirmatrelvir/ritonavir	Co-administration is contraindicated due to potential loss of virologic response and possible resistance (see the CONTRAINDICATIONS section of the Product Monograph).
HIV-Antiretroviral Agents HIV Protease Inhibitors:	fosamprenavir	↑ amprenavir (↑ AUC, ↑ C_max, ↑ C_min)	Refer to the fosamprenavir Product Monograph for details on co-administration of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily or fosamprenavir 1400 mg once daily with ritonavir 200 mg once daily.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	atazanavir	↑ atazanavir (↑ AUC, ↑ C_max, ↑ C_min)	Atazanavir plasma concentrations achieved with atazanavir 300 mg once daily and ritonavir 100 mg once daily are higher than those achieved with atazanavir 400 mg once daily. Refer to the atazanavir Product Monograph for details on co-administration of atazanavir 300 mg once daily, with ritonavir 100 mg once daily.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	darunavir	↑ darunavir (↑ AUC, ↑ C_max, ↑ C_min)	Refer to the darunavir Product Monograph for details on co-administration of darunavir 600 mg twice daily with ritonavir 100 mg twice daily.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	indinavir^a	↑ indinavir (↑ AUC, ↑ C_max, ↑ C_min)	Alterations in concentrations are noted when reduced doses of indinavir are co-administered with reduced dose of ritonavir. The safety and efficacy of this combination have not yet been established. The risk of nephrolithiasis may be increased when doses of indinavir equal to or greater than 800 mg twice daily are given with ritonavir. Adequate hydration and monitoring of the patients is warranted.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	nelfinavir	↑ M8 (major active metabolite of nelfinavir)	Ritonavir increases the concentrations of nelfinavir major active metabolite, M8. This interaction is likely to involve cytochrome P450 inhibition and induction.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	saquinavir	↑ saquinavir (↑ AUC, ↑ C_max, ↑ C_min)	The recommended dosage regimen is saquinavir 1000 mg with ritonavir 100 mg twice daily taken within 2 hours after a meal. Dose adjustment may be needed if other HIV-protease inhibitors are used in combination with saquinavir and ritonavir. Saquinavir and ritonavir should not be given together with rifampin due to risk of severe hepatotoxicity (presenting as increased hepatic transaminases) if the 3 drugs are given together. In some cases, co-administration of saquinavir and ritonavir has led to severe adverse events, mainly diabetic ketoacidosis, and liver disorders, especially in patients with pre-existing liver disease. Refer to the saquinavir Product Monograph for prescribing information.
HIV-Antiretroviral Agents HIV Protease Inhibitors:	tipranavir	↑ tipranavir (↑ AUC, ↑ C_max, ↑ C_min)	Refer to the tipranavir Product Monograph for details on co-administration of tipranavir 500 mg twice daily with ritonavir 200 mg twice daily.
HIV-Antiretroviral Agents Nucleoside Reverse Transcriptase Inhibitors:	didanosine^a	↓ didanosine	Dosing of didanosine and ritonavir should be separated by 2.5 hours to avoid formulation incompatibility.
HIV-Antiretroviral Agents Nucleoside Reverse Transcriptase Inhibitors:	tenofovir	↑ tenofovir	Lopinavir/ritonavir has been shown to increase tenofovir concentrations. Higher tenofovir concentrations could potentiate tenofovir- associated adverse events, including renal disorders. Patients receiving ritonavir and tenofovir disoproxil fumarate should be monitored for tenofovir-associated adverse events. Refer to the tenofovir Product Monograph for more information.
HIV-Antiretroviral Agents Nucleoside Reverse Transcriptase Inhibitors:	zidovudine, emtricitabine	↓ zidovudine ↔ emtricitabine	For further information, refer to the respective anti-HIV drugs prescribing information.
HIV-Antiretroviral Agents Non-Nucleoside Reverse Transcriptase Inhibitors:	delavirdine^_a	↑ ritonavir ↔ delavirdine	When used in combination with delavirdine, a dose reduction of ritonavir should be considered. Based on comparison to historical data, the pharmacokinetics of delavirdine did not appear to be affected by ritonavir. The safety and efficacy of this combination (delavirdine/ ritonavir) have not been established.
HIV-Antiretroviral Agents Non-Nucleoside Reverse Transcriptase Inhibitors:	efavirenz	↑ efavirenz	In healthy volunteers receiving 500 mg ritonavir twice daily with efavirenz 600 mg once daily, the steady state AUC was increased by 21%. An associated increase in the AUC of ritonavir of 17% was observed.
HIV-Antiretroviral Agents Non-Nucleoside Reverse Transcriptase Inhibitors:	nevirapine	↑ nevirapine	For further information, refer to the respective anti-HIV drugs prescribing information.
*HIV-Antiretroviral Agents* Integrase Inhibitor:	raltegravir	↓ raltegravir	A pharmacokinetic study showed that co-administration of ritonavir 100 mg twice daily and raltegravir 400 mg single dose resulted in a reduction in raltegravir plasma concentration.
*HIV-Antiretroviral Agents* Integrase Inhibitor:	bictegravir	↑ bictegravir	For further information, refer to the respective anti-HIV drugs prescribing information.
*HIV-Antiretroviral Agents* CCR5 Antagonist:	maraviroc	↑ maraviroc (↑ AUC, ↑ C_max, ↑ C_min)	When co-administered with reduced doses of ritonavir plasma levels of maraviroc increases. The dose of maraviroc should be decreased during co-administration with ritonavir. Refer to the maraviroc Product Monograph for details on co-administration of maraviroc 150 mg twice daily with ritonavir.
Hypolipidemics, HMG-CoA Reductase Inhibitors:	lovastatin, simvastatin	↑ lovastatin, simvastatin	The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of ritonavir with simvastatin or lovastatin is contraindicated due to an increased risk of myopathy including rhabdomyolysis (see the CONTRAINDICATIONS section of the Product Monograph). Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment and for 5 days after completing PAXLOVID.
Hypolipidemics, HMG-CoA Reductase Inhibitors:	lomitapide	↑ lomitapide	Lomitapide is a sensitive substrate for CYP3A4 metabolism. CYP3A4 inhibitors increase the exposure of lomitapide, with strong inhibitors increasing exposure approximately 27-fold. Concomitant use of moderate or strong CYP3A4 inhibitors with lomitapide is contraindicated.
Hypolipidemics, HMG-CoA Reductase Inhibitors:	atorvastatin, rosuvastatin	↑ atorvastatin, rosuvastatin	Caution must also be exercised, and reduced doses should be considered if ritonavir is used concurrently with atorvastatin, which is metabolized to a lesser extent by CYP3A4. While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration. Atorvastatin and rosuvastatin do not need to be discontinued prior to or after completing PAXLOVID. Use the lowest doses of atorvastatin or rosuvastatin with careful monitoring for signs and symptoms of myopathy or rhabdomyolysis. If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Immunosuppressants:	cyclosporine, tacrolimus, everolimus, sirolimus, rapamycin^a	↑ immunosuppressants	Avoid use of PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. If co-administered, dose adjustment of the imunosuppressant and monitoring for immunosuppressant concentrations and immunosuppressant-associated adverse reactions is recommended. Refer to the individual immunosuppressant product label for further information and obtain expert consultation from the patient's immunosuppressive therapy specialist. Avoid concomitant use of everolimus and sirolimus and PAXLOVID.
Janus kinase (JAK) inhibitors:	tofacitinib	↑ tofacitinib	Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information.
Janus kinase (JAK) inhibitors:	upadacitinib	↑ upadacitinib	Dosing recommendations for co-PAXLOVID depends on upadacitinib indication. Refer to the upadacitinib product label for more information.
Kinase inhibitors (also see Anticancer agents above):	fostamatinib	↑ fostamatinib	Co-administration of fostamatinib with ritonavir could increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity and neutropenia. Monitor for toxicities of fostamatinib that may require fostamatinib dose modification (see fostamatinib Product Monograph).
Long-acting beta adenoceptor agonist:	salmeterol	↑ salmeterol	Co-administration is not recommended. Avoid concomitant use with PAXLOVID. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.
Migraine medications:	eletriptan	↑ eletriptan	Co-administration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events (see the CONTRAINDICATIONS section of the Product Monograph).
Migraine medications:	ubrogepant	↑ ubrogepant	Co-administration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions (see the CONTRAINDICATIONS section of the Product Monograph).
Mineralocorticoid receptor antagonists:	finerenone	↑ finerenone	Co-administration is contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia (see the CONTRAINDICATIONS section of the Product Monograph).
Muscarinic receptor antagonists:	darifenacin	↑ darifenacin	The darifenacin daily dose should not exceed 7.5 mg when co-administered with PAXLOVID. Refer to the darifenacin product label for more information.
Neuroleptics/Antipsychotics:	clozapine	↑ clozapine	If co-administration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.
Neuroleptics/Antipsychotics:	lurasidone	↑ lurasidone	Due to CYP3A inhibition by ritonavir, concentrations of lurasidone are expected to increase. Co-administration of lurasidone with PAXLOVID is contraindicated (see the CONTRAINDICATIONS section of the Product Monograph).
Neuroleptics/Antipsychotics:	perphenazine, risperidone, thioridazine^a	↑ neuroleptics	Ritonavir dosed as a pharmacokinetic enhancer is not expected to result in any clinically meaningful increases in CYP2D6 substrates. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Neuroleptics/Antipsychotics:	pimozide	↑ pimozide	Co-administration of PAXLOVID with pimozide is contraindicated as it may lead to serious and/or life-threatening reactions, such as cardiac arrhythmias (see the CONTRAINDICATIONS section of the Product Monograph).
Neuroleptics/Antipsychotics:	quetiapine	↑ quetiapine	Due to inhibition of CYP3A by PAXLOVID (ritonavir), co-administration of PAXLOVID with quetiapine may result in increased quetiapine concentrations. Serious and life-threatening quetiapine-related adverse reactions have been reported with CYP3A inhibitors. PAXLOVID should not be used in combination with quetiapine. Monitoring and dose reduction may be required if necessary.
Neuropsychiatric agents:	suvorexant^a, aripiprazole, brexpiprazole, cariprazine, iloperidone^a, lumateperone^a, pimavanserin^a	↑ suvorexant ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin	Avoid concomitant use of suvorexant with PAXLOVID. Dosage adjustment of aripirazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to individual product label for more information.
Opioid antagonists:	naloxegol	↑ naloxegol	Co-administration is contraindicated due to the potential for opioid withdrawal symptoms (see the CONTRAINDICATIONS section of the Product Monograph).
Oral Contraceptive or Patch Contraceptive:	ethinyl estradiol	↓ ethinyl estradiol	Co-administration with ritonavir results in reduced ethinyl estradiol concentrations. Dosage increase or alternate contraceptive measures should be considered. An additional, non-hormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.
PDE5 inhibitors (erectile dysfunction agents):	sildenafil, tadalafil, vardenafil	↑ sildenafil	Particular caution should be used when prescribing PDE5 inhibitors for the treatment of erectile dysfunction in patients receiving PAXLOVID. Co-administration of PAXLOVID with these drugs is expected to substantially increase their concentrations and may result in increase in associated adverse events, such as hypotension, syncope, visual changes, and prolonged erection. Use of PDE5 Inhibitors for Erectile Dysfunction Sildenafil may be used with caution at reduced doses of 25 mg every 48 hours with increased monitoring for adverse events. Tadalafil may be used with caution at reduced doses of 10 mg every 72 hours with increased monitoring for adverse events. Vardenafil should not be used with PAXLOVID (see the CONTRAINDICATIONS section of the Product Monograph). Use of PDE5 Inhibitors for Pulmonary Arterial Hypertension Coadministration of PAXLOVID and tadalafil for the treatment of pulmonary arterial hypertension is not recommended. The use of sildenafil or vardenafil is contraindicated with PAXLOVID (see the CONTRAINDICATIONS section of the Product Monograph).
PDE5 inhibitors (pulmonary hypertension agents):	sildenafil (Revatio^®)	↑ sildenafil	Co-administration of sildenafil with PAXLOVID is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope (see the CONTRAINDICATIONS section of the Product Monograph).
PDE5 inhibitors (pulmonary hypertension agents):	tadalafil (Adcirca^®)	↑ tadalafil	Avoid concomitant use of tadalafil with PAXLOVID.
sGC stimulators (pulmonary hypertension agents):	riociguat	↑ riociguat	Dosage adjustment is recommended for riociguat. Refer to the riociguat product label for more information.
Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist:	flibanserin	↑ flibanserin	Co-administration is contraindicated due to potential for hypotension, syncope, and CNS depression (see the CONTRAINDICATIONS section of the Product Monograph).
Stimulants:	methamphetamine	↑ methamphetamine	Ritonavir dosed as a pharmacokinetic enhancer is not expected to result in any clinically meaningful increases in CYP2D6 substrates. Therefore, PAXLOVID should be used with caution, dose reduction of these drugs may be needed.
Vasopressin receptor antagonists:	tolvaptan	↑ tolvaptan	Co-administration is contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see the CONTRAINDICATIONS section of the Product Monograph).

Medicinal Product	Medicinal Products within Class	Clinical Comments
Antiarrhythmics	amiodarone, bepridil, lidocaine (systemic), quinidine	Potentially increased concentration of these antiarrhythmics drugs. If coadministered, refer to individual product label for antiarrhythmics for further information.
Anticancer agents	abemaciclib, ceritinib dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine	Potentially increased concentration of these anticancer agents. Coadministration should be considered only if the benefits outweigh the risks. For further information, refer to individual product label for anticancer drug.
Anticoagulants	warfarin rivaroxaban	Potentially decreased R-warfarin concentrations, which may lead to reduced anticoagulation. Potentially increased rivaroxaban concentrations, which may lead to an increased bleeding risk. Coadministration should be considered only if the benefits outweigh the risks.
Anticonvulsants	carbamazepine phenobarbital, phenytoin	Decreased PAXLOVID™ concentrations. Potentially increased carbamazepine plasma concentrations. Potentially decreased phenytoin and phenobarbital concentrations. Coadministration of PAXLOVID™ with carbamazepine, phenobarbital, or phenytoin is not recommended.
Antidepressants	bupropion trazodone	Potentially decreased bupropion and active metabolite, hydroxy-bupropion, concentrations. Coadministration should be considered only if the benefits outweigh the risks. Potentially increased trazodone concentrations. Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. Refer to trazadone product label for further information.
Antifungals	ketoconazole, itraconazole, voriconazole, isavuconazonium sulfate	Potentially increased concentrations of ketoconazole, itraconazole, and isavuconazonium sulfate. Potentially decreased plasma concentrations of voriconazole. Coadministration should be considered only if the benefits outweigh the risks.
Anti-HIV protease inhibitors	amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, saquinavir, tipranavir	Potentially increased concentrations of protease inhibitors. Coadministration should be considered only if the benefits outweigh the risks. For further information, refer to therespective protease inhibitors’ prescribing information.
Anti-HIV	didanosine, delavirdine, efavirenz, maraviroc, nevirapine, raltegravir, zidovudine	Potentially increased plasma concentrations of didanosine, efavirenz, and maraviroc. Potentially decreased plasma concentrations of raltegravir and zidovudine. For further information, refer to the respective anti-HIV drugs’ prescribing information.
Anti-infective	clarithromycin, erythromycin	Potentially increased plasma concentrations of clarithromycin and erythromycin. Coadministration should be considered only if the benefits outweigh the risks.
Antimycobacterial	bedaquiline rifabutin	Potentially increased plasma concentrations of bedaquiline and rifabutin. Coadministration should be considered only if the benefits outweigh the risks. If coadministered with rifabutin, refer to rifabutin product label for further information.
Antipsychotics	quetiapine	Potentially increased concentrations of quetiapine. Coadministration is not recommended. If coadministered, refer to quetiapine product label for further information.
Calcium channel blockers	amlodipine, diltiazem, felodipine, nicardipine, nifedipine	Potentially increased concentrations of these calcium channel blockers. If coadministered, refer to individual product label for calcium channel blocker for further information.
Cardiac glycosides	digoxin	Potentially increased concentrations. Coadministration is not recommended.
Endothelin receptor antagonists	bosentan	Potentially increased concentrations. Coadministration is not recommended.
Hepatitis C direct-acting antivirals	elbasvir/grazoprevir, glecaprevir/pibrentasvir, simeprevir, sofosbuvir/velpatasvir/voxilaprevir, ombitasvir/paritaprevir/ritonavir and dasabuvir	Potentially increased concentrations. Increased grazoprevir concentrations can result in ALT elevations. Coadministration should be considered only if the benefits outweigh the risks. Coadministration is not recommended.
HMG-CoA reductase inhibitors	atorvastatin, rosuvastatin	Potentially increased concentrations. Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID™.
Hormonal contraceptive	ethinyl estradiol	Potentially decreased ethinyl estradiol concentrations. An additional, nonhormonal method of contraception should be considered.
Immunosuppressants	cyclosporine, tacrolimus, sirolimus	Potentially increased concentrations of cyclosporine, tacrolimus, and sirolimus. If coadministered, refer to individual product label for immununosuppressant for further information.
Long-acting beta-adrenoceptor agonist	salmeterol	Increased concentrations of salmeterol. Coadministration may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. Coadministration should be considered only if the benefits outweigh the risks.
Narcotic analgesics	fentanyl methadone	Potentially increased concentrations of fentanyl possibly leading to fatal respiratory depression. Potentially decreased plasma concentrations of methadone. Coadministration should be considered only if the benefits outweigh the risks.
Sedative/hypnotics	midazolam (administered parenterally)	Potentially increased concentrations of midazolam, possibly leading to respiratory depression and/or prolonged sedation. Coadministration is not recommended.
Systemic corticosteroids	betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, triamcinolone	Potentially increased concentrations of corticosteroids. Coadministration should be considered only if the benefits outweigh the risks.