Nirmatrelvir And Ritonavir

Table 2: Established and Other Potentially Significant Drug Interactions Drug Class Drugs within Class Effect on Concentration Clinical Comments Alpha 1- adrenoreceptor antagonist alfuzosin ↑ alfuzosin Co-administration contraindicated due to potential hypotension [see Contraindications (4) ] .

Co-administration contraindicated due to potential for cardiac arrhythmias.

Anticancer drugs apalutamide, enzalutamide ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4) ].

Co-administration contraindicated due to potential for cardiac arrhythmias.

Anticancer drugs apalutamide, enzalutamide ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4) ].

Co-administration contraindicated due to potential for cardiac arrhythmias.

HMG-CoA reductase inhibitors lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ] . If treatment with PAXLOVID is considered medically necessary, 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.

Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] . midazolam (administered parenterally) ↑ midazolam Co-administration of midazolam (parenteral) 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.

( 4 , 5.1 , 7 , 12.3 ) 7.1 Potential for PAXLOVID to Affect Other Drugs PAXLOVID (nirmatrelvir co-packaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1. 7.2 Potential for Other Drugs to Affect PAXLOVID Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect [see Contraindications (4) and Drug Interactions (7.3) Table 2 ] . Anticancer drugs apalutamide, enzalutamide ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4) ].

Co-administration contraindicated due to potential for cardiac arrhythmias.

Co-administration contraindicated due to potential for cardiac arrhythmias.

Co-administration contraindicated due to potential for serious and/or life-threatening reactions.

HMG-CoA reductase inhibitors lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ] . If treatment with PAXLOVID is considered medically necessary, 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.

Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] .

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

glecaprevir/pibrentasvir Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID.

Narcotic analgesics fentanyl, hydrocodone, oxycodone, meperidine ↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib.

Anticancer drugs abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation.

Narcotic analgesics fentanyl, hydrocodone, oxycodone, meperidine ↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID.

glecaprevir/pibrentasvir Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID.

Avoid concomitant use with PAXLOVID.

Antifungals voriconazole ↓ voriconazole Avoid concomitant use of voriconazole.

Calcium channel blockers amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blocker Caution is warranted and clinical monitoring of patients is recommended.

Antiarrhythmics lidocaine (systemic), disopyramide ↑ antiarrhythmic Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.

Calcium channel blockers amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blocker Caution is warranted and clinical monitoring of patients is recommended.

Caution warranted and therapeutic concentration monitoring recommended for systemic lidocaine.

Calcium channel blockers amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blocker Caution is warranted and clinical monitoring of patients is recommended.

Calcium channel blockers amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blocker Caution is warranted and clinical monitoring of patients is recommended.

aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended.

Anti-HIV protease inhibitors atazanavir, darunavir, tipranavir ↑ protease inhibitor For further information, refer to the respective protease inhibitors' prescribing information.

HMG-CoA reductase inhibitors atorvastatin ↑ atorvastatin Consider temporary discontinuation of atorvastatin during treatment with PAXLOVID. Atorvastatin does not need to be withheld prior to or after completing PAXLOVID.

Anti-HIV efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir ↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir For further information, refer to the respective anti-HIV drugs prescribing information.

aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended.

Anti-infective clarithromycin, erythromycin ↑ clarithromycin ↑ erythromycin Refer to the respective prescribing information for anti-infective dose adjustment.

Anticonvulsants clonazepam ↑ anticonvulsant A dose decrease may be needed for clonazepam when co-administered with PAXLOVID and clinical monitoring is recommended.

Anti-HIV protease inhibitors atazanavir, darunavir, tipranavir ↑ protease inhibitor For further information, refer to the respective protease inhibitors' prescribing information.

ombitasvir/paritaprevir/ritonavir and dasabuvir Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information.

Sedative/hypnotics buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem ↑ sedative/hypnotic A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events.

Hepatitis C direct acting antivirals elbasvir/grazoprevir ↑ antiviral Increased grazoprevir concentrations can result in alanine transaminase (ALT) elevations.

Anti-infective clarithromycin, erythromycin ↑ clarithromycin ↑ erythromycin Refer to the respective prescribing information for anti-infective dose adjustment.

Sedative/hypnotics buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem ↑ sedative/hypnotic A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events.

Sedative/hypnotics buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem ↑ sedative/hypnotic A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events.

Hepatitis C direct acting antivirals elbasvir/grazoprevir ↑ antiviral Increased grazoprevir concentrations can result in alanine transaminase (ALT) elevations.

ketoconazole, isavuconazonium sulfate, itraconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole Refer to the ketoconazole, isavuconazonium sulfate, and itraconazole prescribing information for further information.

ketoconazole, isavuconazonium sulfate, itraconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole Refer to the ketoconazole, isavuconazonium sulfate, and itraconazole prescribing information for further information.

Corticosteroids primarily metabolized by CYP3A betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone ↑ corticosteroid Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression.

ombitasvir/paritaprevir/ritonavir and dasabuvir Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information.

ombitasvir/paritaprevir/ritonavir and dasabuvir Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information.

Corticosteroids primarily metabolized by CYP3A betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone ↑ corticosteroid Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.

( 4 , 5.1 , 7 , 12.3 ) 7.1 Potential for PAXLOVID to Affect Other Drugs PAXLOVID (nirmatrelvir co-packaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1. 7.2 Potential for Other Drugs to Affect PAXLOVID Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect [see Contraindications (4) and Drug Interactions (7.3) Table 2 ] . The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor such as ritonavir.

sofosbuvir/velpatasvir/voxilaprevir Refer to the sofosbuvir/velpatasvir/voxilaprevir prescribing information for further information.

Anti-HIV efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir ↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir For further information, refer to the respective anti-HIV drugs prescribing information.

Anti-HIV protease inhibitors atazanavir, darunavir, tipranavir ↑ protease inhibitor For further information, refer to the respective protease inhibitors' prescribing information.

Janus kinase (JAK) inhibitors tofacitinib ↑ tofacitinib Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib prescribing information for more information.

Corticosteroids primarily metabolized by CYP3A betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone ↑ corticosteroid Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression.

upadacitinib ↑ upadacitinib Dosing recommendations for co-administration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib prescribing information for more information.

sofosbuvir/velpatasvir/voxilaprevir Refer to the sofosbuvir/velpatasvir/voxilaprevir prescribing information for further information.

sofosbuvir/velpatasvir/voxilaprevir Refer to the sofosbuvir/velpatasvir/voxilaprevir prescribing information for further information.