Drug Interactions | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets)

Before you prescribe, understand potential DDIs

WARNING: SIGNIFICANT DRUG INTERACTIONS WITH PAXLOVID¹

PAXLOVID includes ritonavir, a strong CYP3A inhibitor, which may lead to greater exposure of certain concomitant medications, resulting in potentially severe, life-threatening, or fatal events.
Prior to prescribing PAXLOVID: 1) Review all medications taken by the patient to assess for potential drug-drug interactions with a strong CYP3A inhibitor like PAXLOVID and 2) Determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring.
Consider the benefit of PAXLOVID treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed.

Contraindications due to drug interactions¹

PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. There are certain other drugs for which concomitant use with PAXLOVID should be avoided and/or dose adjustment, interruption, or therapeutic monitoring is recommended. Drugs listed in this section are a guide and not considered a comprehensive list of all drugs that may be contraindicated with PAXLOVID. 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 like PAXLOVID.

Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions:

Alpha₁-adrenoreceptor antagonist: alfuzosin
Antianginal: ranolazine
Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
Anti-gout: colchicine (in patients with renal and/or hepatic impairment)
Antipsychotics: lurasidone, pimozide
Benign prostatic hyperplasia agents: silodosin
Cardiovascular agents: eplerenone, ivabradine
Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use)
Immunosuppressants: voclosporin
Microsomal triglyceride transfer protein inhibitor: lomitapide
Migraine medications: eletriptan, ubrogepant
Mineralocorticoid receptor antagonists: finerenone
Opioid antagonists: naloxegol
PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension (PAH)
Sedative/hypnotics: triazolam, oral midazolam
Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
Vasopressin receptor antagonists: tolvaptan

Drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer.

Anticancer drugs: apalutamide
Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
Antimycobacterials: rifampin, rifapentine
Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
Herbal products: St. John’s Wort (hypericum perforatum)

Warnings and precautions¹

Initiation of PAXLOVID, which contains ritonavir, a strong CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A. Medications that induce CYP3A may decrease concentrations of PAXLOVID.

These interactions may lead to:

Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications
Loss of therapeutic effect of PAXLOVID and possible development of viral resistance

Severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with PAXLOVID. The most commonly reported concomitant medications resulting in serious adverse reactions were calcineurin inhibitors (eg, tacrolimus, cyclosporine), followed by calcium channel blockers.

Prior to prescribing PAXLOVID, review all medications taken by the patient to assess potential drug-drug interactions and determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring (eg, calcineurin inhibitors). See Table 1 below for clinically significant drug interactions, including contraindicated drugs. Drugs listed in Table 1 are a guide and not considered a comprehensive list of all possible drugs that may interact with PAXLOVID.

Consider the benefit of PAXLOVID treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed.

The concomitant use of PAXLOVID and certain other drugs may result in potentially significant drug interactions¹

Coadministration of PAXLOVID can alter the plasma concentrations of other drugs

PAXLOVID (nirmatrelvir copackaged with ritonavir) is a strong inhibitor of CYP3A and an inhibitor of CYP2D6, P-gp, and OATP1B1. Coadministration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse events
Coadministration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life‑threatening events is contraindicated
Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring, as described in Table 1 below

Other drugs can alter the plasma concentration of PAXLOVID

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect

Considerations before prescribing¹

Identify any drugs your patient may be taking, including over-the-counter medications, vitamins, and herbal supplements
Consider management strategies. Some potential drug interactions for commonly prescribed drugs may be managed with strategies that include dose adjustment, monitoring, or temporary discontinuation. Not all drug interactions can be managed, and alternative therapy may need to be considered
Consult the table below for clinical comments on managing commonly prescribed drug classes, such as anticoagulants (including warfarin) and HMG-CoA reductase inhibitors (including statins)

Ritonavir has been used in combination with other protease inhibitors to similarly inhibit CYP3A metabolism, so certain healthcare providers may have experience managing its associated drug interactions²

Scroll left to view table

Table 1: Established and Other Potentially Significant Drug Interactions¹
Drug Class	Drugs within Class	Effect on Concentration	Clinical Comments
Alpha₁- adrenoreceptor antagonist	alfuzosin	↑ alfuzosin	Coadministration contraindicated due to potential hypotension [see Contraindications (4)].
Alpha₁- adrenoreceptor antagonist	tamsulosin	↑ tamsulosin	Avoid concomitant use with PAXLOVID.
Antianginal	ranolazine	↑ ranolazine	Coadministration contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)].
Antiarrhythmics	amiodarone, dronedarone, flecainide, propafenone, quinidine	↑ antiarrhythmic	Coadministration contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)].
Antiarrhythmics	lidocaine (systemic), disopyramide	↑ antiarrhythmic	Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.
Anticancer drugs	apalutamide	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Anticancer drugs	abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine	↑ anticancer drug	Avoid coadministration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib. Coadministration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to individual product label for anticancer drug.
Anticoagulants	warfarin rivaroxaban dabigatran^a apixaban	↑↓ warfarin ↑ rivaroxaban ↑ dabigatran ↑ apixaban	Closely monitor international normalized ratio (INR) if coadministration with warfarin is necessary. Increased bleeding risk with rivaroxaban. Avoid concomitant use. Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information. Combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for coadministration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information.
Anticonvulsants	carbamazepine^a, phenobarbital, primidone, phenytoin	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Anticonvulsants	clonazepam	↑ anticonvulsant	A dose decrease may be needed for clonazepam when coadministered with PAXLOVID and clinical monitoring is recommended.
Antidepressants	bupropion trazodone	↓ bupropion and active metabolite hydroxybupropion ↑ trazodone	Monitor for an adequate clinical response to bupropion. Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to trazadone product label for further information.
Antifungals	voriconazole ketoconazole, isavuconazonium sulfate, itraconazole^a	↓ voriconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole ↑ nirmatrelvir/ ritonavir	Avoid concomitant use of voriconazole. Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information. A nirmatrelvir/ ritonavir dose reduction is not needed.
Anti-gout	colchicine	↑ colchicine	Coadministration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment [see Contraindications (4)].
Anti-HIV protease inhibitors	atazanavir, darunavir, tipranavir	↑ protease inhibitor	For further information, refer to the respective protease inhibitors’ prescribing information. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events.
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-infective	clarithromycin, erythromycin	↑ clarithromycin ↑ erythromycin	Refer to the respective prescribing information for anti- infective dose adjustment.
Antimycobacterial	rifampin, rifapentine	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4)].
Antimycobacterial	bedaquiline rifabutin	↑ bedaquiline ↑ rifabutin	Refer to the bedaquiline product label for further information. Refer to rifabutin product label for further information on rifabutin dose reduction.
Antipsychotics	lurasidone, pimozide	↑ lurasidone ↑ pimozide	Coadministration contraindicated due to serious and/or life- threatening reactions such as cardiac arrhythmias [see Contraindications (4)].
Antipsychotics	quetiapine clozapine	↑ quetiapine ↑ clozapine	If coadministration is necessary, reduce quetiapine dose and monitor for quetiapine- associated adverse reactions. Refer to the quetiapine prescribing information for recommendations. If coadministration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.
Benign prostatic hyperplasia agents	silodosin	↑ silodosin	Coadministration contraindicated due to potential for postural hypotension [see Contraindications (4)].
Calcium channel blockers	amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil	↑ calcium channel blocker	Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when coadministered with PAXLOVID. If coadministered, refer to individual product label for calcium channel blocker for further information.
Cardiac glycosides	digoxin	↑ digoxin	Caution should be exercised when coadministering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels. Refer to the digoxin product label for further information.
Cardiovascular agents	eplerenone ivabradine	↑ eplerenone ↑ ivabradine	Coadministration with eplerenone is contraindicated due to potential for hyperkalemia [see Contraindications (4)]. Coadministration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances [see Contraindications (4)].
Cardiovascular agents	aliskiren, ticagrelor, vorapaxar clopidogrel cilostazol	↑ aliskiren ↑ ticagrelor ↑ vorapaxar ↓ clopidogrel active metabolite ↑ cilostazol	Avoid concomitant use with PAXLOVID. Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information.
Corticosteroids primarily metabolized by CYP3A	betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone	↑ corticosteroid	Coadministration 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. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A inhibitor is low. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.
Cystic fibrosis transmembrane conductance regulator potentiators	lumacaftor/ivacaftor	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Cystic fibrosis transmembrane conductance regulator potentiators	ivacaftor elexacaftor/tezacaftor/ ivacaftor tezacaftor/ivacaftor	↑ ivacaftor ↑ elexacaftor/ tezacaftor/ivacaftor ↑ tezacaftor/ ivacaftor	Reduce dosage when coadministered with PAXLOVID. 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 antagonists	bosentan	↑ bosentan ↓ nirmatrelvir/ ritonavir	Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Refer to the bosentan product label for further information.
Ergot derivatives	dihydroergotamine, ergotamine, methylergonovine	↑ dihydroergotamine ↑ ergotamine ↑ methylergonovine	Coadministration 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 Contraindications (4)].
Hepatitis C direct-acting antivirals	elbasvir/grazoprevir glecaprevir/ pibrentasvir ombitasvir/ paritaprevir/ ritonavir and dasabuvir sofosbuvir/ velpatasvir/ voxilaprevir	↑ antiviral	Increased grazoprevir concentrations can result in alanine transaminase (ALT) elevations. 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 HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use.
Herbal products	St. John’s Wort (hypericum perforatum)	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
HMG-CoA reductase inhibitors	lovastatin, simvastatin	↑ lovastatin ↑ simvastatin	Coadministration 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.
HMG-CoA reductase inhibitors	atorvastatin, rosuvastatin	↑ atorvastatin ↑ rosuvastatin	Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be withheld prior to or after completing PAXLOVID.
Hormonal contraceptive	ethinyl estradiol	↓ ethinyl estradiol	An additional, nonhormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.
Immunosuppressants	voclosporin	↑ voclosporin	Coadministration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4)].
Immunosuppressants	calcineurin inhibitors: cyclosporine, tacrolimus mTOR inhibitors: everolimus, sirolimus	↑ cyclosporine ↑ tacrolimus ↑ everolimus ↑ sirolimus	Avoid concomitant use of calcineurin inhibitors with PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. If coadministered, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and adverse reactions are recommended during and after treatment with PAXLOVID. Obtain expert consultation to appropriately manage the complexity of this coadministration [see Warnings and Precautions (5.1)]. Avoid concomitant use of everolimus and sirolimus and PAXLOVID. Refer to the individual immunosuppressant product label and latest guidelines for further information.
Janus kinase (JAK) inhibitors	tofacitinib upadacitinib	↑ tofacitinib ↑ upadacitinib	Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information. Dosing recommendations for coadministration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information.
Long-acting beta-adrenoceptor agonist	salmeterol	↑ salmeterol	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.
Microsomal triglyceride transfer protein (MTTP) inhibitor	lomitapide	↑ lomitapide	Coadministration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions [see Contraindications (4)].
Migraine medications	eletriptan ubrogepant	↑ eletriptan ↑ ubrogepant	Coadministration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events [see Contraindications (4)]. Coadministration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions [see Contraindications (4)].
Migraine medications	rimegepant	↑ rimegepant	Avoid concomitant use with PAXLOVID.
Mineralocorticoid receptor antagonists	finerenone	↑ finerenone	Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)].
Muscarinic receptor antagonists	darifenacin	↑ darifenacin	The darifenacin daily dose should not exceed 7.5 mg when coadministered with PAXLOVID. Refer to the darifenacin product label for more information.
Narcotic analgesics	fentanyl, hydrocodone, oxycodone, meperidine methadone	↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine ↓ methadone	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. 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. Monitor methadone- maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.
Neuropsychiatric agents	suvorexant aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin	↑ suvorexant ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin	Avoid concomitant use of suvorexant with PAXLOVID. Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to individual product label for more information.
Opioid antagonists	naloxegol	↑ naloxegol	Coadministration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4)].
Pulmonary hypertension agents (PDE5 inhibitors)	sildenafil (Revatio®)	↑ sildenafil	Coadministration of sildenafil with PAXLOVID is contraindicated for use in pulmonary hypertension due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope [see Contraindications (4)].
Pulmonary hypertension agents (PDE5 inhibitors) Pulmonary hypertension agents (sGC stimulators)	tadalafil (Adcirca®) riociguat	↑ tadalafil ↑ riociguat	Avoid concomitant use of tadalafil with PAXLOVID for pulmonary hypertension. Dosage adjustment is recommended for riociguat when used for pulmonary hypertension. Refer to the riociguat product label for more information.
Erectile dysfunction agents (PDE5 inhibitors)	avanafil sildenafil, tadalafil, vardenafil	↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil	Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established. Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID when used for erectile dysfunction. Refer to individual product label for more information.
Sedative/hypnotics	triazolam, oral midazolam^a	↑ triazolam ↑ midazolam	Coadministration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4)].
Sedative/hypnotics	buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem midazolam (administered parenterally)	↑ sedative/hypnotic ↑ midazolam	A dose decrease may be needed for these drugs when coadministered with PAXLOVID and monitoring for adverse events. Coadministration 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. Refer to the midazolam product label for further information.
Serotonin receptor 1A agonist/serotonin receptor 2A antagonist	flibanserin	↑ flibanserin	Coadministration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4)].
Vasopressin receptor antagonists	tolvaptan	↑ tolvaptan	Coadministration contraindicated due to potential for dehydration, hypovolemia, and hyperkalemia [see Contraindications (4)].
^aSee Pharmacokinetics, Drug Interaction Studies Conducted with Nirmatrelvir and Ritonavir (see PAXLOVID Prescribing Information section 12.3).

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Table 1: Established and Other Potentially Significant Drug Interactions¹
Drug Class	Drugs within Class	Effect on Concentration	Clinical Comments
Alpha₁- adrenoreceptor antagonist	alfuzosin	↑ alfuzosin	Coadministration contraindicated due to potential hypotension [see Contraindications (4)].
Alpha₁- adrenoreceptor antagonist	tamsulosin	↑ tamsulosin	Avoid concomitant use with PAXLOVID.
Antianginal	ranolazine	↑ ranolazine	Coadministration contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)].
Antiarrhythmics	amiodarone, dronedarone, flecainide, propafenone, quinidine	↑ antiarrhythmic	Coadministration contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)].
Antiarrhythmics	lidocaine (systemic), disopyramide	↑ antiarrhythmic	Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.
Anticancer drugs	apalutamide	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Anticancer drugs	abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine	↑ anticancer drug	Avoid coadministration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib. Coadministration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to individual product label for anticancer drug.
Anticoagulants	warfarin rivaroxaban dabigatran^a apixaban	↑↓ warfarin ↑ rivaroxaban ↑ dabigatran ↑ apixaban	Closely monitor international normalized ratio (INR) if coadministration with warfarin is necessary. Increased bleeding risk with rivaroxaban. Avoid concomitant use. Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information. Combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for coadministration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information.
Anticonvulsants	carbamazepine^a, phenobarbital, primidone, phenytoin	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Anticonvulsants	clonazepam	↑ anticonvulsant	A dose decrease may be needed for clonazepam when coadministered with PAXLOVID and clinical monitoring is recommended.
Antidepressants	bupropion trazodone	↓ bupropion and active metabolite hydroxybupropion ↑ trazodone	Monitor for an adequate clinical response to bupropion. Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to trazadone product label for further information.
Antifungals	voriconazole ketoconazole, isavuconazonium sulfate, itraconazole^a	↓ voriconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole ↑ nirmatrelvir/ ritonavir	Avoid concomitant use of voriconazole. Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information. A nirmatrelvir/ ritonavir dose reduction is not needed.
Anti-gout	colchicine	↑ colchicine	Coadministration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment [see Contraindications (4)].
Anti-HIV protease inhibitors	atazanavir, darunavir, tipranavir	↑ protease inhibitor	For further information, refer to the respective protease inhibitors’ prescribing information. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events.
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-infective	clarithromycin, erythromycin	↑ clarithromycin ↑ erythromycin	Refer to the respective prescribing information for anti- infective dose adjustment.
Antimycobacterial	rifampin, rifapentine	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4)].
Antimycobacterial	bedaquiline rifabutin	↑ bedaquiline ↑ rifabutin	Refer to the bedaquiline product label for further information. Refer to rifabutin product label for further information on rifabutin dose reduction.
Antipsychotics	lurasidone, pimozide	↑ lurasidone ↑ pimozide	Coadministration contraindicated due to serious and/or life- threatening reactions such as cardiac arrhythmias [see Contraindications (4)].
Antipsychotics	quetiapine clozapine	↑ quetiapine ↑ clozapine	If coadministration is necessary, reduce quetiapine dose and monitor for quetiapine- associated adverse reactions. Refer to the quetiapine prescribing information for recommendations. If coadministration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.
Benign prostatic hyperplasia agents	silodosin	↑ silodosin	Coadministration contraindicated due to potential for postural hypotension [see Contraindications (4)].
Calcium channel blockers	amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil	↑ calcium channel blocker	Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when coadministered with PAXLOVID. If coadministered, refer to individual product label for calcium channel blocker for further information.
Cardiac glycosides	digoxin	↑ digoxin	Caution should be exercised when coadministering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels. Refer to the digoxin product label for further information.
Cardiovascular agents	eplerenone ivabradine	↑ eplerenone ↑ ivabradine	Coadministration with eplerenone is contraindicated due to potential for hyperkalemia [see Contraindications (4)]. Coadministration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances [see Contraindications (4)].
Cardiovascular agents	aliskiren, ticagrelor, vorapaxar clopidogrel cilostazol	↑ aliskiren ↑ ticagrelor ↑ vorapaxar ↓ clopidogrel active metabolite ↑ cilostazol	Avoid concomitant use with PAXLOVID. Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information.
Corticosteroids primarily metabolized by CYP3A	betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone	↑ corticosteroid	Coadministration 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. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A inhibitor is low. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.
Cystic fibrosis transmembrane conductance regulator potentiators	lumacaftor/ivacaftor	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Cystic fibrosis transmembrane conductance regulator potentiators	ivacaftor elexacaftor/tezacaftor/ ivacaftor tezacaftor/ivacaftor	↑ ivacaftor ↑ elexacaftor/ tezacaftor/ivacaftor ↑ tezacaftor/ ivacaftor	Reduce dosage when coadministered with PAXLOVID. 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 antagonists	bosentan	↑ bosentan ↓ nirmatrelvir/ ritonavir	Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Refer to the bosentan product label for further information.
Ergot derivatives	dihydroergotamine, ergotamine, methylergonovine	↑ dihydroergotamine ↑ ergotamine ↑ methylergonovine	Coadministration 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 Contraindications (4)].
Hepatitis C direct-acting antivirals	elbasvir/grazoprevir glecaprevir/ pibrentasvir ombitasvir/ paritaprevir/ ritonavir and dasabuvir sofosbuvir/ velpatasvir/ voxilaprevir	↑ antiviral	Increased grazoprevir concentrations can result in alanine transaminase (ALT) elevations. 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 HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use.
Herbal products	St. John’s Wort (hypericum perforatum)	↓ nirmatrelvir/ ritonavir	Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
HMG-CoA reductase inhibitors	lovastatin, simvastatin	↑ lovastatin ↑ simvastatin	Coadministration 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.
HMG-CoA reductase inhibitors	atorvastatin, rosuvastatin	↑ atorvastatin ↑ rosuvastatin	Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be withheld prior to or after completing PAXLOVID.
Hormonal contraceptive	ethinyl estradiol	↓ ethinyl estradiol	An additional, nonhormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.
Immunosuppressants	voclosporin	↑ voclosporin	Coadministration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4)].
Immunosuppressants	calcineurin inhibitors: cyclosporine, tacrolimus mTOR inhibitors: everolimus, sirolimus	↑ cyclosporine ↑ tacrolimus ↑ everolimus ↑ sirolimus	Avoid concomitant use of calcineurin inhibitors with PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. If coadministered, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and adverse reactions are recommended during and after treatment with PAXLOVID. Obtain expert consultation to appropriately manage the complexity of this coadministration [see Warnings and Precautions (5.1)]. Avoid concomitant use of everolimus and sirolimus and PAXLOVID. Refer to the individual immunosuppressant product label and latest guidelines for further information.
Janus kinase (JAK) inhibitors	tofacitinib upadacitinib	↑ tofacitinib ↑ upadacitinib	Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information. Dosing recommendations for coadministration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information.
Long-acting beta-adrenoceptor agonist	salmeterol	↑ salmeterol	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.
Microsomal triglyceride transfer protein (MTTP) inhibitor	lomitapide	↑ lomitapide	Coadministration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions [see Contraindications (4)].
Migraine medications	eletriptan ubrogepant	↑ eletriptan ↑ ubrogepant	Coadministration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events [see Contraindications (4)]. Coadministration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions [see Contraindications (4)].
Migraine medications	rimegepant	rimegepant	Avoid concomitant use with PAXLOVID.
Mineralocorticoid receptor antagonists	finerenone	↑ finerenone	Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)].
Muscarinic receptor antagonists	darifenacin	↑ darifenacin	The darifenacin daily dose should not exceed 7.5 mg when coadministered with PAXLOVID. Refer to the darifenacin product label for more information.
Narcotic analgesics	fentanyl, hydrocodone, oxycodone, meperidine methadone	↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine ↓ methadone	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. 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. Monitor methadone- maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.
Neuropsychiatric agents	suvorexant aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin	↑ suvorexant ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin	Avoid concomitant use of suvorexant with PAXLOVID. Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to individual product label for more information.
Opioid antagonists	naloxegol	↑ naloxegol	Coadministration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4)].
Pulmonary hypertension agents (PDE5 inhibitors)	sildenafil (Revatio®)	↑ sildenafil	Coadministration of sildenafil with PAXLOVID is contraindicated for use in pulmonary hypertension due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope [see Contraindications (4)].
Pulmonary hypertension agents (PDE5 inhibitors)	tadalafil (Adcirca®)	↑ tadalafil	Avoid concomitant use of tadalafil with PAXLOVID for pulmonary hypertension.
Pulmonary hypertension agents (sGC stimulators)	riociguat	↑ riociguat	Dosage adjustment is recommended for riociguat when used for pulmonary hypertension. Refer to the riociguat product label for more information.
Erectile dysfunction agents (PDE5 inhibitors)	avanafil sildenafil, tadalafil, vardenafil	↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil	Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established. Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID when used for erectile dysfunction. Refer to individual product label for more information.
Sedative/hypnotics	triazolam, oral midazolam^a	↑ triazolam ↑ midazolam	Coadministration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4)].
Sedative/hypnotics	buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem midazolam (administered parenterally)	↑ sedative/hypnotic ↑ midazolam	A dose decrease may be needed for these drugs when coadministered with PAXLOVID and monitoring for adverse events. Coadministration 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. Refer to the midazolam product label for further information.
Serotonin receptor 1A agonist/serotonin receptor 2A antagonist	flibanserin	↑ flibanserin	Coadministration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4)].
Vasopressin receptor antagonists	tolvaptan	↑ tolvaptan	Coadministration contraindicated due to potential for dehydration, hypovolemia, and hyperkalemia [see Contraindications (4)].
^aSee Pharmacokinetics, Drug Interaction Studies Conducted with Nirmatrelvir and Ritonavir (see PAXLOVID Prescribing Information section 12.3).

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Safety

Explore safety information, including the BOXED WARNING, contraindications, warnings and precautions, and adverse events with PAXLOVID.

Safety

References:

1. PAXLOVID Prescribing Information. Pfizer Inc.; 2023. 2. Talha B, Dhamoon AS. Ritonavir. StatPearls; 2022. 3. Therapeutic Management of Nonhospitalized Adults COVID-19 Treatment Guidelines. National Institutes of Health. Updated April 20, 2023. Accessed May 19, 2023. https://www.covid19treatmentguidelines.nih.gov/tables/therapeutic-management-of-nonhospitalized-adults/