SAFETY
Drug interactions
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WARNING:
SIGNIFICANT DRUG INTERACTIONS WITH PAXLOVID
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:
- Review all medications taken by the patient to assess for potential drug-drug interactions with a strong CYP3A inhibitor like PAXLOVID and
- 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 interactions
PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir), or any other components of the product. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.
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 here 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:
- Alpha 1-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
- Sedative/hypnotics: triazolam, oral midazolam
- Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
- Vasopressin receptor antagonists: tolvaptan
Drugs that are strong CYP3A inducers:
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, enzalutamide
- Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
- Antimycobacterials: rifampin, rifapentine
- Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
- Herbal products: St. John’s Wort (hypericum perforatum)
Risk of serious adverse reactions due to drug interactions
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 the table below for clinically significant drug interactions, including contraindicated drugs. Drugs listed in the table below 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.
Potential for PAXLOVID to affect other drugs
PAXLOVID 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 shown in the table below.
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.
Established and other potentially significant drug interactions
The table below provides a listing of clinically significant drug interactions, including contraindicated drugs. Drugs listed in the table are a guide and not considered a comprehensive list of all possible drugs that may interact 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, such as ritonavir. References contained in the table below are to the applicable section of the Fact Sheet for Healthcare Providers.
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Alpha 1-adrenoreceptor antagonist
Drugs within Class that are Contraindicated
- alfuzosin
Effect on Concentration
↑ alfuzosin
Clinical Comments
Coadministration contraindicated due to potential hypotension [see Contraindications (4)].
Alpha 1-adrenoreceptor antagonist
Drugs within Class that are Contraindicated
- tamsulosin
Effect on Concentration
↑ tamsulosin
Clinical Comments
Avoid concomitant use with PAXLOVID.
Antianginal
Drugs within Class that are Contraindicated
- ranolazine
Effect on Concentration
↑ ranolazine
Clinical Comments
Coadministration contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)].
Antiarrhythmics
Drugs within Class that are Contraindicated
- amiodarone
- dronedarone
- flecainide
- propafenone
- quinidine
Effect on Concentration
↑ antiarrhythmic
Clinical Comments
Coadministration contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)].
Antiarrhythmics
Drugs within Class that are Contraindicated
- lidocaine (systemic)
- disopyramide
Effect on Concentration
↑ antiarrhythmic
Clinical Comments
Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.
Anticancer drugs
Drugs within Class that are Contraindicated
- apalutamide
- enzalutamide
Effect on Concentration
↓ nirmatrelvir/ritonavir
Clinical Comments
Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Drugs within Class that are Contraindicated
- abemaciclib
- ceritinib
- dasatinib
- encorafenib
- ibrutinib
- ivosidenib
- neratinib
- nilotinib
- venetoclax
- vinblastine
- vincristine
Effect on Concentration
↑ anticancer drugs
Clinical Comments
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
Drugs within Class that are Contraindicated
- warfarin
- rivaroxaban
- dabigatrana
- apixaban
Effect on Concentration
↑↓ warfarin
↑ rivaroxaban
↑ dabigatrana
↑ apixaban
Clinical Comments
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 more 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
Drugs within Class that are Contraindicated
- carbamazepinea
- phenobarbital
- primidone
- phenytoin
Effect on Concentration
↓ nirmatrelvir/ritonavir
Clinical Comments
Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Anticonvulsants
Drugs within Class that are Contraindicated
- clonazepam
Effect on Concentration
↑ anticonvulsant
Clinical Comments
A dose decrease may be needed for clonazepam when coadministered with PAXLOVID and clinical monitoring is recommended.
Antidepressants
Drugs within Class that are Contraindicated
- bupropion
- trazodone
Effect on Concentration
↓ bupropion and active metabolite hydroxy-bupropion
↑ trazodone
Clinical Comments
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 trazodone product label for more information.
Antifungals
Drugs within Class that are Contraindicated
- voriconazole
- ketoconazole
- isavuconazonium sulfate
- itraconazolea
Effect on Concentration
↓ voriconazole
↑ ketoconazole
↑ isavuconazonium sulfate
↑ itraconazole
↑ nirmatrelvir/ritonavir
Clinical Comments
Avoid concomitant use of voriconazole.
Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for more information.
A nirmatrelvir/ritonavir dose reduction is not needed.
Anti-gout
Drugs within Class that are Contraindicated
- colchicine
Effect on Concentration
↑ colchicine
Clinical Comments
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
Drugs within Class that are Contraindicated
- efavirenz
- maraviroc
- nevirapine
- zidovudine
- bictegravir/emtricitabine/tenofovir
Effect on Concentration
↑ efavirenz
↑ maraviroc
↑ nevirapine
↓ zidovudine
↑ bictegravir
←→ emtricitabine
↑ tenofovir
Clinical Comments
For more information, refer to the respective anti-HIV drugs prescribing information.
Anti-HIV protease inhibitors
Drugs within Class that are Contraindicated
- atazanavir
- darunavir
- tipranavir
Effect on Concentration
↑ protease inhibitor
Clinical Comments
For more 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-infective
Drugs within Class that are Contraindicated
- clarithromycin
- erythromycin
Effect on Concentration
↑ clarithromycin
↑ erythromycin
Clinical Comments
Refer to the respective prescribing information for anti-infective dose adjustment.
Antimycobacterial
Drugs within Class that are Contraindicated
- rifampin
- rifapentine
Effect on Concentration
↓ nirmatrelvir/ritonavir
Clinical Comments
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
Drugs within Class that are Contraindicated
- bedaquiline
- rifabutin
Effect on Concentration
↑ bedaquiline
↑ rifabutin
Clinical Comments
Refer to the bedaquiline product label for more information.
Refer to rifabutin product label for more information on rifabutin dose reduction.
Antipsychotics
Drugs within Class that are Contraindicated
- lurasidone
- pimozide
Effect on Concentration
↑ lurasidone
↑ pimozide
Clinical Comments
Coadministration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4)].
Antipsychotics
Drugs within Class that are Contraindicated
- quetiapine
- clozapine
Effect on Concentration
↑ quetiapine
↑ clozapine
Clinical Comments
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
Drugs within Class that are Contraindicated
- silodosin
Effect on Concentration
↑ silodosin
Clinical Comments
Coadministration contraindicated due to potential for postural hypotension [see Contraindications (4)].
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Calcium channel blockers
Drugs within Class that are Contraindicated
- amlodipine
- diltiazem
- felodipine
- nicardipine
- nifedipine
- verapamil
Effect on Concentration
↑ calcium channel blocker
Clinical Comments
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 more information.
Cardiac glycosides
Drugs within Class that are Contraindicated
- digoxin
Effect on Concentration
↑ digoxin
Clinical Comments
Caution should be exercised when coadministering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels.
Refer to the digoxin product label for more information.
Cardiovascular agents
Drugs within Class that are Contraindicated
- eplerenone
- ivabradine
Effect on Concentration
↑ eplerenone
↑ ivabradine
Clinical Comments
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
Drugs within Class that are Contraindicated
- aliskiren
- ticagrelor
- vorapaxar
- clopidogrel
Effect on Concentration
↑ aliskiren
↑ ticagrelor
↑ vorapaxar
↓ clopidogrel active metabolite
Clinical Comments
Avoid concomitant use with PAXLOVID.
Drugs within Class that are Contraindicated
- cilostazol
Effect on Concentration
↑ cilostazol
Clinical Comments
Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information.
Corticosteroids primarily metabolized by CYP3A
Drugs within Class that are Contraindicated
- betamethasone
- budesonide
- ciclesonide
- dexamethasone
- fluticasone
- methylprednisolone
- mometasone
- triamcinolone
Effect on Concentration
↑ corticosteroid
Clinical Comments
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
Drugs within Class that are Contraindicated
- lumacaftor/ivacaftor
Effect on Concentration
↓ nirmatrelvir/ritonavir
Clinical Comments
Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
Cystic fibrosis transmembrane conductance regulator potentiators
Drugs within Class that are Contraindicated
- ivacaftor
- elexacaftor/tezacaftor/ivacaftor
- tezacaftor/ivacaftor
Effect on Concentration
↑ ivacaftor
↑ elexacaftor/tezacaftor/ivacaftor
↑ tezacaftor/ivacaftor
Clinical Comments
Reduce dosage when coadministered with PAXLOVID. Refer to individual product labels for more information.
Dipeptidyl peptidase 4 (DPP4) inhibitors
Drugs within Class that are Contraindicated
- saxagliptin
Effect on Concentration
↑ saxagliptin
Clinical Comments
Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information.
Endothelin receptor antagonists
Drugs within Class that are Contraindicated
- bosentan
Effect on Concentration
↑ bosentan
↓ nirmatrelvir/ritonavir
Clinical Comments
Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID.
Refer to the bosentan product label for more information.
Ergot derivatives
Drugs within Class that are Contraindicated
- dihydroergotamine
- ergotamine
- methylergonovine
Effect on Concentration
↑ dihydroergotamine
↑ ergotamine
↑ methylergonovine
Clinical Comments
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
Drugs within Class that are Contraindicated
- elbasvir/grazoprevir
- glecaprevir/pibrentasvir
- ombitasvir/paritaprevir/ritonavir and dasabuvir
- sofosbuvir/velpatasvir/voxilaprevir
Effect on Concentration
↑ antiviral
Clinical Comments
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 more information.
Refer to the sofosbuvir/velpatasvir/voxilaprevir product label for more 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
Drugs within Class that are Contraindicated
- St. John's Wort (hypericum perforatum)
Effect on Concentration
↓ nirmatrelvir/ritonavir
Clinical Comments
Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].
HMG-CoA reductase inhibitors
Drugs within Class that are Contraindicated
- lovastatin
- simvastatin
Effect on Concentration
↑ lovastatin
↑ simvastatin
Clinical Comments
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
Drugs within Class that are Contraindicated
- atorvastatin
Effect on Concentration
↑ atorvastatin
Clinical Comments
Consider temporary discontinuation of atorvastatin during treatment with PAXLOVID. Atorvastatin does not need to be withheld prior to or after completing PAXLOVID.
Hormonal contraceptive
Drugs within Class that are Contraindicated
- ethinyl estradiol
Effect on Concentration
↓ ethinyl estradiol
Clinical Comments
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
Drugs within Class that are Contraindicated
- voclosporin
Effect on Concentration
↑ voclosporin
Clinical Comments
Coadministration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4)].
Immunosuppressants
Drugs within Class that are Contraindicated
- calcineurin inhibitors:
- cyclosporine
- tacrolimus
- mTOR inhibitors:
- everolimus
- sirolimus
Effect on Concentration
↑ cyclosporine
↑ tacrolimus
↑ everolimus
↑ sirolimus
Clinical Comments
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 more information.
Janus kinase (JAK) inhibitors
Drugs within Class that are Contraindicated
- tofacitinib
- upadacitinib
Effect on Concentration
↑ tofacitinib
↑ upadacitinib
Clinical Comments
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
Drugs within Class that are Contraindicated
- salmeterol
Effect on Concentration
↑ salmeterol
Clinical Comments
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.
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Microsomal triglyceride transfer protein (MTTP) inhibitor
Drugs within Class that are Contraindicated
- lomitapide
Effect on Concentration
↑ lomitapide
Clinical Comments
Coadministration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions [see Contraindications (4)].
Migraine medications
Drugs within Class that are Contraindicated
- eletriptan
Effect on Concentration
↑ eletriptan
Clinical Comments
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)].
Drugs within Class that are Contraindicated
- ubrogepant
Effect on Concentration
↑ ubrogepant
Clinical Comments
Coadministration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions [see Contraindications (4)].
Drugs within Class that are Contraindicated
- rimegepant
Effect on Concentration
↑ rimegepant
Clinical Comments
Avoid concomitant use with PAXLOVID.
Mineralocorticoid receptor antagonists
Drugs within Class that are Contraindicated
- finerenone
Effect on Concentration
↑ finerenone
Clinical Comments
Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)].
Muscarinic receptor antagonists
Drugs within Class that are Contraindicated
- darifenacin
Effect on Concentration
↑ darifenacin
Clinical Comments
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
Drugs within Class that are Contraindicated
- fentanyl
- hydrocodone
- oxycodone
- meperidine
- methadone
Effect on Concentration
↑ fentanyl
↑ hydrocodone
↑ oxycodone
↑ meperidine
↓ methadone
Clinical Comments
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
Drugs within Class that are Contraindicated
- suvorexant
- aripiprazole
- brexpiprazole
- cariprazine
- iloperidone
- lumateperone
- pimavanserin
Effect on Concentration
↑ suvorexant
↑ aripiprazole
↑ brexpiprazole
↑ cariprazine
↑ iloperidone
↑ lumateperone
↑ pimavanserin
Clinical Comments
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
Drugs within Class that are Contraindicated
- naloxegol
Effect on Concentration
↑ naloxegol
Clinical Comments
Coadministration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4)].
Pulmonary hypertension agents (PDE5 inhibitors)
Drugs within Class that are Contraindicated
- sildenafil (Revatio®)
Effect on Concentration
↑ sildenafil
Clinical Comments
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)
Drugs within Class that are Contraindicated
- tadalafil (Adcirca®)
Effect on Concentration
↑ tadalafil
Clinical Comments
Avoid concomitant use of tadalafil with PAXLOVID for pulmonary hypertension.
Pulmonary hypertension agents (sGC stimulators)
Drugs within Class that are Contraindicated
- riociguat
Effect on Concentration
↑ riociguat
Clinical Comments
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)
Drugs within Class that are Contraindicated
- avanafil
- sildenafil
- tadalafil
- vardenafil
Effect on Concentration
↑ avanafil
↑ sildenafil
↑ tadalafil
↑ vardenafil
Clinical Comments
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
Drugs within Class that are Contraindicated
- triazolam
- oral midazolama
Effect on Concentration
↑ triazolam
↑ midazolam
Clinical Comments
Coadministration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4)].
Sedative/hypnotics
Drugs within Class that are Contraindicated
- buspirone
- clorazepate
- diazepam
- estazolam
- flurazepam
- zolpidem
Effect on Concentration
↑ sedative/hypnotic
Clinical Comments
A dose decrease may be needed for these drugs when coadministered with PAXLOVID and monitoring for adverse events.
Drugs within Class that are Contraindicated
- midazolam (administered parenterally)
Effect on Concentration
↑ midazolam
Clinical Comments
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
Drugs within Class that are Contraindicated
- flibanserin
Effect on Concentration
↑ flibanserin
Clinical Comments
Coadministration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4)].
Vasopressin receptor antagonists
Drugs within Class that are Contraindicated
- tolvaptan
Effect on Concentration
↑ tolvaptan
Clinical Comments
Coadministration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia [see Contraindications (4)].
aSee Pharmacokinetics, Drug Interaction Studies Conducted with Nirmatrelvir and Ritonavir (12.3).
CNS=central nervous system; CYP3A=cytochrome P450 3A; HIV=human immunodeficiency virus; HMG-CoA=3-hydroxy-3-methylglutaryl coenzyme A; mTOR=mammalian target of rapamycin; PDE5=phosphodiesterase type 5; P-gp=glycoprotein P; sGC=soluble guanylate cyclase.
Reference:
- Fact Sheet for Healthcare Providers: Emergency Use Authorization for PAXLOVIDTM. Pfizer Inc.; 2025.