Drug Interactions | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) (2024)

Table 1: Established and Other Potentially Significant Drug Interactions¹Drug ClassDrugs within ClassEffect on
ConcentrationClinical CommentsAlpha₁-
adrenoreceptor
antagonistalfuzosin↑ alfuzosinCoadministration
contraindicated due to
potential hypotension
[see Contraindications
(4)].Alpha₁-
adrenoreceptor
antagonisttamsulosin↑ tamsulosinAvoid concomitant
use with PAXLOVID.Antianginalranolazine↑ ranolazineCoadministration
contraindicated due to
potential for serious
and/or life-threatening
reactions[see
Contraindications (4)].Antiarrhythmicsamiodarone,
dronedarone,
flecainide,
propafenone,
quinidine↑ antiarrhythmicCoadministration
contraindicated due to
potential for cardiac
arrhythmias[see
Contraindications (4)].Antiarrhythmicslidocaine (systemic),
disopyramide↑ antiarrhythmicCaution is warranted
and therapeutic
concentration
monitoring is
recommended for
antiarrhythmics if
available.Anticancer drugsapalutamide↓ nirmatrelvir/
ritonavirCoadministration
contraindicated due to
potential loss of
virologic response and
possible resistance
[see Contraindications
(4)].Anticancer drugsabemaciclib,
ceritinib,
dasatinib,
encorafenib,
ibrutinib,
ivosidenib,
neratinib,
nilotinib,
venetoclax,
vinblastine,
vincristine↑ anticancer drugAvoid
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.

Anticoagulantswarfarin

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.

Anticonvulsantscarbamazepine^a,
phenobarbital,
primidone,
phenytoin↓ nirmatrelvir/
ritonavirCoadministration
contraindicated due to
potential loss of
virologic response and
possible resistance
[see Contraindications
(4)].Anticonvulsantsclonazepam↑ anticonvulsantA dose decrease may
be needed for
clonazepam when
coadministered with
PAXLOVID and clinical
monitoring is
recommended.Antidepressantsbupropion

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.

Antifungalsvoriconazole

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-goutcolchicine↑ colchicineCoadministration
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
inhibitorsatazanavir,
darunavir,
tipranavir↑ protease inhibitorFor 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-HIVefavirenz,
maraviroc,
nevirapine,
zidovudine,
bictegravir/
emtricitabine/
tenofovir↑ efavirenz
↑ maraviroc
↑ nevirapine
↓ zidovudine
↑ bictegravir
←→emtricitabine
↑ tenofovirFor further
information, refer to
the respective anti-
HIV drugs prescribing
information.Anti-infectiveclarithromycin,
erythromycin↑ clarithromycin
↑ erythromycinRefer to the
respective
prescribing
information for anti-
infective dose
adjustment.Antimycobacterialrifampin,
rifapentine↓ nirmatrelvir/
ritonavirCoadministration
contraindicated due to
potential loss of
virologic response and
possible resistance.
Alternate
antimycobacterial
drugs such as rifabutin
should be considered
[see Contraindications
(4)].Antimycobacterialbedaquiline

rifabutin

↑ bedaquiline

↑ rifabutin

Refer to the
bedaquiline product
label for further
information.

Refer to rifabutin
product label for
further information on
rifabutin dose
reduction.

Antipsychoticslurasidone,
pimozide↑ lurasidone
↑ pimozideCoadministration
contraindicated due to
serious and/or life-
threatening reactions
such as cardiac
arrhythmias[see
Contraindications (4)].Antipsychoticsquetiapine

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 agentssilodosin↑ silodosinCoadministration
contraindicated due
to potential for
postural hypotension
[see
Contraindications
(4)].Calcium channel
blockersamlodipine,
diltiazem,
felodipine,
nicardipine,
nifedipine,
verapamil↑ calcium channel
blockerCaution 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 glycosidesdigoxin↑ digoxinCaution 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
agentseplerenone

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
agentsaliskiren,
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 CYP3Abetamethasone,
budesonide,
ciclesonide,
dexamethasone,
fluticasone,
methylprednisolone,
mometasone,
triamcinolone↑ corticosteroidCoadministration 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 potentiatorslumacaftor/ivacaftor↓ nirmatrelvir/
ritonavirCoadministration
contraindicated due to
potential loss of
virologic response and
possible resistance
[see Contraindications
(4)].Cystic fibrosis
transmembrane
conductance
regulator potentiatorsivacaftor

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) inhibitorssaxagliptin↑ saxagliptinDosage adjustment of
saxagliptin is
recommended. Refer
to the saxagliptin
product label for
more information.Endothelin receptor
antagonistsbosentan↑ bosentan
↓ nirmatrelvir/
ritonavirDiscontinue use of
bosentan at least 36
hours prior to
initiation of
PAXLOVID.

Refer to the bosentan
product label for
further information.

Ergot derivativesdihydroergotamine,
ergotamine,
methylergonovine↑ dihydroergotamine
↑ ergotamine
↑ methylergonovineCoadministration
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 antiviralselbasvir/grazoprevir

glecaprevir/
pibrentasvir

ombitasvir/
paritaprevir/
ritonavir and
dasabuvir

sofosbuvir/
velpatasvir/
voxilaprevir

↑ antiviralIncreased 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 productsSt. John’s Wort
(hypericum perforatum)↓ nirmatrelvir/
ritonavirCoadministration
contraindicated due to
potential loss of
virologic response and
possible resistance
[see Contraindications (4)].HMG-CoA
reductase
inhibitorslovastatin,
simvastatin↑ lovastatin
↑ simvastatinCoadministration
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
inhibitorsatorvastatin,
rosuvastatin↑ atorvastatin
↑ rosuvastatinConsider 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
contraceptiveethinyl estradiol↓ ethinyl estradiolAn additional,
nonhormonal method
of contraception
should be considered
during the 5 days of
PAXLOVID treatment
and until one
menstrual cycle after
stopping PAXLOVID.Immunosuppressantsvoclosporin↑ voclosporinCoadministration
contraindicated due to
potential for acute
and/or chronic
nephrotoxicity[see
Contraindications (4)].Immunosuppressantscalcineurin 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)
inhibitorstofacitinib

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
agonistsalmeterol↑ salmeterolAvoid 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)
inhibitorlomitapide↑ lomitapideCoadministration
contraindicated due to
potential for
hepatotoxicity and
gastrointestinal
adverse reactions[see
Contraindications (4)].Migraine medicationseletriptan

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 medicationsrimegepantrimegepantAvoid concomitant
use with PAXLOVID.Mineralocorticoid
receptor antagonistsfinerenone↑ finerenoneCoadministration
contraindicated due
to potential for
serious adverse
reactions including
hyperkalemia,
hypotension, and
hyponatremia[see
Contraindications (4)].Muscarinic receptor
antagonistsdarifenacin↑ darifenacinThe darifenacin daily
dose should not
exceed 7.5 mg when
coadministered with
PAXLOVID. Refer to
the darifenacin
product label for
more information.Narcotic analgesicsfentanyl,
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
agentssuvorexant

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 antagonistsnaloxegol↑ naloxegolCoadministration
contraindicated due
to the potential for
opioid withdrawal
symptoms[see
Contraindications (4)].Pulmonary
hypertension agents
(PDE5 inhibitors)sildenafil (Revatio®)↑ sildenafilCoadministration 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®)↑ tadalafilAvoid concomitant
use of tadalafil with
PAXLOVID for
pulmonary
hypertension.Pulmonary
hypertension agents
(sGC stimulators)riociguat↑ riociguatDosage 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/hypnoticstriazolam,
oral midazolam^a↑ triazolam
↑ midazolamCoadministration
contraindicated due
to potential for
extreme sedation and
respiratory depression[see
Contraindications (4)].Sedative/hypnoticsbuspirone,
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
antagonistflibanserin↑ flibanserinCoadministration
contraindicated due
to potential for
hypotension,
syncope, and CNS
depression[see
Contraindications (4)].Vasopressin receptor
antagoniststolvaptan↑ tolvaptanCoadministration
contraindicated due
to potential for
dehydration,
hypovolemia, and
hyperkalemia[see
Contraindications (4)].^aSee Pharmaco*kinetics, Drug Interaction Studies Conducted with Nirmatrelvir and Ritonavir (see PAXLOVID Prescribing Information section 12.3).