Jaypirca (pirtobrutinib) dosing, indications, interactions, adverse effects, and more

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Sections pirtobrutinib
Dosing & Uses
Interactions
Adverse Effects
Warnings
Pregnancy
Pharmacology
Administration
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

50mg
100mg

Mantle Cell Lymphoma

Indicated for relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor

200 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Asymptomatic lymphocytosis: Dose modification not recommended

Asymptomatic lipase increase: May not necessarily warrant a dose modification

Hematologic toxicities

NOTE: Based on starting dose of 200 mg qDay
Absolute neutrophil count (ANC) 0.5 to <1 x 10⁹/L with fever and/or infection
ANC <0.5 x 10⁹/L lasting ≥7 days
Platelet count 25 to <50 x 10⁹/L with bleeding
Platelet count <25 x 10⁹/L
Modification
- First occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at original dose (200 mg qDay)
- Second occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at 100 mg qDay
- Third occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at 50 mg qDay
- Fourth occurrence: Discontinue treatment

Nonhematologic toxicities

Grade ≥3 nonhematologic toxicity
Evaluate benefit-risk before resuming at same dose for a Grade 4 nonhematologic toxicity
First occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at original dose (200 mg qDay)
Second occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at 100 mg qDay
Third occurrence: Interrupt therapy until recovery to Grade 1 or baseline; restart at 50 mg qDay
Fourth occurrence: Discontinue treatment

Coadministration with strong CYP3A inhibitors

Avoid coadministration
If unavoidable, reduce pirtobrutinib to 50 mg
If current pirtobrutinib dose is 50 mg qDay, discontinue treatment for the duration of strong CYP3A inhibitor use
After strong CYP3A inhibitor has been discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before the strong CYP3A inhibitor was initiated

Coadministration with strong or moderate CYP3A inducers

Avoid coadministration
If coadministration with moderate CYP3A inducers is unavoidable
- Current pirtobrutinib dose is 200 mg qDay: Increase to 300 mg qDay
- Current pirtobrutinib dose is 50 mg or 100 mg qDay: Increase dose by 50 mg

Renal impairment

Mild-to-moderate (eGFR 30-89 mL/min): No dosage adjustment necessary
Severe (eGFR 15-29 mL/min)
- Current dose is 200 mg qDay: Reduce to 100 mg qDay
- Current dose is 100 mg qDay: Reduce to 50 mg qDay
- Current dose is 50 mg qDay: Discontinue treatment
Patients on dialysis: Pharmacokinetics are unknown

Hepatic impairment

All severities: No dosage adjustment necessary

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiating

Safety and efficacy not established

Studies did not include enough patients with MCL aged <65 years to compare the differences in effect in relation to age

Patients aged ≥65 years experienced higher rates of Grade ≥3 adverse reactions and serious adverse reactions compared with patients aged <65 years

Interaction Checker

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Serious - Use Alternative (65)

amobarbital
amobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
apalutamide
apalutamide will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
armodafinil
armodafinil will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
atazanavir
atazanavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
belzutifan
belzutifan will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
bexarotene
bexarotene will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
bosentan
bosentan will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
butabarbital
butabarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
butalbital
butalbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
carbamazepine
carbamazepine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cenobamate
cenobamate will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
chloramphenicol
chloramphenicol will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
clarithromycin
clarithromycin will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
cobicistat
cobicistat will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
conivaptan
conivaptan will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
dabrafenib
dabrafenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
darunavir
darunavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
efavirenz
efavirenz will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
encorafenib
encorafenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
enzalutamide
enzalutamide will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
etravirine
etravirine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
fosphenytoin
fosphenytoin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
grapefruit
grapefruit will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
idelalisib
idelalisib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
indinavir
indinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
itraconazole
itraconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
ivosidenib
ivosidenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
ketoconazole
ketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
levoketoconazole
levoketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lonafarnib
lonafarnib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lopinavir
lopinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lorlatinib
lorlatinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mavacamten
mavacamten will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
mifepristone
mifepristone will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
mitapivat
mitapivat will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
mitotane
mitotane will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mobocertinib
mobocertinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
modafinil
modafinil will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
nafcillin
nafcillin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
nelfinavir
nelfinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
olutasidenib
olutasidenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
pentobarbital
pentobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
pexidartinib
pexidartinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
phenobarbital
phenobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phenytoin
phenytoin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
posaconazole
posaconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
primidone
primidone will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rifabutin
rifabutin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
rifampin
rifampin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rifapentine
rifapentine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
rimegepant
pirtobrutinib will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug.
ritonavir
ritonavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
rucaparib
rucaparib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
saquinavir
saquinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
secobarbital
secobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
sotorasib
sotorasib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
St John's Wort
St John's Wort will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
stiripentol
stiripentol will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
telotristat ethyl
telotristat ethyl will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
tucatinib
tucatinib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
voriconazole
voriconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.

Monitor Closely (28)

alfentanil
pirtobrutinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
carbamazepine
pirtobrutinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
clonidine
pirtobrutinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
colchicine
pirtobrutinib will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
cyclosporine
pirtobrutinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
daprodustat
pirtobrutinib will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment
digoxin
pirtobrutinib will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
dihydroergotamine
pirtobrutinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
disopyramide
pirtobrutinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
divalproex sodium
pirtobrutinib will increase the level or effect of divalproex sodium by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C19 inhibitor) may increase plasma concentrations of divalproex sodium (a CYP2C19 substrate), which may increase the risk of adverse reactions related to divalproex sodium.
ergotamine
pirtobrutinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
ethosuximide
pirtobrutinib will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
everolimus
pirtobrutinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
fentanyl
pirtobrutinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
irinotecan
pirtobrutinib will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
methotrexate
pirtobrutinib will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
midazolam
pirtobrutinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
pacritinib
pirtobrutinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
quinidine
pirtobrutinib will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
quinine
pirtobrutinib will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
repaglinide
pirtobrutinib will increase the level or effect of repaglinide by decreasing metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C8 inhibitor) may increase plasma concentrations of repaglinide (a CYP2C8 substrate), which may increase the risk of adverse reactions related to repaglinide.
sirolimus
pirtobrutinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
tacrolimus
pirtobrutinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
temsirolimus
pirtobrutinib will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
topotecan
pirtobrutinib will increase the level or effect of topotecan by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
triazolam
pirtobrutinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
valproic acid
pirtobrutinib will increase the level or effect of valproic acid by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C8 inhibitor) may increase plasma concentrations of repaglinide (a CYP2C8 substrate), which may increase the risk of adverse reactions related to repaglinide.
warfarin
pirtobrutinib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.

Minor (0)

alfentanil
Monitor Closely (1)pirtobrutinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
amobarbital
Serious - Use Alternative (1)amobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
apalutamide
Serious - Use Alternative (1)apalutamide will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
armodafinil
Serious - Use Alternative (1)armodafinil will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
atazanavir
Serious - Use Alternative (1)atazanavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
belzutifan
Serious - Use Alternative (1)belzutifan will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
bexarotene
Serious - Use Alternative (1)bexarotene will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
bosentan
Serious - Use Alternative (1)bosentan will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
butabarbital
Serious - Use Alternative (1)butabarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
butalbital
Serious - Use Alternative (1)butalbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
carbamazepine
Monitor Closely (1)pirtobrutinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates. Serious - Use Alternative (1)carbamazepine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cenobamate
Serious - Use Alternative (1)cenobamate will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
chloramphenicol
Serious - Use Alternative (1)chloramphenicol will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
clarithromycin
Serious - Use Alternative (1)clarithromycin will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
clonidine
Monitor Closely (1)pirtobrutinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
cobicistat
Serious - Use Alternative (1)cobicistat will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
colchicine
Monitor Closely (1)pirtobrutinib will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
conivaptan
Serious - Use Alternative (1)conivaptan will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
cyclosporine
Monitor Closely (1)pirtobrutinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
dabrafenib
Serious - Use Alternative (1)dabrafenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
daprodustat
Monitor Closely (1)pirtobrutinib will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment
darunavir
Serious - Use Alternative (1)darunavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
digoxin
Monitor Closely (1)pirtobrutinib will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
dihydroergotamine
Monitor Closely (1)pirtobrutinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
disopyramide
Monitor Closely (1)pirtobrutinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
divalproex sodium
Monitor Closely (1)pirtobrutinib will increase the level or effect of divalproex sodium by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C19 inhibitor) may increase plasma concentrations of divalproex sodium (a CYP2C19 substrate), which may increase the risk of adverse reactions related to divalproex sodium.
efavirenz
Serious - Use Alternative (1)efavirenz will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
elvitegravir/cobicistat/emtricitabine/tenofovir DF
Serious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
encorafenib
Serious - Use Alternative (1)encorafenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
enzalutamide
Serious - Use Alternative (1)enzalutamide will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ergotamine
Monitor Closely (1)pirtobrutinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
eslicarbazepine acetate
Serious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
ethosuximide
Monitor Closely (1)pirtobrutinib will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
etravirine
Serious - Use Alternative (1)etravirine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
everolimus
Monitor Closely (1)pirtobrutinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
fentanyl
Monitor Closely (1)pirtobrutinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
fosphenytoin
Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
grapefruit
Serious - Use Alternative (1)grapefruit will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
idelalisib
Serious - Use Alternative (1)idelalisib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
indinavir
Serious - Use Alternative (1)indinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
irinotecan
Monitor Closely (1)pirtobrutinib will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
itraconazole
Serious - Use Alternative (1)itraconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
ivosidenib
Serious - Use Alternative (1)ivosidenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
ketoconazole
Serious - Use Alternative (1)ketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
levoketoconazole
Serious - Use Alternative (1)levoketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lonafarnib
Serious - Use Alternative (1)lonafarnib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lopinavir
Serious - Use Alternative (1)lopinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
lorlatinib
Serious - Use Alternative (1)lorlatinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
lumacaftor/ivacaftor
Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mavacamten
Serious - Use Alternative (1)mavacamten will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
methotrexate
Monitor Closely (1)pirtobrutinib will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
midazolam
Monitor Closely (1)pirtobrutinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
mifepristone
Serious - Use Alternative (1)mifepristone will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
mitapivat
Serious - Use Alternative (1)mitapivat will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
mitotane
Serious - Use Alternative (1)mitotane will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mobocertinib
Serious - Use Alternative (1)mobocertinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
modafinil
Serious - Use Alternative (1)modafinil will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
nafcillin
Serious - Use Alternative (1)nafcillin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
nelfinavir
Serious - Use Alternative (1)nelfinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
nirmatrelvir/ritonavir
Serious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
olutasidenib
Serious - Use Alternative (1)olutasidenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
pacritinib
Monitor Closely (1)pirtobrutinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
pentobarbital
Serious - Use Alternative (1)pentobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
pexidartinib
Serious - Use Alternative (1)pexidartinib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
phenobarbital
Serious - Use Alternative (1)phenobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phenytoin
Serious - Use Alternative (1)phenytoin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
posaconazole
Serious - Use Alternative (1)posaconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
primidone
Serious - Use Alternative (1)primidone will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
quinidine
Monitor Closely (1)pirtobrutinib will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
quinine
Monitor Closely (1)pirtobrutinib will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
repaglinide
Monitor Closely (1)pirtobrutinib will increase the level or effect of repaglinide by decreasing metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C8 inhibitor) may increase plasma concentrations of repaglinide (a CYP2C8 substrate), which may increase the risk of adverse reactions related to repaglinide.
rifabutin
Serious - Use Alternative (1)rifabutin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
rifampin
Serious - Use Alternative (1)rifampin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rifapentine
Serious - Use Alternative (1)rifapentine will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
rimegepant
Serious - Use Alternative (1)pirtobrutinib will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug.
ritonavir
Serious - Use Alternative (1)ritonavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
rucaparib
Serious - Use Alternative (1)rucaparib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
saquinavir
Serious - Use Alternative (1)saquinavir will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
secobarbital
Serious - Use Alternative (1)secobarbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
sirolimus
Monitor Closely (1)pirtobrutinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
sotorasib
Serious - Use Alternative (1)sotorasib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
St John's Wort
Serious - Use Alternative (1)St John's Wort will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
stiripentol
Serious - Use Alternative (1)stiripentol will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
tacrolimus
Monitor Closely (1)pirtobrutinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
telotristat ethyl
Serious - Use Alternative (1)telotristat ethyl will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
temsirolimus
Monitor Closely (1)pirtobrutinib will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates.
topotecan
Monitor Closely (1)pirtobrutinib will increase the level or effect of topotecan by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
triazolam
Monitor Closely (1)pirtobrutinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.
tucatinib
Serious - Use Alternative (1)tucatinib will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
valproic acid
Monitor Closely (1)pirtobrutinib will increase the level or effect of valproic acid by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP2C8 inhibitor) may increase plasma concentrations of repaglinide (a CYP2C8 substrate), which may increase the risk of adverse reactions related to repaglinide.
voriconazole
Serious - Use Alternative (1)voriconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.
warfarin
Monitor Closely (1)pirtobrutinib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.

>10%

All grades

Hemoglobin decreased (42%)
Platelet count decreased (39%)
Neutrophil count decreased (36%)
Lymphocyte count decreased (32%)
Creatinine increased (30%)
Fatigue (29%)
Musculoskeletal pain (27%)
Edema (19%)
Diarrhea (19%)
Calcium decreased (19%)
Dyspnea (17%)
AST increased (17%)
Cough (16%)
Bruising (16%)
Pneumonia (16%)
Peripheral neuropathy (14%)
Rash (14%)
Fever (13%)
Constipation (13%)
Potassium decreased (13%)
Sodium decreased (13%)
Lipase increased (12%)
Arthritis or arthralgia (12%)
Abdominal pain (11%)
Nausea (11%)
Hemorrhage (11%)
Alkaline phosphatase increased (11%)
ALT increased (11%)
Potassium increased (11%)

Grade 3-4

Neutrophil count decreased (16%)
Lymphocyte count decreased (15%)
Pneumonia (14%)
Platelet count decreased (14%)

1-10%

All grades

Upper respiratory tract infections (10%)
Dizziness (10%)

Grade 3-4

Hemoglobin decreased (9%)
Lipase increased (4.4%)
Musculoskeletal pain (3.9%)
Hemorrhage (3.1%)
Dyspnea (2.3%)
Fatigue (1.6%)
ALT or AST increased (1.6%)
Creatinine increased (1.6%)
Calcium decreased (1.6%)
Potassium decreased (1.6%)

<1%

Grade 3-4

Edema (0.8%)
Arthritis or arthralgia (0.8%)
Abdominal pain (0.8%)
Upper respiratory tract infections (0.8%)
Peripheral neuropathy (0.8%)
Potassium increased (0.8%)

Contraindications

None

Cautions

For all adverse reactions, based on severity, reduce dose, temporarily withhold, or permanently discontinue

Grade 3 or 4 cytopenias, including neutropenia, anemia, and thrombocytopenia reported; monitor complete blood cell counts regularly during treatment

Atrial fibrillation and atrial flutter occurred; monitor for signs and symptoms of arrhythmias (eg, palpitations, dizziness, syncope, dyspnea) and manage appropriately

Second primary malignancies, including non-skin carcinomas, developed; advise patients to use sun protection and monitor for development of second primary malignancies

Based on findings in animals, fetal harm may occur when administered to pregnant females

Infections

Serious and fatal infections (eg, bacterial, viral, or fungal) and opportunistic infection reported
Consider antimicrobial prophylaxis and vaccinations in patients who are at increased risk for infections
Monitor for signs and symptoms of infection, evaluate promptly, and treat appropriately

Hemorrhage

Serious and fatal hemorrhage occurred
Major hemorrhage occurred at a higher incidence in patients taking pirtobrutinib without antithrombotic agents than in those taking pirtobrutinib with antithrombotic agents (1.7% vs 0.7%)
Consider the risks and benefits of antithrombotic agents when coadministered with pirtobrutinib
Monitor for signs of bleeding
Consider the benefit-risk of withholding pirtobrutinib for 3-7 days pre- and post-surgery depending upon type of surgery and risk of bleeding

Drug interaction overview

CYP3A4 substrate
P-gp inhibitor
Moderate CYP2C8 and BCRP inhibitor
Weak CYP2C19 and CYP3A inhibitor
Strong CYP3A inhibitors
- Avoid coadministration; if unavoidable, reduce pirtobrutinib dose
- Strong CYP3A inhibitors increase pirtobrutinib systemic exposure and risk for adverse reactions
Strong or moderate CYP3A inducers
- Avoid coadministration
- If use of moderate CYP3A inducers is unavoidable, increase pirtobrutinib dose
- Strong or moderate CYP3A inducers decrease pirtobrutinib systemic exposure and may reduce pirtobrutinib efficacy
Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates
- Pirtobrutinib may increase plasma concentrations of sensitive P-gp, CYP2C8, BCRP, which may increase the risk of adverse reactions related to these substrates
- Refer to prescribing information for sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates for dosing recommendations

Pregnancy

Based on findings from animal studies, fetal harm may cause when administered to pregnant females

No data are available on use in pregnant females to evaluate for a drug-associated risk

Verify pregnancy status in females of reproductive potential before initiating

Contraception

Females of reproductive potential: Use effective contraception during treatment and for 1 week after last dose

Animal data

Doses ≥375 mg/kg BID caused decreased fetal body weights and increased incidence of malformations and variations in urinary tract (including absent or abnormal ureters and kidneys), reproductive tract (mispositioned ovaries and misshapen uterus), and bone (misshapen sternebrae)
At 500 mg/kg BID, total resorption observed
At 375 mg/kg BID in rats, maternal systemic exposures (AUC) were ~3 times the human exposure at 200 mg qDay
Advise pregnant females of potential risk to a fetus

Lactation

There are no data on drug presence in human milk or the effects on breastfed children or milk production

Advise females not to breastfeed during treatment and for 1 week after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Bruton tyrosine kinase (BTK) inhibitor

In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion

Pirtobrutinib binds to wild-type BTK and BTK harboring the C481 mutation, ultimately inhibiting BTK kinase activity

Absorption

Peak plasma concentration (Cmax): 3,670 ng/mL (Cycle 1 Day 8); 6,460 ng/mL (steady-state)

Median peak plasma time (tmax): 2 hr

AUC: 81,800 h⋅ng/mL (Cycle 1 Day 8); 91,300 h⋅ng/mL (steady-state)

Steady-state achieved at 5 days

Accumulation ratio: 1.63

Bioavailability: 85.5%

Effects of food

High-fat meal: Decreased Cmax by 23% and delayed tmax by 1 hr

Distribution

Vd: 32.8 L

Protein bound: 96%

Mean blood-to-plasma ratio: 0.79

Metabolism

Primarily metabolized by CYP3A4 and direct glucuronidation by UGT1A8 and UGT1A9

Elimination

Half-life: ~19 hr

Clearance: 2.02 L/hr

Excretion: Feces (37% [18% unchanged]); urine (57% [10% unchanged]

Oral Administration

Take with or without food at the same time each day

Swallow tablets whole with water; do NOT cut, crush, or chew

Missed dose

Missed dose >12 hr: Do not make up dose and take next dose as scheduled

Storage

Tablets: Store at room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

Images

No images available for this drug.

Patient Handout

A Patient Handout is not currently available for this monograph.

Formulary

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View explanations for tiers and restrictions

Tier	Description
1	This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2	This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC	NOT COVERED – Drugs that are not covered by the plan.

Code	Definition
PA	Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL	Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST	Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR	Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.

Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.

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Sections pirtobrutinib
Dosing & Uses
Interactions
Adverse Effects
Warnings
Pregnancy
Pharmacology
Administration
Images
Patient Handout
Formulary

pirtobrutinib (Rx)

Dosing & Uses

Dosage Forms & Strengths

tablet

Mantle Cell Lymphoma

Dosage Modifications

Hematologic toxicities

Modification

Nonhematologic toxicities

Coadministration with strong CYP3A inhibitors

Coadministration with strong or moderate CYP3A inducers

If coadministration with moderate CYP3A inducers is unavoidable

Renal impairment

Severe (eGFR 15-29 mL/min)

Hepatic impairment

Dosing Considerations

Interactions

Interaction Checker

Contraindicated

Serious - Use Alternative

Significant - Monitor Closely

Minor

Contraindicated (0)

Serious - Use Alternative (65)

Monitor Closely (28)

Minor (0)

Adverse Effects

>10%

All grades

Grade 3-4

1-10%

All grades

Grade 3-4

<1%

Grade 3-4

Warnings

Contraindications

Cautions

Infections

Hemorrhage

Drug interaction overview

Strong CYP3A inhibitors

Strong or moderate CYP3A inducers

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates

Pregnancy & Lactation

Pregnancy

Contraception

Animal data

Lactation

Pregnancy Categories

Pharmacology

Mechanism of Action

Absorption

Effects of food

Distribution

Metabolism

Elimination

Administration

Oral Administration

Missed dose

Storage

Images

Patient Handout

Formulary

Plans

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