Dosing & Uses
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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
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)
Adverse Effects
>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%)
Warnings
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 & Lactation
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.Pharmacology
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]
Administration
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)
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Formulary
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