Dosing & Uses
Dosage Forms & Strengths
capsule
- 100mg
Myelofibrosis
Indicated for adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count <50 x 109/L
200 mg PO BID
Dosage Modifications
Dose reductions for adverse reactions
- First dose reduction: Reduce to 100 mg BID
- Second dose reduction: Reduce to 100 mg qDay
- Unable to tolerate 100 mg qDay: Discontinue treatment
Planned surgical procedures or other interventions
- Discontinue 7 days before elective surgery or invasive procedures, owing to risk of hemorrhage, and restart only after hemostasis is assured
Diarrhea
- New onset: Initiate antidiarrheal medications; encourage adequate oral hydration
-
Grade 3 or 4
- Defined as increase of ≥7 stools/day over baseline, or hospitalization indicated, or severe increase in ostomy output over baseline, or if limiting self-care
- Hold until diarrhea resolves to Grade ≤1 or baseline (increase of <4 stools/day or mild increase in ostomy output compared with baseline), then restart at last given dose
- Intensify antidiarrheal regimen and provide fluid replacement
- If recurs, hold until diarrhea resolves to Grade ≤1 or baseline, then restart at 50% of last given dose
- Concomitant antidiarrheal treatment is required if restarting
Thrombocytopenia
- In clinically significant worsening of thrombocytopenia lasting >7 days
- Hold therapy until resolution; restart at 50% of last given dose once resolved
- If recurs, hold therapy until resolution, then restart at 50% of last given dose
Hemorrhage
- Moderate bleeding (intervention indicated): Hold until hemorrhage resolves, then restart at last given dose; if recurs, hold until resolution, then restart at 50% of last given dose
- Severe bleeding (transfusion, invasive intervention, or hospitalization indicated): Hold until hemorrhage resolves, then restart at 50% of last given dose; if recurs, discontinue therapy
- Life-threatening bleeding (urgent intervention indicated): Discontinue therapy
QTc prolongation
- QTc prolongation >500 msec or >60 msec from baseline: Hold until QTc interval resolves to ≤480 msec or baseline within 1 week, then restart at same dose
- If time to resolution >1 week, restart at reduced dose
Renal impairment
- eGFR ≥30 mL/min: No dosage adjustment necessary
- eGFR <30 mL/min: Avoid use
Hepatic impairment
- Mild (Child-Pugh A): Decreases AUC by 8.5%; no dosage adjustment necessary
- Moderate or severe (Child-Pugh B or C): Avoid use; decreases AUC by 36% and 45% respectively
Dosing Considerations
- Before initiating, patients who are on treatment with other kinase inhibitors must taper or discontinue according to the prescribing information for that drug
-
Monitor parameters at baseline and as clinically indicated
- Complete blood count (CBC; including white blood cell count differential and platelet count)
- Coagulation testing (prothrombin time [PT], partial thromboplastin time, thrombin time, and international normalized ratio [INR])
- Electrocardiogram (ECG)
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (35)
- abametapir
abametapir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- atazanavir
atazanavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- chloramphenicol
chloramphenicol will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- clarithromycin
clarithromycin will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- cobicistat
cobicistat will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- conivaptan
conivaptan will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- darunavir
darunavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- encorafenib
encorafenib, pacritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Encorafenib (a CYP3A4 inhibitor and inducer) may increase or decrease levels of pacritinib.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- etravirine
etravirine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- grapefruit
grapefruit will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- idelalisib
idelalisib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- indinavir
indinavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- isoniazid
isoniazid will increase the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Contraindicated.
- itraconazole
itraconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ivosidenib
ivosidenib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ketoconazole
ketoconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- lonafarnib
lonafarnib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- lopinavir
lopinavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- mifepristone
mifepristone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- mitapivat
mitapivat will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- modafinil
modafinil will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nafcillin
nafcillin will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nefazodone
nefazodone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nelfinavir
nelfinavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- pexidartinib
pexidartinib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- posaconazole
posaconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rifabutin
rifabutin will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rifapentine
rifapentine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rucaparib
rucaparib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- saquinavir
saquinavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- sotorasib
sotorasib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- tipranavir
tipranavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- voriconazole
voriconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Serious - Use Alternative (100)
- alfentanil
pacritinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- amiodarone
amiodarone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- aprepitant
aprepitant will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- brigatinib
brigatinib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- calcitriol
calcitriol will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
pacritinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cidofovir
pacritinib will increase the level or effect of cidofovir by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.
- clobazam
clobazam will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clonidine
pacritinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- clopidogrel
clopidogrel will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clotrimazole
clotrimazole will increase the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
- clozapine
clozapine will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- colchicine
colchicine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
pacritinib will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - conjugated estrogens
conjugated estrogens will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- crizotinib
crizotinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cyclosporine
cyclosporine will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
pacritinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - deferasirox
deferasirox will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- desipramine
desipramine will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dexamethasone
dexamethasone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dicloxacillin
dicloxacillin will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- digoxin
pacritinib will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- dihydroergotamine
pacritinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- diltiazem
diltiazem will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- disopyramide
pacritinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- doxycycline
doxycycline will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dronedarone
dronedarone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- entacapone
entacapone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ergotamine
pacritinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin base
erythromycin base will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- estradiol
estradiol will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- estrogens conjugated synthetic
estrogens conjugated synthetic will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ethosuximide
pacritinib will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- everolimus
pacritinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
fedratinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- felbamate
felbamate will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fentanyl
pacritinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fluconazole
fluconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fluvoxamine
fluvoxamine will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fosamprenavir
fosamprenavir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fostamatinib
fostamatinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- griseofulvin
griseofulvin will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- haloperidol
haloperidol will increase the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
- hydrocortisone
hydrocortisone will decrease the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
hydrocortisone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - ibrexafungerp
ibrexafungerp will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- iloperidone
iloperidone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- imatinib
imatinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- irinotecan
pacritinib will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (BCRP inhibitor) with BCRP substrates may increase the plasma concentrations of these substrates.
- isavuconazonium sulfate
isavuconazonium sulfate will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- isoniazid
isoniazid will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- istradefylline
istradefylline will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivacaftor
ivacaftor will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lapatinib
lapatinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- larotrectinib
larotrectinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lefamulin
lefamulin will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lenvatinib
lenvatinib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lesinurad
lesinurad will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- letermovir
letermovir will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- medroxyprogesterone
medroxyprogesterone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- metformin
pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.
- methotrexate
pacritinib will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (BCRP inhibitor) with BCRP substrates may increase the plasma concentrations of these substrates.
- metronidazole
metronidazole will increase the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
- metyrapone
metyrapone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- midazolam
pacritinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nevirapine
nevirapine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- paclitaxel
paclitaxel will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- palifermin
palifermin increases toxicity of pacritinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pentobarbital
pentobarbital will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pimozide
pacritinib will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pioglitazone
pioglitazone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- prednisone
prednisone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinidine
pacritinib will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinine
pacritinib will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ribociclib
ribociclib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritonavir
ritonavir will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rufinamide
rufinamide will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- schisandra
schisandra will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- secobarbital
secobarbital will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sertraline
sertraline will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sirolimus
pacritinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- somatropin
somatropin will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tacrolimus
pacritinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tecovirimat
tecovirimat will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- temsirolimus
pacritinib will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- terbinafine
terbinafine will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tetracycline
tetracycline will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- theophylline
pacritinib will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
- topiramate
topiramate will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- topotecan
pacritinib will increase the level or effect of topotecan by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (BCRP inhibitor) with BCRP substrates may increase the plasma concentrations of these substrates.
- triazolam
pacritinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- vemurafenib
vemurafenib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- verapamil
verapamil will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (1)
- siponimod
siponimod and pacritinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
Minor (0)
Adverse Effects
>10%
All grades
- Diarrhea (48%)
- Thrombocytopenia (34%)
- Nausea (32%)
- Anemia (24%)
- Peripheral edema (20%)
- Vomiting (19%)
- Dizziness (15%)
- Pyrexia (15%)
- Epistaxis (12%)
Grade ≥3
- Thrombocytopenia (32%)
- Anemia (22%)
1-10%
All grades
- Dyspnea (10%)
- Pruritus (10%)
- Upper respiratory tract infection (10%)
- Cough (8%)
Grade ≥3
- Epistaxis (5%)
- Diarrhea (4%)
- Pruritus (2%)
- Cough (2%)
- Nausea (1%)
- Peripheral edema (1%)
- Dizziness (1%)
- Pyrexia (1%)
Warnings
Contraindications
Coadministration with strong CYP3A4 inhibitors or inducers
Cautions
May worsen thrombocytopenia; monitor platelet count before initiating and as clinically indicated during treatment
Manage QTc prolongation using interruption and electrolyte management
Serious bacterial, mycobacterial, fungal, and viral infections may occur with therapy; delay initiating therapy until active serious infections are resolved
Hemorrhage
- Serious and fatal hemorrhages have occurred in treated patients with platelet counts <50 x 109/L
- Avoid use in patients with active bleeding and hold therapy 7 days before any planned surgical or invasive procedures
- Assess platelet counts periodically, as clinically indicated
- Interrupt treatment and treat appropriately, if necessary
Diarrhea
- May cause diarrhea
- Median time to resolution was 2 weeks
- Incidence of reported diarrhea decreased over time
- Control preexisting diarrhea before starting treatment
- Manage diarrhea with antidiarrheal medications, fluid replacement, and dosage modification
- Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms
- Interrupt or reduce dose in patients with significant diarrhea despite optimal supportive care
QTc prolongation
- QTc prolongation may occur; no cases of torsade de pointes were reported
- Avoid use in patients with a baseline QTc of >480 msec
- Avoid coadministration with drugs that cause significant QTc prolongation
- Correct hypokalemia before and during treatment
- Advise patients to consult their healthcare provider immediately if they feel faint, lose consciousness, or have signs or symptoms suggestive of arrhythmia
- Manage QTc prolongation using interruption and electrolyte management
Janus-associated kinase (JAK) inhibitor–associated adverse effects
-
Another JAK inhibitor has increased the risk of the following
- Major adverse cardiac events (MACE; eg, cardiovascular death, myocardial infarction, stroke) in patients with rheumatoid arthritis (RA), a condition for which pacritinib is not indicated
- Thrombosis (eg, deep venous thrombosis, pulmonary embolism, arterial thrombosis) in patients with RA
- Secondary malignancies, such as lymphoma and other malignancies, excluding non-melanoma skin cancer (NMSC), in patients with RA
- Serious infections in patients with myeloproliferative neoplasms
- Consider the benefits and risks before initiating or continuing therapy, particularly in patients who are current or past smokers, patients with other cardiovascular risk factors, and patients with a developed or known malignancy (other than a successfully treated NMSC)
- Consult about symptoms of serious cardiovascular events and the necessary steps to take if they occur
- Monitor for signs and symptoms of infection and manage promptly
- Use active surveillance and prophylactic antibiotics according to clinical guidelines
Drug interaction overview
- Substrate of CYP3A4
- Inhibitor of CYP1A2, CYP3A4, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic cation transporter 1 (OCT1)
-
CYP3A4 inhibitors
- Strong inhibitors: Contraindicated
- Moderate inhibitors: Avoid use
- Coadministration with clarithromycin (a strong CYP3A4 inhibitor) increases AUC and peak plasma concentration of pacritinib by 80% and 30%, respectively; exposure to pacritinib may increase following a longer treatment with clarithromycin that results in maximal CYP3A4 inhibition
- Impact of moderate CYP3A4 inhibition not studied
-
CYP3A4 inducers
- Strong inducers: Contraindicated
- Moderate inducers: Avoid use
- Coadministration with rifampin (a strong CYP3A4 inducer) decreases AUC and peak plasma concentration of pacritinib by 87% and 51%, respectively
- Impact of moderate CYP3A4 inducers not studied
-
Sensitive CYP1A2 or CYP3A4 substrates
- Avoid coadministration
- Pacritinib may increase plasma concentrations of sensitive CYP1A2 or CYP3A4 substrates
-
Sensitive P-gp, BCRP, or OCT1 substrates
- Avoid coadministration
- Pacritinib may increase plasma concentrations of sensitive P-gp, BCRP, or OCT1 substrates
Pregnancy & Lactation
Pregnancy
No data are available on use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Advise pregnant females of potential risk to a fetus
Consider benefits and risks for mother and possible risks to the fetus when prescribing to pregnant females
Infertility
- May reduced male mating and fertility indices in BALB/c mice
- Therefore, may impair male fertility in humans
Animal data
- Pregnant mice: Orally administered doses of 30, 100, or 250 mg/kg/day from gestation day 6 to day 15; the high dose was associated with an increased incidence of an external malformation (cleft palate) in presence of maternal toxicity
- Pregnant rabbits: Orally administered doses of 15, 30, or 60 mg/kg/day from gestation day 7 to day 20
- In both species, pacritinib was associated with maternal toxicity, which resulted in postimplantation loss in mice, abortions in rabbits, and reduced fetal body weights in mice and rabbits at exposures 0.1x (mice) and 0.3x (rabbits) the exposure at the recommended human dose (AUC-based)
Lactation
There are no data on presence in either human or animal milk, effects on breastfed children, or effects on milk production
Unknown whether pacritinib is excreted in human milk
Advise patients that breastfeeding is not recommended during treatment, and for 2 weeks 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
Oral kinase with activity against wild-type JAK2, mutant JAK2V617F, and FMS-like tyrosine kinase 3, which contribute to signaling of cytokines and growth factors that are important for hematopoiesis and immune function
MF is often associated with dysregulated JAK2 signaling
Also exhibits inhibitory activity against additional cellular kinases (eg, CSF1R, IRAK1), clinical relevance of which is unknown
Absorption
Peak plasma concentration: 8.4 mg/mL
Peak plasma time: 4-5 hr
AUC: 95.6 mg·hr/L
Accumulation: 386%
Steady-state reached at 1 week
Distribution
Vd (steady-state): 229 L
Protein bound: 98.8%
Metabolism
Primarily metabolized by CYP3A4
Major circulating component and pharmacologic activity are mainly attributed to parent molecule
Major metabolites: M1 (9.6%) and M2 (10.5%), in human whole plasma of parent drug exposure
Elimination
Clearance: 2.09 L/hr
Half-life: 27.7 hr
Excretion: 87% (feces); 6% (urine; 0.12% [unchanged])
Administration
Oral Administration
May take with or without food
Swallow capsules whole; do not open, break, or chew
Missed dose: Take next prescribed dose at its scheduled time; do not take extra capsules to make up for missed dose
Storage
Store at room temperature (<30ºC [<86ºF])
Keep bottle tightly closed and protect from light
Store in original package; dispense in original package or in light-resistant container
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
