pacritinib (Rx)

Brand and Other Names:Vonjo
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Dosing & Uses

AdultPediatric

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

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Interactions

Interaction Checker

and pacritinib

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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             activity indicator 

            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)

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              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%)
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              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
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              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.

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              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])

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              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

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              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.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

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