Pacritinib: Drug information

(For additional information see "Pacritinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Vonjo

Pharmacologic Category

Antineoplastic Agent, FLT3 Inhibitor;
Antineoplastic Agent, Janus Associated Kinase Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor;
Janus Associated Kinase Inhibitor;
Janus Kinase Inhibitor

Dosing: Adult

Note: Taper or discontinue other kinase inhibitors prior to initiating pacritinib. Avoid pacritinib in patients with active bleeding or a baseline QTc of >480 msec. Due to the risk of hemorrhage, withhold pacritinib 7 days prior to elective surgery (or invasive procedures); reinitiate pacritinib only after hemostasis is established. Control preexisting diarrhea prior to pacritinib initiation. Delay initiation of pacritinib therapy until active serious infections have resolved.

Myelofibrosis

Myelofibrosis: Oral: 200 mg twice daily (Ref).

Missed doses: If a pacritinib dose is missed, the next scheduled dose should be administered at the scheduled time. Do not administer additional capsules to make up for the missed dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: eGFR estimated by MDRD equation.

eGFR ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, C_max and AUC were similar in subjects with eGFR 30 to 89 mL/minute, compared to subjects with eGFR ≥90 mL/minute.

eGFR <30 mL/minute: Avoid pacritinib use.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.

Moderate (Child-Pugh class B) or severe (Child-Pugh class C) impairment: Avoid pacritinib use.

Dosing: Adjustment for Toxicity: Adult

**Recommended Pacritinib Dosage Reduction Levels for Adverse Reactions**
Initial (starting) dose	200 mg twice daily
First dose reduction	100 mg twice daily
Second dose reduction	100 mg once daily
Discontinue pacritinib if unable to tolerate 100 mg once daily.

**Recommended Pacritinib Dosage Modifications for Adverse Reactions**
Toxicity	Severity	Pacritinib dosage modification
^a Increase of ≥7 stools/day over baseline, or hospitalization indicated, or severe increase in ostomy output over baseline, or if limits self-care. ^b Increase of <4 stools/day over baseline or mild increase in ostomy output compared to baseline.
Hematologic toxicity
Thrombocytopenia	Clinically significant worsening of thrombocytopenia that lasts >7 days	Hold pacritinib until thrombocytopenia resolves, then resume with a 50% dose reduction. If thrombocytopenia recurs, hold pacritinib. Once thrombocytopenia resolves, resume pacritinib at 50% of the last administered dose.
Hemorrhage	Moderate bleeding; intervention indicated	Hold pacritinib until hemorrhage resolves, then resume at the last administered dose. If hemorrhage recurs, hold pacritinib. Once hemorrhage resolves, resume pacritinib at 50% of the last administered dose.
	Severe bleeding; transfusion, invasive intervention, or hospitalization indicated	Hold pacritinib until hemorrhage resolves, then resume with a 50% dose reduction. If bleeding recurs, discontinue pacritinib.
	Life-threatening bleeding; urgent intervention indicated	Discontinue pacritinib.
Nonhematologic toxicity
Cardiac	QTc prolongation >500 msec or >60 msec from baseline	Hold pacritinib. If QTc prolongation resolves to ≤480 msec or baseline within 1 week, resume pacritinib at the same dose. If time to resolution is >1 week, resume pacritinib at a reduced dose.
Diarrhea	New onset diarrhea	Initiate antidiarrheal medications and encourage adequate oral hydration.
Diarrhea	Grade 3 or 4^a	Hold pacritinib until diarrhea resolves to ≤ grade 1^b or baseline, then resume at the last administered dose. Intensify antidiarrheal regimen and provide fluid replacement. If diarrhea recurs, hold pacritinib until resolves to ≤ grade 1^b or baseline, then resume at 50% of the last administered dose. Concomitant antidiarrheal management is required when restarting pacritinib.
Infection	Serious	Evaluate and manage promptly for signs/symptoms of infection. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Cardiovascular: Peripheral edema (20%)

Gastrointestinal: Diarrhea (48%, grades ≥3: 4%), nausea (32%; grades ≥3: 1%), vomiting (19%)

Hematologic & oncologic: Anemia (24%; grades ≥3: 22%), hemorrhage (grades ≥3: 15%; major hemorrhage: 11% to 13%), thrombocytopenia (34%; grades ≥3: 32%)

Nervous system: Dizziness (15%)

Respiratory: Epistaxis (12%)

Miscellaneous: Fever (15%)

1% to 10%:

Cardiovascular: Heart failure (4%), prolonged QT interval on ECG (1% to 2%)

Dermatologic: Pruritus (10%)

Hematologic: Squamous cell carcinoma of skin (3%)

Respiratory: Cough (8%), dyspnea (10%), pneumonia (6%), upper respiratory tract infection (10%)

Frequency not defined:

Hematologic & oncologic: Neutropenia

Ophthalmic: Conjunctival hemorrhage

Contraindications

Concomitant use of strong CYP3A4 inhibitors or inducers.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac effects: QTc prolongation (>500 msec, or ≥60 msec increase from baseline) has been reported with pacritinib, although torsades de pointes has not. Another Janus-associated kinase (JAK) inhibitor has increased the risk of major adverse cardiac effects, including cardiovascular death, myocardial infarction, and stroke in patients with rheumatoid arthritis (pacritinib is not approved for the treatment of rheumatoid arthritis).

• GI toxicity: Almost one-half of patients receiving pacritinib in a clinical trial experienced diarrhea; the median time to resolution was 2 weeks. The incidence of diarrhea decreased over time, with over 40% of patients reporting diarrhea in the first 8 weeks of pacritinib, 15% in weeks 8 through 16, and <10% in weeks 16 through 24.

• Hematologic toxicity: Pacritinib administration may result in worsening thrombocytopenia; dose reduction due to decreasing platelet counts occurred in some patients with preexisting moderate and/or severe thrombocytopenia.

• Hemorrhage: Serious and fatal hemorrhages have occurred in patients with moderate to severe thrombocytopenia (platelet counts 50,000 to 100,000/mm³), as well as with severe thrombocytopenia (platelet counts <50,000/mm³). Grade 3 and higher bleeding events (eg, requiring transfusion or invasive intervention) have been reported.

• Infection: Serious bacterial, mycobacterial, fungal, and viral infections may occur in patients treated with JAK inhibitors, including pacritinib.

• Secondary malignancy: Another JAK inhibitor has been associated with an increased risk of lymphoma and other malignancies (excluding nonmelanoma skin cancer) in patients with rheumatoid arthritis (not an approved indication for pacritinib). Patients who are current or past smokers are at additional increased risk.

• Thrombosis: Another JAK inhibitor has increased the risk of thrombosis (eg, deep venous thrombosis, pulmonary embolism, and arterial thrombosis) in patients with rheumatoid arthritis (pacritinib is not approved for the treatment of rheumatoid arthritis).

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as citrate:

Vonjo: 100 mg [contains gelatin (bovine)]

Generic Equivalent Available: US

Pricing: US

Capsules (Vonjo Oral)

100 mg (per each): $258.81

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Prescribing and Access Restrictions

Vonjo is available through specialty pharmacies and distributors. Information regarding access is available from the manufacturer at https://www.ctiaccess.com/pdf/CTI_Access_Distribution_Information.pdf or 1-888-284-3678.

Administration: Adult

Oral: Administer with or without food. Swallow capsules whole; do not open, break, or chew.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Pacritinib may cause reproductive toxicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Myelofibrosis: Treatment of intermediate or high-risk primary or secondary (postpolycythemia vera or postessential thrombocythemia) myelofibrosis in adults with a platelet count <50,000/mm³.

Medication Safety Issues

Sound-alike/look-alike issues:

Pacritinib may be confused with afatinib, baricitinib, ceritinib, dasatinib, entrectinib, fedratinib, gilteritinib, pazopanib, ponatinib, ruxolitinib, tofacitinib, upadacitinib.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Pacritinib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Pacritinib may increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Pacritinib. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Pacritinib. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Pacritinib. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Pacritinib. Risk X: Avoid combination

CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Pacritinib may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

OCT1 Substrates (Clinically Relevant with Inhibitors): Pacritinib may increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Pacritinib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Pacritinib has the potential to impair male fertility (based on animal data).

Pregnancy Considerations

In animal reproduction studies, administration of pacritinib to pregnant mice or rabbits at doses lower than the recommended human dose produced maternal toxicity, embryo, and fetal loss.

Breastfeeding Considerations

It is not known if pacritinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during therapy and for 2 weeks after the last pacritinib dose.

Monitoring Parameters

CBC (including WBC differential and platelets) and coagulation parameters (prothrombin time, partial thromboplastin time, thrombin time, and INR) periodically, as clinically indicated. Obtain a baseline ECG prior to pacritinib initiation, and as clinically necessary. Monitor for signs/symptoms of hemorrhage/bleeding, diarrhea, QTc prolongation, major adverse cardiovascular events, thrombosis, and infection (use active surveillance and prophylactic antibiotics according to clinical guidelines). Monitor for secondary malignancies (particularly in patients with a known malignancy [other than a successfully treated non-melanoma skin cancer], and patients who are current or past smokers). Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Pacritinib is a kinase inhibitor with activity against wild-type Janus-associated kinase 2 (JAK2), mutated JAK2^(V617F), FMS-like tyrosine kinase 3 (FLT3), interleukin 1 receptor associated kinase-1 (IRAK1), and activin A receptor, type 1/activin receptor like-kinase 2 (ACVR1/ALK2). Pacritinib is selective for JAK2, with higher inhibitory activity for JAK2 (versus JAK3 and TYK2); pacritinib does not inhibit JAK1 at clinically relevant concentrations. Abnormal JAK2 activation is associated with myeloproliferative neoplasms, including myelofibrosis and polycythemia vera.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d (median): 229 L (range: 156 to 591 L).

Protein binding: ~99%.

Metabolism: Primarily hepatic via CYP3A4; forms 2 major metabolites (M1 and M2).

Half-life elimination: ~28 hours.

Time to peak: 4 to 5 hours.

Excretion: Feces: 87%; Urine: 6% (<1% as unchanged drug).

Clearance: ~2.1 L/hour.

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74:92.
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Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib versus best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818 [PubMed 29522138]
US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161. Updated September 2016. Accessed March 3, 2022.
Vonjo (pacritinib) [prescribing information]. Seattle, WA: CTI BioPharma Corp; August 2023.
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Pacritinib: Drug information