Pacritinib citrate, a selective inhibitor of Janus kinase (JAK) 2, mutant JAK2V617F, and fms-like tyrosine kinase (FLT) 3, is an antineoplastic agent.1, 6
Intermediate- or High-Risk Myelofibrosis
Pacritinib citrate is used for the treatment of intermediate- or high-risk primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera or post-essential thrombocythemia) in adults with a platelet count <50,000/mm3.1 This indication is approved under accelerated approval based on spleen volume reduction; continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1 Pacritinib is designated an orphan drug by FDA for this use.2
Efficacy and safety of pacritinib were evaluated in 3 randomized, open-label studies (2 phase 3 studies [PERSIST-1 and PERSIST-2] and one phase 2 dose-finding study [PAC203]) in patients with primary or secondary (post polycythemia vera or post-essential thrombocytopenia) myelofibrosis.3, 4, 5, 6 In these studies, patients had palpable splenomegaly ≤5 cm below the costal margin and a risk category of intermediate-1, intermediate-2, or high-risk disease based on the Dynamic International Prognostic Scoring System (DIPSS).3, 4, 5 Patients with prior JAK2 inhibitor (e.g., ruxolitinib) treatment were excluded from PERSIST-1, whereas prior treatment with 1 or 2 other JAK inhibitors was allowed in PERSIST-2; prior ruxolitinib intolerance or treatment failure was a requirement for enrollment in PAC203.3, 4, 5 Platelet count ≤100,000/mm3 was an enrollment criterion for PERSIST-2.4 Pacritinib was compared to best available therapy (BAT), defined as any physician selected treatment for myelofibrosis, symptom-directed treatment, or a watch-and-wait approach in both phase 3 studies (PERSIST-1, PERSIST-2).3, 4 The primary efficacy endpoint was the proportion of patients achieving ≥35% reduction from baseline in spleen volume (measured by MRI or CT), a clinically meaningful reduction and the endpoint used in prior myelofibrosis trials. 1, 3, 4, 5, 6
The median age of the efficacy population in PERSIST-2 was 68 years.1 The median baseline platelet count was 55,000/mm3; 45% of patients had a platelet count <50,000/mm3.1 The majority of patients had primary myelofibrosis (68%); 20% had post-polycythemia vera myelofibrosis and 12% had post-essential thrombocythemia myelofibrosis.1 Forty-six percent and 51% of patients in the pacritinib and BAT treatment arms, respectively, had received prior ruxolitinib therapy.1
PERSIST-2 was stopped prematurely when the FDA placed a clinical hold due to safety issues (e.g., high-grade bleeding and cardiac events) that emerged in PERSIST-1 (pacritinib dosage of 400 mg daily).3, 4 Following the clinical hold, PAC203 was designed to identify the recommended pacritinib dosage and to establish risk minimization measures.5 Based on the safety analysis of all 3 studies, the primary efficacy analysis was performed on only a subset of the patients enrolled in PERSIST-2.1 The subset included patients with a baseline platelet count <50,000/mm3 who were receiving pacritinib 200 mg twice a day or BAT; the most common approaches used in the BAT group were ruxolitinib (39%), watchful waiting (32%), and hydroxyurea (26%).1 Although a pacritinib dosage of 400 mg once daily also was evaluated, the manufacturer states that the safety of this dosage was not established and therefore is not an approved dosage regimen.1
The percentage of patients with baseline platelet counts <50,000/mm3 who achieved a ≥35% reduction in spleen volume from baseline was higher in the pacritinib 200 mg twice daily group compared with the BAT group (29% versus 3.1%).1 Pacritinib has not yet shown a compelling effect on a clinical outcome (e.g., a direct measure of how patients feel, function, or survival).6
Myelofibrosis drug treatment is based upon prognostic risk models.3105, 3106 Observation alone is advised for asymptomatic low-risk patients; for patients with higher-risk disease, allogeneic hematopoietic stem cell transplant (ASCT) is the preferred treatment.3105, 3106 In patients who are not candidates for transplant, JAK inhibitors (i.e., ruxolitinib, pacritinib, fedratinib) may be used to provide symptom-based management and improve quality of life.3105, 3106
The first JAK inhibitors approved for the treatment of myelofibrosis (e.g., ruxolitinib, fedratinib) are associated with significant risks of hematologic toxicities, which may limit the dose administered and preclude their use for some patients.3106 Pacritinib is an additional therapeutic option for patients with symptomatic myelofibrosis who have severe thrombocytopenia.3101, 3106 Specific indications and toxicity profiles of the currently available JAK2 inhibitors differ; treatment should be individualized.1, 3105, 3106
Pacritinib is administered orally without regard to food.1 Swallow pacritinib capsules whole; do not open, break, or chew the capsules.1
If a dose of pacritinib is missed, the prescribed dose should be taken at the next scheduled time; an additional dose should not be administered to replace the missed dose.1
Store pacritinib at room temperature, below 30°C.1 Store in the original packa keep bottle tightly closed.1 Protect from light.1
Dosage of pacritinib citrate is expressed in terms of pacritinib.1
Intermediate- or High-Risk Myelofibrosis
For the treatment of adults with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count <50,000/mm3, the recommended dosage of pacritinib is 200 mg twice daily.1
Dosage Modification for Toxicity
If adverse reactions occur during pacritinib therapy, temporary interruption of therapy, dosage reduction, and/or discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of pacritinib should be reduced as described in Table 1.1
Dose Reduction Level | Dosage Reduction after Recovery from Toxicity (Initial Dosage = 200 mg twice daily) |
|---|---|
First | 100 mg twice daily |
Second | 100 mg once daily |
Third | Discontinue drug |
The following table indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for certain adverse effects according to severity.1
Adverse Reaction and Severity | Modification |
|---|---|
Diarrhea | New onset: Initiate anti-diarrheal medications; encourage adequate oral hydration. Grade 3 or 4: Withhold therapy until diarrhea improves to grade 1 or lower or baseline; resume at last given dose. Intensify antidiarrheal medications and provide fluid replacement. If diarrhea recurs, withhold therapy until resolution to grade 1 or lower or baseline; resume therapy at 50% of the last dose once toxicity has resolved. Concomitant antidiarrheal treatment is required for patients resuming drug. |
Thrombocytopenia | Clinically significant worsening of thrombocytopenia that lasts >7 days: Withhold therapy until thrombocytopenia resolves; resume at 50% of the last dosage. If toxicity recurs, withhold therapy until thrombocytopenia resolves; resume at 50% of the last dosage. |
Hemorrhage | Moderate bleeding, intervention indicated: Withhold therapy until bleeding resolves; resume at same dosage. If hemorrhage recurs, withhold therapy until bleeding resolves; resume at 50% of the last dosage. Severe bleeding, transfusion, invasive intervention, or hospitalization indicated: Withhold therapy until bleeding resolves; resume at 50% of the last dosage. If bleeding recurs, discontinue therapy. Life-threatening bleeding, urgent intervention indicated: Discontinue therapy. |
Prolonged QT Interval | QTc prolongation >500 msec or >60 msec from baseline: Withhold therapy. If QTc prolongation resolves to ≤480 msec or baseline within 1 week, resume at same dosa if time to resolution is >1 week, resume therapy at a reduced dosage. |
The manufacturer states that no dosage adjustments are recommended in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.1
The recommended dosage in patients with severe hepatic impairment (Child-Pugh C) is 100 mg twice daily.1 The dosage may be increased to 200 mg twice daily if pacritinib is ineffective after 12 weeks and no safety concerns are present.1 Patients should be monitored for safety.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer states to avoid pacritinib in patients with an estimated glomerular filtration rate (eGFR), as estimated by the MDRD study equation, <30 mL/minute.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Serious (11%) and fatal (2%) hemorrhages have occurred in pacritinib-treated patients with platelet counts <100,000/mm3.1, 3, 4 Serious (13%) and fatal (2%) hemorrhages have occurred in pacritinib-treated patients with platelet counts <50,000/mm3.1 Grade ≥3 bleeding events (defined as requiring transfusion or invasive intervention) occurred in 15% of patients treated with pacritinib compared to 7% of patients treated in the control group.1 Due to hemorrhage, pacritinib dosage reductions, interruptions, and permanent discontinuations occurred in 3%, 3%, and 5% of patients, respectively.1
Avoid use of pacritinib in patients with active bleeding and hold the drug 7 days prior to any planned surgical or invasive procedures.1
Assess platelet counts periodically, as clinically indicated.1 Manage hemorrhage using treatment interruption and medical intervention.1
Pacritinib caused diarrhea in approximately 48% of patients compared to 15% of patients treated in the control group in a clinical trial.1 The median time to resolution in pacritinib-treated patients was 2 weeks.1 The incidence of reported diarrhea decreased over time with 41% of patients reporting diarrhea in the first 8 weeks of treatment, 15% in weeks 8 through 16, and 8% in weeks 16 through 24.1 Diarrhea resulted in treatment interruption in 3% of pacritinib-treated patients.1 1 Serious diarrhea adverse reactions occurred in 2% of patients treated with pacritinib compared to no such adverse reactions in patients in the control group.1 Severe diarrhea resulting in acute kidney injury and pacritinib discontinuation has been reported in the postmarketing setting.1
Control pre-existing diarrhea before starting pacritinib treatment.1 Manage diarrhea with antidiarrheal medications, fluid replacement, and dosage modification.1 Upon initiation of therapy, prescribe an anti-diarrheal medication and instruct patients to treat diarrhea promptly at the initial onset of symptoms after starting pacritinib.1 Interrupt or reduce pacritinib dosage in patients with significant diarrhea despite optimal supportive care.1
Pacritinib can cause worsening thrombocytopenia.1 Pacritinib dosage was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing moderate to severe thrombocytopenia (platelet count <100,000/mm3) and in 2% of patients with pre-existing severe thrombocytopenia (platelet count <50,000/mm3).1
Monitor platelet count prior to pacritinib treatment and as clinically indicated during treatment.1 Interrupt the drug in patients with clinically significant worsening of thrombocytopenia that lasts for >7 days.1 Restart pacritinib at 50% of the last given dosage once the toxicity has resolved.1 If toxicity recurs, hold pacritinib; resume the drug at 50% of the last given dosage once the toxicity has resolved.1
Pacritinib can cause prolongation of the QTc interval.1 QTc prolongation of >500 msec occurred in more pacritinib-treated patients than in patients in the control group (1.4% versus 1%).1 QTc increased from baseline by ≥60 msec in 1.9% of patients who received the drug versus 1% of those who received control.1 Adverse reactions related to QTc prolongation were reported for 3.8% of pacritinib-treated patients and 2% of control group patients.1 No cases of torsades de pointes were reported.1
Avoid use of pacritinib in patients with a baseline QTc of >480 msec.1 Avoid use of drugs with significant potential for QTc prolongation in combination with pacritinib.1 Correct hypokalemia prior to and during pacritinib treatment.1
Manage QTc prolongation with treatment interruption and electrolyte management.1
Major Adverse Cardiac Events (MACE)
Increased risk (compared to those treated with TNF blockers) of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke, has been reported in patients receiving other JAK inhibitors for the treatment of rheumatoid arthritis, a condition for which pacritinib is not indicated.1
The benefits and risks of pacritinib should be considered prior to initiating or continuing therapy, particularly in patients who are current or past smokers and in those with other cardiovascular risk factors.1 Patients receiving pacritinib should be advised to seek immediate medical attention if symptoms of serious cardiovascular events occur.1
An increased risk of thromboembolic events, including deep-vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, has been reported in patients receiving other JAK inhibitors for the treatment of rheumatoid arthritis, a condition for which pacritinib is not indicated.1
Promptly evaluate and treat any patients who develop symptoms of thrombosis during treatment with pacritinib.1
Another JAK inhibitor has increased the risk of lymphoma and other malignancies excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which pacritinib is not indicated.1 Patients who are current or past smokers are at additional increased risk.1
The risks and benefits of pacritinib should be considered prior to initiating therapy or when considering whether to continue the drug, particularly in patients with a known malignancy (other than a successfully treated NMSC), in those who develop a malignancy, and those who are current or past smokers.1
Another JAK inhibitor increased the risk of serious infections (compared to best available therapy) in patients with myeloproliferative neoplasms.1 Serious bacterial, mycobacterial, fungal, and viral infections may occur in patients treated with pacritinib.1 Resolve active serious infections prior to initiating therapy with pacritinib.1 Clinicians should observe patients receiving pacritinib for signs and symptoms of infection and should promptly initiate treatment.1 Employ active surveillance and prophylactic antibiotics according to clinical guidelines.1
Interactions with CYP3A4 Inhibitors or Inducers
Concomitant use of pacritinib with strong cytochrome P-450 (CYP) 3A4 inhibitors (e.g. clarithromycin) or inducers (e.g., rifampin) is contraindicated.1 Clinicians should monitor for increased adverse reactions related to pacritinib when given with moderate CYP3A4 inhibitors.1
Symptom Exacerbation Following Interruption or Discontinuation of Treatment
Following discontinuation of pacritinib, signs and symptoms from myeloproliferative neoplasms may flare including fever, respiratory distress, hypotension, disseminated intravascular coagulation, or multi-organ failure.1
If one or more of these signs and symptoms occur after pacritinib discontinuation, clinicians should evaluate for and treat any intercurrent illness and consider resumption of pacritinib.1 Patients should be advised not to interrupt or discontinue therapy without consulting their clinician.1 When discontinuing or interrupting therapy for reasons other than potentially life-threatening toxicities, clinicians should consider tapering pacritinib gradually rather than discontinuing abruptly.1
There are no available data on pacritinib use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1
Maternal toxicity and embryonic and fetal loss have been observed in animal studies when pacritinib was administered to pregnant mice or rabbits at dosages considerably lower than the recommended human dose.1 Advise pregnant women of the potential risk to a fetus.1 Consider the benefits and risks of pacritinib for the mother and possible risks to the fetus when prescribing pacritinib to a pregnant woman.1
There are no data on the presence of pacritinib in either human or animal milk, the effects on the breast-fed child, or the effects on milk production.1 Because of the potential for serious adverse reactions in the breast-fed child, advise patients that breast-feeding is not recommended during treatment with pacritinib, and for 2 weeks after the last dose.1
Females and Males of Reproductive Potential
When exposed to 3-times the recommended human dose, pacritinib reduced male mating and fertility indices in BALB/c mice.1 Pacritinib may impair male fertility in humans.1
Safety and efficacy of pacritinib have not been established in pediatric patients.1
Clinical studies of pacritinib did not include sufficient numbers of subjects ≥65 years of age to determine whether they respond differently from younger subjects.1
The effect of hepatic impairment on the pharmacokinetics of pacritinib was studied in subjects with normal or impaired hepatic function at a pacritinib dosage of 200 mg twice daily for 14 days.1 The geometric mean AUC of total pacritinib decreased in subjects with moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) compared to subjects with normal hepatic function due to reduced plasma protein binding.1 The geometric mean AUC of unbound pacritinib, the pharmacologically relevant parameter, was similar in healthy subjects compared to subjects with moderate hepatic impairment and increased by 23% in subjects with severe hepatic impairment.1
Administration of a single dose of pacritinib 400 mg to subjects with renal impairment, as estimated by the MDRD study equation, resulted in an approximately 30% increase in peak plasma concentration and AUC of pacritinib in subjects with estimated glomerular filtration rate (eGFR) 15 to 29 mL/minute and eGFR <15 mL/minute on hemodialysis compared to subjects with normal renal function (eGFR ≥90 mL/minute).1 Avoid use of pacritinib in patients with eGFR <30 mL/minute.1
Adverse effects reported in ≥20% of patients include diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema.1
In vitro studies indicate that pacritinib is metabolized mainly by cytochrome P-450 (CYP) isoenzyme 3A4.1
In vitro studies indicate pacritinib is a time dependent inhibitor of CYP1A2 and 3A4, and a reversible inhibitor of 3A4 and 2C19.1 The drug exhibits less potent inhibition of CYP1A2, 2B6, 2C8, 2C9, and 2D6.1, 6
In vitro studies indicate pacritinib is an inducer of CYP1A2 and 3A4.1
Pacritinib is not a substrate of breast cancer resistance protein (BCRP), multidrug resistance-associated protein (MRP) 2, organic anion-transporters (OAT) 1 and 3, organic anion-transporting polypeptides (OATP) 1B1 and 1B3, organic cation transporters (OCT) 1 and 2, or P-glycoprotein (P-gp).1
In vitro studies indicate pacritinib is an inhibitor of BCRP, OCT1, OCT2 (weak), and P-gp, but not an inhibitor of bile salt export pump (BSEP), MRP2, OAT1, or OAT3.1, 6
Drugs Affecting Hepatic Microsomal Enzymes
Because pacritinib is mainly metabolized by CYP3A4, strong inhibitors or inducers of this isoenzyme are expected to alter the drug's pharmacokinetics.1 Concomitant use of pacritinib with strong and moderate inhibitors of CYP3A4 has resulted in increased exposure of pacritinib, which may increase the risk of adverse reactions.1 The concomitant administration of pacritinib with strong CYP3A4 inhibitors is contraindicated.1 Patients administered pacritinib concomitantly with moderate CYP3A4 inhibitors should be monitored for adverse effects and potentially undergo a pacritinib dose modification.1
Concomitant use of pacritinib with strong inducers of CYP3A4 has resulted in decreased exposure of pacritinib, which may reduce efficacy.1 Concomitant use of strong CYP3A4 inducers is contraindicated.1
Drugs Affected by Hepatic Microsomal Enzymes
Concomitant administration of pacritinib with CYP1A2 substrates may increase the plasma concentrations of these substrates, which may elevate the risk of adverse reactions.1 Patients administered pacritinib with CYP1A2 substrates should be monitored more frequently for substrate related adverse reactions where minimal substrate concentration changes may lead to serious adverse reactions (unless otherwise recommended in the substrate prescribing information).1
Concomitant administration of pacritinib with CYP2C19 substrates may decrease the plasma concentrations of these substrates, which may reduce efficacy.1 Patients administered pacritinib with CYP2C19 substrates should be monitored more frequently for efficacy where minimal substrate concentration changes may lead to diminished efficacy (unless otherwise recommended in the substrate prescribing information).1 A dose adjustment of the CYP2C19 substrate may be necessary.1
Concomitant administration of pacritinib with CYP3A4 substrates may decrease the plasma concentrations of these substrates, which may reduce efficacy.1 Patients administered pacritinib with CYP3A4 substrates should be monitored more frequently for efficacy where minimal substrate concentration changes may lead to diminished efficacy (unless otherwise recommended in the substrate prescribing information).1 A dose adjustment of the CYP3A4 substrate may be necessary.1
Drugs Affecting or Affected by Transport Systems
Coadministration of pacritinib with P-gp or BCRP substrates may increase the plasma concentrations of these substrates, which may increase the risk of adverse reactions.1 Patients administered pacritinib with P-gp substrates should be monitored more frequently for substrate related adverse reactions where minimal substrate concentration changes may lead to serious adverse reactions (unless otherwise recommended in the substrate prescribing information).1
Patients administered pacritinib with BCRP substrates should be monitored more frequently for substrate related adverse reactions and consider dose reduction of the BCRP substrate per its prescribing information.1
Drugs Associated with QT Prolongation
Avoid use of drugs with significant potential for QTc prolongation in combination with pacritinib.1
Concomitant administration of pacritinib with hormonal contraceptives (except for intrauterine systems containing levonorgestrel) should be avoided due to the potential for reduced contraceptive efficacy.1
If contraception is desired during pacritinib therapy, an alternative contraceptive that is not affected by CYP3A4 inducers (e.g., an intrauterine system) or an additional nonhormonal contraceptive should be used.1 This alternative or additional nonhormonal contraceptive method should be continued for 30 days after the final dose of pacritinib.1
The exposure of pacritinib increases when used concomitantly with strong inhibitors of CYP3A4.1 Peak plasma concentrations and AUC increased 30 and 80%, respectively, when pacritinib was used concomitantly with clarithromycin 500 mg twice daily for 5 days.1 The manufacturer states exposure to pacritinib may be even higher following a longer treatment with clarithromycin that results in maximal CYP3A4 inhibition.1 Concomitant use of pacritinib with strong CYP3A4 inhibitors is contraindicated.1
Serum digoxin levels should be measured prior to initiating concurrent use with pacritinib, with continued monitoring of serum digoxin levels as recommended in the digoxin prescribing information.1
Patients administered pacritinib concomitantly with fluconazole should be monitored for adverse effects and potentially undergo a pacritinib dose modification.1 Concomitant doses of fluconazole >200 mg once daily with pacritinib have not been studied.1
The exposure of pacritinib decreases when used concomitantly with strong inducers of CYP3A4.1 Peak plasma concentrations and AUC decreased 51 and 87%, respectively, when pacritinib was used concomitantly with rifampin 600 mg once daily for 10 days.1 Concomitant use of pacritinib with strong CYP3A4 inducers is contraindicated.1
With concurrent administration of pacritinib and rosuvastatin, the dose of rosuvastatin should not exceed 20 mg once daily.1
Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, FMS-like tyrosine kinase 3 (FLT3), and interleukin 1 receptor associated kinase-1 (IRAK1), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.1 The drug is also an inhibitor of activin A receptor, type 1/activin receptor like-kinase 2 (ACVR1/ALK2).1 Myelofibrosis is often associated with dysregulated JAK2 signaling.1 Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and TYK2.1 At clinically relevant concentrations, pacritinib does not inhibit JAK1.1, 3 Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R), the clinical relevance of which is unknown.1, 3
Following administration of pacritinib 200 mg twice daily in patients with myelofibrosis, peak plasma concentrations occur in approximately 4 to 5 hours and steady-state is achieved within a week.1, 5 No significant effect on pharmacokinetics is observed when pacritinib 200 mg is administered with a high-fat meal.1 Plasma protein binding (primarily albumin and α1-acidic glycoprotein) of pacritinib is approximately 98.8%.1, 6
Pacritinib is predominantly metabolized by cytochrome P-450 (CYP) isoenzyme 3A4.1 Two major metabolites, M1 and M2, represent 9.6 and 10.5% of parent drug exposure, respectively, however pharmacologic activity is mainly attributed to the parent molecule.1, 6 Following oral administration of radiolabeled pacritinib, 6 and 87% of radioactivity was recovered in the urine and feces, respectively; no unchanged drug was excreted in feces and 0.12% of unchanged drug was excreted in urine.1, 6
The mean effective pacritinib half-life is 27.7 hours.1 The mean terminal half-life is approximately 33.5 hours (range 22.3 to 44.6 hours).6
No clinically significant differences in the pharmacokinetics of pacritinib were observed based on age, sex, body weight, or race.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Pacritinib is available only from designated specialty distributors and pharmacies. The manufacturer should be contacted for additional information. [Web]
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 100 mg (of pacritinib) | Vonjo® | CTI BioPharma |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Sobi Inc. Vonjo® (Pacritinib) ORAL prescribing information. Waltham, MA; 2026 Mar. [Web]
2. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD; 2018 Feb 14. From FDA website. Accessed 2025 Mar 31. [Web]
3. Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, Perkins A, Prasad R, Mayer J, Demeter J, Ganly P, Singer JW, Zhou H, Dean JP, Te Boekhorst PA, Nangalia J, Kiladjian JJ, Harrison CN. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-e236. Epub 2017 Mar 20. [PubMed 28336242]
4. Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):652-659. [PubMed 29522138]
5. Gerds AT, Savona MR, Scott BL, Talpaz M, Egyed M, Harrison CN, Yacoub A, Vannucchi A, Mead AJ, Kiladjian JJ, O'Sullivan J, García-Gutiérrez V, Bose P, Rampal RK, Miller CB, Palmer J, Oh ST, Buckley SA, Mould DR, Ito K, Tyavanagimatt S, Smith JA, Roman-Torres K, Devineni S, Craig AR, Mascarenhas JO. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv. 2020 Nov 24;4(22):5825-5835. [PubMed 33232476]
6. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 208712: Integrated review. From FDA website. [Web]
3101. Tremblay D, Mascarenhas J. Next Generation Therapeutics for the Treatment of Myelofibrosis. Cells. 2021; 10 [PubMed 33925695]
3105. Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021 Jan;96(1):145-162. Epub 2020 Dec 2. [PubMed 33197049]
3106. Reynolds SB, Pettit K. New approaches to tackle cytopenic myelofibrosis. Hematology Am Soc Hematol Educ Program. 2022 Dec 9;2022(1):235-244. [PubMed 36485113]