Pacritinib is a Janus associated kinase-2 (JAK2) and FMS-like tyrosine kinase-3 (FLT3) inhibitor approved for the treatment of adult patients with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 X 109 cells/L. Concomitant use with strong CYP3A4 inhibitors or inducers is contraindicated. QT-interval prolongation has been reported with pacritinib therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Take pacritinib with or without food.
-Swallow capsules whole; do not open, break, or chew capsules.
-If a dose is missed, take the next dose at its scheduled time; do not take extra capsules to make up for the missed dose.
-Taper or discontinue other kinase inhibitors (according to their prescribing information) prior to starting pacritinib.
Thrombocytopenia (34%; grade 3 or higher, 32%) and anemia (24%; grade 3 or higher, 22%) occurred in patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial. Additionally, neutropenia that resulted in a dosage reduction was reported in 2% of patients. Monitor complete blood counts (CBC) prior to and as and as clinically indicated during treatment. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop worsening thrombocytopenia.
Peripheral edema was reported in 20% (grade 3 or higher, 1%) of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Cough (8%; grade 3 or higher, 2%) and dyspnea (10%) occurred in patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Dizziness was reported in 15% (grade 3 or higher, 1%) of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Fever was reported in 15% (grade 3 or higher, 1%) of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Pruritus was reported in 10% (grade 3 or higher, 2%) of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Epistaxis was reported in 12% (grade 3 or higher, 5%) of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
Conjunctival/ocular hemorrhage that resulted in a dosage reduction was reported in 2% of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
In patients with primary or secondary myelofibrosis who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial, serious bleeding occurred in 11% (grade 5, 2%) of patients who had a baseline platelet count of 100 X 109 cells/L or less (n = 106) and 13% (grade 5, 2%) of patients who had a baseline platelet count of 50 X 109 cells/L or less (n = 47). Grade or higher bleeding events (defined as requiring transfusion or invasive intervention) occurred in 15% of patients with myelofibrosis who received pacritinib; additionally, fatal cerebral hemorrhage and meningorrhagia were each reported in less than 1% of patients. Perform coagulation testing (e.g., prothrombin time, partial thromboplastin time, thrombin time, and INR) prior to starting pacritinib and as clinically indicated during treatment. Monitor patients for signs and symptom of bleeding. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop bleeding; medically manage bleeding episodes as appropriate.
Serious bacterial, mycobacterial, fungal, and viral infection may occur with pacritinib therapy. Monitor patients for signs and symptom of infection. Use active surveillance and prophylactic antibiotics according to clinical guidelines and treat infections promptly. Upper respiratory tract infection (10%) and pneumonia (6%) were reported in patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
QT prolongation has been reported with pacritinib therapy. Obtain a baseline electrocardiogram (ECG) prior to starting pacritinib and patients who develop QTc prolongation greater than 500 msec or greater than 60 msec from baseline as clinically indicated during treatment. Do not start pacritinib in patient with a baseline QTc greater than 480 milliseconds (msec). Correct serum electrolyte levels prior to and during pacritinib therapy as appropriate. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop QT prolongation. QTc prolongation was reported in 3.8% of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial. There were no reported cases of torsade de pointes. QTc prolongation greater than 500 msec (1.4%) or greater than 60 msec from baseline (1.9%) occurred in pacritinib-treated patients in this trial. Additionally, the maximum mean change in QTcF from baseline was 11 (90% CI, 5 to 17) msec in patients with myelofibrosis who received the recommended dosage of pacritinib in a 24-week electrophysiology study (n = 54).
Heart failure was reported in 4% of patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial.
New primary malignancy including squamous cell skin cancer (3%) and fatal acute myeloid leukemia (less than 1%) occurred in patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial. Consider the benefits and risks for continuing pacritinib therapy in patients who develop a malignancy during therapy.
Diarrhea has been reported with pacritinib therapy; most cases occur during the first 8 weeks. Advise patients to start anti-diarrheal medications and ensure adequate oral fluid intake for new onset diarrhea. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe diarrhea; intensify the anti-diarrheal treatment regimen and administer fluid replacement in these patients. Diarrhea (48%; grade 3 or higher, 4%), nausea (32%; grade 3 or higher, 1%), and vomiting (19%) occurred in patients with primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 106) in a randomized trial. The median time to diarrhea resolution was 2 weeks.
Worsening thrombocytopenia has been reported with pacritinib therapy in patients with baseline platelet count less 100 X 109 cells/L. Monitor complete blood counts (CBC) prior to and as clinically indicated during treatment. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop worsening thrombocytopenia.
Serious bleeding has been reported with pacritinib therapy in patients with thrombocytopenia (platelet count less 100 X 109 cells/L); some cases were fatal. Perform coagulation testing (e.g., prothrombin time, partial thromboplastin time, thrombin time, and INR) prior to starting pacritinib and as clinically indicated during treatment. Monitor patients for signs and symptoms of bleeding. Do not administer pacritinib in patients with active bleeding. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop bleeding; medically manage bleeding episodes as appropriate. Discontinue pacritinib 7 days prior to elective surgery or invasive procedures due to the risk of bleeding; restart therapy after hemostasis is achieved.
An increased risk of serious infection was reported in patients with myeloproliferative neoplasms who have received other JAK inhibitors. Do not start pacritinib therapy until the infection has resolved in patients who have an active serious infection. Monitor patients for signs and symptom of infection. Use active surveillance and prophylactic antibiotics according to clinical guidelines and treat infections promptly.
An increased risk of major adverse cardiac events (e.g., cardiovascular death, myocardial infarction, and stroke) was reported in patients with rheumatoid arthritis (off-label use) who have received other JAK inhibitors. Consider the benefits and risks for patients with cardiac disease or cardiovascular risk factors prior to starting pacritinib. Educate patients about the signs and symptoms of cardiovascular events and what to do if they occur.
Current or past tobacco smoking may increase the risk of major adverse cardiac events and/or developing a new primary malignancy. Consider the benefits and risks prior to starting or continuing pacritinib therapy in patients with a known malignancy (excluding a treated non-melanoma skin cancer), patients who develop a malignancy during therapy, and for patients with a current of past history of tobacco smoking.
QT prolongation was reported with pacritinib therapy; there were no cases of torsades de pointes. Obtain a baseline electrocardiogram prior to starting pacritinib and as clinically indicated during treatment. Do not start pacritinib in patient with a baseline QTc greater than 480 milliseconds (msec). Correct serum electrolyte levels (e.g., hypokalemia) prior to and during pacritinib therapy as appropriate. Avoid the concurrent use of other medications that have a significant potential to prolong the QT interval. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop QTc prolongation greater than 500 msec or greater than 60 msec from baseline. Use pacritinib with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause an electrolyte imbalance. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.
An increased risk of thrombosis (e.g., deep vein thrombosis, pulmonary embolism, and arterial thrombosis) was reported in patients with rheumatoid arthritis (off-label use) who have received other JAK inhibitors. Evaluate patients who develop symptoms of thrombosis promptly and treat as clinically appropriate.
Diarrhea was reported with pacritinib therapy; most cases occur during the first 8 weeks. Pre-existing diarrhea should be controlled prior to starting pacritinib. Advise patients to start anti-diarrheal medications and ensure adequate oral fluid intake for new onset diarrhea. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe diarrhea; intensify the anti-diarrheal treatment regimen and administer fluid replacement in these patients.
Use of pacritinib is not recommended in patients with moderate (Child-Pugh class B) or severe hepatic (Child-Pugh class C) impairment/hepatic disease.
Use of pacritinib is not recommended in patients with severe renal impairment (estimated glomerular filtration rate of less than 30 mL/min).
Consider the benefits versus the risk of therapy prior to administering pacritinib during pregnancy. There are no drug-related data to evaluate the use of pacritinib in pregnant women. Oral administration of pacritinib during organogenesis at doses (15, 30, or 60 mg/kg/day) that led to drug exposures 0.1 times (in mice) and 0.3 times (in rabbits) the exposures observed with the recommended human dose resulted in post implantation loss and an increased incidence of external malformations (cleft palate) in mice, fetal loss in rabbits, and reduced fetal body weights in both species. Increased gestation length and dystocia, lowered mean birth weights and neonatal survival, and transiently delayed startle response, learning, and memory development at weaning were observed in the offspring of pregnant mice who received pacritinib 250 mg/kg/day starting at implantation through lactation.
Impaired fertility/infertility may occur in male patients who receive pacritinib, based on data from a fertility study in mice.
It is not known if pacritinib is secreted in human milk or if it has effects on the breast-fed child or on milk production. Because there is a potential for serious adverse reactions in a nursing child, breast-feeding is not recommended during pacritinib therapy and for 2 weeks after the last dose.
For the treatment of myelofibrosis:
-for the treatment of intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis in patients with a platelet count below 50 X 109 cells/L:
Oral dosage:
Adults: 200 mg orally twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. If applicable, taper or discontinue other kinase inhibitors (according to their prescribing information) prior to starting pacritinib. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe toxicity. The rates of patients achieving 35% or more spleen volume reduction (SVR; 22% vs. 3%; p = 0.001) and 50% or more reduction in total symptom score (TSS; 32% vs. 14%; p = 0.01) at week 24 were significantly higher in patients (median age, 67 years; range, 39 to 85 years) with intermediate- or high-risk primary or secondary myelofibrosis and a baseline platelet count of 100 X 109 cells/L or less who received pacritinib 200 mg PO twice daily (n = 74) compared with physician choice best available therapy (n = 72) in a multicenter, randomized (1:1:1), 3-arm, phase 3 (PERSIST-2) trial. In patients who had a baseline platelet count of 50 X 109 cells/L or less, a 35% or more SVR was achieved in 29% of patients in the pacritinib arm (n = 31) and 3% of patients in the best available therapy arm (n = 32); a 50% or more reduction in TSS occurred in 23% and 13% of patients, respectively. Additionally, patients with a baseline platelet count of 50 X 109 cells/L or less had a median reduction in spleen volume of 27.3% in the pacritinib 200 mg PO twice daily arm compared with 0.9% in the best available therapy arm. The most common best available therapy given in patients with a baseline platelet count of 50 X 109 cells/L or less consisted of ruxolitinib (39%), no treatment/watchful waiting (32%), and hydroxyurea (26%). Of note, 50% of patients in the best available therapy arm crossed-over to the pacritinib arm.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Dosage Reduction Recommendations:
First dosage reduction: 100 mg PO twice daily.
Second dosage reduction: 100 mg PO once daily; permanently discontinue therapy in patients unable to tolerate 100 mg PO once daily.
Bleeding
Moderate bleeding (intervention indicated): Hold therapy until toxicity resolves; resume pacritinib at the last given dosage. If the toxicity recurs, hold therapy until the toxicity resolves and then resume pacritinib at a reduced dose.
Severe bleeding (transfusion, invasive intervention, or hospitalization indicated): Hold therapy until toxicity resolves; resume pacritinib at a reduced dose. If the toxicity recurs, discontinue pacritinib therapy.
Life-threatening bleeding (urgent intervention indicated): Discontinue pacritinib therapy.
Diarrhea
New onset diarrhea: Start anti-diarrheal medications and ensure adequate oral hydration.
Grade 3 or 4 diarrhea (e.g., increase of at least 7 stools per day over baseline, hospitalization indicated, severe increase in ostomy output over baseline, or if limiting self-care): Hold therapy until the toxicity resolves to baseline or grade 1 or less (e.g., increase of less than 4 stools per day over baseline or mild increase in ostomy output compared to baseline), intensify the anti-diarrheal treatment regimen, and administer fluid replacement. Resume pacritinib at the last given dosage. If the toxicity recurs, hold therapy until the toxicity resolves to baseline or grade 1 or less and then resume pacritinib at a reduced dose; continue concomitant antidiarrheal treatment.
QT Prolongation
QTc prolongation greater than 500 milliseconds (msec) or greater than 60 msec from baseline: Hold therapy. If QTc prolongation resolves to baseline or 480 msec or less within 1 week, restart pacritinib at the last given dosage. If QTc prolongation does not resolve within 1 week, restart pacritinib at a reduced dose.
Thrombocytopenia
Clinically significant worsening of thrombocytopenia that lasts more than 7 days: Hold therapy until toxicity resolves; resume pacritinib at a reduced dose. If the toxicity recurs, repeat this management.
Maximum Dosage Limits:
-Adults
400 mg/day PO.
-Geriatric
400 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild hepatic impairment (Child-Pugh class A): Specific guidelines for dosage adjustments in mild hepatic impairment are not available; it appears that no dosage adjustments are needed.
Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment: Use not recommended.
Patients with Renal Impairment Dosing
Estimated glomerular filtration rate (eGFR) of 30 to 89 mL/min: Specific guidelines for dosage adjustments in mild to moderate renal impairment are not available; it appears that no dosage adjustments are needed.
eGFR less than 30 mL/min: Use not recommended.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pacritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate; pacritinib is a BCRP and P-gp inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with pacritinib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Pacritinib is a weak inhibitor of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like pacritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pacritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Contraindicated) Concurrent use of pacritinib with adagrasib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use also increases the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Both medications have been associated with QT interval prolongation.
Afatinib: (Moderate) If the concomitant use of pacritinib and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of pacritinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-gp substrate and pacritinib is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If pacritinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alfuzosin: (Major) Concomitant use of pacritinib and alfuzosin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alpelisib: (Major) Avoid coadministration of alpelisib with pacritinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pacritinib is a BCRP inhibitor.
Alprazolam: (Major) Avoid coadministration of alprazolam and pacritinib due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with pacritinib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Amiodarone: (Major) Concomitant use of amiodarone and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Concomitant use of pacritinib and amisulpride increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Amobarbital: (Major) Avoid concurrent use of pacritinib with amobarbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and amobarbital is a moderate CYP3A inducer.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concurrent use of pacritinib with clarithromycin is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin 500 mg twice a day for 5 days increased pacritinib exposure by 80%.
Anagrelide: (Major) Concomitant use of pacritinib and anagrelide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Apalutamide: (Contraindicated) Concurrent use of pacritinib with apalutamide is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Apomorphine: (Major) Concomitant use of pacritinib and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aprepitant, Fosaprepitant: (Major) Avoid concurrent use of pacritinib with a multi-day regimen of oral aprepitant due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate. Aprepitant is a moderate CYP3A inhibitor when administered as a 3-day oral regimen; single oral and IV doses of aprepitant/fosaprepitant have not been shown to alter concentrations of CYP3A4 substrates.
Aripiprazole: (Major) Avoid concomitant use of aripiprazole and pacritinib, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary, patients receiving both a CYP2D6 inhibitor plus pacritinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and risk for QT prolongation and TdP. Aripiprazole is a CYP3A and CYP2D6 substrate, pacritinib is a weak CYP3A inhibitor, and both medications have been associated with QT prolongation.
Arsenic Trioxide: (Major) Concomitant use of pacritinib and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) Concomitant use of pacritinib and artemether increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of pacritinib and artemether; lumefantrine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Asenapine: (Major) Concomitant use of pacritinib and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concurrent use of pacritinib with butalbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and butalbital is a moderate CYP3A inducer. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like pacritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pacritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Contraindicated) Concurrent use of pacritinib with atazanavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Contraindicated) Concurrent use of pacritinib with atazanavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Atomoxetine: (Major) Concomitant use of pacritinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Azithromycin: (Major) Concomitant use of pacritinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Concomitant use of pacritinib and bedaquiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bendamustine: (Major) Consider the use of an alternative therapy if pacritinib treatment is needed in patients receiving bendamustine. Concomitant use of pacritinib may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Consider a reduced dose of benzhydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of benzhydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to benzhydrocodone.
Berotralstat: (Major) Avoid concurrent use of pacritinib with berotralstat due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving pacritinib. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving pacritinib. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate; pacritinib is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3-fold.
Bexarotene: (Major) Avoid concurrent use of pacritinib with bexarotene due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of pacritinib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of pacritinib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bosentan: (Major) Avoid concurrent use of pacritinib with bosentan due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and bosentan is a moderate CYP3A inducer.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Buprenorphine: (Major) Concomitant use of buprenorphine and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase buprenorphine exposure resulting in increased or prolonged opioid effects, particularly when pacritinib is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concurrent use is necessary, consider a dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping pacritinib, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If pacritinib is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Buprenorphine is a substrate of CYP3A4 and pacritinib is a CYP3A4 inhibitor.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase buprenorphine exposure resulting in increased or prolonged opioid effects, particularly when pacritinib is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concurrent use is necessary, consider a dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping pacritinib, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If pacritinib is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Buprenorphine is a substrate of CYP3A4 and pacritinib is a CYP3A4 inhibitor.
Butalbital; Acetaminophen: (Major) Avoid concurrent use of pacritinib with butalbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and butalbital is a moderate CYP3A inducer.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concurrent use of pacritinib with butalbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and butalbital is a moderate CYP3A inducer. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concurrent use of pacritinib with butalbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and butalbital is a moderate CYP3A inducer. (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concurrent use of pacritinib with butalbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and butalbital is a moderate CYP3A inducer. (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Cabotegravir; Rilpivirine: (Major) Concomitant use of pacritinib and rilpivirine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Caffeine; Sodium Benzoate: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Carbamazepine: (Contraindicated) Concurrent use of pacritinib with carbamazepine is contraindicated due to decreased pacritinib exposure which may impair efficacy. Carbamazepine exposure may also increase. Pacritinib is a CYP3A substrate and weak inhibitor. Carbamazepine is a strong CYP3A inducer and a CYP3A4 substrate. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with pacritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of pacritinib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Cenobamate: (Major) Avoid concurrent use of pacritinib with cenobamate due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and cenobamate is a moderate CYP3A inducer.
Ceritinib: (Contraindicated) Concurrent use of pacritinib with ceritinib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Chloramphenicol: (Contraindicated) Concurrent use of pacritinib with chloramphenicol is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Chloroquine: (Major) Concomitant use of pacritinib and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpromazine: (Major) Concomitant use of pacritinib and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ciprofloxacin: (Major) Avoid concurrent use of pacritinib with ciprofloxacin due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor.
Cisapride: (Contraindicated) Avoid concomitant use of cisapride and pacritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of pacritinib and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Contraindicated) Concurrent use of pacritinib with clarithromycin is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin 500 mg twice a day for 5 days increased pacritinib exposure by 80%.
Clofazimine: (Major) Concomitant use of pacritinib and clofazimine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clomipramine: (Moderate) Monitor for an increase in clomipramine-related adverse reactions if concomitant use of pacritinib is necessary; a clomipramine dose reduction may be necessary. Concomitant use may increase clomipramine exposure; clomipramine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Clozapine: (Major) Concomitant use of clozapine and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase clozapine exposure and the risk for other clozapine-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concurrent use is necessary, consider a dosage reduction of clozapine and monitor for adverse reactions. If pacritinib is discontinued, monitor for lack of clozapine effect and increase dose if necessary. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Clozapine is a substrate of CYP3A4 and CYP1A2; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Cobicistat: (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with pacritinib is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-gp substrate; pacritinib is a P-gp inhibitor.
Codeine: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of pacritinib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Codeine; Promethazine: (Major) Concomitant use of pacritinib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of codeine with pacritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of pacritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If pacritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Pacritinib is a weak inhibitor of CYP3A.
Colchicine: (Major) Avoid concomitant use of colchicine and pacritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Conivaptan: (Major) Avoid concurrent use of pacritinib with conivaptan due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Contraindicated) Concurrent use of pacritinib with crizotinib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and crizotinib is a strong CYP3A inhibitor.
Cyclosporine: (Major) Avoid concurrent use of pacritinib with cyclosporine due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Cyclosporine exposure may also increase. Pacritinib is a CYP3A substrate, a weak CYP3A4 inhibitor, and a P-gp inhibitor; cyclosporine is a moderate CYP3A inhibitor, a CYP3A4 substrate, and a P-gp substrate. The manufacturer of cyclosporine recommends closely monitoring cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with a weak CYP3A4 inhibitor is necessary.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with pacritinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and pacritinib is a P-gp inhibitor.
Dabrafenib: (Major) Avoid concurrent use of pacritinib with dabrafenib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Danazol: (Major) Avoid concurrent use of pacritinib with danazol due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Darunavir: (Contraindicated) Concurrent use of pacritinib with darunavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Contraindicated) Concurrent use of pacritinib with darunavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Contraindicated) Concurrent use of pacritinib with darunavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Dasatinib: (Major) Concomitant use of pacritinib and dasatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Degarelix: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., degarelix) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Delavirdine: (Contraindicated) Concurrent use of pacritinib with delavirdine is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Desflurane: (Major) Concomitant use of pacritinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Major) Concomitant use of pacritinib and deutetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) Concomitant use of pacritinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with pacritinib is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A substrate and pacritinib is a CYP3A inhibitor.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing pacritinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and pacritinib is a P-gp inhibitor.
Diltiazem: (Major) Avoid concurrent use of pacritinib with diltiazem due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor.
Disopyramide: (Major) Concomitant use of disopyramide and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase disopyramide exposure and the risk for other disopyramide-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Disopyramide is a substrate of CYP3A4 and pacritinib is a weak CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A4 inhibitors.
Dofetilide: (Major) Concomitant use of dofetilide and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase dofetilide exposure and the risk for other dofetilide-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Pacritinib is a weak CYP3A4 inhibitor. Dofetilide is a minor CYP3A4 substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A4 inhibitors may increase the risk of TdP.
Dolasetron: (Major) Concomitant use of pacritinib and dolasetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pacritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate; pacritinib is a BCRP and P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pacritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate; pacritinib is a BCRP and P-gp inhibitor.
Dolutegravir; Rilpivirine: (Major) Concomitant use of pacritinib and rilpivirine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pacritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate; pacritinib is a BCRP and P-gp inhibitor.
Donepezil: (Major) Concomitant use of pacritinib and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Donepezil; Memantine: (Major) Concomitant use of pacritinib and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Doxorubicin Liposomal: (Major) Avoid coadministration of pacritinib with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and pacritinib is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of pacritinib with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and pacritinib is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Contraindicated) Avoid concomitant use of dronedarone and pacritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase pacritinib exposure and the risk for other pacritinib-related adverse effects; pacritinib is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
Droperidol: (Major) Concomitant use of pacritinib and droperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Duvelisib: (Major) Avoid concurrent use of pacritinib with duvelisib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of pacritinib is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and pacritinib is a P-gp inhibitor. An edoxaban dose reduction to 30 mg PO once daily is recommended by the manufacturer for use with certain P-gp inhibitors; however, because use of concomitant P-gp inhibitors was limited to only certain drugs that inhibit P-gp in DVT/PE clinical trials, clinicians should use professional judgment and guide edoxaban dose adjustments based on patient response if coadministered with pacritinib. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of pacritinib. Increased concentrations of edoxaban may occur during concomitant use of pacritinib; monitor for increased adverse effects of edoxaban.
Efavirenz: (Major) Avoid concurrent use of pacritinib with efavirenz due to the risk of decreased pacritinib exposure which may impair efficacy. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of pacritinib with efavirenz due to the risk of decreased pacritinib exposure which may impair efficacy. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of pacritinib with efavirenz due to the risk of decreased pacritinib exposure which may impair efficacy. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Elagolix: (Major) Avoid concurrent use of pacritinib with elagolix due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of pacritinib with elagolix due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Eliglustat: (Major) Concomitant use of eliglustat and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase eliglustat exposure and the risk for other eliglustat-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Coadministration of eliglustat and pacritinib is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Pacritinib is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of pacritinib with cobicistat is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concomitant use of pacritinib and rilpivirine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of pacritinib and rilpivirine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Encorafenib: (Contraindicated) Concurrent use of pacritinib with encorafenib is contraindicated due to decreased pacritinib exposure which may impair efficacy. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate, encorafenib is a strong CYP3A inducer, and both medications have been associated with QT/QTc prolongation. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Entrectinib: (Major) Concomitant use of pacritinib and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Enzalutamide: (Contraindicated) Concurrent use of pacritinib with enzalutamide is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Ergotamine; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Eribulin: (Major) Concomitant use of pacritinib and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin: (Major) Avoid concurrent use of pacritinib with erythromycin due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Escitalopram: (Major) Concomitant use of pacritinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Eslicarbazepine: (Major) Avoid concurrent use of pacritinib with eslicarbazepine due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Etrasimod: (Major) Concomitant use of etrasimod and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Etravirine: (Major) Avoid concurrent use of pacritinib with etravirine due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with pacritinib is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Fedratinib: (Major) Avoid concurrent use of pacritinib with fedratinib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Felodipine: (Moderate) Concurrent use of felodipine and pacritinib should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A substrate and pacritinib is a weak CYP3A inhibitor. Concurrent use of another weak CYP3A inhibitor increased felodipine AUC and Cmax by approximately 50%.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If pacritinib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Fexinidazole: (Major) Concomitant use of pacritinib and fexinidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and pacritinib is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; pacritinib is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or pacritinib; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Fingolimod: (Major) Concomitant use of pacritinib and fingolimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flecainide: (Major) Concomitant use of pacritinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including pacritinib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Fluconazole: (Contraindicated) Concurrent use of pacritinib with fluconazole is contraindicated due to an increased risk for QT/QTc prolongation and torsade de pointes (TdP). Increased pacritinib exposure may also occur which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and fluconazole is a mosderate CYP3A inhibitor.
Fluoxetine: (Major) Concomitant use of pacritinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and fluphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Fluvoxamine: (Major) Avoid concurrent use of pacritinib with fluvoxamine due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor.
Fosamprenavir: (Major) Avoid concurrent use of pacritinib with fosamprenavir due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Foscarnet: (Major) Concomitant use of pacritinib and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Contraindicated) Concurrent use of pacritinib with fosphenytoin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Fostemsavir: (Major) Concomitant use of pacritinib and fostemsavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gemifloxacin: (Major) Concomitant use of pacritinib and gemifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Gemtuzumab Ozogamicin: (Major) Concomitant use of pacritinib and gemtuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Gilteritinib: (Major) Concomitant use of pacritinib and gilteritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Glasdegib: (Major) Concomitant use of pacritinib and glasdegib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and pacritinib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-gp and BCRP; pacritinib is a P-gp and BCRP inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of pacritinib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and BCRP; pacritinib is a P-gp and BCRP inhibitor.
Goserelin: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., goserelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Granisetron: (Major) Concomitant use of pacritinib and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Grapefruit juice: (Contraindicated) Advise patients to avoid grapefruit and grapefruit juice during pacritinib treatment due to the risk of increased pacritinib exposure and adverse reactions. Pacritinib is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Halogenated Anesthetics: (Major) Concomitant use of pacritinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Major) Concomitant use of pacritinib and haloperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Histrelin: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., histrelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like pacritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If pacritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxychloroquine: (Major) Concomitant use of pacritinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of pacritinib and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like pacritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pacritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ibutilide: (Major) Concomitant use of pacritinib and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Idelalisib: (Contraindicated) Concurrent use of pacritinib with idelalisib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Iloperidone: (Major) Concomitant use of pacritinib and iloperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Imatinib: (Major) Avoid concurrent use of pacritinib with imatinib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Indinavir: (Contraindicated) Concurrent use of pacritinib with indinavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor.
Inotuzumab Ozogamicin: (Major) Concomitant use of pacritinib and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isavuconazonium: (Major) Avoid concurrent use of pacritinib with isavuconazonium due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Isoflurane: (Major) Concomitant use of pacritinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concurrent use of pacritinib with rifampin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased pacritinib exposure by 87%.
Isoniazid, INH; Rifampin: (Contraindicated) Concurrent use of pacritinib with rifampin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased pacritinib exposure by 87%.
Isradipine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with pacritinib is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Itraconazole: (Contraindicated) Concurrent use of pacritinib with itraconazole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor.
Ivosidenib: (Major) Concomitant use of pacritinib and ivosidenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of pacritinib is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Ketoconazole: (Contraindicated) Concurrent use of pacritinib with ketoconazole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concurrent use of pacritinib with clarithromycin is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin 500 mg twice a day for 5 days increased pacritinib exposure by 80%.
Lapatinib: (Major) Concomitant use of lapatinib and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Lapatinib exposure may also increase, increasing the risk of adverse reactions. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for an increase in lapatinib-related adverse reactions. Lapatinib is a P-gp substrate and pacritinib is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Major) Avoid concurrent use of pacritinib with lefamulin due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Lefamulin exposure may also increase in patients taking the oral dosage form, increasing the risk of adverse reactions; lefamulin exposure should not increase if pacritinib is given with the IV formulation. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and P-gp inhibitor; lefamulin is a moderate CYP3A inhibitor and a P-gp substrate.
Lemborexant: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with pacritinib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; pacritinib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lenacapavir: (Major) Avoid concurrent use of pacritinib with lenacapavir due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Lenvatinib: (Major) Concomitant use of pacritinib and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letermovir: (Major) Avoid concurrent use of pacritinib with letermovir due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concurrent use of pacritinib with combination letermovir/cyclosporine is contraindicated. Pacritinib is a CYP3A substrate. Letermovir is a moderate CYP3A inhibitor and combination letermovir/cyclosporine is a strong CYP3A inhibitor.
Leuprolide: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide; Norethindrone: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levofloxacin: (Major) Concomitant use of pacritinib and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Concurrent use of pacritinib with ketoconazole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Lithium: (Major) Concomitant use of pacritinib and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Concomitant use of pacritinib and lofexidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lomitapide: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with pacritinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Pacritinib is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Lonafarnib: (Contraindicated) Concurrent use of pacritinib with lonafarnib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Lonafarnib exposure may also increase, increasing the risk for adverse reactions. Pacritinib is a CYP3A substrate and a weak CYP3A4 inhibitor. Lonafarnib is a sensitive CYP3A4 substrate and a strong CYP3A inhibitor. The manufacturer of lonafarnib recommends a dose reduction when given concurrently with weak CYP3A4 inhibitors.
Loperamide: (Major) Concomitant use of loperamide and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) Concurrent use of pacritinib with lopinavir; ritonavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and lopinavir; ritonavir is a strong CYP3A inhibitor. (Contraindicated) Concurrent use of pacritinib with ritonavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Lorlatinib: (Major) Avoid concurrent use of pacritinib with lorlatinib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Lumacaftor; Ivacaftor: (Contraindicated) Concurrent use of pacritinib with lumacaftor; ivacaftor is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Lumacaftor; Ivacaftor: (Contraindicated) Concurrent use of pacritinib with lumacaftor; ivacaftor is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Macimorelin: (Major) Concomitant use of pacritinib and macimorelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Maprotiline: (Major) Concomitant use of pacritinib and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with pacritinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; pacritinib is a P-gp inhibitor.
Mavacamten: (Major) Avoid concurrent use of pacritinib with mavacamten due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Mefloquine: (Major) Concomitant use of pacritinib and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Mefloquine exposure may also increase, increasing the risk of adverse reactions. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Mefloquine is a CYP3A4 and P-gp substrate; pacritinib is a weak CYP3A4 inhibitor and a P-gp inhibitor.
Meperidine: (Moderate) Consider a reduced dose of meperidine with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, meperidine plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to meperidine. Meperidine is a substrate of CYP3A and pacritinib is a weak CYP3A inhibitor. Concomitant use with pacritinib can increase meperidine exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of meperidine.
Methadone: (Major) Concomitant use of pacritinib and methadone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Methadone exposure may also increase. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation. If pacritinib is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A4; pacritinib is a CYP3A4 inhibitor. Concomitant use with pacritinib can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Methohexital: (Major) Avoid concurrent use of pacritinib with methohexital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and methohexital is a moderate CYP3A inducer.
Metronidazole: (Major) Concomitant use of pacritinib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mexiletine: (Moderate) Monitor for increased toxicity of mexiletine if coadministered with pacritinib. Coadministration may increase serum concentrations of mexiletine. Mexiletine is a CYP1A2 substrate and pacritinib is a weak CYP1A2 inhibitor.
Midazolam: (Moderate) Use caution when midazolam is coadministered with pacritinib. Concurrent use may increase midazolam exposure leading to prolonged sedation. Midazolam is a sensitive CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Midostaurin: (Major) Concomitant use of pacritinib and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Contraindicated) Concurrent use of pacritinib with mifepristone is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Mirtazapine: (Major) Concomitant use of pacritinib and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Contraindicated) Concurrent use of pacritinib with mitotane is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and mitotane is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Mobocertinib: (Major) Concomitant use of pacritinib and mobocertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with pacritinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with pacritinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Moxifloxacin: (Major) Concomitant use of pacritinib and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nafcillin: (Major) Avoid concurrent use of pacritinib with nafcillin due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and nafcillin is a moderate CYP3A inducer.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with pacritinib. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a P-gp substrate; pacritinib is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and pacritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and pacritinib is a weak CYP3A and P-gp inhibitor.
Nefazodone: (Contraindicated) Concurrent use of pacritinib with nefazodone is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Contraindicated) Concurrent use of pacritinib with nelfinavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid concurrent use of pacritinib with netupitant due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nilotinib: (Major) Avoid concurrent use of pacritinib with nilotinib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nimodipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with pacritinib is necessary. Concurrent use may increase nimodipine exposure. Nimodipine is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Nintedanib: (Moderate) Monitor for nintedanib-related adverse reactions if concomitant use of pacritinib is necessary. Concomitant use may increase nintedanib exposure. Nintedanib is a P-gp substrate, and a minor substrate of CYP3A and pacritinib is a dual P-gp and CYP3A inhibitor. Coadministration with another dual P-gp and CYP3A inhibitor increased nintedanib AUC by 60%.
Nirmatrelvir; Ritonavir: (Contraindicated) Concurrent use of pacritinib with ritonavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Nirogacestat: (Major) Avoid concurrent use of pacritinib with nirogacestat due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with pacritinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and pacritinib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Ofloxacin: (Major) Concomitant use of pacritinib and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Concomitant use of pacritinib and olanzapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Fluoxetine: (Major) Concomitant use of pacritinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of pacritinib and olanzapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Concomitant use of pacritinib and olanzapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concurrent use of pacritinib with rifabutin due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Ondansetron: (Major) Concomitant use of pacritinib and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Concomitant use of pacritinib and osilodrostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of pacritinib and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of pacritinib and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like pacritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pacritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ozanimod: (Major) Concomitant use of pacritinib and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Paliperidone: (Major) Concomitant use of pacritinib and paliperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Panobinostat: (Major) Concomitant use of pacritinib and panobinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pasireotide: (Major) Concomitant use of pacritinib and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Avoid coadministration of pazopanib and pacritinib due to the potential for increased pazopanib exposure. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). Pazopanib is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
Pentamidine: (Major) Concomitant use of pacritinib and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perphenazine: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and perphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Perphenazine; Amitriptyline: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and perphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Pexidartinib: (Major) Avoid concurrent use of pacritinib with pexidartinib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Phenobarbital: (Contraindicated) Concurrent use of pacritinib with phenobarbital is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Concurrent use of pacritinib with phenobarbital is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Phenytoin: (Contraindicated) Concurrent use of pacritinib with phenytoin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and phenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Pimavanserin: (Major) Concomitant use of pacritinib and pimavanserin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of pimozide and pacritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase pimozide exposure and the risk for other pimozide-related adverse effects. Pimozide is a CYP3A and CYP1A2 substrate; pazopanib is a weak CYP3A and CYP1A2 inhibitor.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Pitolisant: (Major) Concomitant use of pacritinib and pitolisant increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) Concomitant use of pacritinib and ponesimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ponesimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Posaconazole: (Contraindicated) Concurrent use of pacritinib with posacaonzole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and posacaonzole is a strong CYP3A inhibitor.
Pralsetinib: (Major) Avoid concomitant use of pacritinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Primaquine: (Major) Concomitant use of pacritinib and primaquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Primidone: (Contraindicated) Concurrent use of pacritinib with primidone is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and primidone is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and pacritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Procainamide: (Major) Concomitant use of pacritinib and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and prochlorperazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Promethazine: (Major) Concomitant use of pacritinib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of pacritinib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of pacritinib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase propafenone exposure and the risk for other propafenone-related adverse effects. Avoid simultaneous use of propafenone and pacritinib with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Propafenone is a substrate of CYP3A4, CYP2D6, and CYP1A2; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Quetiapine: (Major) Concomitant use of pacritinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Concomitant use of pacritinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinine: (Major) Concomitant use of pacritinib and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quizartinib: (Major) Concomitant use of quizartinib and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Concomitant use of ranolazine and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase ranolazine exposure and the risk for other ranolazine-related adverse effects; a dose adjustment of ranolazine may be necessary. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ranolazine is a substrate of P-gp and pacritinib is a P-gp inhibitor.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and pacritinib. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; pacritinib is a weak CYP1A2 inhibitor. When administered with a strong CYP1A2 inhibitor, the AUC of rasagiline was increased by 83%.
Relugolix: (Major) Avoid concomitant use of relugolix and pacritinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, administer pacritinib at least 6 hours after relugolix and monitor for adverse reactions. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Relugolix is a P-gp substrate and pacritinib is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and pacritinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, administer pacritinib at least 6 hours after relugolix and monitor for adverse reactions. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Relugolix is a P-gp substrate and pacritinib is a P-gp inhibitor.
Repotrectinib: (Major) Avoid concurrent use of pacritinib with repotrectinib. Concomitant use may decrease pacritinib exposure and efficacy and increase repotrectinib exposure and the risk for repotrectinib-related adverse effects. Pacritinib is a CYP3A substrate and P-gp inhibitor; repotrectinib is a P-gp substrate and moderate CYP3A inducer.
Ribociclib: (Contraindicated) Concurrent use of pacritinib with ribociclib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Contraindicated) Concurrent use of pacritinib with ribociclib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifabutin: (Major) Avoid concurrent use of pacritinib with rifabutin due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Rifampin: (Contraindicated) Concurrent use of pacritinib with rifampin is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased pacritinib exposure by 87%.
Rifapentine: (Contraindicated) Concurrent use of pacritinib with rifapentine is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with pacritinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Concomitant use of pacritinib and rilpivirine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with pacritinib; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and pacritinib is a P-gp inhibitor.
Risperidone: (Major) Concomitant use of pacritinib and risperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ritlecitinib: (Major) Avoid concurrent use of pacritinib with ritlecitinib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Contraindicated) Concurrent use of pacritinib with ritonavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Romidepsin: (Major) Concomitant use of pacritinib and romidepsin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with pacritinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and pacritinib is a BCRP inhibitor.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with pacritinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and pacritinib is a BCRP inhibitor.
Saquinavir: (Contraindicated) Concurrent use of pacritinib with saquinavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor.
Secobarbital: (Major) Avoid concurrent use of pacritinib with secobarbital due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and secobarbital is a moderate CYP3A inducer.
Selpercatinib: (Major) Concomitant use of pacritinib and selpercatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Major) Concomitant use of pacritinib and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Concomitant use of pacritinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Silodosin: (Major) Avoid coadministration of silodosin and pacritinib due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; pacritinib is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with pacritinib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; pacritinib is a P-gp inhibitor.
Siponimod: (Major) Concomitant use of pacritinib and siponimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of pacritinib. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and pacritinib is a weak CYP3A and P-gp inhibitor.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Concomitant use of pacritinib and solifenacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sorafenib: (Major) Concomitant use of pacritinib and sorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of pacritinib and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotorasib: (Major) Avoid concurrent use of pacritinib with sotorasib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and sotorasib is a moderate CYP3A inducer.
St. John's Wort, Hypericum perforatum: (Contraindicated) Concurrent use of pacritinib with St. John's Wort is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and St. John's Wort is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pacritinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of pacritinib is necessary. If pacritinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like pacritinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If pacritinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sunitinib: (Major) Concomitant use of pacritinib and sunitinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tacrolimus: (Major) Concomitant use of tacrolimus and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase tacrolimus exposure and the risk for other tacrolimus-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, monitor tacrolimus serum concentrations as appropriate; the dose of tacrolimus may need to be reduced. Also, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Tacrolimus is a sensitive substrate of CYP3A4 with a narrow therapeutic range. Pacritinib is a weak CYP3A4 inhibitor.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of pacritinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Tamoxifen: (Major) Concomitant use of pacritinib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Concomitant use of pacritinib and telavancin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with pacritinib is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Tetrabenazine: (Major) Concomitant use of pacritinib and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations and watch for an increase in theophylline-related adverse reactions if coadministration with pacritinib is necessary; a theophylline dose reduction may be necessary. Theophylline is a CYP1A2 substrate with a narrow therapeutic index and pacritinib is a CYP1A2 inhibitor.
Thioridazine: (Contraindicated) Avoid concomitant use of pacritinib and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with pacritinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and pacritinib is a P-gp inhibitor.
Tipranavir: (Contraindicated) Concurrent use of pacritinib with tipranavir is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Tipranavir exposure may also increase. Pacritinib is a CYP3A substrate and a P-gp inhibitor; tipranavir is a strong CYP3A inhibitor and a P-gp substrate.
Tizanidine: (Major) Avoid concomitant use of tizanidine and pacritinib as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg per day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and pacritinib is a weak CYP1A2 inhibitor.
Tolterodine: (Major) Concomitant use of pacritinib and tolterodine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The risk for tolterodine-associated QT/QTc prolongation may be increased in poor CYP2D6 metabolizers.
Topotecan: (Major) Avoid coadministration of pacritinib with oral topotecan due to increased topotecan exposure; pacritinib may be administered with intravenous topotecan. Oral topotecan is a substrate of P-gp and BCRP; pacritinib is a P-gp and BCRP inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Concomitant use of pacritinib and toremifene increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with pacritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of pacritinib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with pacritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of pacritinib, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Trandolapril; Verapamil: (Major) Avoid concurrent use of pacritinib with verapamil due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Trazodone: (Major) Concomitant use of pacritinib and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with pacritinib. Coadministration may increase the exposure of triazolam. Triazolam is a sensitive CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Triclabendazole: (Major) Concomitant use of pacritinib and triclabendazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and trifluoperazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Triptorelin: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., triptorelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tucatinib: (Contraindicated) Concurrent use of pacritinib with tucatinib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with pacritinib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of CYP3A4, P-gp, and BCRP; pacritinib is a weak CYP3A4 inhibitor, a P-gp inhibitor, and a BCRP inhibitor.
Vandetanib: (Major) Concomitant use of pacritinib and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Concomitant use of pacritinib and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Concomitant use of pacritinib and vemurafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with pacritinib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of pacritinib. Venetoclax is a P-gp substrate; pacritinib is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Major) Concomitant use of pacritinib and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Major) Avoid concurrent use of pacritinib with verapamil due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Vincristine Liposomal: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of pacritinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of pacritinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with pacritinib is necessary. Vinorelbine is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Voclosporin: (Major) Concomitant use of pacritinib and voclosporin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concurrent use of pacritinib with clarithromycin is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with clarithromycin 500 mg twice a day for 5 days increased pacritinib exposure by 80%.
Voriconazole: (Contraindicated) Concurrent use of pacritinib with voriconazole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor.
Vorinostat: (Major) Concomitant use of pacritinib and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voxelotor: (Major) Avoid concurrent use of pacritinib with voxelotor due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with pacritinib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Pacritinib is a weak CYP3A4 and CYP1A2 inhibitor and the R-enantiomer of warfarin is both a CYP3A4 and CYP1A2 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Ziprasidone: (Major) Concomitant use of pacritinib and ziprasidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pacritinib is a kinase inhibitor that works by blocking the signaling of cytokines and growth factors that are important for hematopoiesis and immune function. It has activity against wild-type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F, 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 inhibits additional cellular kinases, such as colony stimulating factor 1 receptor (CSF1R). Myelofibrosis is associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 compared with JAK3 and TYK2 and does not inhibit JAK1 at therapeutic concentrations.
Pacritinib is administered orally. It is about 98.8% bound to plasma proteins. The median apparent steady-state volume of distribution was 229 L (range, 156 to 591 L), the mean apparent steady-state clearance was 2.09 L/hour (coefficient of variation (CV), 33.1%), and the mean effective half-life was 27.7 hours (CV, 17%) in patients with myelofibrosis who received pacritinib 200 mg PO twice daily. Pacritinib is primarily metabolized by CYP3A; it forms 2 major metabolites (M1 and M2) that account for 9.6% and 10.5% of the parent drug exposure, respectively. Pacritinib is the major circulating component and accounts for the main pharmacological activity. After a single oral radiolabeled dose, 87% of the dose was recovered in the feces (0% unchanged) and 6% of the dose was recovered in the urine (0.12% unchanged).
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A, CYP1A2, P-gp, BCRP, and OCT1
Pacritinib is a substrate of CYP3A and a weak inhibitor of CYP3A4 and CYP1A2. In vitro, pacritinib is an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic cation transporter (OCT)-1, and OCT2 and an inducer of CYP1A2 and CYP3A4.
-Route-Specific Pharmacokinetics
Oral Route
Following pacritinib 200 mg PO twice daily, the steady-state mean Cmax level was 8.4 mg/L (coefficient of variation (CV), 32.4%) and the steady-state mean AUC(0-12h) value was 95.6 mg X hour/L (CV, 33.1%) in patients with myelofibrosis. The time to peak concentration (Tmax) was about 4 to 5 hours post-dose. Pacritinib pharmacokinetics (PK) demonstrate a less than dose-proportional increase. The recommended pacritinib dosage accumulates 386%; steady-state levels are achieved within 1 week. Administering a 200-mg oral dose of pacritinib with a high-fat meal resulted in no significant change in pacritinib PK values compared with the fasting state.
-Special Populations
Hepatic Impairment
Following a single, oral 400-mg dose of pacritinib in 28 healthy subjects, the geometric mean Cmax values of pacritinib decreased by 22% in subjects with mild hepatic impairment (Child-Pugh class A), 47% in subjects with moderate hepatic impairment (Child-Pugh class B), and 57% in subjects with severe hepatic impairment (Child-Pugh class C) compared with subjects who had normal hepatic function. Additionally, the geometric mean AUC values of pacritinib decreased by 8.5%, 36%, and 45% in subjects with Child-Pugh class A, B, and C, respectively, compared with normal hepatic function.
Renal Impairment
The Cmax and AUC values increased by about 30% in subjects with an estimated glomerular filtration rate (eGFR) of 15 to 29 mL/min and eGFR less than 15 mL/min on hemodialysis compared with subjects who had an eGRF of 90 mL/min or higher. Cmax and AUC values were similar in subjects with an eGFR of 30 to 89 mL/min compared with subjects who had an eGRF of 90 mL/min or higher. eGRF was estimated using the modification of diet in renal disease (MDRD) study equation.
Geriatric
Age has no clinically significant impact on the pharmacokinetics of pacritinib.
Gender Differences
Sex has no clinically significant impact on the pharmacokinetics of pacritinib.
Ethnic Differences
Race has no clinically significant impact on the pharmacokinetics of pacritinib.
Obesity
Body weight has no clinically significant impact on the pharmacokinetics of pacritinib.