- May 6, 2022
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Brand Name :
Vonjo
Synonyms :
pacritinib
Class :
Tyrosine Kinase Inhibitors, Antineoplastics,; JAK Inhibitors, Antineoplastics
Dosage Forms & Strengths
Capsule
100mg
Indicated to patients with moderate or high-risk primary or secondary myelofibrosis
:
200mg orally twice a day
Dose Adjustments
Adverse reactions for dosage reduction
First dosage reduction: Reduce the dose to 100mg twice a day
Second dosage reduction: Reduce the dose to 100mg every day
Inability to tolerate 100 mg every day: Stop treatment
Surgical procedures or other interventions planned
Due to the risk of bleeding, discontinue seven days before elective surgery or invasive procedures, and resume only after hemostasis is assured.
Diarrhea
Initiate antidiarrheal medications and promote adequate oral hydration at the onset of diarrhea.
Grade 3 or 4 characterized as an increase of ≥7 stools/day over baseline, hospitalization being contemplated, a substantial increase in ostomy output above baseline, or self-care is being restricted.
Hold until diarrhea improves to Grade ≤1 or baseline (an increase of 4 or more stools per day or a slight rise in ostomy output relative to baseline), then resume at the previous dosage administered.
If restarting antidiarrheal therapy, concomitant treatment is required.
Thrombocytopenia
In clinically substantial thrombocytopenia deterioration persisting >7 days
Until resolution, hold therapy; resume at 50% of the last administered dose.
In the event of a recurrence, therapy should be withheld until resolution, after which it should be resumed at 50% of the previous dose.
Hemorrhage
Moderate bleeding (intervention needed): Hold until the bleeding stops, then continue at the previous dosage; if it happens again, hold until it stops, then restart at 50% of the last dose.
Severe bleeding: Withhold until the hemorrhage subsides, then resume at 50% of the last given dosage; if it recurs, cease medication.
Life-threatening bleeding: Stop treatment.
QTc prolongation
QTc prolongation is more significant than 500 or >60 milliseconds from baseline Hold for one week or until the QTc interval returns to baseline or ≤480 msec, then continue at the exact dosage. Restart at a lower dosage if the time to resolution exceeds a week.
Renal impairment
eGFR ≥30 mL/min: No dose adjustment is needed
eGFR <30 mL/min: Avoid usage
Hepatic impairment
Mild (Child-Pugh A): 8.5% reduction in AUC; no dose.
Moderate to severe(Child-Pugh B or C): Use caution; it lowers AUC by 36% and 45%, respectively.
Indicated to patients with moderate or high-risk primary or secondary myelofibrosis
:
200mg orally twice a day
Dose Adjustments
Adverse reactions for dosage reduction
First dosage reduction: Reduce the dose to 100mg twice a day
Second dosage reduction: Reduce the dose to 100mg every day
Inability to tolerate 100 mg every day: Stop treatment
Surgical procedures or other interventions planned
Due to the risk of bleeding, discontinue seven days before elective surgery or invasive procedures, and resume only after hemostasis is assured.
Diarrhea
Initiate antidiarrheal medications and promote adequate oral hydration at the onset of diarrhea.
Grade 3 or 4 characterized as an increase of ≥7 stools/day over baseline, hospitalization being contemplated, a substantial increase in ostomy output above baseline, or self-care is being restricted.
Hold until diarrhea improves to Grade ≤1 or baseline (an increase of 4 or more stools per day or a slight rise in ostomy output relative to baseline), then resume at the previous dosage administered.
If restarting antidiarrheal therapy, concomitant treatment is required.
Thrombocytopenia
In clinically substantial thrombocytopenia deterioration persisting >7 days
Until resolution, hold therapy; resume at 50% of the last administered dose.
In the event of a recurrence, therapy should be withheld until resolution, after which it should be resumed at 50% of the previous dose.
Hemorrhage
Moderate bleeding (intervention needed): Hold until the bleeding stops, then continue at the previous dosage; if it happens again, hold until it stops, then restart at 50% of the last dose.
Severe bleeding: Withhold until the hemorrhage subsides, then resume at 50% of the last given dosage; if it recurs, cease medication.
Life-threatening bleeding: Stop treatment.
QTc prolongation
QTc prolongation is more significant than 500 or >60 milliseconds from baseline Hold for one week or until the QTc interval returns to baseline or ≤480 msec, then continue at the exact dosage. Restart at a lower dosage if the time to resolution exceeds a week.
Renal impairment
eGFR ≥30 mL/min: No dose adjustment is needed
eGFR <30 mL/min: Avoid usage
Hepatic impairment
Mild (Child-Pugh A): 8.5% reduction in AUC; no dose.
Moderate to severe(Child-Pugh B or C): Use caution; it lowers AUC by 36% and 45%, respectively.
Safety and efficacy not established
Refer adult dosing
It may enhance the effect when combined with grapefruit by CYP3A4 metabolism
may decrease the diagnostic effect of immunosuppressants
may decrease the therapeutic effect of Immunosuppressants
may increase the immunosuppressive effect of Immunosuppressants
may decrease the therapeutic effect of Immunosuppressants
may increase the immunosuppressive effect of Immunosuppressants
respiratory syncytial virus vaccine, adjuvanted
may decrease the therapeutic effect of Immunosuppressants
respiratory syncytial virus (RSV) vaccine
may decrease the therapeutic effect of Immunosuppressants
poliovirus vaccine, live, trivalent
may decrease the therapeutic effect of Immunosuppressants
poliovirus vaccine inactivated
may decrease the therapeutic effect of Immunosuppressants
when both drugs are combined, there may be a decreased effect of pacritinib by affecting hepatic or intestinal enzyme cyp3a4 metabolism
pexidartinib decreases the effect or level of pacritinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
it increases the concentration of OCT1 substrates in the serum
CYP3A4 Inhibitors (Moderate) may increase the serum concentration when combined with Pacritinib
CYP3A4 Inhibitors (Moderate) may increase the serum concentration when combined with Pacritinib
CYP3A4 Inhibitors (Moderate) may increase the serum concentration when combined with Pacritinib
CYP3A4 Inhibitors (Moderate) may increase the serum concentration when combined with Pacritinib
CYP3A4 Inhibitors (Moderate) may increase the serum concentration when combined with Pacritinib
pacritinib may elevate the levels of OCT1 substrates in the bloodstream, which is clinically relevant primarily when used with inhibitors
may increase the immunosuppressive effect of Immunosuppressants
may enhance the concentration of serum when combined with CYP3A4 substrates
may enhance the concentration of serum when combined with CYP3A4 substrates
may enhance the concentration of serum when combined with CYP3A4 substrates
may enhance the concentration of serum when combined with CYP3A4 substrates
may enhance the concentration of serum when combined with CYP3A4 substrates
It may diminish the effect when combined with griseofulvin by CYP3A4 metabolism
pacritinib: they may enhance the serum concentration of CYP3A Inhibitors
pacritinib: they may enhance the serum concentration of CYP3A Inhibitors
pacritinib: they may enhance the serum concentration of CYP3A Inhibitors
pacritinib: they may enhance the serum concentration of CYP3A Inhibitors
pacritinib: they may enhance the serum concentration of CYP3A Inhibitors
the impact of pacritinib is decreased by lenvatinib by altering intestinal or hepatic CYP3A4 enzyme metabolism. Avoid or take an alternate medicine.
lapatinib increases the effect of pacritinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
CYP3A strong enhancers of the small intestine may reduce the bioavailability of pacritinib
pacritinib increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
it increases the concentration of CYP3A4 in serum
it increases the concentration of CYP3A4 in serum
tecovirimat decreases the effect of pacritinib by altering CYP3A4 enzyme metabolism
it decreases by affecting the hepatic enzyme CYP3A4 metabolism
may enhance the serum concentration of CYP1A2 substrates
may enhance the serum concentration of CYP3A4 Inhibitors
may enhance the serum concentration when combined
may enhance the serum concentration of BCRP/ABCG2 Substrates
it may diminish the excretion rate when combined with benzodiazepines, resulting in an enhanced serum level
it may diminish the excretion rate when combined with benzodiazepines, resulting in an enhanced serum level
pacritinib: they may increase the QTc-prolonging effect of QTc-prolonging Agents
pacritinib: they may increase the QTc-prolonging effect of QTc-prolonging Agents
pacritinib: they may increase the QTc-prolonging effect of QTc-prolonging Agents
pacritinib: they may increase the QTc-prolonging effect of QTc-prolonging Agents
pacritinib: they may increase the QTc-prolonging effect of QTc-prolonging Agents
when bromazepam and pacritinib are used together, there is a potential reduction in the bromazepam's metabolism
when both drugs are combined, there may be an increased level of serum concentration of vincristine
when both drugs are combined, there may be a reduced excretion rate of topotecan and result in an elevated level of serum concentration
may enhance the risk of ventricular arrhythmias
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
may decrease the levels of serum concentration
Actions and Spectrum:
The mechanism of action of pacritinib involves its activity as a kinase inhibitor.
Frequency defined
>10%
All grades
Thrombocytopenia (34%)
Anemia (24%)
Vomiting (19%)
Pyrexia (15%)
Diarrhea (48%)
Nausea (32%)
Peripheral edema (20%)
Dizziness (15%)
Epistaxis (12%)
Grade ≥3
Anemia (22%)
Thrombocytopenia (32%)
1-10%
All grades
Pruritus (10%)
Cough (8%)
Dyspnea (10%)
Upper respiratory tract infection (10%)
Grade ≥3
Diarrhea (4%)
Cough (2%)
Peripheral edema (1%)
Pyrexia (1%)
Epistaxis (5%)
Pruritus (2%)
Nausea (1%)
Dizziness (1%)
Black box warning:
None
Contraindications/caution:
Contraindications:
Caution:
Pregnancy consideration: Insufficient data available
Lactation: Excretion of the drug in human breast milk is unknown
Pregnancy category:
Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.
Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.
Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.
Category N: There is no data available for the drug under this category
Pharmacology:
pacritinib is a kinase inhibitor with selectivity for Janus kinase (JAK) family enzymes. It exerts its pharmacological effects by inhibiting the activity of JAK2 and FMS-like tyrosine kinase 3 (FLT3). The critical aspects of the pharmacology of pacritinib:
pacritinib is a small molecule that binds to and inhibits the activity of JAK2 and FLT3 enzymes. JAK2 is involved in the signaling pathways of various cytokines and growth factors, including those associated with myelofibrosis, such as the JAK-STAT pathway. By inhibiting JAK2, pacritinib reduces abnormal signaling and the overproduction of blood cells seen in myelofibrosis.
Pharmacodynamics:
The pharmacodynamics of pacritinib involve inhibiting JAK2 and FLT3, modulating cytokine levels, and influencing the bone marrow microenvironment. These actions contribute to the therapeutic effects of pacritinib in conditions like myelofibrosis.
Pharmacokinetics:
Absorption
pacritinib is administered orally and rapidly absorbed from the gastrointestinal tract after ingestion.
Distribution
pacritinib has a moderate distribution volume, indicating that it distributes well into tissues after absorption. It is likely to reach various organs and tissues throughout the body.
Metabolism
pacritinib undergoes extensive metabolism, primarily in the liver. The main enzymes in its metabolism are cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19. These enzymes convert pacritinib into metabolites that are less pharmacologically active.
Elimination and Excretion
pacritinib and its metabolites are eliminated from the body primarily via feces (approximately 75% of the administered dose). Renal excretion plays a minor role, accounting for approximately 20% of the dose.
Administration:
pacritinib is typically administered orally in the form of capsules. Here are some general guidelines for the administration of pacritinib:
Patient information leaflet
Generic Name: pacritinib
Why do we use pacritinib?
pacritinib is a medication primarily used for treating myelofibrosis, a rare type of bone marrow disorder characterized by the excessive production of fibrous tissue in the bone marrow. Here are the primary uses of pacritinib:
