Pacritinib

Pacritinib is a prescription medication used for the treatment of intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 109/L in adults.

• Pacritinib is available under the following different brand names: Vonjo.

Common side effects of pacritinib include:

• diarrhea
• low platelets (thrombocytopenia)
• nausea
• anemia
• swelling of extremities
• vomiting
• dizziness
• fever
• nosebleed
• shortness of breath
• itching
• upper respiratory tract infection
• cough

Serious side effects of pacritinib include:

• black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• body aches or pain
• chills
• cough
• diarrhea
• ear congestion
• fever
• headache
• loss of voice
• pale skin
• pinpoint red spots on the skin
• rapid weight gain
• sneezing
• sore throat
• stuffy or runny nose
• tingling of the hands or feet
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss

Rare side effects of pacritinib include:

none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 100 mg

Myelofibrosis

Adult dosage

• 200 mg orally two times a day

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Pacritinib has severe interactions with at least 35 other drugs
• Pacritinib has serious interactions with at least 103 other drugs
• Pacritinib has moderate interactions with the following drugs:
  • omaveloxolone
  • siponimod
  • teclistamab
  • trofinetide
  • turmeric
  • ublituximab
• Pacritinib has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Coadministration with strong CYP3A4 inhibitors or inducers

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pacritinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pacritinib?”

Cautions

• May worsen thrombocytopenia; monitor platelet count before initiating and as clinically indicated during treatment
• Manage QTc prolongation using interruption and electrolyte management
• Serious bacterial, mycobacterial, fungal, and viral infections may occur with therapy; delay initiating therapy until active serious infections are resolved
• Hemorrhage
  • Serious and fatal hemorrhages have occurred in treated patients with platelet counts less than 50 * 109/L
  • Avoid use in patients with active bleeding and hold therapy 7 days before any planned surgical or invasive procedures
  • Assess platelet counts periodically, as clinically indicated
  • Interrupt treatment and treat appropriately, if necessary
• Diarrhea
  • May cause diarrhea
  • The median time to resolution was 2 weeks
  • The incidence of reported diarrhea decreased over time
  • Control preexisting diarrhea before starting treatment
  • Manage diarrhea with antidiarrheal medications, fluid replacement, and dosage modification
  • Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms
  • Interrupt or reduce dose in patients with significant diarrhea despite optimal supportive care
• QTc prolongation
  • QTc prolongation may occur; no cases of torsade de pointes were reported
  • Avoid use in patients with a baseline QTc of above 480 msec
  • Avoid coadministration with drugs that cause significant QTc prolongation
  • Correct hypokalemia before and during treatment
  • Advise patients to consult their healthcare provider immediately if they feel faint, lose consciousness, or have signs or symptoms suggestive of arrhythmia
  • Manage QTc prolongation using interruption and electrolyte management
• Janus-associated kinase (JAK) inhibitor-associated adverse effects
  • Another JAK inhibitor has increased the risk of the following
• Major adverse cardiac events; (e.g., cardiovascular death, myocardial infarction, stroke) in patients with rheumatoid arthritis (RA), a condition for which Pacritinib is not indicated
  • Thrombosis (e.g., deep venous thrombosis, pulmonary embolism, arterial thrombosis) in patients with RA
  • Secondary malignancies, such as lymphoma and other malignancies, excluding non-melanoma skin cancer, in patients with RA
• Serious infections in patients with myeloproliferative neoplasms
  • Consider the benefits and risks before initiating or continuing therapy, particularly in patients who are current or past smokers, patients with other cardiovascular risk factors, and patients with a developed or known malignancy (other than a successfully treated NMSC)
  • Consult about symptoms of serious cardiovascular events and the necessary steps to take if they occur
  • Monitor for signs and symptoms of infection and manage promptly
  • Use active surveillance and prophylactic antibiotics according to clinical guidelines
• Drug interaction overview
  • Substrate of CYP3A4
    • Inhibitor of CYP1A2, CYP3A4, P-glycoprotein, breast cancer resistance protein, and organic cation transporter 1
  • CYP3A4 inhibitors
    • Strong inhibitors: Contraindicated
    • Moderate inhibitors: Avoid use
    • Coadministration with clarithromycin (a strong CYP3A4 inhibitor) increases AUC and peak plasma concentration of Pacritinib by 80% and 30%, respectively; exposure to Pacritinib may increase following a longer treatment with clarithromycin that results in maximal CYP3A4 inhibition
    • Impact of moderate CYP3A4 inhibition not studied
  • CYP3A4 inducers
    • Strong inducers: Contraindicated
    • Moderate inducers: Avoid use
    • Coadministration with rifampin (a strong CYP3A4 inducer) decreases AUC and peak plasma concentration of Pacritinib by 87% and 51%, respectively
    • Impact of moderate CYP3A4 inducers not studied
  • Sensitive CYP1A2 or CYP3A4 substrates
    • Avoid coadministration
    • Pacritinib may increase plasma concentrations of sensitive CYP1A2 or CYP3A4 substrates
    • Sensitive P-gp, BCRP, or OCT1 substrates
  • Avoid coadministration
    • Pacritinib may increase plasma concentrations of sensitive P-gp, BCRP, or OCT1 substrates

Pregnancy and Lactation

• No data are available on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Advise pregnant women of the potential risk to a fetus
• Consider the benefits and risks for the mother and possible risks to the fetus when prescribing to pregnant women
• Infertility
  • May reduce male mating and fertility indices in BALB/c mice
  • Therefore, may impair male fertility in humans
• Lactation
  • There is no data on the presence of either human or animal milk, its effects on breastfed children, or its effects on milk production
  • Unknown whether Pacritinib is excreted in human milk
  • Advise patients that breastfeeding is not recommended during treatment and for 2 weeks after the last dose