Pacritinib

Pacritinib (brand name Vonjo) is used to treat types of myelofibrosis with low platelet counts (cytopenic myelofibrosis) to help reduce spleen volume. Myelofibrosis is a rare type of bone marrow disorder.

Pacritinib's mechanism of action involves blocking certain types of enzymes called kinases that are overactive in myelofibrosis, such as Janus-associated kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3), and interleukin 1 receptor associated kinase-1 (IRAK1). These enzymes are involved in signaling pathways that contribute to excessive inflammation in bone marrow, an enlarged spleen, and symptoms of myelofibrosis. Pacritinib belongs to the drug class called kinase inhibitors.

Pacritinib gained FDA approval on February 28, 2022, under the accelerated approval designation. The accelerated approval is based on spleen volume reduction, and continued approval for this indication will depend on positive results in future trials.

There is no pacritinib generic, it is only available under the brand name Vonjo.

Pacritinib is approved under the accelerated approval designation for adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109 /L.

29% of patients had a reduction in their spleen volume of at least 35% compared to 3% of patients receiving the best available therapy, which included ruxolitinib, in the PERSIST-2 clinical trial. Patients had myelofibrosis with platelet counts less than or equal to 100 × 109/L and took Pacritinib 200mg twice daily for 24 weeks.

Pacritinib is usually taken 2 times a day, with or without food.

• Swallow the capsule whole and do not crush, chew, break, or open it.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed. Do not change your dose or stop taking Pacritinib without first talking to your healthcare provider. If you stop treatment, symptoms of your condition may return.

• You will need blood tests and an electrocardiogram (ECG) before you start taking Pacritinib and as needed during treatment to check for side effects.
• Your treatment with Pacritinib may be delayed or permanently discontinued if you have certain side effects.

If you notice any change in how often you have bowel movements, if they become softer or you have diarrhea, start taking an antidiarrheal medicine (for example, loperamide) as soon as you notice changes, as directed by your healthcare provider.

Pacritinib should not be used with certain medicines, especially strong hepatic enzyme CYP3A4 inhibitors or inducers or medicines that prolong the QTc interval, such as:

• nefazodone;
• St. John's wort;
• an antibiotic - clarithromycin, rifabutin, rifampin, rifapentine, telithromycin;
• antifungal medicine - fluconazole, itraconazole, ketoconazole;
• antinausea agents - ondansetron;
• antiviral medicine for HIV or hepatitis C - boceprevir, cobicistat, dasabuvir, elvitegravir, indinavir, lopinavir/ritonavir, nelfinavir, ombitasvir, paritaprevir, saquinavir, telaprevir, tipranavir;
• cancer medicine - apalutamide, enzalutamide, mitotane;
• migraine agents - sumatriptan;
• opioids - methadone;
• seizure medicine - carbamazepine, oxcarbazepine, phenytoin, primidone; or
• steroid medicine - dexamethasone, prednisone.

If you take other kinase inhibitors, such as fedratinib or ruxolitinib, your healthcare provider should taper your dose before starting pacritinib. Do not stop taking these medicines suddenly.

Tell your healthcare provider if you take any of these medicines.

Also, tell your healthcare provider if you have ever had:

• liver or kidney disease;
• any other cancers;
• a blood clot, or stroke;
• a heart attack, or other heart problem;
• if you have an infection;
• if you have diarrhea (or loose stools), nausea or vomiting;
• if you smoke or were a smoker; or
• if you have active bleeding, have had severe bleeding, or plan to have surgery.
• low blood levels of potassium.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant, as it is not known if Pacritinib will harm an unborn baby. It may be harder for you to get a woman pregnant while you are using this medicine.

Pacritinib may affect fertility in males. You may have problems fathering a child. Talk to your healthcare provider if this is a concern for you.

Breastfeeding

Do not breastfeed while using Pacritinib and for at least 2 weeks after your last dose.

The most common side effects of pacritinib are:

• diarrhea
• low platelet counts (thrombocytopenia)
• feeling sick (nausea)
• low red blood cell counts (anemia)
• swelling in ankles, legs, and feet.

Serious side effects and warnings

Pacritinib may cause the following serious side effects.

Serious bleeding and hemorrhage. Pacritinib can cause serious and fatal bleeding and you should seek emergency attention for any bleeding that does not stop. Your healthcare provider should hold pacritinib 7 days before any planned surgical or invasive procedures.

Diarrhea. Almost half of patients taking pacritinib get diarrhea after taking pacritinib which usually takes approximately 2 weeks to resolve. Diarrhea can be severe and cause loss of too much body fluid (dehydration), which can lead to kidney problems. Your healthcare provider should manage any diarrhea you have with antidiarrheal medicines, fluid replacement, and dose modification.

Low platelets (thrombocytopenia). Pacritinib can worsen thrombocytopenia and your healthcare provider will monitor your platelet levels and adjust your dosage if necessary.

Prolonged QT interval. Pacritinib can prolong the QTc interval and should not be used in patients with a baseline QTc of 480 msec. Tell your healthcare provider about all the medicines you take as medicines that also cause QTc prolongation should be avoided.

Allergic reaction. Pacritinib may cause an allergic reaction. Get emergency medical help if you have signs of an allergic reaction: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

There is also a risk that pacritinib may also cause major cardiac adverse events (MACE), blood clots, secondary cancers, and an increase in the risk of infection.

Call your doctor at once if you have any of the following symptoms after taking pacritinib:

• bleeding, bruising, and fever;
• severe or ongoing diarrhea;
• dizziness, a light-headed feeling, like you might pass out;
• signs of a stroke - sudden numbness or weakness, severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot in the lung - chest pain, sudden cough or shortness of breath, dizziness, coughing up blood;
• signs of a blood clot deep in the body - pain, swelling, or warmth in one leg;
• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating; or
• signs of infection - fever, chills, sore throat, body aches, unusual tiredness, loss of appetite, bruising or bleeding.
• worsening of symptoms after stopping treatment - fever, trouble breathing, feeling dizzy or lightheaded, weakness, night sweats, or pain in your left upper stomach area or left shoulder.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The usual adult dose for myelofibrosis is pacritinib 200 mg orally 2 times a day.

Pacritinib is available in 100mg capsules.

If you miss a dose, skip the dose and just take your next dose at your regularly scheduled time. Do not take 2 doses at the same time to make up for the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Pacritinib with certain other medicines may affect the amount of Pacritinib in your blood, and may increase your risk of side effects or affect how well Pacritinib works.

Especially tell your doctor if you are taking any of the following medicines:

• macrolide antibiotics (clarithromycin, erythromycin)
• antifungal medicines (itraconazole, ketoconazole, posaconazole, voriconazole)
• HIV medicines that contain atazanavir, darunavir, efavirenz, etravirine, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, or cobicistat
• heart or blood pressure medicines (quinidine, amiodarone, diltiazem, verapamil)
• cimetidine
• mifepristone
• nefazodone
• cannabidiol
• cyclosporine
• phenytoin
• rifampin
• St. John's wort;
• ondansetron
• apalutamide, enzalutamide, mitotane
• sumatriptan
• methadone;
• carbamazepine, oxcarbazepine, phenytoin, primidone
• dexamethasone, prednisone.
• hormonal contraceptives (birth control).

Not all possible interactions are listed here. Know the medicines you take. Keep a list of the medicines you take to show your healthcare provider and pharmacist when you get a new medicine.

Hormonal birth control methods, except for intrauterine systems containing levonorgestrel, may not work during treatment with pacritinib and for 30 days after your last dose. Talk to your healthcare provider about birth control methods that may be right for you.

Review the Vonjo (pacritinib) Package Insert for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

• Store Pacritinib capsules at room temperature, below 86°F (30°C).
• Store the capsules in the original package.
• Keep the bottle tightly closed to protect the capsules from light.

Active ingredient: pacritinib Inactive ingredients: microcrystalline cellulose, polyethylene glycol 8000 (PEG 8000), and magnesium stearate. The capsule shell contains gelatin, titanium dioxide, black iron oxide, erythrosine, red iron oxide and printing ink containing shellac, titanium dioxide, propylene glycol, sodium hydroxide, and povidone.

Sobi Inc. manufactures pacritinib.