Pacritinib 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.

The accelerated approval is based on spleen volume reduction.

Myelofibrosis

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.

Oral kinase with activity against wild-type JAK2, mutant JAK2V617F, and FMS-like tyrosine kinase 3, which contribute to signaling of cytokines and growth factors that are important for hematopoiesis and immune function.

MF is often associated with dysregulated JAK2 signaling.

Also exhibits inhibitory activity against additional cellular kinases (e.g., CSF1R, IRAK1), the clinical relevance of which is unknown.

May take with or without food.

Swallow capsules whole; do not open, break, or chew.

Missed dose: Take the next prescribed dose at its scheduled time; do not take extra capsules to make up for the missed dose.

Most common side effects:

Diarrhea

Low platelet counts (thrombocytopenia)

Feeling sick (nausea)

Low red blood cell counts (anemia)

Swelling in ankles, legs, and feet.

Serious side effects:

Serious bleeding and hemorrhage

Diarrhea

Low platelets (thrombocytopenia)

Prolonged QT interval

Allergic reaction—hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

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 include 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.

There are 749 drugs known to interact with pacritinib, along with 7 disease interactions, and 2 alcohol/food interactions. Of the total drug interactions, 332 are major, 407 are moderate, and 10 are minor.

Pacritinib may increase the blood levels and effects of caffeine. This may increase the risk and/or severity of side effects of caffeine.

Grapefruit juice may increase the blood levels of pacritinib. This can increase the risk of side effects such as diarrhea, low blood platelet count, infection, and an irregular heart rhythm that may be serious or life-threatening. You should avoid consuming grapefruit and grapefruit juice during treatment with pacritinib.

There are 7 disease interactions with Pacritinib, which include:

Cardiovascular risk

Malignancy

Thrombosis

Pacritinib-diarrhea

Pacritinib-infection

Pacritinib-hemorrhage

Pacritinib-QT prolongation

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.

Advise patients who are currently taking a kinase inhibitor that they must taper or discontinue their current kinase inhibitor therapy according to the package insert for that drug prior to starting pacritinib.

Advise patients that pacritinib can cause hemorrhage. Inform patients about how to recognize bleeding, and advise them to consult their healthcare provider right away if bleeding occurs. Patients should urgently seek emergency medical attention for any bleeding that cannot be stopped.

Advise patients that pacritinib can cause diarrhea. Advise patients to stay hydrated while taking pacritinib and to inform their physician if they experience diarrhea. Instruct patients to initiate antidiarrheal medications (e.g., loperamide) if diarrhea occurs. Advise patients to urgently seek emergency medical attention if diarrhea becomes severe.

Advise patients that pacritinib can cause thrombocytopenia and of the need to monitor complete blood counts 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. Advise patients with a history of hypokalemia of the importance of monitoring their electrolytes.

Advise patients that major adverse cardiac events (MACE), including myocardial infarction, stroke, and cardiovascular death, have been reported in clinical studies with another JAK inhibitor used to treat rheumatoid arthritis, a condition for which pacritinib is not indicated. Advise patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.

Advise patients that events of deep vein thrombosis and pulmonary embolism have been reported in clinical studies with another JAK inhibitor used to treat rheumatoid arthritis, a condition for which pacritinib is not indicated. Advise patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE.

Advise patients, especially current or past smokers and patients with a known secondary malignancy (other than a successfully treated NMSC), that lymphoma and other malignancies (excluding NMSC) have been reported in clinical studies with another JAK inhibitor used to treat rheumatoid arthritis, a condition for which pacritinib is not indicated.

Advise patients that treatment with another JAK inhibitor has increased the risk of serious infections in patients with myeloproliferative neoplasms and that serious bacterial, mycobacterial, fungal, and viral infections may occur in patients treated with pacritinib. Inform patients of the signs and symptoms of infection and to report any such signs and symptoms promptly.

Advise patients that nausea and vomiting may occur during treatment with pacritinib. Instruct them on how to manage nausea and vomiting and to immediately inform their healthcare provider if nausea/vomiting becomes severe.

Instruct patients to discontinue pacritinib 7 days prior to any surgery or invasive procedures (e.g., cardiac catheterization, coronary stenting, or varicose vein ablation) due to the risk of bleeding and to only restart pacritinib on the instruction of their healthcare provider.

Patients should not change or stop taking pacritinib without first consulting their physician.

Stress the importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.