Momelotinib is an oral kinase inhibitor indicated for the treatment of adults with intermediate or high-risk myelofibrosis with anemia, including primary and secondary myelofibrosis.

I. What is Momelotinib?

1. Drug Class

Momelotinib belongs to the class of Janus kinase (JAK) inhibitors. It blocks aberrant signaling pathways by inhibiting the activity of JAK1, JAK2, and the mutant JAK2⁶¹⁷⁺.

2. Therapeutic Indication

(1) Specifically indicated for patients with myelofibrosis who already have anemia.

(2) Clinical studies have demonstrated that this drug not only reduces enlarged spleen size and alleviates systemic symptoms (such as fatigue, night sweats, bone pain, early satiety), but also significantly decreases the need for blood transfusions and improves quality of life.

II. Mechanism of Action and Drug Interactions

1. Mechanism of Action

(1) Momelotinib simultaneously inhibits JAK1, JAK2, and activin A receptor type I (ACVR1, also known as ALK2).

(2) Inhibition of JAK signaling reduces inflammatory responses and reduces spleen volume; inhibition of ACVR1 reduces the expression of hepcidin in the liver, increasing the availability of iron, thereby promoting erythropoiesis and correcting anemia.

2. Drug Interactions

(1) OATP1B1/B3 inhibitors (e.g., rifampin): Increase momelotinib plasma concentrations, raising the risk of adverse effects. Close monitoring is required when coadministered.

(2) BCRP substrate drugs: Momelotinib can substantially increase the exposure of BCRP substrates such as rosuvastatin. When coadministered, the starting dose of rosuvastatin should be 5 mg, not exceeding 10 mg daily.

(3) Strong CYP3A4 inducers/inhibitors and acid-reducing agents: No significant interactions were found in clinical studies; generally no dose adjustment is needed.

III. Management of Missed or Overdose

1. Missed Dose

(1) If a dose is missed, skip the missed dose entirely and take the next dose at the regular scheduled time the following day.

(2) Do not take two doses at once to make up for a missed dose, as this increases the risk of adverse effects.

2. Overdose

(1) If an overdose is discovered, stop taking the drug immediately and contact a doctor or call a poison help line.

(2) There is no specific antidote. Management consists of supportive care, with close monitoring for signs of bleeding, infection, liver injury, etc.

(3) Hemodialysis is not effective in removing this drug.

3. Daily Dosing Recommendations

(1) It is recommended to take the once-daily 200 mg dose at the same time each day (e.g., after breakfast or at bedtime) using an alarm as a reminder.

(2) Tablets should be swallowed whole, not cut, crushed, or chewed, and may be taken with or without food.