Momelotinib is a Janus kinase (JAK) 1 and 2 inhibitor. It is primarily indicated for the treatment of adult patients with anemia associated with intermediate- or high-risk myelofibrosis, whether it is primary myelofibrosis or myelofibrosis secondary to polycythemia vera or essential thrombocythemia.

What Are the Precautions for Momelotinib Administration?

Evaluations Prior to Initiation of Treatment

Infection status: If there is any active infection (such as bacterial or viral infection, including COVID-19), treatment must not be initiated until the infection is completely controlled.

History of hepatitis: For patients with chronic hepatitis B virus (HBV) infection, HBV serological testing is required. Momelotinib administration may lead to HBV reactivation.

Liver function: Baseline liver function values should be obtained.

Cardiac and thrombotic risk: Physicians need to carefully weigh the benefits against the risks if the patient is a current or former smoker, or has a history of cardiovascular events such as myocardial infarction or stroke.

Current or prior malignancy: Especially for current or former smokers, the risks of drug administration require individualized assessment.

Drug Interactions

OATP1B1/B3 inhibitors: Concomitant use may increase the plasma concentration of momelotinib and elevate the risk of adverse reactions, thus enhanced monitoring is recommended.

Breast cancer resistance protein (BCRP) substrates: Momelotinib may increase the exposure of BCRP substrate drugs (e.g., rosuvastatin). If co-administration is necessary, the starting dose of rosuvastatin should be adjusted to 5 mg, and should not exceed 10 mg per day.

Momelotinib Administration Monitoring

Routine Hematological Monitoring

Monitoring parameters: Including complete blood count, as well as platelet and neutrophil counts.

Monitoring frequency: Testing is mandatory before the initiation of treatment. During treatment, re-examination should be performed regularly based on clinical needs.

Purpose: Momelotinib may cause thrombocytopenia and neutropenia. The incidence of new-onset or worsening thrombocytopenia in clinical trials was approximately 20%, while the incidence of severe neutropenia was about 2%.

Liver Function Monitoring

Monitoring parameters: Liver function tests.

Monitoring frequency: Testing is mandatory before the initiation of treatment. During the first 6 months after treatment initiation, testing should be conducted once a month, followed by regular re-examination based on clinical needs thereafter.

Purpose: To monitor potential drug-induced hepatotoxicity. In clinical trials, elevated transaminases occurred in approximately 23%–24% of patients, and elevated total bilirubin was observed in about 16% of patients.

If an elevation in liver enzymes or bilirubin is suspected to be drug-related, dosage adjustment should be performed according to standard protocols. Permanent discontinuation of the drug is required if significant elevation recurs.