Momelotinib

OJJAARA

What it isJAK- and ACVR1-pathway inhibitor; myelofibrosis in patients with anemia.

Why this oneIts hepcidin suppression can improve anemia while treating splenomegaly and constitutional symptoms, unlike other JAK inhibitors.

What limits itSerious infection, thrombocytopenia, liver injury, and peripheral neuropathy require surveillance.

FDA label

FDA dosing	Population	Start	Target	Max
Myelofibrosis (trials: MF with anemia, JAK-inhibitor-naive or -experienced)	Adults	200 mg QD	200 mg QD	200 mg QD
Myelofibrosis — severe hepatic impairment (Child-Pugh C)	Adults	150 mg QD	150 mg QD	150 mg QD

Renal Undefined

Hepatic Severe (Child-Pugh C): start 150 mg QD; no adjustment mild/moderate

Dose-reduce in 50 mg steps for thrombocytopenia, neutropenia, hepatotoxicity, or Grade ≥3 toxicity; discontinue if unable to tolerate 100 mg QD

Swallow tablets whole — do not cut/crush/chew; with or without food
Missed dose: take next scheduled dose the following day
When stopping for non-life-threatening reasons, consider gradual taper rather than abrupt discontinuation (symptom-flare risk)
CBC with platelets and hepatic panel before starting, periodically during treatment

Infections (serious/fatal, incl. hepatitis B reactivation) — do not start with active infection; check HBV serologies in HBV patients
Thrombocytopenia and neutropenia — manage by dose reduction/interruption
Hepatotoxicity — LFTs at baseline, monthly × 6 months, then periodically
Severe cutaneous adverse reactions incl. TEN — interrupt until etiology determined; discontinue permanently if drug-related
MACE, thrombosis, secondary malignancies (JAK-inhibitor class effects) — weigh risk, especially smokers
Symptom exacerbation after interruption/discontinuation (fever, respiratory distress, hypotension, DIC, multi-organ failure)

Most common (≥20%): thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, nausea
Serious: infections, acute kidney injury, pneumonia, thrombosis
Postmarketing: hypersensitivity, hypoglycemia, erythema multiforme, TEN

Pregnancy Insufficient human data; embryo-fetal toxicity in animals at/below human exposure — use only if benefit outweighs fetal risk

Lactation Do not breastfeed during treatment and for at least 1 week after last dose

NO BOXED WARNINGS

Principal riskNo FDA boxed warning.

Direct muscarinic antagonism0 / 4