momelotinib (Ojjaara)
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Indications
- treatment of myelofibrosis
Contraindications
- do not initiate in patients with active infection
- pregnancy: may cause fetal harm
- lactation: breastfeeding not recommended
Dosage
200 mg PO QD with or without food*
Tablets: 100, 150, 200 mg
* reduced starting dose to 150 mg if severe hepatic impairment
Pharmacokinetics
- metabolized by multiple cytochrome P450 enzymes including: CYP3A4 (36%), CYP2C8 (19%), CYP2C9 (17%), CYP2C19 (19%), & CYP1A2 (9%)
- M21 is an active metabolite with 40% activity of momelotinib
- M21 is formed by CYP followed by aldehyde oxidase metabolism
- 1/2life of momelotinib & M21 is 4-8 hours
Monitor
- liver function tests prior to initiation & periodically durinng treatment
Adverse effects
- bacterial infection
- thrombocytopenia*, neutropenia (reduce dose)
- hepatotoxicity
- major cardiovascular events
- thrombosis
- secondary malignancy, especially smokers
- hemorrhage*
- fatigue*, dizziness*
- nausea*, diarrhea*
* common, >= 20%
- drug adverse effects of tyrosine kinase inhibitor(s)
- drug adverse effects of janus kinase inhibitors
Mechanism of action
- inhibition of JAK1 & JAK2
- inhibition of activin A receptor, type 1[1]
- inhibits STAT3 phosphorylation
More general terms
References
- ↑ 1.0 1.1 Tefferi A, Pardanani A, Gangat N. Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis. Haematologica. 2023 Mar 2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36861402 Free article.
- ↑ Highlights of Prescribing Information OJJAARA (momelotinib) tablets, for oral use https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF