momelotinib

Contraindicated in:

Active infection;
Lactation: Lactation.

Use Cautiously in:

Hepatitis B;
Severe hepatic impairment (↓ dose);
>50 yr old with ≥1 cardiovascular risk factor (may ↑ risk of all-cause mortality, cardiovascular death, MI, stroke, and thrombosis);
Current or past history of smoking (may ↑ risk of malignancy, cardiovascular death, MI, or stroke);
Known malignancy (other than a successfully treated nonmelanoma skin cancer or cervical cancer);
Rep: Women of reproductive potential;
OB: Safety not established in pregnancy;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, peripheral edema, arrhythmia, ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS (DVT), MI

Derm: pruritus, rash, flushing

EENT: blurred vision

GI: ↑liver enzymes, abdominal pain, diarrhea, nausea, HEPATOTOXICITY, vomiting

Hemat: bleeding, thrombocytopenia, neutropenia

MS: pain

Neuro: dizziness, fatigue, headache, neuralgia, paresthesia, STROKE

Resp: cough, PULMONARY EMBOLISM (PE)

Misc: fever, infection (including hepatitis B virus [HBV] reactivation), MALIGNANCY, vitamin B₁ deficiency

Interactions ⬆ ⬇

Drug-drug:

Organic anion transporting polypeptide (OATP) 1B1/B3 inhibitors, including rifampin, may ↑ levels and the risk of toxicity.
May ↑ levels and the risk of toxicity of breast cancer resistance protein (BCRP) substrates, including rosuvastatin; may need to ↓ dose of BCRP substrate.

Availability ⬆ ⬇

Tablets: 100 mg; 150 mg; 200 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 200 mg once daily.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 150 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits wild type Janus kinase 1 and 2 (JAK1/JAK2) and mutant version of JAK2, which decreases production of a number of cytokines and growth factors needed for hematopoiesis and immune function. It also inhibits activin A receptor type 1, which increases the availability of iron availability and increased red blood cell production.

Therapeutic effects:

Reduction in symptoms associated with myelofibrosis.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption following oral administration unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 91%.

Metabolism/Excretion: Metabolized by the liver via the CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP1A2 isoenzymes into an active metabolite (M21). Primarily excreted in the feces (69%; 13% as unchanged drug), with 28% excreted in the urine (<1% as unchanged drug).

Half-Life: Momelotinib and M21: 4–8 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. If a dose is missed, omit and take next scheduled dose the following day. Advise patient to read Patient Information before starting therapy.
Notify patients, especially past or current smokers or those with cardiovascular risk factors, that the risk of stroke, heart attack, and related death is ↑ while using momelotinib. Instruct patient to notify health care professional immediately if symptoms (confusion, headache, paralysis, double vision, chest pain) occur.
Advise patient to notify health care professional immediately if symptoms of DVT (edema, pain, redness in lower leg) or PE (difficulty breathing, rapid heartbeat, dizziness) occur.
Inform patient of ↑ risk of lymphoma and other malignancies, especially if a past or current smoker.
Advise to notify health care professional of signs and symptoms of infection, easy bleeding or bruising, abdominal pain, or jaundice.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: Advise women of reproductive potential to use effective contraception and not to breastfeed during therapy and for 1 wk after final dose. Instruct women of reproductive potential to notify health care professional if pregnancy is planned or suspected.

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Indications ⬇

Contraind./Precautions ⬆ ⬇