Dosing & Uses
Dosage Forms & Strengths
tablet
- 100mg
- 150mg
- 200mg
Myelofibrosis
Indicated for intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [post polycythemia vera (PV) and post essential thrombocythemia (ET)], in adults with anemia
200 mg PO qDay with or without food
Dosage Modifications
Discontinue in patients unable to tolerate 100 mg qDay
Thrombocytopenia
May reinitiate or increase dose up to starting dose as clinically appropriate
-
Reduce daily dose by 50 mg from last given dose if
- Baseline ≥100 x 109/L, then decreased to 20 to <50 x 109/L
-
Interrupt treatment until platelets recover to 50 x 109/L if
- Baseline ≥100 x 109/L, then decreased to <20 x 109/L
- Baseline 50 to <100 x 109/L, then decreased to <20 x 109/L
- Restart at a daily dose of 50 mg below the last given dose
- May reinitiate treatment at 100 mg if previously dosed at 100 mg
-
Interrupt treatment until platelets recover to baseline
- Baseline <50 x 109/L, then decreased to <20 x 109/L
- Restart at a daily dose of 50 mg below the last given dose
- May reinitiate treatment at 100 mg if previously dosed at 100 mg
Neutropenia
- Defined as absolute neutrophil count (ANC) <0.5 x 109/L
- Interrupt treatment until ANC ≥0.75 x 109/L
- Restart at a daily dose of 50 mg below last given dose
- May reinitiate treatment at 100 mg if previously dosed at 100 mg
Hepatoxicity
- Defined as ALT and/or AST >5x ULN (or >5x baseline, if baseline is abnormal) and/or total bilirubin >2x ULN (or >2x baseline, if baseline is abnormal)
- Interrupt treatment until AST and ALT ≤2x ULN or baseline and total bilirubin ≤1.5x ULN or baseline (if baseline >2x ULN)
- Restart at a daily dose of 50 mg below the last given dose; may reinitiate treatment at 100 mg if previously dosed at 100 mg
- If reoccurrence of ALT or AST elevations >5x ULN, permanently discontinue
Other nonhematologic toxicities
- Interrupt treatment until the toxicity resolves to Grade ≤1 (or baseline)
- Restart at a daily dose of 50 mg below the last given dose; may reinitiate treatment at 100 mg if previously dosed at 100 mg
Renal impairment
- All severities (eGFR ≥16.4 mL/min/1.73 m2): No dosage adjustment necessary
- End-stage renal disease receiving dialysis: Pharmacokinetics is unknown
Hepatic impairment
- Mild or moderate (Child-Pugh Class A or B): No dosage adjustment necessary
- Severe (Child-Pugh Class C): Reduce starting dose to 150 mg qDay
Dosing Considerations
Monitoring parameters
- Complete blood cell (CBC) count with platelets at baseline and periodically during treatment as clinically indicated
- Monitor liver tests at baseline, every month for 6 months during treatment, then periodically as clinically indicated
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (1)
- rimegepant
momelotinib increases toxicity of rimegepant by plasma protein binding competition. Avoid or Use Alternate Drug. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. .
Monitor Closely (55)
- alpelisib
momelotinib increases toxicity of alpelisib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- atorvastatin
momelotinib increases toxicity of atorvastatin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- chlorothiazide
momelotinib increases toxicity of chlorothiazide by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- cimetidine
momelotinib increases toxicity of cimetidine by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- clarithromycin
clarithromycin increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- clotrimazole
clotrimazole increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- cyclosporine
cyclosporine increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- daunorubicin
momelotinib increases toxicity of daunorubicin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- dipyridamole
momelotinib increases toxicity of dipyridamole by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- doxorubicin
momelotinib increases toxicity of doxorubicin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- encorafenib
encorafenib increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- erythromycin base
erythromycin base increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- erythromycin lactobionate
erythromycin lactobionate increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- erythromycin stearate
erythromycin stearate increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- ethinylestradiol
momelotinib increases toxicity of ethinylestradiol by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- fluvastatin
momelotinib increases toxicity of fluvastatin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- fostemsavir
fostemsavir increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- gemfibrozil
gemfibrozil increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- glyburide
momelotinib increases toxicity of glyburide by plasma protein binding competition. Use Caution/Monitor. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- imatinib
momelotinib increases toxicity of imatinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- irinotecan
momelotinib increases toxicity of irinotecan by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- lapatinib
momelotinib increases toxicity of lapatinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- ledipasvir/sofosbuvir
momelotinib increases toxicity of ledipasvir/sofosbuvir by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- leflunomide
momelotinib increases toxicity of leflunomide by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- leniolisib
leniolisib increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- lenvatinib
lenvatinib increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
momelotinib increases toxicity of lenvatinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary. - methotrexate
momelotinib increases toxicity of methotrexate by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- mitoxantrone
momelotinib increases toxicity of mitoxantrone by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- nitrofurantoin
momelotinib increases toxicity of nitrofurantoin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- osimertinib
momelotinib increases toxicity of osimertinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- ozanimod
momelotinib increases toxicity of ozanimod by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- pantoprazole
momelotinib increases toxicity of pantoprazole by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- pazopanib
pazopanib increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
momelotinib increases toxicity of pazopanib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary. - pitavastatin
momelotinib increases toxicity of pitavastatin by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- rifampin
rifampin increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- riociguat
momelotinib increases toxicity of riociguat by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- ritonavir
ritonavir increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- rosuvastatin
momelotinib increases toxicity of rosuvastatin by plasma protein binding competition. Modify Therapy/Monitor Closely. When coadministered with momelotinib (BCRP inhibitor), initiate rosuvastatin (BCRP substrate) at 5 mg and not to exceed 10 mg once daily.
- selexipag
momelotinib increases toxicity of selexipag by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- selumetinib
momelotinib increases toxicity of selumetinib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- sofosbuvir
momelotinib increases toxicity of sofosbuvir by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- sulfasalazine
momelotinib increases toxicity of sulfasalazine by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- tacrolimus
tacrolimus increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- talazoparib
momelotinib increases toxicity of talazoparib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- telmisartan
telmisartan increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- tenofovir AF
momelotinib increases toxicity of tenofovir AF by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- topotecan
momelotinib increases toxicity of topotecan by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- trofinetide
trofinetide increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
- ublituximab
ublituximab and momelotinib both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered
- ubrogepant
momelotinib increases toxicity of ubrogepant by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- velpatasvir
velpatasvir increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
momelotinib increases toxicity of velpatasvir by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary. - vemurafenib
momelotinib increases toxicity of vemurafenib by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- voxilaprevir
voxilaprevir increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.
momelotinib increases toxicity of voxilaprevir by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
Minor (0)
Adverse Effects
>10%
All grades
- Thrombocytopenia (21-28%)
- Diarrhea (20-22%)
- Hemorrhage (21-22%)
- Dizziness (8-24%)
- Fatigue (21-22%)
- Bacterial infection (15-21%)
- Nausea (16-20%)
- Abdominal pain (13-18%)
- Cough (8-14%)
- Hypotension(14%)
- Viral infection (12%)
- Pain in extremity (12%)
- Pyrexia (10-12%)
- Rash (6-12%)
- Renal and urinary tract infection (6-12%)
- Pruritus (11%)
- Headache (11%)
- Peripheral edema (11%)
- Elevated liver enzymes (10-11%)
Grade 3 or 4
- Thrombocytopenia (11-22%)
1-10%
All grades
- Paresthesia (8%)
- Vomiting (8%)
- Pneumonia (8%)
- Arrhythmias (5-8%)
- Back pain (7%)
- Viral infection (6%)
- Vitamin B12 deficiency (6%)
- Neutropenia (5%)
- Blurred vision (<5%)
- Fungal infection (excludes opportunistic infections) (<5%)
- Neuralgia (<5%)
- Peripheral neuropathy (<5%)
- Peripheral motor neuropathy(<5%)
- Polyneuropathy (<5%)
- Flushing (<5%)
Grade 3 or 4
- Bacterial infection (8%)
- Pneumonia (8%)
- Viral infection (5%)
- Neutropenia (5%)
- Elevated liver enzymes (2-4%)
- Hemorrhage (1-2%)
- Fatigue (2%)
- Nausea (2%)
- Pruritus (2%)
- Pyrexia (2%)
- Dizziness (1-2%)
- Renal and urinary tract infection (1-2%)
- Arrhythmias (1-2%)
- Hypotension (2%)
- Abdominal pain (1%)
- Paresthesia (1%)
- Vomiting (1%)
- Diarrhea (1%)
- Pyrexia (1%)
- Back pain (1%)
Warnings
Contraindications
None
Cautions
Serious (including fatal) infections (eg, bacterial and viral, including COVID-19) occurred; delay starting therapy until active infections have resolved; monitor patients for signs and symptoms of infection and initiate appropriate treatment promptly
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated AST/ALT, reported in patients with chronic hepatitis B virus (HBV) infection taking Janus kinase (JAK) inhibitors; treated patients with chronic HBV infection should have their chronic HBV infection treated and monitored according to clinical HBV guidelines
Another JAK inhibitor increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis; evaluate if symptoms of thrombosis arise and treat appropriately
May cause thrombocytopenia and neutropenia; assess CBC count, including platelet and neutrophil counts, before initiating treatment and periodically during treatment as clinically indicated; interrupt dosing or reduce the dose for thrombocytopenia or neutropenia
Hepatotoxicity
- Two patients with MF who received at least one dose in clinical trials experienced reversible drug-induced liver injury
- Overall, new or worsening elevations of ALT and AST (all grades) occurred in 23% and 24%, respectively, of treated patients
- Median time to onset of any grade transaminase elevation was 2 months, with 75% of cases occurring within 4 months
- Delay starting therapy in patients presenting with uncontrolled acute and chronic liver disease until apparent causes have been investigated and treated as clinically indicated
- Refer to dosing for hepatic impairment when initiating
- Monitor liver tests at baseline, every month for 6 months during treatment, then periodically as clinically indicated
- If ALT, AST, or bilirubin increases during treatment, modify dosage
Major adverse cardiovascular events (MACE)
- Another JAK inhibitor increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke
- Consider the benefits and risks before initiating or continuing therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors
- Inform treated patients of the symptoms of serious cardiovascular events and steps to take if they occur
Malignancies
- Another JAK inhibitor increased the risk of lymphoma and other malignancies excluding nonmelanoma skin cancer (NMSC) in patients with rheumatoid arthritis
- Current or past smokers were at increased risk
- Consider the benefits and risks before initiating or continuing therapy particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
Drug interaction overview
- Organic anion transporting polypeptide (OATP)1B1/B3 substrate
- Breast cancer resistance protein (BCRP) inhibitor
-
OATP1B1/B3 inhibitors
- Monitor and consider momelotinib dose modifications
- OATP1B1/B3 inhibitor increases momelotinib maximal concentrations and area under the concentration-time curve, which may increase the risk of adverse reactions with momelotinib
-
Breast cancer resistance protein (BCRP) substrates
- Rosuvastatin: When coadministered with momelotinib, initiate rosuvastatin (BCRP substrate) at 5 mg and do not increase to more than 10 mg once daily
- Dose adjustment of other BCRP substrates may also be needed
- Momelotinib may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions
Pregnancy & Lactation
Pregnancy
Insufficient data are available on use in pregnant females to determine whether there is a drug-associated risk for major birth defects or miscarriage
Contraception
- Advise females of reproductive potential who are not pregnant to use highly effective contraception during therapy and for at least 1 week after last dose
Animal data
- Momelotinib may cause embryofetal toxicity at exposures lower than expected exposure in patients receiving 200 mg once daily
- Only use during pregnancy if the expected benefits to the mother outweigh the potential risks to the fetus
Lactation
There are no data on the presence of momelotinib or its metabolites in human milk, effects on breastfed children, or effects on milk production
It is not known whether momelotinib is excreted in human milk
Momelotinib was present in rat pups following nursing from treated dams with adverse effects observed in offspring
When a drug is present in animal milk, it is likely that the drug will be present in human milk
Advise females not to breastfeed during treatment, and for at least 1 week after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits signals along 3 pathways – Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1)
Competes with JAK1/2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and therefore, induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells
JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorder
ACVR1 is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2 (activin receptor-like kinase-2); transduces signals of bone morphogenetic protein (BMP)
Absorption
Peak plasma concentration (steady-state): 479 ng/mL
Peak plasma time (steady-state): 2 hr
AUC: 3,288 ng⋅hr/mL
Distribution
Vd: 984 L
Protein-bound: 91%
Metabolism
Momelotinib is metabolized by multiple CYP enzymes including CYP3A4 (36%), CYP2C8 (19%), CYP2C9 (17%), CYP2C19 (19%), and CYP1A2 (9%)
M21 is an active human metabolite (~40% of pharmacological activity of parent drug)
M21 is formed by CYP followed by aldehyde oxidase metabolism of momelotinib
Elimination
Clearance: 103 L/hr
Half-life: 4-8 hr
Excretion
- Feces: 69% (13% unchanged)
- Urine: (28%)
- Approximately 12% of the administered dose was excreted in urine as M21
Administration
Oral Administration
Take with or without food
Swallow tablets whole; do not cut, crush, or chew
Missed dose: Take next scheduled dose the following day
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Dispense to patient in original bottle only
Store in original bottle to protect from moisture
Replace cap securely each time after opening; do not discard desiccant
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Formulary
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