Version May 2024
Note: Delay momelotinib treatment initiation until active infections have resolved.
Myelofibrosis: Oral: 200 mg once daily until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Missed doses: If a dose is missed, the next scheduled dose should be administered on the following day.
eGFR ≥16.4 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant difference in momelotinib pharmacokinetics were observed.
eGFR <16.4 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage kidney disease on dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hepatic impairment prior to treatment initiation: Note: Delay treatment initiation in uncontrolled acute and chronic liver disease until apparent causes have been investigated and managed as clinically indicated.
Child-Turcotte-Pugh class A, B: No dosage adjustment necessary.
Child-Turcotte-Pugh class C: Reduce initial dose to 150 mg once daily.
Acute hepatotoxicity during treatment: Note: Evaluate and rule out other apparent causes of hepatic toxicity.
ALT and/or AST >5 times ULN (or >5 times baseline, if baseline is abnormal) and/or total bilirubin >2 times ULN (or >2 times baseline, if baseline is abnormal): Interrupt momelotinib until AST and ALT ≤2 times ULN or baseline (if baseline >2 times ULN) and total bilirubin ≤1.5 times ULN or baseline (if baseline >1.5 times ULN); restart momelotinib at a daily dose reduced by 50 mg below the last administered dose (if previous dose administered was 100 mg once daily, may reinitiate dose at 100 mg once daily). Reinitiate or escalate treatment up to the starting dose as clinically appropriate.
Recurrence of ALT or AST elevations >5 times ULN: Permanently discontinue momelotinib.
|
Adverse reaction |
Severity |
Dose modificationa |
|---|---|---|
|
a Reinitiate or escalate treatment up to the starting dose as clinically appropriate. | ||
|
b If previous dose administered was 100 mg once daily, may reinitiate dose at 100 mg once daily. Discontinue if unable to tolerate 100 mg once daily. | ||
|
c HBV = hepatitis B virus. | ||
|
Hematologic toxicity | ||
|
Thrombocytopenia Baseline platelet count: ≥100,000/mm3 |
Platelet count: 20,000 to <50,000/mm3 |
Reduce the daily dose by 50 mg from the last administered dose. |
|
Platelet count: <20,000/mm3 |
Interrupt treatment until platelets ≥50,000/mm3; restart momelotinib at a daily dose reduced by 50 mg below the last administered dose.b | |
|
Thrombocytopenia Baseline platelet count: ≥50,000 to <100,000/mm3 |
Platelet count: <20,000/mm3 |
Interrupt treatment until platelets ≥50,000/mm3; restart momelotinib at a daily dose reduced by 50 mg below the last administered dose.b |
|
Thrombocytopenia Baseline platelet count: <50,000/mm3 |
Platelet counts: <20,000/mm3 |
Interrupt treatment until platelets recover to baseline; restart momelotinib at a daily dose reduced by 50 mg below the last administered dose.b |
|
Neutropenia |
ANC <500/mm3 |
Interrupt treatment until ANC ≥750/mm3; restart momelotinib at a daily dose reduced by 50 mg below the last administered dose.b |
|
Nonhematologic toxicity | ||
|
Infection |
Any |
Initiate appropriate treatment promptly. Monitor and treat chronic HBVc reactivation according to clinical HBV guidelines. |
|
Secondary malignancy |
Any |
Consider the benefits versus individual patient risks prior to continuing momelotinib in patients who develop a malignancy (other than a successfully treated nonmelanoma skin cancer). |
|
Thrombosis symptoms |
Any |
Evaluate and treat appropriately. |
|
Other adverse reactions |
≥ Grade 3 |
Interrupt treatment until toxicity resolves to ≤ grade 1 (or baseline); restart momelotinib at a daily dose reduced by 50 mg below the last administered dose.b |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypotension (14%), peripheral edema (11%)
Dermatologic: Pruritus (11%), skin rash (6% to 12%)
Gastrointestinal: Abdominal pain (13% to 18%), diarrhea (20% to 22%; grades ≥3: 1%), nausea (16% to 20%; grades ≥3: 2%)
Genitourinary: Urinary tract infection (≤12%)
Hematologic & oncologic: Hemorrhage (21% to 22%; grades ≥3: 1% to 2%), thrombocytopenia (21% to 28%; grades ≥3: 11% to 22%)
Hepatic: Increased serum alanine aminotransferase (23%), increased serum aspartate aminotransferase (24%), increased serum bilirubin (16%)
Infection: Infection (38%; including bacterial infection [15% to 21%], fungal infection [excluding opportunistic infections: <5%], kidney infection [≤12%], serious infection [13%], viral infection [6% to 12%])
Nervous system: Dizziness (8% to 24%), fatigue (21% to 22%), headache (11%)
Neuromuscular & skeletal: Limb pain (12%)
Respiratory: Cough (8% to 14%)
Miscellaneous: Fever (10% to 12%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (5% to 8%), flushing (<5%), heart failure (4%), syncope (2%), thrombosis (3%)
Endocrine & metabolic: Vitamin B deficiency (B1: 6%)
Gastrointestinal: Vomiting (8%; grades ≥3: 1%)
Hematologic & oncologic: Neutropenia (5%; grades ≥3: 5%)
Nervous system: Neuralgia (<5%), paresthesia (8%), peripheral motor neuropathy (<5%), peripheral neuropathy (<5%), polyneuropathy (<5%)
Neuromuscular & skeletal: Back pain (7%)
Ophthalmic: Blurred vision (<5%)
Renal: Acute kidney injury (3%)
Respiratory: Pneumonia (8%), respiratory failure (2%)
<1%: Hepatic: Hepatic injury
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiac effects: An increased the risk of major adverse cardiovascular events, including cardiovascular death, myocardial infarction, and stroke, has been reported with another Janus Kinase (JAK) inhibitor when used for the treatment of rheumatoid arthritis (not an approved use for momelotinib). Consider individual patient benefits versus cardiovascular risks prior to initiating or continuing momelotinib, particularly in patients with current (or history of) smoking or with other cardiovascular risk factors. Patients should be aware of symptoms of serious cardiovascular events and the steps to take if they occur.
• Hematologic toxicity: Momelotinib may cause thrombocytopenia and neutropenia; new or worsening thrombocytopenia (platelets <50,000/mm3) was observed in one-fifth of patients who received momelotinib. Some patients treated with momelotinib had baseline platelets <50,000/mm3. Severe neutropenia (ANC <500/mm3) was observed in a small percentage of patients.
• Hepatotoxicity: Cases of reversible drug-induced liver injury have been observed with momelotinib. Overall, new or worsening ALT and AST elevations (all grades) occurred in nearly one-fourth of patients and grade 3 and 4 transaminase elevations occurred in a small percentage of patients. Grade 1 or 2, new or worsening total bilirubin elevations have occurred. The median time to onset of any grade transaminase elevation was 2 months, with most cases occurring within 4 months.
• Infections: Serious infections (eg, bacterial and viral, including COVID-19) have occurred with momelotinib, including fatal cases. Infections of any grade occurred in over one-third of patients. Hepatitis B viral load (HBV-DNA titer) increases (with or without associated ALT or AST elevations) have been reported with JAK inhibitors (including momelotinib) in patients with chronic hepatitis B virus (HBV) infection. The effect of momelotinib on viral replication in chronic HBV infection is unknown. If HBsAg and/or anti-HBc antibody is positive, consider a hepatology consultation regarding monitoring for reactivation versus prophylactic hepatitis B therapy.
• Secondary malignancies: An increased risk of lymphoma and other malignancies (excluding nonmelanoma skin cancer) has been demonstrated with another JAK inhibitor when used for the treatment of rheumatoid arthritis (not an approved use for momelotinib). Smoking (current or past history) increased the risk for malignancy. Consider the benefits versus individual patient risks prior to initiating or continuing momelotinib, particularly in patients with a known malignancy (other than a successfully treated nonmelanoma skin cancer) or who develop a malignancy, and patients who are current or past smokers.
• Thrombosis: The risk for thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, was increased with another JAK inhibitor when used for the treatment of rheumatoid arthritis (not an approved use for momelotinib).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as dihydrochloride:
Ojjaara: 100 mg, 150 mg, 200 mg
No
Tablets (Ojjaara Oral)
100 mg (per each): $1,076.00
150 mg (per each): $1,076.00
200 mg (per each): $1,076.00
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Oral: Administer with or without food. Swallow tablets whole; do not cut, crush, or chew.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Momelotinib may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Myelofibrosis: Treatment of 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.
Momelotinib may be confused with erlotinib, mobocertinib, nilotinib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP1A2 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Momelotinib. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rosuvastatin: Momelotinib may increase the serum concentration of Rosuvastatin. Management: In patients who are receiving momelotinib, initiate rosuvastatin at a dose of 5 mg once daily and limit the rosuvastatin dose to a maximum of 10 mg once daily. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who could become pregnant should use highly effective contraception during therapy and for at least 1 week after the last momelotinib dose.
Based on data from animal reproduction studies, in utero exposure to momelotinib may cause fetal harm.
It is not known if momelotinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 1 week after the last momelotinib dose.
CBC with differential (baseline, periodically during treatment, and as clinically indicated); hepatic function tests (baseline, every month for 6 months during treatment, then periodically as clinically indicated). Monitor for signs/symptoms of infection, cardiovascular adverse events, thrombosis, and secondary malignancies. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Momelotinib HBV monitoring: Assess hepatitis B serologies (prior to treatment initiation in patients with hepatitis B virus infection; if HBsAg and/or anti-HBc antibody is positive, consider a hepatology consultation regarding monitoring for reactivation versus prophylactic hepatitis B therapy). Monitor for signs/symptoms of hepatitis B infection (including reactivation).
Momelotinib inhibits wild type Janus Kinase 1 and 2 (JAK1/JAK2), and selectively inhibits activin A receptor type 1 (ACVR1). In addition to inhibiting wild type JAK1 and JAK2, momelotinib also inhibits mutant JAK2V617F, all of which contribute to cytokine and growth factor signaling necessary for hematopoiesis and immune function. ACVR1 inhibition reduces circulating hepcidin, an iron hematopoiesis regulator, which increases availability of iron for erythropoiesis and increased RBC production (Mesa 2017; Verstovsek 2023; manufacturer’s labeling). Myelofibrosis is associated with constitutive activation and dysregulated JAK signaling which contributes to inflammation and hyperactivation of ACVR1. JAK signaling recruits and activates signal transducers and activation of transcription (STAT) proteins, resulting in nuclear localization and subsequent gene transcription regulation.
Onset: Maximal inhibition of STAT3 phosphorylation occurred 2 hours after dosing.
Duration: Inhibition of STAT3 phosphorylation persisted for ≥6 hours after dosing. A sustained reduction in circulating hepcidin was observed for the 24-week treatment period.
Distribution: Vdss: 984 L.
Protein binding: ~91% (healthy volunteers).
Metabolism: Momelotinib is extensively metabolized via multiple cytochrome P450 (CYP) enzymes, including CYP3A4 (36%), CYP2C8 (19%), CYP2C9 (17%), CYP2C19 (19%), and CYP1A2 (9%). M21 is an active human metabolite (formed by CYP followed by aldehyde oxidase metabolism of momelotinib) with ~40% of the pharmacologic activity of momelotinib.
Half-life elimination: Momelotinib and M21 (active metabolite): 4 to 8 hours.
Time to peak: 2 hours.
Excretion: Feces: 69% (13% as unchanged drug); urine: 28% (<1% as unchanged drug; ~12% as the active metabolite M21).
Clearance: 103 L/hour.
Hepatic function impairment: Momelotinib Cmax and AUC are increased by 13% and 97%, respectively, in patients with severe hepatic impairment (Child-Turcotte-Pugh class C); the M21 (active) metabolite Cmax and AUC are decreased by 76% and 48%, respectively, in patients with severe hepatic impairment (Child-Turcotte-Pugh class C).
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