Omjjara

/ GSK

The recommended dose is 200 mg once daily.
Complete blood cell count and liver function tests must be performed before initiating treatment, periodically during treatment, and as clinically indicated. Should not be used in combination with other JAK inhibitors.
See prescribing information for full details.

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.

* Hypersensitivity to the active substance or to any of the excipients
* Pregnancy and breast-feeding

Infections
Infections, including serious and fatal bacterial and viral infections (including COVID-19), have occurred. This medical product should not be initiated in patients with active infections. should carefully observe patients receiving momelotinib for signs and symptoms of infection (including but not limited to fever, cough, diarrhoea, vomiting, nausea, and pain upon urination) and initiate appropriate treatment promptly.
Hepatitis B reactivation
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine transaminase (ALT) or aspartate transaminase (AST), have been reported in patients with chronic hepatitis B virus (HBV) infection taking JAK inhibitors, including momelotinib. The effect of momelotinib on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection who receive momelotinib should have their chronic HBV infection treated and monitored.
Thrombocytopenia and neutropenia
New onset of severe (Grade ≥3) thrombocytopenia and neutropenia was observed. A complete blood count including platelet count should be obtained before initiating treatment periodically during treatment, and as clinically indicated. Dose interruption or reduction may be required.
Hepatic monitoring
Liver function tests should be obtained before initiating treatment, periodically during treatment, and as clinically indicated. If increases in ALT, AST or bilirubin related to treatment are suspected, dose interruption or reduction may be required.
Major adverse cardiovascular events (MACE)
Events of MACE have been reported in patients receiving momelotinib, however, a causal relationship has not been established. Prior to initiating or continuing therapy, the benefits and risks for the individual patient should be considered particularly in patients 65 years of age and older, patients who are current or past long-time smokers, and patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors.
Thrombosis
Events of DVT and PE have been reported in patients receiving momelotinib. However, a causal association has not been established. In patients with myelofibrosis treated with momelotinib in clinical trials, the rates of thromboembolic events were similar in momelotinib and control-treated patients. Prior to initiating or continuing therapy, the benefits and risks for the individual patient should be considered particularly in patients with cardiovascular risk factors.
Second primary malignancies
Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including momelotinib. However, a causal association has not been established.
Interactions
Based on the potential of momelotinib to increase the plasma concentrations of certain medicinal products (e.g., sensitive breast cancer resistance protein [BCRP] substrates, such as rosuvastatin and sulfasalazine), patients should be monitored for adverse reactions with co-administration. Co-administration of strong cytochrome P450 (CYP) 3A4 inducers may lead to decreased exposure of momelotinib and consequently a risk for reduced efficacy. Therefore, additional monitoring of the clinical signs and symptoms of myelofibrosis is recommended with concomitant use of momelotinib and strong CYP3A4 inducers (including but not limited to carbamazepine, phenobarbital, phenytoin, and St John’s wort [Hypericum perforatum]).
Women of childbearing potential
Given uncertainties whether momelotinib may reduce the effectiveness of hormonal contraceptives, women using systemically acting hormonal contraceptives should add a barrier method during treatment and for at least 1 week after the last dose.
See prescribing information for full details.

Common: Urinary tract infection, upper respiratory tract infection, pneumonia, nasopharyngitis, COVID-19, cystitis, bronchitis, oral herpes, sinusitis, herpes zoster, cellulitis, respiratory tract infection, sepsis, lower respiratory tract infection, oral candidiasis, skin infection, gastroenteritis, neutropenia, vitamin B1 deficiency, syncope, peripheral neuropathy, paraesthesia, blurred vision, vertigo, hypotension, haematoma, flushing, vomiting, constipation, rash, arthralgia, pain in extremity, pyrexia, alanine transaminase (ALT) increased, aspartate transaminase (AST) increased, contusion.
Very common: thrombocytopenia, dizziness, headache, cough, diarrhoea, abdominal pain, nausea, asthenia, fatigue.
See prescribing information for full details.

Effect of other medicinal products on momelotinib
Momelotinib undergoes metabolism though multiple CYP enzymes (including CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP1A2) and aldehyde oxidase, with CYP3A4 having the greatest contribution.
Strong CYP3A4 inducers: Co-administration of strong CYP3A4 inducers may lead to decreased momelotinib exposure and consequently a risk for reduced efficacy. Therefore, additional monitoring of the clinical signs and symptoms of myelofibrosis is recommended with concomitant use of momelotinib and strong CYP3A4 inducers (including but not limited to carbamazepine, phenobarbital, phenytoin, and St John’s wort [Hypericum perforatum]).
Transporters: Momelotinib is a substrate of OATP1B1 and OATP1B3 transporters. Co-administration with a single dose of rifampicin, capturing the OATP1B1/1B3 inhibition effect, moderately increased momelotinib exposure (Cmax by 40.4% and AUCinf by 57.1%). Therefore, caution and monitoring for adverse reactions is advised with concomitant use of OATP1B1/1B3 inhibitors, including ciclosporin.
Effect of momelotinib on other medicinal products
Transporters: Momelotinib is an inhibitor of BCRP. Co-administration of a single dose of rosuvastatin at 10 mg (a BCRP substrate) with multiple doses of momelotinib (200 mg once daily) increased rosuvastatin Cmax by 3.2-fold and AUC by 2.7-fold, which may increase the risk of adverse reactions of rosuvastatin. Tmax and t1/2 of rosuvastatin remained unchanged.
Momelotinib may increase exposure to other sensitive BCRP substrates, including sulfasalazine.
Momelotinib may inhibit P-gp in the gut and increase exposure to P-gp substrates. Therefore, caution is advised when administering momelotinib with P-gp substrates with a narrow therapeutic index.
Momelotinib may inhibit organic cation transporter 1 (OCT1). The active metabolite of momelotinib, M21, may inhibit multidrug and toxic compound extrusion transporter 1 (MATE1). Momelotinib and M21 have not been evaluated for MATE2-K inhibition. Therefore, caution is advised when administering momelotinib with sensitive substrates of OCT1, MATE1 and MATE2-K (e.g., metformin).
CYP450 substrates: Momelotinib may induce CYP1A2 and CYP2B6 and may inhibit CYP2B6. Therefore, narrow therapeutic index or sensitive substrate medicinal products of CYP1A2 (e.g., theophylline, tizanidine) or CYP2B6 (e.g., cyclophosphamide) should be co-administered with momelotinib with caution.
See prescribing information for full details.

Women of childbearing potential/Contraception
Women of childbearing potential should be advised to avoid becoming pregnant whilst receiving momelotinib. It is currently unknown whether momelotinib may reduce the effectiveness of systemically acting hormonal contraceptives, therefore women using systemically acting hormonal contraceptives should add a barrier method during treatment and for at least 1 week after the last dose.
Pregnancy: There are no data from the use of momelotinib in pregnant women. Based on its mechanism of action, momelotinib may cause foetal harm. This medical product is contraindicated during pregnancy. If momelotinib is used during pregnancy, or if the patient becomes pregnant while taking this medicinal product, the patient should discontinue treatment and be advised of the potential hazard to the foetus.
Lactation: It is unknown whether momelotinib/metabolites are excreted in human milk. A risk to the breast-fed child cannot be excluded. This medical product is contraindicated during breast-feeding.

If overdose is suspected, the patient should be monitored for any signs or symptoms of adverse reactions or effects, and appropriate standard of care measures should be instituted immediately. Further management should be as clinically indicated. Haemodialysis is not expected to enhance the elimination of momelotinib.