Omjjara · 4.4 Special warnings and precautions for use · 1

HOS-288529 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile The safety of Omjjara, evaluated in three randomised, active-controlled, multicentre studies in adults with myelofibrosis (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), is presented below (table 2). Among patients treated with Omjjara 200 mg daily in the randomised treatment period of the clinical trials (n = 448), the most common adverse reactions were diarrhoea (23%), thrombocytopenia (21%), nausea (17%), headache (13%), dizziness (13%), fatigue (12%), asthenia (11%), abdominal pain (11%), and cough (10%). The most common severe adverse reaction (≥ Grade 3) was thrombocytopenia (12%). The most common adverse reaction leading to discontinuation of Omjjara was thrombocytopenia (2.5%). The most common adverse reaction requiring dosage reduction and/or treatment interruption was thrombocytopenia (7%). Tabulated list of adverse reactions The following adverse reactions have been identified in 448 patients exposed to Omjjara during a median duration of 24 weeks during clinical trials (see section 5.1). Adverse reactions are listed by MedDRA system organ classification (SOC) and by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as: Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1 000 to <1/100 Rare: ≥1/10 000 to <1/1 000 Not known: cannot be estimated from the available data Table 2: Summary of adverse reactions reported in Phase 3 studies in adults with myelofibrosis System organ class (SOC) Adverse reaction Frequency category Infections and infestations Urinary tract infection, upper respiratory Common 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 COVID-19 pneumonia Uncommon Blood and lymphatic system Thrombocytopenia a Very common disorders Neutropeniab

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HOS-288525 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Pregnancy and breast-feeding (see section 4.6).

HOS-288524 · has-indication-information · PDF-Seite 3

Omjjara is indicated for the treatment of disease-related splenomegaly or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib.

HOS-288527 · has-interaction-information · PDF-Seite 7

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 Multiple doses of rifampicin (600 mg daily for 7 days) decreased momelotinib Cmax by 29.4% and AUCinf by 46.1% when compared with momelotinib (200 mg single dose) plus rifampicin single‑dose (600 mg), to capture the induction effect of rifampicin. 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]). Multiple doses of rifampicin (600 mg daily for 7 days) did not change momelotinib Cmax and decreased momelotinib AUCinf by 15.3% when compared with momelotinib alone (200 mg single dose), capturing the combined effect of CYP3A4 induction and organic anion transporting peptide (OATP)1B1 and OATP1B3 inhibition. Momelotinib can be co-administered with rifampicin without a dose modification. 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. 7 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

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HOS-288528 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception Women of childbearing potential should be advised to avoid becoming pregnant whilst receiving Omjjara. It is currently unknown whether Omjjara 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 of Omjjara (see sections 4.4 and 4.5). Pregnancy There are no data from the use of momelotinib in pregnant women. Studies in animals have shown embryo-foetal toxicity at exposures lower than human exposure at the recommended dose (see section 5.3). Based on its mechanism of action, Omjjara may cause foetal harm. As a JAK inhibitor, Omjjara has been shown to cause embryo-foetal mortality and teratogenicity in pregnant rats and rabbits at clinically-relevant exposures. Omjjara is contraindicated during pregnancy (see section 4.3). If Omjjara 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. Breast-feeding It is unknown whether momelotinib/metabolites are excreted in human milk. Momelotinib was present in rat pups following nursing from treated dams with adverse events in the offspring (see section 5.3). A risk to the breast-fed child cannot be excluded. Omjjara is contraindicated during breast-feeding (see section 4.3). Fertility There are no data on the effects of momelotinib on human male or female fertility. In animal studies, momelotinib impaired fertility in male and female rats (see section 5.3). 8

HOS-288526 · has-warning-information · PDF-Seite 5

Infections Infections, including serious and fatal bacterial and viral infections (including COVID-19), have occurred in patients treated with Omjjara (see section 4.8). Omjjara should not be initiated in patients with active infections. Physicians should carefully observe patients receiving Omjjara 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 Omjjara. The effect of Omjjara on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection who receive Omjjara should have their chronic HBV infection treated and monitored according to clinical HBV guidelines. Thrombocytopenia and neutropenia New onset of severe (Grade ≥3) thrombocytopenia and neutropenia was observed in patients treated with Omjjara (see section 4.8). A complete blood count including platelet count should be obtained before initiating treatment with Omjjara, periodically during treatment, and as clinically indicated. 5 Dose interruption or reduction may be required (see section 4.2). Hepatic monitoring Liver function tests should be obtained before initiating treatment with Omjjara, 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 (see section 4.2). Major adverse cardiovascular events (MACE) In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of MACE, defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke, was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. Events of MACE have been reported in patients receiving Omjjara, however, a causal relationship has not been established. Prior to initiating or continuing therapy with Omjjara, the benefits and risks for the individual patient should be considered particularly in patients

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