Jyseleca · 4.6 Fertility, pregnancy and lactation · 1

HOS-099177 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile Rheumatoid arthritis The most frequently reported adverse reactions are nausea (3.5%), upper respiratory tract infection (URTI, 3.3%), urinary tract infection (UTI, 1.7%), dizziness (1.2%) and lymphopenia (1.0%). Ulcerative colitis In general, the overall safety profile observed in filgotinib-treated patients with ulcerative colitis was generally consistent with the safety profile observed in patients with rheumatoid arthritis. Tabulated list of adverse reactions The following adverse reactions are based on clinical studies (Table 2). The adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1 000 to < 1/100). Table 2: Adverse reactions Frequency a Adverse reaction Infections and infestations Common Urinary tract infection (UTI) Upper respiratory tract infection (URTI) Uncommon Herpes zoster Pneumonia Sepsis Blood and lymphatic system disorders Common Lymphopenia Uncommon Neutropenia Metabolism and nutrition disorders Uncommon Hypercholesterolaemia Nervous system disorders Common Dizziness Ear and labyrinth disorders Uncommon Vertigo Gastrointestinal disorders Common Nausea 9  Frequency a Adverse reaction Investigations Common Blood phosphorus decreased Uncommon Blood creatine phosphokinase increased a Frequency based on placebo-controlled pre-rescue period (week 12) pooled across FINCH 1 and 2, and DARWIN 1 and 2, for patients with rheumatoid arthritis who received filgotinib 200 mg. Frequencies reported in the SELECTION study in patients with ulcerative colitis who received filgotinib 200 mg were generally consistent with those reported in the rheumatoid arthritis studies. Laboratory changes Creatinine An increase in serum creatinine occurred with filgotinib treatment. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), the mean (SD) increase from baseline in serum creatinine was 0.07 (0.12) and 0.04 (0.11) mg/dL for filgotinib 200 mg and 100 mg, respectively. Mean creatinine values remained within the normal range. Lipids Tr

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HOS-099173 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Active tuberculosis (TB) or active serious infections (see section 4.4). Pregnancy (see section 4.6).

HOS-099172 · has-indication-information · PDF-Seite 2

Rheumatoid arthritis Jyseleca is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). Ulcerative colitis Jyseleca is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent. 2

HOS-099175 · has-interaction-information · PDF-Seite 8

Effect of other medicinal products on filgotinib Filgotinib is primarily metabolised by carboxylesterase 2 (CES2), which can be inhibited in vitro by medicinal products such as fenofibrate, carvedilol, diltiazem or simvastatin. The clinical relevance of this interaction is unknown. Effect of filgotinib on other medicinal products Filgotinib is not a clinically relevant inhibitor or inducer of most enzymes or transporters commonly involved in interactions such as cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGT). In vitro studies are inconclusive regarding the potential of filgotinib to induce CYP2B6. In vivo induction cannot be excluded. In vitro studies are inconclusive regarding the potential of filgotinib to induce or inhibit CYP1A2. No clinical studies have been performed to investigate interactions with CYP1A2 substrates and therefore the potential in vivo effect of concomitant induction and inhibition of CYP1A2 by filgotinib is unknown. Caution is recommended when filgotinib is co-administered with CYP1A2 substrates with a narrow therapeutic index. In a clinical pharmacology study, there was no effect on the pharmacokinetics of the combined contraceptive ethinyl estradiol and levonorgestrel when co-administered with filgotinib; thus no dose adjustment of oral contraceptives is required.

HOS-099176 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential / Contraception Women of childbearing potential have to use effective contraception during and for at least 1 week after cessation of filgotinib treatment. Pregnancy There are no or limited amount of data from the use of filgotinib in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Based on findings in animals, filgotinib may cause foetal harm and is therefore contraindicated during pregnancy (see section 4.3). Breast-feeding It is unknown whether filgotinib is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. Therefore, Jyseleca should not be used during breast-feeding. Fertility In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed (see section 5.3). The data from two dedicated Phase 2 clinical 8 studies (MANTA and MANTA RAy, n=240) to evaluate the human testicular safety in men with inflammatory arthritis diseases and inflammatory bowel diseases did not reveal a difference between treatment groups in the proportion of patients who had a 50% or more decrease from baseline in semen parameters at week 13 (pooled primary endpoint: filgotinib 6.7%, placebo 8.3%) and at week 26. Further, the data did not show any relevant changes in sex hormone levels or change from baseline in semen parameters across treatment groups. Overall, these clinical data were not suggestive of filgotinib-related effects on testicular function. Animal studies did not indicate effects with respect to fertility in females.

HOS-099174 · has-warning-information · PDF-Seite 5

Filgotinib should only be used if no suitable treatment alternatives are available in patients: -65 years of age and older; -patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers); -patients with malignancy risk factors (e.g. current malignancy or history of malignancy) Immunosuppressive medicinal products Combination of filgotinib with other potent immunosuppressants such as ciclosporin, tacrolimus, biologics or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections Infections, including serious infections, have been reported in patients receiving filgotinib. The most frequent serious infection reported with filgotinib was pneumonia (see section 4.8). Among opportunistic infections, TB, oesophageal candidiasis, and cryptococcosis were reported with filgotinib. The risks and benefits of treatment should be considered prior to initiating filgotinib in patients: • with chronic or recurrent infection • who have been exposed to TB • with a history of a serious or an opportunistic infection • who have resided or travelled in areas of endemic TB or endemic mycoses; or • with underlying conditions that may predispose them to infection. Patients should be closely monitored for the development of signs and symptoms of infections during and after filgotinib treatment. If an infection develops during treatment with filgotinib, the patient should be carefully monitored and filgotinib treatment should be temporarily interrupted if the patient is not responding to standard antimicrobial therapy. Filgotinib treatment may be resumed once the infection is controlled. As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. In patients 65 years of age 5 and older, filgotinib should only be used if no suitable treatment alternatives are available (see section 4.2). Tuberculosis Patients should be screened for TB before initiating filgotinib. Filgotinib should not be administered to patients with active TB (see section 4.3). In patients with latent TB, standard antimycobacterial therapy should be initiated before administering filgotinib. Patients should be monitored for the development of signs and symptoms o

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