Jyseleca Special Precautions

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 Adverse Reactions). 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 and older, filgotinib should only be used if no suitable treatment alternatives are available (see Dosage & Administration).
Tuberculosis: Patients should be screened for TB before initiating filgotinib. Filgotinib should not be administered to patients with active TB (see Contraindications). 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 of TB, including patients who tested negative for latent TB infection prior to initiating treatment.
Viral reactivation: Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies (see Adverse Reactions). In rheumatoid arthritis clinical studies, the risk of herpes zoster appeared to be higher in female patients, Asian patients, patients ≥50 years of age, patients with a medical history of herpes zoster, patients with a medical history of chronic lung disease and patients treated with filgotinib 200 mg once daily. If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves.
Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during treatment with filgotinib. Patients who were positive for both hepatitis C antibody and hepatitis C virus RNA were excluded from clinical studies. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical studies.
Malignancy: Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including filgotinib. 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 malignancies, particularly lung cancer, lymphoma and non melanoma skin cancer (NMSC) was observed with tofacitinib compared to TNF inhibitors.
In patients 65 years of age and older, patients who are current or past long-time smokers, or with other malignancy risk factors (e.g. current malignancy or history of malignancy), filgotinib should only be used if no suitable treatment alternatives are available.
Non-melanoma skin cancer: NMSCs have been reported in patients treated with filgotinib. Periodic skin examination is recommended for all patients, particularly those who are at increased risk for skin cancer.
Haematological abnormalities: ANC <1 × 10⁹ cells/L (see Adverse Reactions) and ALC <0.5 × 10⁹ cells/L were reported in ≤1% of patients in the rheumatoid arthritis clinical studies and in <3% of patients in the ulcerative colitis clinical studies. Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC <1 × 10⁹ cells/L, ALC <0.5 × 10⁹ cells/L or haemoglobin <8 g/dL observed during routine patient management (see Dosage & Administration).
Vaccinations: Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. It is recommended that immunisations, including prophylactic zoster vaccinations, be updated in agreement with current immunisation guidelines prior to initiating filgotinib treatment.
Lipids: Treatment with filgotinib was associated with dose-dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low-density-lipoprotein (LDL) levels were slightly increased (see Adverse Reactions). LDL cholesterol returned to pre treatment-levels in the majority of patients who started statin therapy while taking filgotinib. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined (see Dosage & Administration for monitoring guidance).
Major adverse cardiovascular events (MACE): Events of MACE have been observed in patients taking filgotinib.
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 major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors.
Therefore, 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, filgotinib should only be used if no suitable treatment alternatives are available.
Venous thromboembolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including filgotinib.
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 dose dependent higher rate of VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) was observed with tofacitinib compared to TNF inhibitors.
In patients with cardiovascular or malignancy risk factors (see also "Major adverse cardiovascular events (MACE)" and "Malignancy" as previously mentioned) filgotinib should only be used if no suitable treatment alternatives are available.
In patients with known VTE risk factors other than cardiovascular or malignancy risk factors, filgotinib should be used with caution. VTE risk factors other than cardiovascular or malignancy risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, inherited coagulation disorder.
Patients should be re-evaluated periodically during filgotinib treatment to assess for changes in VTE risk.
Promptly evaluate patients with signs and symptoms of VTE and discontinue filgotinib in patients with suspected VTE, regardless of dose.
Lactose content: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Mortality: In a large, randomised, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with tumour necrosis factor inhibitors.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with filgotinib.
Gastrointestinal perforation: Events of gastrointestinal perforation have been reported in patients receiving JAK inhibitors including filgotinib. Filgotinib should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis, patients with concomitant use of corticosteroids and/or nonsteroidal anti-inflammatory drugs). Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of gastrointestinal perforation.
Effects on ability to drive and use machines: Filgotinib has minor influence on the ability to drive and use machines. Patients should be advised that dizziness and vertigo have been reported during treatment with Jyseleca (see Adverse Reactions).
Use in the Elderly: Use in patients over 65 years of age and older: Considering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients 65 years of age and older, as observed in a large randomised study of tofacitinib (another JAK inhibitor), filgotinib should only be used in these patients if no suitable treatment alternatives are available.