Infections: Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo (see Adverse Reactions). In rheumatoid arthritis clinical studies, in treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy. The risks and benefits of treatment with Olumiant should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections (see Dosage & Administration). If an infection develops, the patient should be monitored carefully and Olumiant therapy should be temporarily interrupted if the patient is not responding to standard therapy. Olumiant treatment should not be resumed until the infection resolves.
Tuberculosis: Patients should be screened for tuberculosis (TB) before starting Olumiant therapy. Olumiant should not be given to patients with active TB. Anti-TB therapy should be considered prior to initiation of Olumiant in patients with previously untreated latent TB.
Haematological abnormalities: Absolute Neutrophil Count (ANC) < 1 x 109 cells/L and Absolute Lymphocyte Count (ALC) < 0.5 x 109 cells/L and haemoglobin < 8 g/dL were reported in less than 1% of patients in clinical trials. Haemoglobin < 8 g/dL was reported in less than 1% of patients in rheumatoid arthritis clinical trials.
Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC < 1 x 109 cells/L, ALC < 0.5 x 109 cells/L or haemoglobin < 8 g/dL observed during routine patient management (see Dosage & Administration).
The risk of lymphocytosis is increased in elderly patients with rheumatoid arthritis. Rare cases of lymphoproliferative disorders have been reported.
Viral reactivation: Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies (see Adverse Reactions). In rheumatoid arthritis clinical studies, herpes zoster was reported more commonly in patients ≥ 65 years of age who had previously been treated with both biologic and conventional DMARDs. If a patient develops herpes zoster, Olumiant treatment should be temporarily interrupted until the episode resolves.
Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with Olumiant. Patients with evidence of active hepatitis B or C infection were excluded from clinical trials. Patients, who were positive for hepatitis C antibody but negative for hepatitis C virus RNA, were allowed to participate. Patients with hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were also allowed to participate; such patients should be monitored for expression of hepatitis B virus (HBV) DNA. If HBV DNA is detected, a liver specialist should be consulted to determine if treatment interruption is warranted.
Vaccination: No data are available on the response to vaccination with live vaccines in patients receiving baricitinib. Use with live, attenuated vaccines during, or immediately prior to, Olumiant therapy is not recommended. Prior to initiating Olumiant, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines.
Lipids: Dose dependent increases in blood lipid parameters were reported in patients treated with baricitinib compared to placebo (see Adverse Reactions). Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy. Lipid parameters should be assessed approximately 12 weeks following initiation of Olumiant therapy and thereafter patients should be managed according to international clinical guidelines for hyperlipidaemia. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.
Hepatic transaminase elevations: Dose dependent increases in blood alanine transaminase (ALT) and aspartate transaminase (AST) activity were reported in patients treated with baricitinib compared to placebo (see Adverse Reactions). Increases in alanine transaminase (ALT) and aspartate transaminase (AST) to ≥ 5 and ≥ 10 x upper limit of normal (ULN) were reported in less than 1% of patients in clinical trials. In treatment-naïve patients, combination with methotrexate resulted in increased frequency of hepatic transaminase elevations compared with baricitinib monotherapy (see Adverse Reactions). If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, Olumiant should be temporarily interrupted until this diagnosis is excluded.
Malignancy: The risk of malignancies including lymphoma is increased in patients with rheumatoid arthritis. Immunomodulatory medicinal products may increase the risk of malignancies including lymphoma. The clinical data are insufficient to assess the potential incidence of malignancies following exposure to baricitinib. Long-term safety evaluations are ongoing.
Venous Thromboembolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving baricitinib. Olumiant should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery and immobilisation. If clinical features of DVT/PE occur, Olumiant treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.
Laboratory monitoring: See Table 7.
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Immunosuppressive medicinal products: Combination with biologic DMARDs, biologic immunomodulators or other Janus kinase (JAK) inhibitors is not recommended, as a risk of additive immunosuppression cannot be excluded.
In rheumatoid arthritis, data concerning use of baricitinib with potent immunosuppressive medicinal products (e.g., azathioprine, tacrolimus, ciclosporin) are limited and caution should be exercised when using such combinations (see Interactions).
In atopic dermatitis, combination with ciclosporin or other potent immunosuppressants has not been studied and is not recommended (see Interactions).
Hypersensitivity: In post-marketing experience, cases of drug hypersensitivity associated with baricitinib administration have been reported. If any serious allergic or anaphylactic reaction occurs, baricitinib should be discontinued immediately.
Diverticulitis: Events of diverticulitis and gastrointestinal perforation have been reported in clinical trials and from postmarketing sources. Baricitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis: nonsteroidal anti-inflammatory drugs, corticosteroids, and opioids. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation.
Excipients: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e., essentially "sodium-free".
Effects on ability to drive and use machines: Olumiant has no or negligible influence on the ability to drive and use machines.