Presentation and Status in Health Basket
Film Coated Tablets
28 X 2 mg
Film Coated Tablets
28 X 4 mg
Treatment should be initiated by physicians experienced in the diagnosis and treatment of rheumatoid arthritis.
The recommended dose of Olumiant is 4 mg once daily. A dose of 2 mg once daily is appropriate for patients such as those aged ≥ 75 years and may be appropriate for patients with a history of chronic or recurrent infections. A dose of 2 mg once daily may also be considered for patients who have achieved sustained control of disease activity with 4 mg once daily and are eligible for dose tapering.
Treatment should not be initiated in patients with an absolute lymphocyte count (ALC) less than 0.5 x 109 cells/L, an absolute neutrophil count (ANC) less than 1 x 109 cells/L, or who have a haemoglobin value less than 8 g/dL. Treatment may be initiated once values have improved above these limits.
Renal impairment: The recommended dose is 2 mg once daily in patients with creatinine clearance between 30 and 60 mL/min. Olumiant is not recommended for use in patients with creatinine clearance < 30 mL/min.
Hepatic impairment: No dose adjustment is required in patients with mild or moderate hepatic impairment. Olumiant is not recommended for use in patients with severe hepatic impairment.
Co-administration with OAT3 inhibitors: The recommended dose is 2 mg once daily in patients taking Organic Anion Transporter 3 (OAT3) inhibitors with a strong inhibition potential, such as probenecid.
Elderly: Clinical experience in patients ≥ 75 years is very limited and in these patients a starting dose of 2 mg is appropriate.
Paediatric population: The safety and efficacy of Olumiant in children and adolescents aged 0 to 18 years have not yet been established. No data are available.
Method of administration: Oral use. Olumiant is to be taken once daily with or without food and may be taken at any time of the day.
Olumiant 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. Olumiant may be used as monotherapy or in combination with methotrexate.
Hypersensitivity to the active substance or to any of the excipients. Pregnancy.
Infections: Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. 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. 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 10^9 cells/L, Absolute Lymphocyte Count (ALC) < 0.5 x 10^9 cells/L and haemoglobin < 8 g/dL were reported in less than 1 % of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC < 1 x 10^9 cells/L, ALC < 0.5 x 10^9 cells/L or haemoglobin < 8 g/dL observed during routine patient management.
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. 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. 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: 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. 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 temporarily interrupted and patients should be evaluated promptly, followed by appropriate treatment.
Immunosuppressive medicinal products: Combination with biologic DMARDs or other Janus kinase (JAK) inhibitors is not recommended, as a risk of additive immunosuppression cannot be excluded. 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 prescribing information for full details.
The most commonly reported adverse drug reactions (ADRs) occurring in ≥ 2 % of patients treated with Olumiant monotherapy or in combination with conventional synthetic DMARDs were increased LDL cholesterol (33.6 %), upper respiratory tract infections (14.7 %) and nausea (2.8 %). Infections reported with Olumiant treatment included Herpes zoster.
See prescribing information for full details.
Immunosuppressive medicinal products: Combination with biologic DMARDs or other JAK inhibitors has not been studied. Use of baricitinib with potent immunosuppressive medicinal products such as azathioprine, tacrolimus, or ciclosporin was limited in clinical studies of baricitinib, and a risk of additive immunosuppression cannot be excluded.
Potential for other medicinal products to affect the pharmacokinetics of baricitinib
Transporters: In vitro, baricitinib is a substrate for organic anionic transporter (OAT)3, P-glycoprotein (Pgp), breast cancer resistance protein (BCRP) and multidrug and toxic extrusion protein (MATE)2-K. In a clinical pharmacology study, dosing of probenecid (an OAT3 inhibitor with strong inhibition potential)
resulted in approximately a 2-fold increase in AUC(0-∞) with no change in tmax or Cmax of baricitinib. Consequently, the recommended dose in patients taking OAT3 inhibitors with a strong inhibition potential, such as probenecid, is 2 mg once daily (see section 4.2). No clinical pharmacology study has been conducted with OAT3 inhibitors with less inhibition potential. The prodrug leflunomide rapidly converts to teriflunomide which is a weak OAT3 inhibitor and therefore may lead to an increase in baricitinib exposure. Since dedicated interaction studies have not been conducted, caution should be used when leflunomide or teriflunomide are given concomitantly with baricitinib. Concomitant use of the OAT3 inhibitors ibuprofen and diclofenac may lead to increased exposure of baricitinib, however their inhibition potential of OAT3 is less compared to probenecid and thus a clinically relevant interaction is not expected. Coadministration of baricitinib with ciclosporin (Pgp/BCRP inhibitor) or methotrexate (substrate of several transporters including OATP1B1, OAT1, OAT3, BCRP, MRP2, MRP3, and MRP4) resulted in no clinically meaningful effects on baricitinib exposure.
Cytochrome P450 enzymes: In vitro, baricitinib is a cytochrome P450 enzyme (CYP)3A4 substrate although less than 10 % of the dose is metabolised via oxidation. In clinical pharmacology studies, coadministration of baricitinib with ketoconazole (strong CYP3A inhibitor) resulted in no clinically meaningful effect on the PK of baricitinib. Coadministration of baricitinib with fluconazole (moderate CYP3A/CYP2C19/CYP2C9 inhibitor) or rifampicin (strong CYP3A inducer) resulted in no clinically meaningful changes to baricitinib exposure.
Gastric pH modifying agents: Elevating gastric pH with omeprazole had no clinically significant effect on baricitinib exposure.
Potential for baricitinib to affect the pharmacokinetics of other medicinal products
Transporters: In vitro, baricitinib is not an inhibitor of OAT1, OAT2, OAT3, organic cationic transporter (OCT) 2, OATP1B1, OATP1B3, BCRP and MATE1 and MATE2-K at clinically relevant concentrations. Baricitinib may be a clinically relevant inhibitor of OCT1, however there are currently no known selective OCT1 substrates for which clinically significant interactions might be predicted. In clinical pharmacology studies there were no clinically meaningful effects on exposure when baricitinib was coadministered with digoxin (Pgp substrate) or methotrexate (substrate of several transporters).
Cytochrome P450 enzymes: In clinical pharmacology studies, coadministration of baricitinib with the CYP3A substrates simvastatin, ethinyl oestradiol, or levonorgestrel resulted in no clinically meaningful changes in the PK of these medicinal products.
Pregnancy and Lactation
Pregnancy: The JAK/STAT pathway has been shown to be involved in cell adhesion and cell polarity which can affect early embryonic development. There are no adequate data from the use of baricitinib in pregnant women.
Olumiant is contraindicated during pregnancy. Women of childbearing potential have to use effective contraception during and for at least 1 week after treatment. If a patient becomes pregnant while taking Olumiant the parents should be informed of the potential risk to the foetus.
Lactation: It is unknown whether baricitinib/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of baricitinib in milk. A risk to newborns/infants cannot be excluded and Olumiant should not be used during breast-feeding. A decision must be made whether to discontinue breast-feeding or to discontinue Olumiant therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
See prescribing information for full details.
Single doses up to 40 mg and multiple doses of up to 20 mg daily for 10 days have been administered in clinical trials without dose-limiting toxicity. Adverse events were comparable to those seen at lower doses and no specific toxicities were identified. Pharmacokinetic data of a single dose of 40 mg in healthy volunteers indicate that more than 90 % of the administered dose is expected to be eliminated within 24 hours. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate treatment.
Storage: Store below 30°C.