Baricitinib

Oral
Rheumatoid arthritis
Adult: For the treatment of moderate to severe active cases in patients with inadequate response to or are intolerant of 1 or more DMARDs: As monotherapy or in combination with methotrexate or other conventional DMARDs: 4 mg once daily, may gradually reduce to 2 mg once daily once sustained control of disease activity is achieved. Do not initiate treatment in patients with absolute lymphocyte count (ALC) <500 cells/mm³, ANC <1,000 cells/mm³, or Hb level <8 g/dL. Dosing interruption may be required if serious infection occurs or according to the severity of the patient's laboratory abnormalities (refer to detailed product guidelines).
Elderly: ≥75 years 2 mg once daily. Dosage recommendations may vary among countries (refer to specific product guidelines).
Renal impairment: Dosage recommendations may vary among countries (refer to specific product guidelines).

CrCl (ml/min)	Dosage Recommendation
<30	Not recommended.
30-60	2 mg once daily.

Hepatic impairment: Severe: Not recommended.

Oral
Atopic dermatitis
Adult: For the treatment of moderate to severe cases in patients who are candidates for systemic therapy: 4 mg once daily, may gradually reduce to 2 mg once daily once sustained control of disease activity is achieved. Consider discontinuation of treatment if no response is evident after 8 weeks. Do not initiate treatment in patients with ALC <500 cells/mm³, ANC <1,000 cells/mm³, or Hb level <8 g/dL. Dosing interruption may be required if serious infection occurs or according to the severity of the patient's laboratory abnormalities (refer to detailed product guidelines).
Elderly: ≥75 years 2 mg once daily. Dosage recommendations may vary among countries (refer to specific product guidelines).
Renal impairment: Dosage recommendations may vary among countries (refer to specific product guidelines).

CrCl (ml/min)	Dosage Recommendation
<30	Not recommended.
30-60	2 mg once daily.

Hepatic impairment: Severe: Not recommended.

Oral
Coronavirus disease 2019 (COVID-19)
Adult: In hospitalised patients requiring supplemental oxygen, invasive or non-invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO): As part of appropriate combination therapy: 4 mg once daily for 14 days or until hospital discharge, whichever occurs 1st. Do not initiate treatment in patients with ALC <200 cells/mm³ or ANC <500 cells/mm³. Dosing interruption may be required if serious infection occurs or according to the severity of the patient's laboratory abnormalities. Treatment recommendations may vary among countries. Refer to local treatment or specific product guidelines for further information, including alternative administration for patients unable to swallow the whole tab.
Child: In hospitalised patients requiring supplemental oxygen, invasive or non-invasive mechanical ventilation, or ECMO: 2-<9 years 2 mg once daily; ≥9 years 4 mg once daily. Recommended treatment duration: 14 days or until hospital discharge, whichever occurs 1st. Dosing interruption may be required if serious infection occurs or according to the severity of the patient's laboratory abnormalities. Dosage recommendation is based on limited data from clinical studies and may vary among countries. Refer to local treatment or specific product guidelines for further information, including alternative administration for patients unable to swallow the whole tab.
Elderly: Same as adult dose.
Renal impairment: Adult: Patients on dialysis, with acute kidney injury, ESRD or eGFR <15 mL/min/1.73 m²: Not recommended. eGFR 15-<30 mL/min/1.73 m²: 1 mg once daily. eGFR 30-<60 mL/min/1.73 m²: 2 mg once daily. Child: 2-<9 years eGFR <30 mL/min/1.73 m²: Not recommended; eGFR 30-<60 mL/min/1.73 m²: 1 mg once daily. ≥9 years eGFR <15 mL/min/1.73 m²: Not recommended; eGFR 15-<30 mL/min/1.73 m²: 1 mg once daily; eGFR 30-<60 mL/min/1.73 m²: 2 mg once daily.
Hepatic impairment: Severe: Use only if the potential benefit outweighs the potential risk.

Oral
Severe alopecia areata
Adult: 2 mg once daily, may increase to 4 mg once daily if response is inadequate. For patients with nearly complete or complete scalp hair loss, consider treatment with 4 mg once daily. Once an adequate response is achieved in patients receiving 4 mg once daily, dose may be gradually reduced to 2 mg once daily. Consider discontinuation of treatment if no response is evident after 36 weeks. Do not initiate treatment in patients with ALC <500 cells/mm³, ANC <1,000 cells/mm³, or Hb level <8 g/dL. Dosing interruption may be required if serious infection occurs or according to the severity of the patient's laboratory abnormalities (refer to detailed product guidelines).
Elderly: ≥75 years 2 mg once daily. Dosage recommendations may vary among countries (refer to specific product guidelines).
Renal impairment: eGFR <30 mL/min/1.73 m²: Not recommended. eGFR 30-60 mL/min/1.73 m²: If the recommended dose is 2 mg once daily, reduce dose to 1 mg once daily; if the recommended dose is 4 mg once daily, reduce dose to 2 mg once daily. Dosage recommendations may vary among countries (refer to specific product guidelines).
Hepatic impairment: Severe: Not recommended.

Special Populations: Patients taking potent organic anion transporter 3 (OAT3) inhibitors (e.g. probenecid): Reduce the recommended baricitinib dose from 4 mg once daily to 2 mg once daily or from 2 mg once daily to 1 mg once daily. If the recommended dose is 1 mg once daily, consider discontinuing probenecid. Dosage recommendations may vary among countries (refer to local treatment or detailed product guidelines). Rheumatoid arthritis; Atopic dermatitis; Severe alopecia areata: Patients with history of chronic or recurrent infections: 2 mg once daily.

Film-Coated Tab: May be taken with or without food. For patients w/ difficulty swallowing, tab may be dispersed/crushed in approx 10 mL of water. Drink the dispersion liqd & then the glass rinse immediately. The mixt may also be administered via nasogastric, orogastric, & gastronomy tubes followed by the container rinse. Consult product literature for specific instructions.

Active, opportunistic, or serious infections (other than COVID-19), including localised infections and active TB. Pregnancy and lactation. Concurrent administration of live vaccines.

Patient with CV risk factors, known malignancy (apart from successfully treated non-melanoma skin cancer), risk factors for gastrointestinal perforation (e.g. history of diverticulitis); chronic or recurrent infection, underlying condition predisposing to infection; risk factors for DVT or pulmonary embolism (e.g. obesity, history of DVT or pulmonary embolism, undergoing major surgery, immobilisation). Patient who has been exposed to TB or who travelled or resided in areas where mycoses or TB are endemic. Patient taking potent OAT3 inhibitors (e.g. probenecid). Concomitant use with other Janus kinase (JAK) inhibitors, biologic DMARDs, biologic immunomodulators, or strong immunosuppressants (e.g. azathioprine, ciclosporin) is not recommended. Current or past smokers. Renal and severe hepatic impairment. Children (when used for COVID-19) and elderly. Patient Counselling Women of childbearing potential must use an effective birth control method during therapy and for at least 1 week after treatment. Discontinue breastfeeding during treatment and for 4 days after the last dose. Monitoring Parameters Monitor lymphocyte, neutrophil, platelet counts, Hb, renal function and LFTs at baseline and periodically thereafter; lipid parameters approx 12 weeks after treatment initiation and periodically thereafter. Screen for latent or active TB infection and viral hepatitis before starting treatment. Assess for signs and symptoms of infection, including TB (during and after treatment), thrombosis, and abdominal symptoms. Perform skin examinations periodically in patients at increased risk for skin cancer. It should be noted that: - Baricitinib may be available for use in some countries under emergency use authorisation (EUA) or conditional approval for the treatment of COVID-19. Registration status and/or availability may vary between countries. Check local health authorities for the most recent authorisations and recommendations. - The safety and efficacy of baricitinib for the treatment of COVID-19 continue to be evaluated. Preliminary clinical trial results have shown that baricitinib in addition to standard care significantly reduced mortality, disease severity, and duration of hospitalisation. - The role of baricitinib in COVID-19 treatment may vary among local guidelines. Current guidelines recommend its use in addition to corticosteroids and/or remdesivir for adult patients hospitalised with severe COVID-19. It may be used as an alternative to interleukin-6 (IL-6) blockers (tocilizumab or sarilumab) or in combination with corticosteroids and IL-6 blockers according to clinical judgement. Treatment decisions should be made based on local guidelines, drug availability, and patient comorbidities. - Administration of prophylaxis for venous thromboembolism in patients with COVID-19 is recommended unless contraindicated. For healthcare professionals: - Refer to the local health authority for the most up-to-date information when prescribing baricitinib for COVID-19. - To alleviate the risks of this drug during pandemic use, local regulatory agencies may require healthcare facilities and healthcare providers to comply with certain regulations for the administration of baricitinib. Please refer to respective local regulatory agencies for further information.

Significant: Malignancies (e.g. lymphoma, non-melanoma skin cancer), reactivation of viral (e.g. herpes zoster, herpes simplex) or latent infections (e.g. TB), diverticulitis, gastrointestinal perforation, lymphocytopenia, anaemia, neutropenia, increased AST and ALT, lipid elevations (e.g. dose-related increases in total cholesterol, triglycerides, LDL and HDL cholesterol levels), hypersensitivity reactions (e.g. angioedema, urticaria, rash). Rarely, lymphoproliferative disorders. Blood and lymphatic system disorders: Thrombocytosis. Gastrointestinal disorders: Gastroenteritis, nausea, abdominal pain. Investigations: Increased creatine phosphokinase, serum creatinine, and weight. Nervous system disorders: Headache. Respiratory, thoracic and mediastinal disorders: URTI. Skin and subcutaneous tissue disorders: Acne, folliculitis.
Potentially Fatal: Serious bacterial, invasive fungal, viral or opportunistic infections (e.g. pneumonia, UTI, herpes zoster, active pulmonary or extrapulmonary TB, oesophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus disease, BK virus); increased risk of major adverse CV events (e.g. sudden CV death, MI, stroke); thrombosis (e.g. DVT, pulmonary embolism, arterial thrombosis).

May increase the risk of additive immunosuppression with other JAK inhibitors, biologic DMARDs, biologic immunomodulators, or potent immunosuppressants (e.g. azathioprine, ciclosporin). Increased serum concentration with potent OAT3 inhibitors (e.g. probenecid).
Potentially Fatal: May increase the risk of vaccine-associated infection with live vaccines.

Baricitinib is a reversible Janus kinase (JAK) inhibitor that is selective for JAK1 and JAK2, which are intracellular enzymes involved in the stimulation of haematopoiesis and immune cell function via a signalling pathway. JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which regulate intracellular activity, including gene expression. Inhibition of JAKs leads to reduced phosphorylation and activation of STATs and decreases in serum IgG, IgM, IgA, and C-reactive protein.
Absorption: Rapidly absorbed. Bioavailability: Approx 80%. Time to peak plasma concentration: Approx 1 hour.
Distribution: Volume of distribution: 76 L. Plasma protein binding: Approx 50%.
Metabolism: Metabolised in the liver by CYP3A4 isoenzyme.
Excretion: Mainly via urine (approx 75%; 69% as unchanged drug); faeces (approx 20%; 15% as unchanged drug). Elimination half-life: Approx 12-16 hours.

Oral: Store between 15-30°C.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AF02 - baricitinib