Baricent2 mg

Baricent is a targeted synthetic disease-modifying antirheumatic drug (Janus kinase inhibitor) with the following evidence-graded uses:

Established / approved uses

• Rheumatoid arthritis (RA): Moderately to severely active RA in adults who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. May be used as monotherapy or in combination with methotrexate or other conventional disease-modifying antirheumatic drugs (DMARDs).
• Severe alopecia areata: Adults with severe patchy, multifocal, or total/universal hair loss.
• COVID-19 (hospitalized adults): Treatment of COVID-19 in hospitalized adults who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO), used in combination with standard-of-care therapy.

Approved in some international markets (not FDA-approved in the United States)

• Moderate-to-severe atopic dermatitis: In adults whose disease is not adequately controlled with other systemic therapies, including biologics, or when those therapies are not advisable — approved for this use in the European Union, United Kingdom, Japan and certain other countries.

Baricent should not be combined with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressants such as azathioprine or cyclosporine.

Each film-coated tablet contains Baricitinib INN 2 mg or 4 mg. Baricitinib is also available as 1 mg tablets in some markets for renal-adjusted dosing. Tablets are available in Bangladesh in 2 mg and 4 mg strengths.

Baricent is an orally administered, small-molecule Janus kinase (JAK) inhibitor. It selectively and reversibly inhibits JAK1 and JAK2, enzymes that mediate intracellular signaling for a number of cytokines involved in inflammatory and immune responses, including several interleukins and interferons implicated in rheumatoid arthritis, alopecia areata, atopic dermatitis and the hyperinflammatory response seen in severe COVID-19.

Baricent carries a boxed warning shared by the JAK inhibitor class for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis (see Precautions and Warnings).

Janus kinase (JAK) inhibitor; targeted synthetic disease-modifying antirheumatic drug (tsDMARD)

Baricitinib is a selective and reversible inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), with lower potency against JAK3 and tyrosine kinase 2 (TYK2). JAK enzymes transduce intracellular signals from cytokine and growth-factor receptors on the cell membrane, activating STAT (signal transducer and activator of transcription) proteins that influence hematopoiesis and immune-cell function.

By inhibiting JAK1/JAK2-dependent signaling of cytokines such as interleukin-6, interleukin-15, and various interferons, Baricitinib reduces the inflammatory cascade responsible for joint inflammation in rheumatoid arthritis, hair-follicle immune attack in alopecia areata, skin inflammation in atopic dermatitis, and the cytokine-driven lung injury seen in severe COVID-19.

Pharmacokinetics: Baricitinib is rapidly absorbed after oral administration (peak plasma concentration in about 1 hour), has an elimination half-life of approximately 12 hours, and is primarily eliminated renally (about 75% of the dose), with the remainder cleared via CYP3A4-mediated hepatic metabolism. This is why dose adjustment is required in renal impairment.

Baricent is administered orally as a film-coated tablet, once daily, with or without food, swallowed whole with water. It should be taken at a consistent time each day. Tablets should not be crushed, split, or chewed unless specifically advised by a physician or pharmacist. Continue taking it exactly as prescribed and do not discontinue abruptly without medical advice.

• Strong OAT3 inhibitors (e.g., probenecid): co-administration significantly increases Baricent plasma exposure; a dose reduction may be required.
• Other JAK inhibitors, biologic DMARDs, or potent immunosuppressants (e.g., azathioprine, cyclosporine): combination is not recommended due to increased risk of additive immunosuppression and infection.
• Live attenuated vaccines: avoid administering live vaccines during and immediately before/after treatment with Baricent due to the risk of disseminated infection from the vaccine strain.
• CYP3A4 substrates/inducers or inhibitors: clinically significant interaction is unlikely as Baricent is only partially metabolized by CYP3A4, but caution is advised with strong enzyme inducers that may reduce efficacy.

Baricent carries a boxed warning for serious infections, increased mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis — see Precautions and Warnings for details.

Common side effects

• Upper respiratory tract infections
• Nausea
• Headache
• Herpes simplex and herpes zoster (shingles) reactivation
• Increased LDL ("bad") cholesterol
• Increased creatine phosphokinase (CPK)
• Acne
• Thrombocytosis (elevated platelet count)

Serious side effects (seek prompt medical attention)

• Signs of serious infection (fever, chills, persistent cough, night sweats)
• Signs of blood clots (leg swelling/pain, sudden shortness of breath, chest pain)
• Signs of a heart attack or stroke (chest pain, weakness on one side, slurred speech)
• Unusual bruising, bleeding, or signs of low blood counts
• Symptoms suggestive of gastrointestinal perforation (severe abdominal pain, fever)

Pregnancy: Baricent should be strictly avoided during pregnancy. Animal reproduction studies showed embryo-fetal toxicity, including skeletal malformations, at clinically relevant exposures. There is insufficient human data to establish safety. Baricent should be used in pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus, and only under close physician supervision. Women of reproductive potential are advised to use effective contraception during treatment and for at least one week after the final dose.

Lactation: It is not known whether Baricent passes into human breast milk, but it is present in the milk of lactating animals. Because of the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment and for at least 4 days after the final dose. Consult a physician before breastfeeding.

Boxed warnings (class warning for Janus kinase inhibitors)

• Serious infections: including tuberculosis reactivation, invasive fungal infections, and other opportunistic infections. Screen for latent tuberculosis and viral hepatitis (B and C) before starting Baricent; treat latent TB before initiation.
• Increased mortality: a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with another JAK inhibitor compared with TNF blockers in a large rheumatoid arthritis safety trial; this is applied as a class warning to Baricent.
• Malignancy: including lymphoma and other malignancies have been observed with JAK inhibitor use.
• Major adverse cardiovascular events (MACE): including cardiovascular death, myocardial infarction, and stroke, particularly in patients over 50 years of age with at least one additional cardiovascular risk factor.
• Thrombosis: deep vein thrombosis, pulmonary embolism, and arterial thrombosis have occurred, some fatal.

Because of these risks, Baricent should generally be reserved for patients with an inadequate response or intolerance to one or more TNF antagonists, and a careful individual risk-benefit assessment is required, especially in patients over 50 years with cardiovascular risk factors, current or past smokers, and those with a history of malignancy or thrombosis.

Other precautions

• Avoid initiating in patients with an absolute lymphocyte count <500 cells/mm³, absolute neutrophil count <1000 cells/mm³, or hemoglobin <8 g/dL; monitor blood counts periodically during treatment.
• Avoid live attenuated vaccines during treatment; ensure immunizations are up to date before starting.
• Monitor lipid profile approximately 12 weeks after starting therapy and manage per standard cardiovascular guidelines, as Baricent can raise LDL and HDL cholesterol.
• Use with caution in patients with a history of chronic lung disease, diverticulitis, or other conditions that may increase the risk of gastrointestinal perforation.
• Renal impairment requires dose reduction (see Dosage and Use in Special Populations).

There is limited clinical experience with Baricent overdose. In case of a suspected overdose, seek immediate medical attention or contact a poison control center / emergency services. Management should include monitoring for signs and symptoms of adverse reactions (such as infection, unusual bleeding, or cardiovascular symptoms), and supportive care as clinically indicated. Since Baricent is predominantly renally eliminated, hemodialysis may have limited additional benefit; treatment decisions should be made by a physician based on the clinical situation. Do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Baricent is primarily cleared renally, so dose reduction is required in moderate renal impairment (eGFR 30–60 mL/min/1.73m²); use is generally not recommended in severe renal impairment (eGFR <30 mL/min/1.73m²) or in patients on dialysis, as safety and adequate dosing have not been established.

Hepatic impairment

No dose adjustment is needed in mild-to-moderate hepatic impairment. Baricent has not been studied in severe hepatic impairment and is not recommended in this population.

Elderly patients

Patients over 65 years of age, and particularly those over 75 years, may be at higher risk of serious infection and should be dosed with caution after individualized risk-benefit assessment, especially where additional cardiovascular risk factors are present.

Pediatric use

Safety and efficacy of Baricent have not been established in pediatric patients; it is not currently approved for use in children.

The duration of Baricent therapy depends on the indication and clinical response. For rheumatoid arthritis and alopecia areata, treatment is generally long-term and continued as long as benefit is observed and no contraindicating adverse effects develop; response should be reassessed periodically by the treating physician, and if no meaningful improvement is seen after an adequate trial period, discontinuation should be considered. For hospitalized COVID-19, Baricent is used for a defined short course of up to 14 days or until hospital discharge, whichever occurs first. Do not extend or shorten the course without physician guidance.

Janus kinase (JAK) inhibitors (JAKinibs); targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs)

Baricitinib selectively and reversibly inhibits Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2). These intracellular enzymes are required for signal transduction from multiple cytokine and growth-factor receptors that use the JAK-STAT pathway. By blocking JAK1/JAK2 activity, Baricitinib reduces phosphorylation and activation of STAT proteins, thereby dampening the downstream inflammatory gene expression driven by cytokines such as interleukin-6 and various interferons — the pathway implicated in the joint inflammation of rheumatoid arthritis, the autoimmune hair-follicle attack of alopecia areata, and the hyperinflammatory cytokine response seen in severe COVID-19.

The safety and efficacy of Baricent have not been established in pediatric patients for any indication. Baricent is not currently approved for use in children and adolescents, and no pediatric dosing regimen has been established. Use in this population should only occur under specialist supervision in the rare circumstance a physician determines it necessary, outside routine practice.