Baricit Tablet

Rheumatoid Arthritis, Alopecia Areata, COVID-19

Rheumatoid Arthritis Indicated for adults with moderately to severely active rheumatoid arthritis (RA) 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 nonbiologic disease-modifying antirheumatic drugs (DMARDs) 2 mg PO once daily Alopecia Areata Indicated for adults with severe alopecia areata 2 mg PO once daily; increase to 4 mg once daily if inadequate response With nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider 4 mg once daily Once adequate response achieved with 4 mg/day, decrease to 2 mg/day COVID-19 Indicated for treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) in hospitalized adults who require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) 4 mg PO once daily Recommended treatment duration is 14 days or until hospital discharge, whichever comes first

COVID-19 (EUA) November 19, 2020: Emergency use authorization (EUA) issued by the FDA for treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) in hospitalized patients aged 2 to <18 years who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) <2 years: Not authorized 2 to <9 years: 2 mg PO once daily 9 to <18 years: 4 mg PO once daily Recommended treatment duration is 14 days or until hospital discharge, whichever comes first; optimal treatment duration unknown

Renal impairment RA Mild (eGFR 60 to <90 mL/min/1.73 m2): No dose adjustment required Moderate (eGFR 30 to <60 mL/min/1.73 m2): Decrease to 1 mg/day Severe (eGFR <30 mL/min/1.73 m2): Not recommended (not studied) Alopecia areata Mild (eGFR 60 to <90 mL/min/1.73 m2): No dose adjustment required Moderate (eGFR 30 to <60 mL/min/1.73 m2): Reduce dose by 50% Severe (eGFR <30 mL/min/1.73 m2): Not recommended COVID-19 Mild (eGFR 60 to <90 mL/min/1.73 m2): No dose adjustment Moderate (eGFR 30 to <60 mL/min/1.73 m2): Decrease to 2 mg/day Severe (eGFR 15 to <30 mL/min/1.73 m2): Decrease to 1 mg/day eGFR <15 mL/min/1.73 m2, patients on dialysis, have end-stage renal disease, or have acute kidney injury: Not recommended

Of the 2558 patients treated in the COVID-19 clinical trials, a total of 791 were 65 years of age and older, including 295 patients 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Baricitinib is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because geriatric patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Hepatic impairment RA or alopecia areata Interrupt if ALT/AST increased and drug-induced liver injury (DILI) suspected, until DILI diagnosis excluded Mild or moderate: No dose adjustment required Severe: Not recommended COVID-19 Interrupt if ALT/AST increased and DILI suspected, until DILI diagnosis excluded Increased ALT/AST: Consider interruption until the diagnosis of drug-induced liver injury is excluded Severe: Not studied; use only if benefits outweigh risks

May take with or without food

Increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with Baricitinib if serious infection occurs until the infection is controlled. Baricitinib should not be given to patients with active tuberculosis. Test for latent TB before and during therapy, except for COVID-19; treat latent TB prior to use. Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. Malignancies have occurred in patients treated with Baricitinib. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. Thrombosis has occurred in patients treated with Baricitinib. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. Gastrointestinal Perforations: Monitor patients who may be at increased risk and evaluate promptly new onset of abdominal symptoms. Vaccinations: Avoid use with live vaccines. Hypersensitivity: Serious reactions have been reported. Monitoring Parameters Monitor laboratory values (lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids) at baseline and periodically during treatment Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. Monitor patients with hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, for expression of hepatitis B virus (HBV) DNA—if HBV DNA detected, consult liver specialist for advice. Monitor lipid profile 12 weeks after treatment initiation—hyperlipidaemia should be managed according to international clinical guidelines; Monitor hepatic transaminases routinely—interrupt

Not Classi Pregnancy Based on findings from animal reproduction studies, therapy may cause fetal harm during pregnancy; available data from clinical trials and postmarketing reports of exposure in pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes There are no human data on chronic baricitinib exposure throughout pregnancy; there are risks to mother and the fetus associated with rheumatoid arthritis in pregnancy; consider risks and benefits with chronic use during pregnancy Published data suggest that increased disease activity is associated with risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis; adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth Based on animal studies, therapy may cause fetal harm when administered during pregnancy; consider pregnancy planning and prevention for females of reproductive potential Animal studies In animal embryo-fetal development studies, oral baricitinib administration to pregnant rats and rabbits at exposures equal to and greater than ~20 and 84 times the maximum recommended human dose (MRHD), respectively, resulted in reduced fetal body weights, increased embryo lethality (rabbits only), and dose-related increases in skeletal malformations Lactation Unknown if distributed in human breast milk Baricitinib is present in the milk of lactating rats Owing to species-specific differences in lactation physiology, the clinical relevance of these data are not clear Because of the potential for serious adverse reactions in nursing infants, advise women with rheumatoid arthritis not to breastfeed while taking baricitinib

Avoid use of live vaccines; update immunizations in agreement with current immunization guidelines before initiating Coadministration with strong OAT3 inhibitors may increase baricitinib systemic exposure Contraindicated (1) upadacitinib

>10% RA Upper respiratory tract infections (16.3%) COVID-19 ALT >3 x ULN (18.1%) AST >3 x ULN (11.8%) 1-10% RA Increased ALT/AST (1.3-4.7%) Nausea (2.7-2.8%) Platelet elevations (1-2%) Herpes zoster infection (1-1.4%) Herpes simplex infection (0.8-1.4%) COVID-19 *Reported incidence less than placebo Thrombocytosis >600,000 cells/mm3 (7.9%) CPK >5 x ULN (4.5%)* Neutropenia <1000 cells/mm3 (2.2%) Deep vein thrombosis (1.5%) Pulmonary embolism (1.5%) Urinary tract infection (1.5%) <1% RA Acne (<1%) Neutropenia (0.3%)

Janus kinases (JAKs) pathways inhibitor; JAK consists of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoieses and immune cell function Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which modulate intracellular activity including gene expression; baricitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs

Baricit 4mg Tablet manufactured by Delta Pharma Limited. Its generic name is Baricitinib.