Serious and sometimes fatal bacterial infection, mycobacterial infection, invasive fungal infection, viral infection, or infections due to other opportunistic pathogens have been reported in patients receiving baricitinib. Pooled safety data from 2 COVID-19 clinical trials identified infections in 14.8% of baricitinib treated patients (n = 194/1,307) and 16.7% of patients who received placebo (n = 219/1,310). Serious infections were reported in 7.5% of baricitinib treated patients (n = 98/1,307) and 9.2% of patients who received placebo (n = 120/1,310). The most commonly reported serious infections were pneumonia (2.1%) and septic shock (2.1%). Opportunistic infections were identified in 0.9% of baricitinib patients (n = 12/1,307) and 1.1% of placebo patients (n = 14/1,310), with tuberculosis being reported in 1 patient treated with baricitinib and no patients treated with placebo. The most commonly reported adverse reactions during baricitinib clinical trials for alopecia areata and rheumatoid arthritis (RA) were upper respiratory tract infections (16.3% to 21.3% vs. 11.7% to 19.9% placebo). Included in upper respiratory tract infections were acute sinusitis, sinusitis, acute tonsillitis, tonsillitis, adenoiditis, epiglottitis, influenza, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, rhinovirus infection, sinobronchitis, and tracheitis. Other infections reported by alopecia areata patients during clinical trials included urinary tract infections (3%, cystitis and pyelonephritis), lower respiratory tract infections (2%, bronchitis, bronchiolitis, pneumonia), vulvovaginal candidiasis (2%), herpes zoster (1%), and fungal skin infections (less than 1%). In the RA clinical trials, overall infections during the 16-week treatment period were reported in 139 patients (99.1 events per 100 patient-years) treated with baricitinib 2 mg compared to 253 patients (82.1 events per 100 patient-years) receiving placebo. During 0 to 52-week exposure, infections were reported in 200 patients (59.6 events per 100 patient-years) receiving baricitinib 2 mg. During the 0 to 52 week exposure, the most commonly reported infections included viral upper respiratory infection, upper respiratory tract infection, urinary tract infection, and bronchitis. During the 16-week treatment period, serious infections were reported in 5 patients (3.6 events per 100 patient-years) receiving baricitinib 2 mg and in 13 patients (4.2 events per 100 patient-years) receiving placebo. During the 0 to 52 week exposure, serious infection was reported in 14 patients (4.2 events per 100 patient-years) receiving baricitinib 2 mg. The most common serious infections reported with baricitinib included pneumonia, herpes zoster, and urinary tract infections. Among opportunistic infections, tuberculosis, cryptococcosis, acute histoplasmosis, esophageal candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus infections, and BK virus were reported with baricitinib. During the 0 to 16 week treatment period for RA, an opportunistic infection was reported in 2 placebo patients (0.6 events per 100 patient-years), no patients taking baricitinib 2 mg, and two patients taking baricitinib 4 mg (0.7 events per 100 patient-years). In the 0 to 52 week treatment period, opportunistic infections were reported in 1 patient (0.1 events per 100 patient-years) and 5 patients (0.6 per 100 patient-years) with baricitinib 2 mg and baricitinib 4 mg, respectively. Viral reactivation, including cases of herpes infection reactivation (e.g., herpes zoster), were observed in RA clinical studies. Herpes simplex and herpes zoster were reported in 0.8% and 1% of patients treated with baricitinib 2 mg, respectively compared to 0.7% and 0.4% of those receiving placebo, respectively. Included in herpes simplex were eczema herpeticum, genital herpes, ophthalmic herpes simplex, and oral herpes. If a patient develops herpes zoster, interrupt baricitinib therapy until the episode resolves. Baricitinib should not be administered to patients with active tuberculosis. Patients should be evaluated and tested for latent or active TB infection prior to and per applicable guidelines during baricitinib administration. There were no reported cases of tuberculosis during the 0 to 16 week treatment period. In the 0 to 52 week treatment period, tuberculosis was reported in 1 patient taking baricitinib 4 mg and 0 patients on baricitinib 2 mg. Cases of disseminated tuberculosis also were reported. Some patients have presented with disseminated rather than localized infection and were often taking concomitant immunosuppression agents such as methotrexate or corticosteroid therapy. Patients should be closely monitored for the development of signs and symptoms of infection during and after baricitinib treatment. Interrupt therapy with baricitinib if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with baricitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.[63229]

Hematologic laboratory abnormalities have been reported during baricitinib clinical trials. In rheumatoid arthritis (RA) and alopecia areata patients, neutropenia, defined as an absolute neutrophil count (ANC) below 1,000 cells/mm³, was reported in up to 1.3% of patients receiving baricitinib. Avoid or interrupt baricitinib treatment in RA and alopecia areata patients with an ANC less than 1,000 cells/mm³. Anemia, defined as hemoglobin less than 8 grams/dL, was also reported in up to 1.3% of baricitinib recipients during clinical trials. Avoid or interrupt treatment in RA and alopecia areata patients with a hemoglobin less than 8 grams/dL. Lymphopenia, defined as absolute lymphocyte count (ALC) less than 500 cells/mm³ was reported during baricitinib clinical trials in less than 1% of patients. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with baricitinib but not in those receiving placebo. Avoid or interrupt baricitinib treatment in RA and alopecia areata patients with an ALC less than 500 cells/mm³. Increases in platelet counts (thrombocytosis) above 600,000 cells/mm³ were reported in 1.1% of RA patients receiving 2 mg/day baricitinib and 1.1% in those receiving placebo. After 16 weeks of treatment, the mean platelet count increased by 3,000 cells/mm³ in patients receiving placebo and by 15,000 cells/mm³ in patients treated with baricitinib 2 mg. Hematologic laboratory abnormalities have also been reported in patients who received baricitinib for COVID-19. Pooled safety data from 2 COVID-19 clinical trials identified neutropenia and thrombocytosis in 2.2% and 7.9% of baricitinib treated patients, respectively. For COVID-19 patients with an ANC less than 500 cells/mm³, delay or interruption in baricitinib therapy until ANC is 500 cells/mm³ or more. For COVID-19 patients with an ALC less than 200 cells/mm³, delay or interruption in baricitinib therapy until ALC is 200 cells/mm³ or more.[63229]

Serious and even fatal venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism (PE), have been reported during baricitinib clinical trials. Pooled safety data from 2 COVID-19 clinical trials identified venous thrombotic events in 3% of baricitinib treated patients (n = 40/1,307) and 2.2% of patients who received placebo (n = 29/1,310). More specifically, among baricitinib recipients, 20 patients (1.5%) developed a PE and 20 patients (1.5%) experienced a DVT. In clinical trials of patients with alopecia areata, venous thromboembolic events (including DVT and PE) were observed after Week 52. Additionally, less than 1% of baricitinib recipients developed an arterial thrombosis. In a rheumatoid arthritis (RA) trial, during the 16-week treatment period, DVT or PE was reported in 5 patients (1.7 events per 100 patient-years) receiving 4 mg daily; DVT or PE was not reported in those receiving placebo or 2 mg daily. Arterial thrombosis during the 16-week treatment period was reported in 1 patient receiving placebo (0.3 events per 100 patient-years), 2 patients receiving baricitinib 2 mg (1.4 events per 100 patient-years) and 2 patients (0.7 events per 100 patient-years) receiving baricitinib 4 mg per day. During the 0 to 52 week treatment period, venous thromboses were reported in 2 patients (0.6 events per 100 patient-years) receiving 2 mg per day and 7 patients (0.8 events per 100 patient-years) receiving 4 mg per day. Arterial thromboses were reported in 3 patients (0.9 events per 100 patient-years) receiving baricitinib 2 mg/day and 3 patients (0.3 events per 100 patient-years) receiving 4 mg/day. Baricitinib may cause increases in platelet counts (thrombocytosis). There is no clear relationship between platelet count elevations and thrombotic events. Higher rates of all cause mortality, including sudden cardiac death, and major cardiovascular adverse events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke were reported with tofacitinib, another Janus kinase (JAK) inhibitor, compared to tumor necrosis factor (TNF) inhibitors in a large, postmarketing, randomized, safety study involving rheumatoid arthritis patients aged 50 years an older with one or more cardiovascular risk factors. Risks may be similar with all JAK inhibitors used for inflammatory conditions. Current and past tobacco smokers have an additional risk for these adverse events. Advise patients to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, DVT, PE, or arterial thrombosis. Discontinue therapy if a patient develops a thromboembolic event.[63229]

During clinical trials, abdominal pain and nausea were reported in up to 3.8% and up to 2.7% of patients receiving baricitinib, respectively. Gastrointestinal (GI) serious reactions, such as GI perforation, have been noted among baricitinib recipients. Promptly evaluate patients presenting with new-onset abdominal symptoms, such as abdominal pain, for early identification of GI perforation. Cautious use of baricitinib is advised for patients who may be at increased risk for GI perforation.[63229]

Elevated hepatic enzymes have been reported in clinical trials with the use of baricitinib. During clinical trials of patients with alopecia areata, elevated hepatic enzymes were observed in 1.1% of patients receiving baricitinib 2 mg and 3% of patients receiving the 4 mg dose (vs. 2.4% placebo). Among rheumatoid arthritis (RA) patients receiving baricitinib 2 mg during a 16-week treatment period, alanine aminotransferase (ALT) elevations 3-times the upper limit of normal (ULN) or greater occurred in 1.7% of patients (vs. 1% placebo) and aspartate aminotransferase (AST) elevations 3-times the ULN or greater were reported in 1.3% of patients (vs. 0.8% placebo). Increases 5-times the ULN or more and 10-times the ULN or more were observed for both ALT and AST in patients in clinical trials. Elevated hepatic enzymes have also been reported in patients who received baricitinib for COVID-19. Pooled safety data from 2 COVID-19 clinical trials identified increases in the ALT and AST of at least 3-times the ULN in 18.1% and 11.8% of baricitinib treated patients, respectively. Prompt investigation of the cause of hepatic enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases are observed and drug-induced hepatotoxicity is suspected, interrupt baricitinib treatment until this diagnosis is excluded.[63229]

During baricitinib clinical trials, dose-related increases in lipid parameters were reported. In the alopecia areata clinical trials, 3.6% of patients receiving baricitinib 2 mg and 5.9% receiving the 4 mg dose developed hyperlipidemia, defined as hypercholesterolemia, hypertriglyceridemia, or dyslipidemia. During the rheumatoid arthritis (RA) trials, lipid elevations were observed at 12 weeks and remained stable thereafter. In RA patients treated with baricitinib 2 mg for 12 weeks, mean LDL cholesterol, mean HDL cholesterol, and mean triglycerides increased by 8 mg/dL, 7 mg/dL, and 7 mg/dL, respectively. The mean LDL/HDL ratio remained stable. Manage alopecia areata and RA patients according to clinical guidelines for the management of hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia as per standards of care. Other laboratory alterations have also been reported. Baricitinib treatment was associated with increases in creatine phosphokinase (CPK) within 1 week of starting the drug in RA patients, but the CPK elevation leveled off after 8 to 12 weeks. At 16 weeks, the mean change in CPK for baricitinib 2 mg/day was 37 International Units/L. Elevated CPK concentrations have also been reported in patients who received baricitinib for alopecia areata and COVID-19. In alopecia areata patients, increased CPK was observed in 0.8% of patients receiving baricitinib 2 mg and 4.3% of patients receiving the 4 mg dose. Safety data from a COVID-19 clinical trial identified increased CPK concentrations greater than 5-times the ULN in 4.5% of baricitinib treated patients. In controlled clinical trials, dose-related increases in serum creatinine (SCr) were also observed; at 52 weeks, the mean increase in SCr was less than 0.1 mg/dL with baricitinib 4 mg. The clinical significance of the observed SCr increases is unknown.[63229]

Baricitinib may cause a new primary malignancy; malignancies were reported during clinical trials. During clinical trials of patients with alopecia areata, B cell lymphoma was noted in less than 1% of drug recipients, and malignancy, including non-melanoma skin cancer (NMSC), was observed after Week 52. Among rheumatoid arthritis (RA) patients, 1 patient (0.7 events per 100 patient-years) receiving baricitinib 2 mg per day during the 16-week treatment period developed a malignancy other than NMSC; no events were reported in the placebo group. During the 0 to 52 week treatment period, malignancies other than NMSC were reported in 2 patients (0.6 events per 100 patient-years) receiving baricitinib 2 mg per day. NMSC has also been reported in patients treated with baricitinib. Periodic skin evaluations are recommended for patients at an increased risk of skin cancer. Consider the risks and benefits of baricitinib when considering the continuation of the drug in patients with a known malignancy (other than successfully treated NMSC), who develop a malignancy and patients who are current or past smokers.[63229]

Acne (i.e., acneiform rash or dermatitis and acne vulgaris) was reported in up to 5.9% of patients receiving baricitinib during clinical trials. Additionally, 1.4% to 2.2% of patients receiving baricitinib for treatment of alopecia areata developed folliculitis during the clinical trials. Folliculitis was most commonly localized in the scalp region associated with hair regrowth.[63229]

Angioedema, rash, and urticaria have been reported with postmarketing use of baricitinib and may reflect a serious hypersensitivity reaction. Promptly discontinue baricitinib therapy if a hypersensitivity reaction is suspected.[63229]

Patients receiving treatment with baricitinib for alopecia areata during clinical trials reported headache (5.5% to 6.6%), fatigue (0.8% to 2.2%), and weight gain (0.9% to 1.6%).[63229]

Avoid the use of baricitinib in rheumatoid arthritis and alopecia areata patients with an active, serious or opportunistic infection, including localized infections. In patients with COVID-19 and concomitant active serious infections, data are limited; therefore, the risks and benefits of baricitinib treatment in COVID-19 patients with other concurrent infections should be considered. Serious and sometimes fatal bacterial infection, mycobacterial infection, invasive fungal infection, viral infection, or infections due to other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib. The risks and benefits of treatment should be considered prior to initiating baricitinib in patients: 1) with chronic or recurrent infection; 2) who have been exposed to tuberculosis; 3) with a history of a serious or an opportunistic infection; 4) who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or 5) with underlying conditions that may predispose them to infection (e.g., diabetes mellitus, human immunodeficiency virus (HIV) infection, chronic pulmonary disease, low lymphocyte counts, and pre-existing immunosuppression). The most common serious infections reported with baricitinib included pneumonia, herpes zoster, and urinary tract infections. Among opportunistic infections, tuberculosis, cryptococcosis, acute histoplasmosis, esophageal candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus infections, and BK virus were reported with baricitinib. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppression agents such as methotrexate or corticosteroid therapy. Ask patients if they have lived or have traveled to the Ohio and Mississippi River valleys or the Southwest because of an increased chance of acquiring certain kinds of fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis. Viral reactivation, including cases of herpes infection reactivation (e.g., herpes zoster), were observed in clinical studies. If a patient develops herpes zoster, interrupt baricitinib therapy until the episode resolves. Carefully consider the risks and benefits of baricitinib before starting the drug in patients who have been exposed to tuberculosis (TB). Baricitinib should not be administered to patients with active tuberculosis. Patients, except those with COVID-19, should be evaluated and tested for latent TB infection prior to and per applicable guidelines during baricitinib administration. Consider anti-tuberculosis therapy before baricitinib administration in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and for patients with a negative test for latent tuberculosis but who have risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision about whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of tuberculosis in all patients during treatment. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with baricitinib. Therapy with baricitinib should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with baricitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.[63229]

Perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy with baricitinib. The impact of baricitinib on chronic viral hepatitis reactivation is unknown. Patients with evidence of active hepatitis B or hepatitis C infection were excluded from clinical trials. In clinical trials in patients with rheumatoid arthritis or alopecia areata, patients who were positive for hepatitis C antibody but negative for hepatitis C virus RNA were permitted to enroll. Patients with positive hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were permitted to enroll; such patients should be monitored for expression of hepatitis B virus (HBV) DNA. Should HBV DNA be detected, consult with a hepatologist. Use baricitinib with caution in any other patient with hepatic disease or impairment. Increases in liver enzymes of 5-times and up to 10-times the upper limit of normal (ULN) were reported for both ALT and AST in clinical trials. Liver function tests (LFTs) should be evaluated at baseline and thereafter according to routine patient management. If increases in ALT or AST are seen and drug-induced liver toxicity is suspected, interrupt baricitinib treatment until drug-induced toxicity is excluded. Baricitinib is not recommended for rheumatoid arthritis or alopecia areata patients with severe hepatic impairment. For patients with COVID-19, baricitinib has not been studied in patients with severe hepatic impairment and should only be used if the potential benefit outweighs the potential risk.[63229]

Determine neutrophil and lymphocyte counts before baricitinib initiation. Do not start the drug in rheumatoid arthritis or alopecia areata patients with an absolute lymphocyte count (ALC) less than 500 cells/mm³ or in patients with absolute neutrophil count (ANC) less than 1,000 cells/mm³. For COVID-19 patients, do not start the drug if the ALC is less than 200 cells/mm³ or the ANC is less than 500 cells/mm³. Baricitinib may cause lymphopenia and neutropenia. Monitor the ANC and ALC periodically during baricitinib treatment according to routine patient management. Interrupt treatment in rheumatoid arthritis and alopecia areata patients with an ANC less than 1,000 cells/mm³ or an ALC less than 500 cells/mm³ until the counts have recovered to amounts equal to or above these thresholds. Interrupt treatment in COVID-19 patients with an ANC less than 500 cells/mm³ or an ALC less than 200 cells/mm³ until the counts have recovered to amounts equal to or above these thresholds.[63229]

Determine the hemoglobin concentration before baricitinib initiation, and do not start the drug in rheumatoid arthritis or alopecia areata patients with anemia defined as hemoglobin less than 8 grams/dL. Baricitinib may cause anemia. For patients who have hemoglobin 8 grams/dL or greater, monitor the hemoglobin concentration according to routine patient management. Treatment with baricitinib should be interrupted in patients who develop hemoglobin levels less than 8 grams/dL until the hemoglobin has recovered to 8 grams/dL or higher. There are limited data regarding the use of baricitinib in patients with COVID-19 and a hemoglobin less than 8 grams/dL.[63229]

Baricitinib may increase the risk for a new primary malignancy.[63229] In a large, postmarketing, randomized safety clinical trial in rheumatoid arthritis patients 50 years of age and older with one or more CV risk factors, higher rates of cancer [excluding non-melanoma skin cancer (NMSC)] and lymphoma were observed with use of tofacitinib, another JAK inhibitor, compared to tumor necrosis factor (TNF) inhibitors. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions. A higher rate of lung cancer was also observed in patients with a history of current or past tobacco smoking treated with the JAK inhibitor compared to those treated with a TNF inhibitor. Patients with a history of current or past tobacco smoking were at also at an increased risk of overall cancers. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particular in those with risk factors such as smoking, those who develop malignancy, and those with a known malignancy other than successfully treated non-melanoma skin cancer (NMCS). Reserve baricitinib for patients who have an inadequate response or intolerance to one or more TNF inhibitors.[63229] [66958] NMSCs have also been reported in patients treated with baricitinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.[63229]

Avoid use of baricitinib in patients who are at an increased risk of thrombosis and thromboembolism, including those with thromboembolic disease. Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, have been reported with baricitinib therapy. Many of these events were serious and some resulted in death. In COVID-19 patients, baricitinib has been associated with increases in platelet counts (thrombocytosis) and serious venous thrombosis, including PE. COVID-19 patients receiving baricitinib during clinical trials, were recommended or required to receive venous thromboembolism (VTE) prophylaxis unless a major contraindication was noted. In a large, postmarketing, randomized safety clinical trial in rheumatoid arthritis patients 50 years of age and older with one or more CV risk factors, higher rates of all-cause mortality (including sudden CV death), major adverse CV events (MACE; defined as CV death, non-fatal myocardial infarction (MI), and non-fatal stroke), and thrombosis (including DVT and PE) were observed in patients taking tofacitinib, another Janus kinase (JAK) inhibitor, compared to patients taking tumor necrosis factor (TNF) inhibitors. Many of the observed thrombotic events were serious and some resulted in death. Baricitinib has not been studied in similar trials; however, the risks may be similar for all JAK inhibitors used for inflammatory conditions. Current or past tobacco smokers have an additional increased risk of major CV adverse events. Consider the benefits and risks for the individual patient before initiation or continuation of therapy, particular in those with cardiovascular risk factors (e.g., cardiac disease, hypertension, previous myocardial infarction) or those who are current or past smokers. Reserve baricitinib for patients who have an inadequate response or intolerance to one or more TNF inhibitors. Advise patients of the potential increased risk for major adverse CV events and to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot. If a patient develops a thromboembolic event, discontinue the drug.[63229] [66958]

Use baricitinib with caution in patients with renal impairment. Dosage reductions are recommended in patients with an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73 m². For rheumatoid arthritis and alopecia areata patients, treatment with baricitinib is not recommended in patients with severe renal impairment or renal failure (i.e., eGFR less than 30 mL/minute/1.73 m²). For adult COVID-19 patients, baricitinib is not recommended in patients who have end-stage renal disease (ESRD, eGFR less than 15 mL/minute/1.73 m²), are on dialysis, or who have acute kidney injury.[63229] Per the COVID-19 per the Emergency Use Authorization (EUA), the eGFR must be obtained prior to administration of the first baricitinib dose. Baricitinib is not recommended in pediatric COVID-19 patients on dialysis, who have end-stage renal disease (ESRD, eGFR less than 15 mL/minute/1.73 m²), or who have acute kidney injury. Dosage reductions are recommended in pediatric patients 2 years and older with an eGFR of 30 to 59 mL/minute/1.73 m². In pediatric patients 9 years and older with an eGFR of 15 to 29 mL/minute/1.73 m², reduced dose baricitinib should only be used if the potential benefit outweighs the potential risk. Baricitinib therapy is not recommended in pediatric patients 2 years to less than 9 years with an eGFR less than 30 mL/minute/1.73 m².[66126]

Update immunizations in agreement with current immunization guidelines prior to initiating baricitinib therapy in patients with rheumatoid arthritis or alopecia areata. Patients who are taking baricitinib should not receive vaccination with live vaccines. These patients may receive non-live vaccines during baricitinib therapy. The interval between live vaccinations and the initiation of baricitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.[63229]

Cautious use of baricitinib is advised for patients who may be at increased risk for gastrointestinal (GI) perforation (e.g., patients with a history of diverticulitis). GI perforation has been noted among baricitinib recipients. Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of GI perforation.[63229]

Use baricitinib with caution in patients with hyperlipidemia or hypercholesterolemia. Treatment with baricitinib was associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Assessment of lipid parameters should be performed approximately 12 weeks following initiation of baricitinib therapy in patients with rheumatoid arthritis or alopecia areata. Manage patients according to clinical guidelines for the management of hyperlipidemia.[63229]

During clinical trials, no overall differences in safety or effectiveness were noted between geriatric and younger adult patients receiving baricitinib for rheumatoid arthritis. However, greater sensitivity of some older individuals cannot be ruled out. Baricitinib is extensively excreted by the kidney, and the risk of adverse reactions may be greater for patients with impaired renal function. Geriatric patients are more likely to have decreased renal function; therefore, cautious dose selection and monitoring of renal function may be warranted in geriatric patients.[63229]

Available data from clinical trials and postmarketing case reports regarding use of baricitinib during human pregnancy are insufficient to inform a drug-associated risk for major birth defects, miscarriages, or other adverse maternal or fetal outcomes. There are no human data on chronic baricitinib exposure throughout pregnancy; therefore, the risks and benefits with chronic use of the drug should be considered. When deciding whether to use the drug in pregnant patients with rheumatoid arthritis, consider that published data suggest increased disease activity is associated with risk of developing adverse pregnancy outcomes, including preterm delivery (before 37 weeks gestation), low birth weight (less than 2,500 grams) infants, and small for gestational age at birth. Based on finding from animal studies, exposure to baricitinib during pregnancy may cause fetal harm. In embryofetal development studies, oral administration to rats and rabbits at exposures at least 11- and 46-times the maximum recommended human dose (MRHD) of 4 mg per day, respectively, resulted in reduced fetal body weights, increased embryolethality (rabbits only), and dose-related increases in skeletal malformations. Developmental toxicity was not observed in pregnant rats and rabbits treated with baricitinib at approximately 2- and 7-times the MRHD, respectively. In a pre- and post-development study in pregnant rats, oral baricitinib administration at exposures approximately 24-times the MRHD resulted in a reduction in pup viability, decreased fetal birth weight, reduced fetal body weight gain, decreased cytotoxic T cells on post-natal day 35 with no evidence of recovery by day 65, and developmental delays that might be attributable to decreased body weight gain. No developmental toxicity was observed at exposures approximately 5-times the MRHD.[63229] The National Institutes of Health (NIH) states that there are limited data available on the use of Janus kinase (JAK) inhibitors, such as baricitinib, during pregnancy in patients with COVID-19. Among 33 reported cases of JAK inhibitor use during pregnancy in patients with non-COVID-19 indications (e.g., ulcerative colitis, rheumatoid arthritis, psoriasis), the outcomes were similar to those of the general population. However, because of the small molecular size, JAK inhibitors are likely to pass through the placenta; thus, fetal risk cannot be ruled out. The decision to administer baricitinib to a pregnant patient with COVID-19 must be shared between the patient and their healthcare providers, and potential maternal benefit and fetal risks must be considered.[65314] Consider pregnancy planning and contraception requirements for patients of childbearing potential. Report drug exposures during pregnancy to the manufacturer at 1-800-545-5979.[63229]

Due to the potential for serious adverse reactions in a nursing infant, breast-feeding is not recommended during baricitinib therapy and for 4 days after the last dose (approximately 5 to 6 elimination half-lives). No data are available on the presence of baricitinib in human milk, the effects of the drug on the breast-fed infant, or the effects on milk production. Baricitinib is present in the milk of lactating rats; the clinical relevance of this to human lactation is not known.[63229] Etanercept and infliximab may be potential alternatives to consider during breast-feeding. However, assessment of indication and patient-specific factors should be performed before considering an alternative agent.[61808] [62180]

The safety and efficacy of baricitinib in infants, children, and adolescents under the age of 18 years have not been established.[63229]

Angioedema, urticaria, and rash have been reported with baricitinib therapy and may be a result of serious hypersensitivity reactions or anaphylaxis. Promptly discontinue baricitinib therapy if a serious hypersensitivity reaction is suspected.[63229]