Interactions between Baricitinib and Option 2

The levonorgestrel in Option 2 has a major potential interaction with Abnormal Uterine Bleeding.

The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.

The levonorgestrel in Option 2 has a moderate potential interaction with Asthma.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Baricitinib has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Treatment with baricitinib was associated with an increased incidence of neutropenia, lymphopenia, and anemia compared to placebo. Therapy should not be started or should be interrupted in patients with rheumatoid arthritis or alopecia areata with an absolute lymphocyte count (ALC) less than 500 cells/mm3, absolute neutrophil count (ANC) less than 1000 cells/mm3, or hemoglobin level less than 8 g/dL; therapy should not be started or should be interrupted in patients with coronavirus disease 2019 (COVID-19) with an ALC less than 200 cells/mm3 or ANC less than 500 cells/mm3. Evaluation at baseline and thereafter according to routine patient management is recommended; dosing should be modified based on ALC, ANC, and/or hemoglobin levels. Caution is recommended in patients who may be at increased risk.

The levonorgestrel in Option 2 has a major potential interaction with Breast Cancer.

The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.

Baricitinib has a major potential interaction with Cardiovascular Conditions and Disorders.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

The levonorgestrel in Option 2 has a moderate potential interaction with Cerebral Vascular Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

The levonorgestrel in Option 2 has a moderate potential interaction with Depression.

The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

Baricitinib has a major potential interaction with Diabetes Mellitus.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib; the most common serious infections reported included pneumonia, herpes zoster, and urinary tract infection. Use of baricitinib should be avoided in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered before starting baricitinib in patients: with chronic/recurrent infection, who have been exposed to tuberculosis, with history of serious/opportunistic infection, who have resided/traveled in areas of endemic tuberculosis/mycoses, with underlying conditions that may predispose them to infection (e.g., diabetes, chronic lung disease, HIV, weak immune system), or with COVID-19 plus other concomitant infections. During and after baricitinib treatment, patients with rheumatoid arthritis or alopecia areata should be closely monitored for signs/symptoms of infection and patients with COVID-19 should be monitored for signs/symptoms of new infections.

The levonorgestrel in Option 2 has a moderate potential interaction with Diabetes Mellitus.

Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

The levonorgestrel in Option 2 has a moderate potential interaction with Fluid Retention.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Baricitinib has a moderate potential interaction with Gastrointestinal Diverticula.

Baricitinib may cause gastrointestinal perforation. Baricitinib-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with history of diverticulitis) should be monitored. Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of gastrointestinal perforation. Caution is recommended for patients who may be at increased risk.

Baricitinib has a moderate potential interaction with Gastrointestinal Perforation.

Baricitinib may cause gastrointestinal perforation. Baricitinib-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with history of diverticulitis) should be monitored. Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of gastrointestinal perforation. Caution is recommended for patients who may be at increased risk.

The levonorgestrel in Option 2 has a moderate potential interaction with Heart Failure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The levonorgestrel in Option 2 has a major potential interaction with Hepatic Tumor.

The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

The levonorgestrel in Option 2 has a moderate potential interaction with High Blood Pressure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The levonorgestrel in Option 2 has a moderate potential interaction with High Cholesterol.

Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

The levonorgestrel in Option 2 has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Baricitinib has a major potential interaction with History, Tuberculosis.

Baricitinib should not be given to patients with active tuberculosis (TB); patients should be evaluated for active infection before administering this agent. Patients with rheumatoid arthritis or alopecia areata should be tested for latent TB; if positive, patients should be treated with standard antimycobacterial therapy before starting baricitinib. Anti-TB therapy should be considered prior to initiating treatment with baricitinib in patients with history of latent/active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. During baricitinib use, patients should be monitored for signs/symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Baricitinib has a major potential interaction with Immunodeficiency.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib; the most common serious infections reported included pneumonia, herpes zoster, and urinary tract infection. Use of baricitinib should be avoided in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered before starting baricitinib in patients: with chronic/recurrent infection, who have been exposed to tuberculosis, with history of serious/opportunistic infection, who have resided/traveled in areas of endemic tuberculosis/mycoses, with underlying conditions that may predispose them to infection (e.g., diabetes, chronic lung disease, HIV, weak immune system), or with COVID-19 plus other concomitant infections. During and after baricitinib treatment, patients with rheumatoid arthritis or alopecia areata should be closely monitored for signs/symptoms of infection and patients with COVID-19 should be monitored for signs/symptoms of new infections.

Baricitinib has a major potential interaction with Infection.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib; the most common serious infections reported included pneumonia, herpes zoster, and urinary tract infection. Use of baricitinib should be avoided in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered before starting baricitinib in patients: with chronic/recurrent infection, who have been exposed to tuberculosis, with history of serious/opportunistic infection, who have resided/traveled in areas of endemic tuberculosis/mycoses, with underlying conditions that may predispose them to infection (e.g., diabetes, chronic lung disease, HIV, weak immune system), or with COVID-19 plus other concomitant infections. During and after baricitinib treatment, patients with rheumatoid arthritis or alopecia areata should be closely monitored for signs/symptoms of infection and patients with COVID-19 should be monitored for signs/symptoms of new infections.

Baricitinib has a moderate potential interaction with Infectious Hepatitis.

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was reported in clinical studies with baricitinib. Patients should be screened for viral hepatitis in accordance with clinical guidelines before starting therapy with baricitinib. If a patient develops herpes zoster during therapy, treatment with baricitinib should be interrupted until the episode resolves.

The levonorgestrel in Option 2 has a major potential interaction with Liver Disease.

The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.

Baricitinib has a moderate potential interaction with Liver Disease.

Baricitinib is not recommended in patients with rheumatoid arthritis or alopecia areata with severe liver dysfunction; baricitinib should only be used in patients with coronavirus disease 2019 (COVID-19) and severe liver dysfunction if the potential benefit outweighs the potential risk. No dose adjustment is necessary in patients with mild or moderate liver dysfunction. Treatment with baricitinib was associated with increased incidence of liver enzyme elevation compared to placebo. Liver enzymes should be evaluated at baseline and thereafter according to routine patient management; prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, baricitinib should be interrupted until this diagnosis is excluded.

The levonorgestrel in Option 2 has a moderate potential interaction with Migraine.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Baricitinib has a moderate potential interaction with Peritoneal dialysis.

Renal function significantly affects baricitinib exposure; renal elimination is the principal clearance mechanism for baricitinib through filtration and active secretion. Baricitinib is not recommended in patients with rheumatoid arthritis or alopecia areata and severe renal dysfunction (estimated GFR [eGFR] less than 30 mL/min/1.73 m2); baricitinib is not recommended in patients with coronavirus disease 2019 (COVID-19) who are on dialysis, have ESRD, or have acute kidney injury (eGFR less than 15 mL/min/1.73 m2). Dosage modifications are recommended for patients with rheumatoid arthritis or alopecia areata with moderate renal dysfunction (eGFR 30 to less than 60 mL/min/1.73 m2) and COVID-19 patients with moderate or severe renal dysfunction (eGFR 15 to less than 60 mL/min/1.73 m2); care should be exercised when using this agent in such patients.

Baricitinib has a major potential interaction with Pulmonary Impairment.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving baricitinib; the most common serious infections reported included pneumonia, herpes zoster, and urinary tract infection. Use of baricitinib should be avoided in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered before starting baricitinib in patients: with chronic/recurrent infection, who have been exposed to tuberculosis, with history of serious/opportunistic infection, who have resided/traveled in areas of endemic tuberculosis/mycoses, with underlying conditions that may predispose them to infection (e.g., diabetes, chronic lung disease, HIV, weak immune system), or with COVID-19 plus other concomitant infections. During and after baricitinib treatment, patients with rheumatoid arthritis or alopecia areata should be closely monitored for signs/symptoms of infection and patients with COVID-19 should be monitored for signs/symptoms of new infections.

Baricitinib has a moderate potential interaction with Renal Dysfunction.

Renal function significantly affects baricitinib exposure; renal elimination is the principal clearance mechanism for baricitinib through filtration and active secretion. Baricitinib is not recommended in patients with rheumatoid arthritis or alopecia areata and severe renal dysfunction (estimated GFR [eGFR] less than 30 mL/min/1.73 m2); baricitinib is not recommended in patients with coronavirus disease 2019 (COVID-19) who are on dialysis, have ESRD, or have acute kidney injury (eGFR less than 15 mL/min/1.73 m2). Dosage modifications are recommended for patients with rheumatoid arthritis or alopecia areata with moderate renal dysfunction (eGFR 30 to less than 60 mL/min/1.73 m2) and COVID-19 patients with moderate or severe renal dysfunction (eGFR 15 to less than 60 mL/min/1.73 m2); care should be exercised when using this agent in such patients.

The levonorgestrel in Option 2 has a moderate potential interaction with Renal Dysfunction.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The levonorgestrel in Option 2 has a moderate potential interaction with Seizures.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Baricitinib has a major potential interaction with Smoking.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

Baricitinib has a major potential interaction with Smoking.

Malignancies (including lymphomas and solid tumors) have been reported in patients treated with tofacitinib, baricitinib, upadacitinib, deuruxolitinib and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk of malignancies. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, pacritinib, and fedratinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy during therapy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Baricitinib has a major potential interaction with Thrombotic/Thromboembolic Disorder.

Thrombosis (including deep venous thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, and arterial thrombosis) has occurred in patients treated for inflammatory conditions with Janus kinase (JAK) inhibitors, including baricitinib, tofacitinib, deuruxolitinib and upadacitinib. Many of these adverse events were serious and some resulted in death. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, fedratinib, and pacritinib. In general, JAK inhibitors should be avoided in patients who may be at increased risk of thrombosis. Tofacitinib should be used at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response when treating ulcerative colitis. If symptoms of thrombosis occur in any patients receiving JAK inhibitors, treatment should be discontinued and patients should be evaluated promptly and treated appropriately.

The levonorgestrel in Option 2 has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

The levonorgestrel in Option 2 has a moderate potential interaction with Thyroid Disease.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

Baricitinib has a major potential interaction with Tuberculosis, Active.

Baricitinib should not be given to patients with active tuberculosis (TB); patients should be evaluated for active infection before administering this agent. Patients with rheumatoid arthritis or alopecia areata should be tested for latent TB; if positive, patients should be treated with standard antimycobacterial therapy before starting baricitinib. Anti-TB therapy should be considered prior to initiating treatment with baricitinib in patients with history of latent/active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. During baricitinib use, patients should be monitored for signs/symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Baricitinib has a major potential interaction with Tuberculosis, Latent.

Baricitinib should not be given to patients with active tuberculosis (TB); patients should be evaluated for active infection before administering this agent. Patients with rheumatoid arthritis or alopecia areata should be tested for latent TB; if positive, patients should be treated with standard antimycobacterial therapy before starting baricitinib. Anti-TB therapy should be considered prior to initiating treatment with baricitinib in patients with history of latent/active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. During baricitinib use, patients should be monitored for signs/symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Baricitinib has a moderate potential interaction with Varicella-Zoster.

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was reported in clinical studies with baricitinib. Patients should be screened for viral hepatitis in accordance with clinical guidelines before starting therapy with baricitinib. If a patient develops herpes zoster during therapy, treatment with baricitinib should be interrupted until the episode resolves.

The levonorgestrel in Option 2 has a minor potential interaction with Weight Loss.

Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.