Drug Safety-related Labeling Changes (SrLC)

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OLUMIANT (NDA-207924)

(BARICITINIB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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06/13/2022 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Serious Infections

Additions and/or revisions underlined:

…

In patients with rheumatoid arthritis or alopecia areata, closely monitor for the development of signs and symptoms of infection during and after treatment with OLUMIANT. Interrupt OLUMIANT in patients with rheumatoid arthritis or alopecia areata, if the patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with OLUMIANT should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and OLUMIANT should be interrupted if the patient is not responding to therapy. Do not resume OLUMIANT until the infection is controlled.

In patients with COVID-19, monitor for signs and symptoms of new infections during and after treatment with OLUMIANT. There is limited information regarding the use of OLUMIANT in patients with COVID-19 and concomitant active serious infections. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered.
Tuberculosis

Evaluate patients for active infection prior to administration of OLUMIANT. OLUMIANT should not be given to patients with active TB.

Test patients with rheumatoid arthritis or alopecia areata for latent tuberculosis. Patients with rheumatoid arthritis or alopecia areata and latent tuberculosis (TB) should be treated with standard antimycobacterial therapy before initiating OLUMIANT. Consider anti-TB therapy prior to initiation of OLUMIANT in patients with a history of latent or active TB in whom an adequate course of treatment cannotbe 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 OLUMIANT use, monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with OLUMIANT. If a patient develops herpes zoster, interrupt OLUMIANT treatment until the episode resolves.

The impact of OLUMIANT on chronic viral hepatitis reactivation is unknown. Patients with evidence of active hepatitis B or 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. Perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy with OLUMIANT.

5.8 Laboratory Abnormalities

Additions and/or revisions underlined:

…

In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ANC less than 1000 cells/mm3.

…

Lymphopenia – ALC less than 500 cells/mm3 were reported in OLUMIANT clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with OLUMIANT, but not placebo.

In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ALC less than 500 cells/mm3.

In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ALC less than 200 cells/mm3. Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ALC less than 200 cells/mm3.

Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ALC [see Dosage and Administration (2.1, 2.5)].

Anemia – Decreases in hemoglobin levels to less than 8 g/dL were reported in OLUMIANT clinical trials. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with hemoglobin less than 8 g/dL. Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on hemoglobin levels [see Dosage and Administration (2.1, 2.5)].

…

Lipid Elevations – Treatment with OLUMIANT 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 OLUMIANT initiation in patients with rheumatoidarthritis or alopecia areata [see Adverse Reactions (6.1)]. Manage patients according to clinical guidelines for the management of hyperlipidemia.

5.9 Vaccinations

Additions and/or revisions underlined:

Avoid use of live vaccines with OLUMIANT. Update immunizations in patients with rheumatoid arthritis or alopecia areata prior to initiating OLUMIANT therapy in agreement with current immunization guidelines.

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label

7 Drug Interactions

7.1 Strong OAT3 Inhibitors

Additions and/or revisions underlined:

Baricitinib exposure is increased when OLUMIANT is co-administered with strong OAT3 inhibitors (such as probenecid), hence the dosage of baricitinib should be reduced by half the recommended dose [see Dosage and Administration (2.2, 2.3) and Clinical Pharmacology (12.3)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Based on the findings from animal reproduction studies, OLUMIANT may cause fetal harm during pregnancy. Available data from clinical trials and postmarketing case reports with OLUMIANT 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 the mother and the fetus associated with rheumatoid arthritis in pregnancy (see Clinical Considerations). Consider the risks and benefits with chronic use of OLUMIANT during pregnancy.

In animal embryo-fetal development studies, oral baricitinib administration to pregnant rats and rabbits at exposures equal to and greater than approximately 11 and 46 times the maximum recommended human dose (MRHD) of 4 mg/day, respectively, resulted in reduced fetal body weights, increased embryolethality (rabbitsonly), and dose-related increases in skeletal malformations. No developmental toxicity was observed in pregnant rats and rabbits treated with oral baricitinib during organogenesis at approximately 2 and 7 times the exposure at the MRHD, respectively. In a pre- and post-natal development study in pregnant female rats, oral baricitinib administration at exposures approximately 24 times the MRHD

resulted in reduction in pup viability (increased incidence of stillborn pups and early neonatal deaths), decreased fetal birth weight, reduced fetal body weight gain, decreased cytotoxic T cells on post-natal day (PND) 35 with evidence of recovery by PND 65, and developmental delays that might be attributable to decreased body weight gain. No developmental toxicity was observed at an exposure approximately 5 times the exposure at the MRHD (see Data).

The background risks of major birth defects and miscarriage for the indicated population(s) are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Report pregnancies to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data suggest that increased disease activity is associated with the 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.

Data

Animal Data

In an embryofetal development study in pregnant rats, dosed orally during the period of organogenesis from gestation days 6 to 17, baricitinib was teratogenic (skeletal malformations that consisted of bent limb bones and rib anomalies) at exposures equal to or greater than approximately 11 times the MRHD (on an AUC basis at maternal oral doses of

10 mg/kg/day and higher). No developmental toxicity was observed in rats at an exposure approximately 2 times the MRHD (on an AUC basis at a maternal oral dose of 2 mg/kg/day).

In an embryofetal development study in pregnant rabbits, dosed orally during the period of organogenesis from gestation days 7 to 20, embryolethality, decreased fetal body weights, and skeletal malformations (rib anomalies) were observed in the presence of maternal toxicity at an exposure approximately 46 times the MRHD (on an AUC basis at a maternal oral dose of 30 mg/kg/day). Embryolethality consisted of increased post-implantation loss that was due to elevated incidences of both early and late resorptions. No developmental toxicity was observed in rabbits at an exposure approximately 7 times the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).

In a pre- and post-natal development study in pregnant female rats dosed orally from gestation day 6 through lactation day 20, adverse findings observed in pups included decreased survival from birth to post-natal day 4 (due to increased stillbirths and early neonatal deaths), decreased birth weight, decreased body weight gain during the pre-weaning phase, increased incidence of malrotated forelimbs during the pre-weaning phase, and decreased cytotoxic T cells on PND 35 with recovery by PND 65 at exposures approximately 24 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day). Developmental delays (that may be secondary to decreased body weight gain) were observed in males and females at exposures approximately 24 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day). These findings included decreased forelimb and hindlimb grip strengths, and delayed mean age of sexual maturity. No developmental toxicity was observed in rats at an exposure approximately 5 times the MRHD (on an AUC basis at a maternal oral dose of 5 mg/kg/day).

8.2 Lactation

Additions and/or revisions underlined:
Risk Summary

No information is available on the presence of OLUMIANT in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Baricitinib is present in the milk of lactating rats (see Data). Because of the potential for serious adverse reactions in nursing infants advise women not to breastfeed during treatment with OLUMIANT and for 4 days after the last dose (approximately 5 to 6 elimination half-lives).

Data

A single oral dose of 25 mg/kg radiolabeled baricitinib was administered to lactating female Sprague-Dawley rats on post- partum day 13. Drug exposure was approximately 45-fold greater in milk than in plasma based on AUC0-t values.

8.3 Females and Males of Resporductive Potential

Newly added subsection

Contraception

Based on animal studies, OLUMIANT may cause fetal harm when administered during pregnancy [see Use in Specific Populations (8.1)]. Consider pregnancy planning and prevention for females of reproductive potential.

8.5 Geriatric Use

Additions and/or revisions underlined:

Of the 3100 patients treated in the rheumatoid arthritis clinical trials, a total of 537 patients were 65 years of age and older, including 71 patients 75 years of age and older. 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 [see Clinical Pharmacology (12.3)].

Of the 1200 patients in the alopecia areata clinical trials, a total of 29 patients were 65 years of age or older. The number of patients aged 65 years and older was not sufficient to determine whether they respond differently from younger patients.

OLUMIANT 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 [see Dosage and Administration (2.6)].

8.6 Hepatic Impairment

Additions and/or revisions underlined:

No dose adjustment is necessary in patients with mild or moderate hepatic impairment.

The use of OLUMIANT has not been studied in patients with rheumatoid arthritis or alopecia areata and severe hepatic impairment and is therefore not recommended. OLUMIANT has not been studied in patients with COVID-19 and severe hepatic impairment. OLUMIANT should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

8.7 Renal Impairment

Additions and/or revisions underlined:

Renal function was found to significantly affect baricitinib exposure.

Rheumatoid Arthritis and Alopecia Areata - The recommended dosage of OLUMIANT in patients with moderate renal impairment (estimated glomerular filtration rate (GFR) between 30 and <60 mL/min/1.73 m2) should be reduced by half the recommended dose. OLUMIANT is not recommended for use in patients with rheumatoid arthritis or alopecia areata and severe renal impairment (estimated GFR of less than 30 mL/min/1.73 m2) [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

COVID-19 - The recommended dosage of OLUMIANT in patients with moderate renal impairment (estimated GFR between 30 and <60 mL/min/1.732) or severe renal impairment (estimated GFR between 15 and <30 mL/min/1.73 m2) is 2 mg once daily and 1 mg once daily, respectively. OLUMIANT is not recommended for use in patients who are on dialysis, haveend-stage renal disease (ESRD), or with estimated GFR of <15 mL/min/1.73 m2 [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Extensive changes; please refer to label

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Infections

Inform patients that they may be more likely to develop infections when taking OLUMIANT. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection [see Warnings and Precautions (5.1)].

Advise patients that the risk of herpes zoster is increased in patients treated with OLUMIANT and some cases can be serious [see Warnings and Precautions (5.1)].

Malignancies and Lymphoproliferative Disorders

Inform patients that OLUMIANT may increase their risk of developing lymphomas and other malignancies, including of the skin and that periodic skin examinations should be performed while using OLUMIANT. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.3)].

Major Adverse Cardiovascular Events

Inform patients that OLUMIANT may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)].

Thrombosis

Advise patients that events of DVT and PE have been reported in clinical studies with OLUMIANT. Instruct patients to seek immediate medical attention if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)].

Hypersensitivity Reactions

Advise patients to discontinue OLUMIANT and seek immediate medical attention if they develop any signs and symptoms of serious allergic reactions [see Warnings and Precautions (5.6)].

Gastrointestinal Perforations

Inform patients that gastrointestinal perforations have been reported in clinical trials with OLUMIANT. Instruct patients to seek medical care immediately if they experience new onset of abdominal pain, fever, chills, nausea, or vomiting [see Warnings and Precautions (5.7)].

Laboratory Abnormalities

Inform patients that OLUMIANT may affect certain lab tests, and that blood tests are required before and during OLUMIANT treatment [see Warnings and Precautions (5.8)].

Live Vaccines

Instruct patients to inform the healthcare practitioner that they are taking OLUMIANT prior to a potential vaccination since the use of live vaccine is not recommended [see Warnings and Precautions (5.9)].

Pregnancy

Advise pregnant females and females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider if they are pregnant or intend to become pregnant during treatment with OLUMIANT. Inform patients to report their pregnancy to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) [see Use in Specific Populations (8.1, 8.3)].

Lactation

Advise a woman not to breastfeed during treatment with OLUMIANT and for four days after the last dose[see Use in Specific Populations (8.2)]

05/10/2022 (SUPPL-6)

Approved Drug Label (PDF)

Boxed Warning

SERIOUS INFECTIONS

Additions and revisions underlined:

Patients treated with OLUMIANT are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)]. Most patients with rheumatoid arthritis who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt OLUMIANT until the infection is controlled. Reported infections include:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. OLUMIANT should not be given to patients with active tuberculosis. Patients, except those with COVID-19, should be tested for latent tuberculosis before initiating OLUMIANT and during therapy. If positive, start treatment for latent infection prior to OLUMIANT use.

5 Warnings and Precautions

Extensive changes related to addition of new indication for COVID-19; please refer to label

6 Adverse Reactions

Newly added information:

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Serious Infections [see Warnings and Precautions (5.1)]

• Mortality [see Warnings and Precautions (5.2)]

• Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3)]

• Major Adverse Cardiovascular Events [see Warnings and Precautions (5.4)]

• Thrombosis [see Warnings and Precautions (5.5)]

• Gastrointestinal Perforations [see Warnings and Precautions (5.6)]

• Laboratory Abnormalities [see Warnings and Precautions (5.7)]

• Hypersensitivity [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Newly added information and table, Adverse Reactions in Patients with COVID-19; please refer to label

8 Use in Specific Populations

8.1 Pregnancy

Extensive changes; please refer to label

8.2 Lactation

Additions and revisions underlined:

Because of the potential for serious adverse reactions in nursing infants, advise an OLUMIANT-treated woman with rheumatoid arthritis not to breastfeed.

8.5 Geriatric Use

Additions and revisions underlined:

Of the 3100 patients treated in the rheumatoid arthritis clinical trials, a total of 537 patients were 65 years of age and older, including 71 patients 75 years and older. 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.

8.6 Hepatic Impairment

Additions and revisions underlined:

No dose adjustment is necessary in patients with mild or moderate hepatic impairment.

The use of OLUMIANT has not been studied in patients with rheumatoid arthritis and severe hepatic impairment and is therefore not recommended. OLUMIANT has not been studied in patients with COVID-19 and severe hepatic impairment. OLUMIANT should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk [see Dosage and Administration (2.2, 2.3) and Clinical Pharmacology (12.3)].

8.7 Renal Impairment

Additions and revisions underlined:

Renal function was found to significantly affect baricitinib exposure.

Rheumatoid Arthritis - The recommended dose of OLUMIANT in patients with moderate renal impairment (estimated glomerular filtration rate (GFR) between 30 and <60 mL/min/1.73 m2) is 1 mg once daily. OLUMIANT is not recommended for use in patients with rheumatoid arthritis and severe renal impairment (estimated GFR of less than 30 mL/min/1.73 m2) [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

COVID-19 - The recommended dose of OLUMIANT in patients with moderate renal impairment (estimated GFR between 30 and <60 mL/min/1.732) or severe renal impairment (estimated GFR between 15 and <30 mL/min/1.73 m2) is 2 mg once daily and 1 mg once daily, respectively. OLUMIANT is not recommended for use in patients who are on dialysis, have end-stage renal disease (ESRD), or with estimated GFR of <15 mL/min/1.73 m2 [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

Additions and revisions underlined:

• Your healthcare provider should test you for TB before starting treatment for rheumatoid arthritis with OLUMIANT.

Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) and arteries (arterial thrombosis) can happen in some people taking OLUMIANT.

You may also have changes in other laboratory tests, such as your blood cholesterol levels. If you are being treated for rheumatoid arthritis, your healthcare provider should do blood tests to check your cholesterol levels approximately 12 weeks after you start taking OLUMIANT, and as needed after that.

What is OLUMIANT?

• OLUMIANT is a prescription medicine used to treat:

o adults with moderately to severely active rheumatoid arthritis after treatment with 1 or more medicines called

tumor necrosis factor (TNF) blockers have been used and did not work well enough or could not be tolerated.

o adult patients hospitalized with coronavirus disease 2019 (COVID-19) requiring oxygen or assistance with

breathing.

How should I take OLUMIANT?

• Take OLUMIANT exactly as your healthcare provider tells you to take it.

• For people with rheumatoid arthritis, take OLUMIANT 1 time a day by mouth with or without food.

• For patients with COVID-19, OLUMIANT will be given to you 1 time a day by mouth with or without food, for up to 14

days or until you are discharged from the hospital (whichever comes first), as instructed by your healthcare provider.

• Talk to your healthcare provider if you cannot swallow tablets whole.

12/02/2021 (SUPPL-4)

Approved Drug Label (PDF)

Boxed Warning

Box Warning has been revised; see full information below:

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), AND THROMBOSIS

See full prescribing information for complete boxed warning.

• Increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with OLUMIANT if serious infection occurs until the infection is controlled. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. (5.1)

• Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. (5.2)

• Malignancies have occurred in patients treated with OLUMIANT. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. (5.3)

• Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. (5.4)

• Thrombosis has occurred in patients treated with OLUMIANT. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. (5.5)

5 Warnings and Precautions

5.2 Mortality

Newly added subsection:

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT.

5.3 Malignancy and Lymphoproliferative Disorders

Additions and/or revisions underlined:

Malignancies were observed in clinical studies of OLUMIANT [see Adverse Reactions (6.1)].

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

Non-melanoma skin cancers

Non-melanoma skin cancers (NMSCs) have been reported in patients treated with OLUMIANT. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

5.4 Major Adverse Cardiovascular Events

Newly added subsection:

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OLUMIANT in patients that have experienced a myocardial infarction or stroke.

5.5 Thrombosis

Additions and/or revisions underlined:

Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with OLUMIANT compared to placebo. In addition, arterial thrombosis events in the extremities have been reported in clinical studies with OLUMIANT. Many of these adverse events were serious and some resulted in death. There was no clear relationship between platelet count elevations and thrombotic events. In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.

If clinical features of DVT/PE or arterial thrombosis occur, patients should discontinue OLUMIANT and be evaluated promptly and treated appropriately. Avoid OLUMIANT in patients that may be at increased risk of thrombosis.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Patient Counseling

Advise patients of the potential benefits and risks of OLUMIANT.

Infections

Inform patients that they may be more likely to develop infections when taking OLUMIANT. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection [see Warnings and Precautions (5.1)].

Advise patients that the risk of herpes zoster is increased in patients treated with OLUMIANT and some cases can be serious [see Warnings and Precautions (5.1)].

Malignancies and Lymphoproliferative Disorders

Inform patients that OLUMIANT may increase their risk of developing lymphomas and other malignancies, including of the skin. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.3)].

Major Adverse Cardiovascular Events

Inform patients that OLUMIANT may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)].

Thrombosis

Advise patients that events of DVT and PE have been reported in clinical studies with OLUMIANT. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)].

Laboratory Abnormalities

Inform patients that OLUMIANT may affect certain lab tests, and that blood tests are required before and during OLUMIANT treatment [see Warnings and Precautions (5.7)].

Lactation

Advise a woman not to breastfeed during treatment with OLUMIANT [see Use in Specific Populations (8.2)].

07/08/2020 (SUPPL-2)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.7 Hypersensitivity

(New subsection added)

Reactions such as angioedema, urticaria, and rash that may reflect drug hypersensitivity have been observed in patients receiving OLUMIANT, including serious reactions. If a serious hypersensitivity reaction occurs, promptly discontinue OLUMIANT while evaluating the potential causes of the reaction [see Adverse Reactions (6.2)].

6 Adverse Reactions

6.2 Postmarketing Experience

(New subsection added)

The following adverse reactions have been identified during post-approval use of OLUMIANT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Drug hypersensitivity (events such as rash, urticaria, and angioedema have been observed) [see Warnings and Precautions (5.7)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Additions underlined)

What is the most important information I should know about OLUMIANT?

 OLUMIANT may cause serious side effects, including:

…

6.   Allergic Reactions.

Symptoms such as rash, swelling of your lips, tongue, or throat, or hives (raised, red patches of skin that are often very itchy) that may mean you are having an allergic reaction have been seen in patients taking OLUMIANT. Some of these reactions were serious. If any of these symptoms occur while you are taking OLUMIANT, stop taking OLUMIANT and call your healthcare provider right away.

…

PATIENT COUNSELING INFORMATION

(Additions underlined)

…

Malignancies and Lymphoproliferative Disorders

Inform patients that OLUMIANT may increase their risk of developing lymphomas and other malignancies, including of the skin. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.2)].

…

10/08/2019 (SUPPL-1)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.7 Renal Impairment

Additions and/or revisions underlined:
Renal function was found to significantly affect baricitinib exposure. The recommended dose of OLUMIANT in patients with moderate renal impairment (estimated glomerular filtration rate (GFR) between 30 and 60 mL/min/1.73 m2) is 1 mg once daily. OLUMIANT is not recommended for use in patients with severe renal impairment (estimated GFR of less than 30 mL/min/1.73 m2).