Dosage and Administration

Recommended Evaluations Prior to Treatment Initiation¹

Prior to Olumiant treatment initiation, consider performing the following evaluations:

Active and latent tuberculosis (TB) infection evaluation — Olumiant should not be given to patients with active tuberculosis (TB).
Viral hepatitis screening in accordance with clinical guidelines.
Complete blood count — Assess baseline values and verify whether treatment can be initiated:
- Olumiant initiation is not recommended if the ALC is <200 cells/µl or if the ANC is <500 cells/µl.
Monitor complete blood counts during treatment and modify dosage as recommended.
Baseline hepatic and renal function — Assess baseline values and monitor patients for laboratory changes. Modify dosage based on hepatic and renal impairment, and laboratory abnormalities.

Dosage Recommendations in COVID-19¹

The recommended dosage of Olumiant for adults is 4 mg once daily orally, with or without food, for 14 days or until hospital discharge, whichever occurs first. An alternative administration for patients unable to swallow tablets may be used. See "Alternative Administration" section.

Dosage Modifications Due to Infections and Cytopenias¹

Monitor patients for signs and symptoms of new infections during treatment with Olumiant. The risks and benefits of treatment with Olumiant in COVID-19 patients with other concurrent infections should be considered.
Dosage modifications for patients with COVID-19 and cytopenias are described in Table 1.

Table 1: Dosage Modifications for Cytopenias in Patients with COVID-19¹

Laboratory Analyte	Laboratory Analyte Value	Recommendation
Absolute Lymphocyte Count (ALC)	Laboratory Analyte Value: ≥200 cells/µL	Recommendation: Maintain dosage
Absolute Lymphocyte Count (ALC)	Laboratory Analyte Value: <200 cells/µL	Recommendation: Interrupt Olumiant until ALC ≥200 cells/µL
Absolute Neutrophil Count (ANC)	Laboratory Analyte Value: ≥500 cells/µL	Recommendation: Maintain dosage
Absolute Neutrophil Count (ANC)	Laboratory Analyte Value: <500 cells/µL	Recommendation: Interrupt Olumiant until ANC ≥500 cells/µL

Dosage Modifications for Patients with Renal Impairment or Hepatic Impairment¹

Renal Impairment

Dosage modifications for patients with COVID-19 and renal impairment are described in Table 2.

Table 2: Dosage Modifications for Patients with COVID-19 and Renal Impairment¹

Renal Impairment Stage	Estimated Glomerular Filtration Rate (eGFR)	Recommendation
Renal Impairment Stage: Mild	Estimated Glomerular Filtration Rate (eGFR): 60 - <90 mL/min/1.73m²	Recommendation: 4 mg once daily
Renal Impairment Stage: Moderate	Estimated Glomerular Filtration Rate (eGFR): 30 - <60 mL/min/1.73m²	Recommendation: 2 mg once daily
Renal Impairment Stage: Severe	Estimated Glomerular Filtration Rate (eGFR): 15 - <30 mL/min/1.73m²	Recommendation: 1 mg once daily
Renal Impairment Stage: End Stage Renal Disease, Patients on Dialysis, or Acute Kidney Injury	Estimated Glomerular Filtration Rate (eGFR): <15 mL/min/1.73m²	Recommendation: Not recommended

Hepatic Impairment

It is not known if dosage adjustment is needed 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.
Interrupt Olumiant, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded.

ALT=alanine transaminase; AST=aspartate transaminase; DILI=Drug-induced liver injury.

Dosage Modifications Due to Drug Interactions¹

The recommended dosages of Olumiant in patients with COVID-19 taking strong OAT3 inhibitors, such as probenecid, are shown in Table 3:

Table 3: Dosage Modifications when Coadministered with Strong OAT3 Inhibitors in Patients With COVID-19¹

Concomitant Medication	Recommendation
Concomitant Medication: Strong OAT3 inhibitors (e.g., probenecid)	Recommendation: If the recommended dosage is 4 mg once daily, reduce dosage to 2 mg once daily.
	Recommendation: If the recommended dosage is 2 mg once daily, reduce dosage to 1 mg once daily.
	Recommendation: If the recommended dosage is 1 mg once daily, consider discontinuing probenecid.

OAT3=Organic Anion Transporter 3.

SELECT IMPORTANT SAFETY INFORMATION RELATED TO THROMBOSIS

Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), was observed at an increased incidence in Olumiant-treated patients compared to patients treated with placebo. Arterial thrombosis events in the extremities have also reported in clinical studies with Olumiant. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, 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, discontinue Olumiant and promptly evaluate and appropriately treat patients. Avoid Olumiant in patients that may be at increased risk for thrombosis.

Alternative Administration

Alternative Administration for Patients Unable to Swallow Tablets¹

For patients who are unable to swallow whole tablets, an alternative mode of administration may be considered:

Oral dispersion
Gastrostomy tube (G tube)
Nasogastric tube (NG tube) or orogastric tube (OG tube)

Intact tablets are not hazardous. Tablets may be crushed to facilitate dispersion. It is not known if powder from the crushed tablets may constitute a reproductive hazard to the preparer. If tablets are crushed, use proper control measures (e.g., ventilated enclosure) or personal protective equipment (i.e., N95 respirator). Dispersed tablets are stable in water for up to 4 hours.

Preparation Instructions for Alternative Administration¹
Oral Administration of Dispersed Tablets in Water¹

Place tablet(s) in container with ~10 mL (5 mL minimum) of room temperature water and disperse by gently swirling tablet(s).
Take orally immediately.
Rinse container with additional 10 mL (5 mL minimum) of room temperature water and swallow entire contents.

Administration via G Tube¹

Place tablet(s) in container with ~15 mL (10 mL minimum) of room temperature water and disperse with gentle swirling.
Ensure tablet(s) are sufficiently dispersed to allow free passage through syringe tip.
Withdraw entire contents from container into appropriate syringe and immediately administer through gastric feeding tube.
Rinse container with ~15 mL (10 mL minimum) of room temperature water, withdraw contents into syringe, and administer through tube.

Administration via NG or OG Tube¹

Place tablet(s) in container with ~30 mL of room temperature water and disperse with gentle swirling.
Ensure tablet(s) are sufficiently dispersed to allow free passage through syringe tip.
Withdraw entire contents from container into appropriate syringe and immediately administer through enteral feeding tube.
To avoid clogging of small diameter tubes (smaller than 12 Fr), syringe can be held horizontally and shaken during administration.
Rinse container with sufficient amount (15 mL minimum) of room temperature water, withdraw contents into syringe, and administer through tube.

Table 4: Dispersion and Rinse Volume for Alternative Administration¹

Administration via	Dispersion Volume	Container Rinse Volume
Oral dispersion	Dispersion Volume: 10 mL	Container Rinse Volume: 10 mL
G tube	Dispersion Volume: 15 mL	Container Rinse Volume: 15 mL
NG tube or OG tube	Dispersion Volume: 30 mL	Container Rinse Volume: 15 mL

Reference

Olumiant. Prescribing information. Lilly USA, LLC.

IMPORTANT SAFETY INFORMATION

WARNING:

SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

SERIOUS INFECTIONS -

Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients with rheumatoid arthritis (RA) 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 (TB), which may present with pulmonary or extrapulmonary disease. Olumiant should not be given to patients with active tuberculosis. Test patients, except those with COVID-19, for latent TB before initiating Olumiant and during therapy. If positive, start treatment for latent infection prior to Olumiant use.
Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
Bacterial, viral, and other infections due to opportunistic pathogens.

Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Avoid use of Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients: with chronic or recurrent infection; who have been exposed to TB; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.

The risks and benefits of treatment with Olumiant in COVID-19 patients with other concurrent infections should be considered.

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 cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.

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. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.

MORTALITY

In a large, randomized, postmarketing safety study in RA patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with Olumiant. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. 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 and an additional increased risk of overall malignancies were observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers.

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.

NMSCs have been reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

MAJOR ADVERSE CARDIOVASCULAR EVENTS

In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction [MI], and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue Olumiant in patients that have experienced a myocardial infarction or stroke.

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. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur.

THROMBOSIS

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, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid Olumiant in patients at risk. Discontinue Olumiant and promptly evaluate patients with symptoms of thrombosis.

HYPERSENSITIVITY

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.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal perforations have been reported in Olumiant clinical studies. Monitor Olumiant-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.

LABORATORY ABNORMALITIES

Neutropenia - Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm³) compared to placebo. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA or alopecia areata (AA), avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm³. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ANC <500 cells/mm³.

Lymphopenia - Absolute lymphocyte count (ALC) <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. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA or AA, avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm³. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ALC <200 cells/mm³.

Anemia - Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Evaluate at baseline and thereafter according to routine patient management.

In patients with RA or AA, avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. In patients with COVID-19, there is limited information regarding use of Olumiant in patients with hemoglobin less than 8 g/dL.

Liver Enzyme Elevations - Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of alanine transaminase (ALT) ≥5x upper limit of normal (ULN) and increases of aspartate transaminase (AST) ≥10x ULN were observed in patients in Olumiant clinical trials.

Evaluate at baseline and thereafter according to routine patient management. Promptly investigate the cause of liver enzyme elevation to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.

Lipid Elevations - Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation in patients with RA or AA. Manage patients according to clinical guidelines for the management of hyperlipidemia.

VACCINATIONS

Avoid use of live vaccines with Olumiant. Update immunizations in patients with RA or AA prior to initiating Olumiant therapy in agreement with current immunization guidelines.

ADVERSE REACTIONS

In RA trials, the most common adverse reactions (≥1%) reported with Olumiant were: upper respiratory tract infections, nausea, herpes simplex, and herpes zoster.

In COVID-19 trials, the most common adverse reactions (≥1%) reported with Olumiant were: ALT ≥3x ULN, AST ≥3x ULN, thrombocytosis (platelets >600,000 cells/mm³), creatine phosphokinase >5x ULN, neutropenia (ANC <1000 cells/mm³), DVT, PE, and urinary tract infection.

In AA trials, the most common adverse reactions (≥1%) reported with Olumiant were: upper respiratory tract infections, headache, acne, hyperlipidemia, creatine phosphokinase increase, urinary tract infections, liver enzyme elevations, folliculitis, fatigue, lower respiratory tract infections, nausea, genital Candida infections, anemia, neutropenia, abdominal pain, herpes zoster, and weight increase.

PREGNANCY AND LACTATION

Based on animal studies, Olumiant may cause fetal harm when administered during pregnancy. Advise pregnant women and women of reproductive potential of the potential risk to a fetus. Consider pregnancy planning and prevention for women of reproductive potential. Advise women not to breastfeed during treatment with Olumiant and for 4 days after the last dose.

HEPATIC AND RENAL IMPAIRMENT

Olumiant is not recommended in patients with RA or AA and severe hepatic impairment or severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m²).

Olumiant should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk. Olumiant is not recommended in patients with COVID-19 who are on dialysis, have end-stage renal disease, or with eGFR <15 mL/min/1.73m².

BA HCP ISI ALL 14SEP2022

Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.

INDICATIONS

Alopecia Areata

Olumiant is indicated for the treatment of adult patients with severe alopecia areata.

Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.

Rheumatoid Arthritis

Olumiant is a Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) blockers.

Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants, such as azathioprine and cyclosporine.

COVID-19

Olumiant is a Janus kinase (JAK) inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).