Dosage & Administration
Administration Instructions:
Recommended Dosage:
Rheumatoid Arthritis:
COVID-19:
Alopecia Areata:
Dosage Modifications in Patients with Renal or Hepatic Impairment, or Cytopenias
Olumiant Prescribing Information
SERIOUS INFECTIONS
Patients treated with OLUMIANT are at risk for developing serious infections that may lead to hospitalization or death[see Warnings and Precautions and Adverse Reactions ]. 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.
- 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.
The risks and benefits of treatment with OLUMIANT should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with OLUMIANT including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy[see Warnings and Precautions ].
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (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[see Warnings and Precautions ].
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[see Warnings and Precautions ].
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, 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[see Warnings and Precautions ].
THROMBOSIS
Thrombosis, including deep venous thrombosis and pulmonary embolism, 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. Patients with symptoms of thrombosis should discontinue OLUMIANT and be promptly evaluated.[see Warnings and Precautions ].
Rheumatoid Arthritis
OLUMIANT® (baricitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis 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.
Coronavirus Disease 2019 (COVID-19)
OLUMIANT is 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).
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.
Recommended Evaluations and Immunization Prior to Treatment Initiation
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). If latent infection is positive in patients with rheumatoid arthritis or alopecia areata, consider treatment for TB prior to OLUMIANT use [see Warnings and Precautions ].
- Viral hepatitis screening in accordance with clinical guidelines [see Warnings and Precautions ].
- Complete blood count – Assess baseline values and verify whether treatment can be initiated:
- -
- In patients with rheumatoid arthritis or alopecia areata, OLUMIANT initiation is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/μl, absolute neutrophil count (ANC) <1000 cells/μl, or hemoglobin level <8 g/dL.
- -
- In patients with COVID-19, 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 [see Dosage and Administration and Warnings and Precautions ].
- 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 [see Dosage and Administration and Warnings and Precautions ].
In patients with rheumatoid arthritis or alopecia areata, update immunizations in agreement with current immunization guidelines [see Warnings and Precautions ].
Dosage Recommendations in Rheumatoid Arthritis
The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food [see Clinical Pharmacology ]. An alternative administration for patients unable to swallow tablets may be used [see Dosage and Administration ]. OLUMIANT may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs.
Dosage Recommendations in COVID-19
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 Dosage and Administration ].
Dosage Recommendations in Alopecia Areata
The recommended dosage of OLUMIANT is 2 mg once daily orally, with or without food. Increase to 4 mg once daily if the response to treatment is not adequate.
For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily, with or without food.
Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily.
Dosage Modifications Due to Infections, Cytopenias and Anemia
Rheumatoid Arthritis and Alopecia Areata
- Avoid use of OLUMIANT in patients with active, serious or opportunistic infection, including localized infections. If a patient develops a serious infection hold treatment with OLUMIANT until the infection is controlled [see Warnings and Precautions ].
- Dosage modifications for patients with rheumatoid arthritis or alopecia areata and cytopenias or anemia are described in Table 1.
| Laboratory Analyte | Laboratory Analyte Value | Recommendation |
| Absolute Lymphocyte Count (ALC) | ≥500 cells/μL | Maintain dosage |
| <500 cells/μL | Interrupt OLUMIANT until ALC ≥500 cells/μL | |
| Absolute Neutrophil Count (ANC) | ≥1000 cells/μL | Maintain dosage |
| <1000 cells/μL | Interrupt OLUMIANT until ANC ≥1000 cells/μL | |
| Hemoglobin | ≥8 g/dL | Maintain dosage |
| <8 g/dL | Interrupt OLUMIANT until hemoglobin ≥8 g/dL |
COVID-19
- 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 [see Warnings and Precautions ].
- Dosage modifications for patients with COVID-19 and cytopenias are described in Table 2.
| Laboratory Analyte | Laboratory Analyte Value | Recommendation |
| Absolute Lymphocyte Count (ALC) | ≥200 cells/μL | Maintain dosage |
| <200 cells/μL | Interrupt OLUMIANT until ALC ≥200 cells/μL | |
| Absolute Neutrophil Count (ANC) | ≥500 cells/μL | Maintain dosage |
| <500 cells/μL | Interrupt OLUMIANT until ANC ≥500 cells/μL |
Dosage Modifications for Patients with Renal Impairment or Hepatic Impairment
Rheumatoid Arthritis
Renal Impairment
Dosage modifications for patients with rheumatoid arthritis and renal impairment are described in Table 3.
| Renal Impairment Stage | Estimated Glomerular Filtration Rate (eGFR) | Recommendation |
| Mild | 60 – <90 mL/minute/1.73 m2 | 2 mg once daily |
| Moderate | 30 - <60 mL/min/1.73 m2 | 1 mg once daily |
| Severe | <30 mL/minute/1.73 m2 | Not recommended |
Hepatic Impairment
- OLUMIANT is not recommended for use in patients with severe hepatic impairment.
- Interrupt OLUMIANT, if increases in ALT or AST are observed and drug-induced liver injury (DILI) is suspected, until the diagnosis of DILI is excluded [see Warnings and Precautions ].
COVID-19
Renal Impairment
- Dosage modifications for patients with COVID-19 and renal impairment are described in Table 4.
| Renal Impairment Stage | Estimated Glomerular Filtration Rate (eGFR) | Recommendation |
| Mild | 60 - <90 mL/min/1.73m2 | 4 mg once daily |
| Moderate | 30 - <60 mL/min/1.73m2 | 2 mg once daily |
| Severe | 15 - <30 mL/min/1.73m2 | 1 mg once daily |
| End Stage Renal Disease, Patients on Dialysis, or Acute Kidney Injury | <15 mL/min/1.73m2 | 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 [see Warnings and Precautions ].
Alopecia Areata
Renal Impairment
Dosage modifications for patients with alopecia areata and renal impairment are described in Table 5.
| Renal Impairment Stage | Estimated Glomerular Filtration Rate (eGFR) | Recommendation | |
| If the recommended dosage is 2 mg once daily | If the recommended dosage is 4 mg once daily | ||
| Mild | 60 – <90 mL/minute/1.73 m2 | Maintain dosage | |
| Moderate | 30 – <60 mL/min/1.73 m2 | Reduce to 1 mg once daily | Reduce to 2 mg once daily |
| Severe | <30 mL/minute/1.73 m2 | Not recommended | |
Hepatic Impairment
- OLUMIANT is not recommended for use in patients with severe hepatic impairment.
- Interrupt OLUMIANT, if increases in ALT or AST are observed and DILI is suspected, until the diagnosis of DILI is excluded [see Warnings and Precautions ].
Dosage Modifications Due to Drug Interactions
Rheumatoid Arthritis, COVID-19 or Alopecia Areata
The recommended dosage of OLUMIANT in patients taking strong Organic Anion Transporter 3 (OAT3) inhibitors, such as probenecid, are shown in Table 6[see Drug Interactions and Clinical Pharmacology ].
| Concomitant Medication | Recommendation |
Strong OAT3 inhibitors (e.g., probenecid) | If the recommended dosage is 4 mg once daily, reduce dosage to 2 mg once daily. |
| If the recommended dosage is 2 mg once daily, reduce dosage to 1 mg once daily. | |
| If the recommended dosage is 1 mg once daily, consider discontinuing probenecid. |
Alternative Administration for Patients Unable to Swallow Tablets
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 Administration:
- Oral administration of dispersed tablets in water: For patients who are unable to swallow whole tablets, 1-mg, 2-mg, or 4-mg baricitinib tablet(s), or any combination of tablets necessary to achieve the desired dose up to 4-mg may be placed in a container with approximately 10 mL (5 mL minimum) of room temperature water, dispersed by gently swirling the tablet(s) and immediately taken orally. The container should be rinsed with an additional 10 mL (5 mL minimum) of room temperature water and the entire contents swallowed by the patient .
- Administration via G tube: For patients with a G tube, 1-mg, 2-mg, or 4-mg baricitinib tablet(s), or any combination of tablets necessary to achieve the desired dose up to 4-mg may be placed in a container with approximately 15 mL (10 mL minimum) of room temperature water and dispersed with gentle swirling. Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe. Withdraw entire contents from the container into an appropriate syringe and immediately administer through the gastric feeding tube. Rinse container with approximately 15 mL (10 mL minimum) of room temperature water, withdraw the contents into the syringe, and administer through the tube .
- Administration via NG or OG tube: For patients with a NG or OG tube, 1-mg, 2-mg, or 4-mg baricitinib tablet(s), or a combination of tablets necessary to achieve the desired dose up to 4-mg may be placed into a container with approximately 30 mL of room temperature water and dispersed with gentle swirling. Ensure the tablet(s) are sufficiently dispersed to allow free passage through the tip of the syringe. Withdraw the entire contents from the container into an appropriate syringe and immediately administer through the enteral feeding tube. To avoid clogging of small diameter tubes (smaller than 12 Fr), the syringe can be held horizontally and shaken during administration. Rinse container with a sufficient amount (minimum of 15 mL) of room temperature water, withdraw the contents into the syringe, and administer through the tube .
| Administration via | Dispersion Volume | Container Rinse Volume |
| Oral dispersion | 10 mL | 10 mL |
| G tube | 15 mL | 15 mL |
| NG tube or OG tube | 30 mL | 15 mL |
3 DOSAGE FORMS AND STRENGTHS
OLUMIANT is available as debossed, film-coated tablets:
- 1 mg tablet contains a recessed area on each face of the tablet surface, is very light pink, round, debossed with “Lilly” on one side and “1” on the other.
- 2 mg tablet contains a recessed area on each face of the tablet surface, is light pink, oblong, debossed with “Lilly” on one side and “2” on the other.
- 4 mg tablet contains a recessed area on each face of the tablet surface, is medium pink, round, debossed with “Lilly” on one side and “4” on the other.
3 DOSAGE FORMS AND STRENGTHS
OLUMIANT is available as debossed, film-coated tablets:
- 1 mg tablet contains a recessed area on each face of the tablet surface, is very light pink, round, debossed with “Lilly” on one side and “1” on the other.
- 2 mg tablet contains a recessed area on each face of the tablet surface, is light pink, oblong, debossed with “Lilly” on one side and “2” on the other.
- 4 mg tablet contains a recessed area on each face of the tablet surface, is medium pink, round, debossed with “Lilly” on one side and “4” on the other.
Pregnancy
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 (rabbits only), 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).
Lactation
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.
Females and Males of Reproductive Potential
Contraception
Based on animal studies, OLUMIANT may cause fetal harm when administered during pregnancy [see Use in Specific Populations ]. Consider pregnancy planning and prevention for females of reproductive potential.
Pediatric Use
The safety and effectiveness of OLUMIANT in pediatric patients have not been established.
Geriatric Use
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 ].
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 ].
Hepatic Impairment
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 and Clinical Pharmacology ].
Renal Impairment
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 and Clinical Pharmacology ].
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, have end-stage renal disease (ESRD), or with estimated GFR of <15 mL/min/1.73 m2[see Dosage and Administration and Clinical Pharmacology ].
None.