Dosing

Patient Selection

• Evaluate baseline estimated glomerular filtration rate (eGFR), liver enzymes, and complete blood count to determine treatment suitability and dose. Monitor closely patients with abnormal baseline and post-baseline laboratory values. See Table 1 for dosage adjustments for patients with laboratory abnormalities.
• Baricitinib is not recommended for:
  • Patients who are on dialysis, have end-stage renal disease (ESRD, eGFR <15 mL/min/1.73 m²), or have acute kidney injury
  • Patients with known active tuberculosis
• There is currently limited information on the use of baricitinib in combination with systemic corticosteroids for treating patients with COVID-19. However, use of baricitinib in patients receiving systemic corticosteroids is not precluded.

Adult Patients

• The recommended dosage in adults with eGFR ≥60 mL/min/1.73 m² is 4 mg once daily for 14 days of total treatment or until hospital discharge, whichever is first. See Table 1 below for dosage adjustments for patients with laboratory abnormalities.
• Dosage adjustments in patients with renal or hepatic impairment are recommended.
• Dosage adjustments due to drug interactions are recommended.
• In hospitalized patients with COVID-19, prophylaxis for venous thromboembolism (VTE) is recommended unless contraindicated.

Pediatric Patients

Limited data informing baricitinib dosing in pediatric patients comes from ongoing clinical trials for other uses. Based on the available information, treatment for COVID-19 in pediatric population under this EUA is as follows:

• The recommended dosage for patients 9 years of age and older is 4 mg once daily for 14 days of total treatment or until hospital discharge, whichever is first.
• The recommended dosage for patients ages 2 years through less than 9 years of age is 2 mg once daily for 14 days of total treatment or until hospital discharge, whichever is first.
• Baricitinib is not recommended for patients younger than 2 years of age.
• Dosage adjustments in patients with renal or hepatic impairment are recommended.

Table 1: Dosage Adjustments for Patients with Abnormal Laboratory Values^a,b

^aAbbreviations: ALT=alanine transaminase; AST=aspartate transaminase; DILI=drug induced liver injury.

^bIf a laboratory abnormality is likely due to the underlying disease state, consider the risks and benefits of continuing baricitinib at the same or a reduced dose.

Dosage Adjustments Due to Drug Interactions

Strong OAT3 Inhibitors: Baricitinib exposure is increased when baricitinib is co-administered with strong OAT3 inhibitors (such as probenecid). In patients taking strong OAT3 inhibitors, such as probenecid, reduce the recommended dose as follows:

• If the recommended dose is 4 mg once daily, reduce dose to 2 mg once daily.
• If the recommended dose is 2 mg once daily, reduce dose to 1 mg once daily.
• If the recommended dose is 1 mg once daily, consider discontinuing probenecid.

Pregnancy

Baricitinib should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus. Consistent with the mechanism of action, embryo-fetal toxicities including skeletal anomalies and reduced fertility have been observed in animals dosed in excess of the maximum human exposure. The limited human data on use of baricitinib in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage.

See also Section 8.1 Pregnancy in the FDA approved full prescribing information for more information by clicking here.

Renal Impairment

There are limited data for baricitinib in patients with severe renal impairment.

• Baricitinib is not recommended for patients who are on dialysis, have ESRD, or have acute kidney injury.
• See Table 1 above for treatment modifications for patients with laboratory abnormalities.
  • Baricitinib should only be used in adults and pediatric patients 9 years of age and older with eGFR 15 to <30 mL/min/1.73 m² if the potential benefit outweighs the potential risk.
  • Baricitinib is not recommended for pediatric patients ages 2 years through less than 9 years of age with eGFR <30 mL/min/1.73 m².

Hepatic Impairment

Baricitinib has not been studied in patients with severe hepatic impairment. Baricitinib should only be used in patients with severe hepatic impairment if the potential benefit outweighs the potential risk. It is not known if dosage adjustment is needed in patients with severe hepatic impairment.

See Table 1 above for dosage adjustments for patients with abnormal laboratory values.

Administration

Baricitinib tablets are given orally once daily with or without food.

Alternate Administration

For patients who are unable to swallow whole tablets, alternate administration may be considered:

• Oral dispersion
• Gastrostomy tube (G tube)
• Nasogastric tube (NG tube)

Preparation for Alternate Administration

• Oral administration of dispersed tablets in water:
  For patients who are unable to swallow whole tables, 1-mg and/or 2-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 the additional 10 mL (5 mL minimum) of room temperature water and the entire contents swallowed by the patient (see Table 2).
• Administration via gastrostomy feeding tube:
  For patients with a gastrostomy feeding tube, 1-mg and/or 2-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 (see Table 2).
• Administration via nasogastric feeding tube:
  For patients with an enteral feeding tube, 1-mg and/or 2-mg baricitinib tablet(s), or a combination of tablets necessary to achieve the desired dose 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 (see Table 2).

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. 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.

Table 2: Dispersion and Rinse Volume for Alternate Administration