Health Canada has previously communicated on the risks of major adverse cardiovascular events (MACE), thrombosis, malignancy, fatal events, and serious infections with the Janus kinase (JAK) inhibitor tofacitinib (Xeljanz/Xeljanz XR) and updated the Canadian product monograph to reflect these risks. Based on these safety findings and similar mechanisms of action to tofacitinib, Health Canada cannot rule out the risks of MACE, thrombosis (including fatal events), and malignancies for all other JAK inhibitors, including abrocitinib (Cibinqo), baricitinib (Olumiant), fedratinib (Inrebic), ruxolitinib (Jakavi), and upadacitinib (Rinvoq). Health Canada is working with manufacturers to update the Canadian product monographs for these products to include the risks of serious heart-related problems, fatal blood clots, and cancer, as a precautionary measure.
Further information may be found at https://recalls-rappels.canada.ca/en/alert-recall/janus-kinase-inhibitors-and-risk-major-adverse-cardiovascular-events-thrombosis.
Patients treated with baricitinib are at risk for developing serious infections that may lead to hospitalization or death. Most patients with rheumatoid arthritis who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt baricitinib until the infection is controlled.
Reported infections include:
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Baricitinib should not be given to patients with active tuberculosis. Patients, except those with COVID-19, should be tested for latent tuberculosis before initiating baricitinib and during therapy. If positive, start treatment for latent infection prior to baricitinib 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 baricitinib 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 baricitinib including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients ≥50 years of age with ≥1 cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.
Lymphoma and other malignancies have been observed in patients treated with baricitinib. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding nonmelanoma skin cancer) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
In RA patients ≥50 years of age with ≥1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (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 baricitinib in patients that have experienced a myocardial infarction or stroke.
Thrombosis, including deep venous thrombosis and pulmonary embolism, has been observed at an increased incidence in patients treated with baricitinib 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 with ≥1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid baricitinib in patients at risk. Patients with symptoms of thrombosis should discontinue baricitinib and be promptly evaluated.
Alopecia areata:
Note: Do not use in combination with other Janus kinase inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants; do not initiate in patients with an absolute lymphocyte count <500 cells/mm3, ANC <1,000 cells/mm3, or Hb <8 g/dL.
Oral: Initial: 2 mg once daily; if response is inadequate may increase to 4 mg once daily. For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider initiating therapy with 4 mg once daily. In patients receiving 4 mg once daily (as initial therapy or after a dose increase), reduce dose to 2 mg once daily once an adequate response is achieved.
COVID-19, hospitalized patients:
Note: For use in hospitalized patients with significant oxygen requirements (eg, high-flow oxygen, noninvasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation) and those with lower but increasing oxygen requirements and evidence of systemic inflammation (Ref). Do not initiate if absolute lymphocyte count is <200 cells/mm3 or if ANC is <500 cells/mm3.
Oral: 4 mg once daily, as part of an appropriate combination regimen, for 14 days or until hospital discharge, whichever is first (Ref).
Rheumatoid arthritis:
Note: For use as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy; may also be used off-label as an alternative to methotrexate in disease-modifying antirheumatic drug (DMARD)–naive patients with moderate to high disease activity (Ref). Do not use in combination with biologic DMARDs or with strong immunosuppressants (eg, azathioprine, cyclosporine); do not initiate in patients with an absolute lymphocyte count <500 cells/mm3, ANC <1,000 cells/mm3, or Hb <8 g/dL.
Oral: 2 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral:
Alopecia areata:
If initial recommended dose is 2 mg once daily:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: Reduce dose to 1 mg once daily.
eGFR <30 mL/minute/1.73 m2: Use is not recommended.
If initial recommended dose is 4 mg once daily:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: Reduce dose to 2 mg once daily.
eGFR <30 mL/minute/1.73 m2: Use is not recommended.
COVID-19:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: 2 mg once daily.
eGFR 15 to <30 mL/minute/1.73 m2: 1 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Rheumatoid arthritis:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: 1 mg once daily.
eGFR <30 mL/minute/1.73 m2: Use is not recommended.
Hemodialysis, intermittent (thrice weekly): Some removal possible based on drug characteristics (expert opinion): Oral: Use is not recommended (has not been studied) (manufacturer's labeling).
Peritoneal dialysis: Some removal possible based on drug characteristics (expert opinion): Oral: Use is not recommended (has not been studied) (manufacturer's labeling).
CRRT: Oral: Some removal possible based on drug characteristics (expert opinion): Use is not recommended (has not been studied) (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Some removal possible based on drug characteristics (expert opinion):Oral: Use is not recommended (has not been studied) (expert opinion).
Hepatic impairment prior to treatment initiation:
Alopecia areata or rheumatoid arthritis:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended (has not been studied).
COVID-19:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution and only if benefit outweighs risk.
Hepatotoxicity during treatment:
ALT/AST increased: If baricitinib-induced liver injury is suspected, interrupt therapy and further evaluate.
(For additional information see "Baricitinib: Pediatric drug information")
COVID-19 (hospitalized patients), treatment: Very limited data available:
Note: The NIH states that data are insufficient to recommend for or against the use of baricitinib in pediatric patients (Ref). Pediatric dosing is based on ongoing clinical trials for other indications (Ref).
Children 2 to <9 years: Oral: 2 mg once daily for 14 days or until hospital discharge, whichever is first (Ref).
Children ≥9 years and Adolescents: Oral: 4 mg once daily for 14 days or until hospital discharge, whichever is first (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children ≥2 years and Adolescents (Ref):
Absolute lymphocyte count (ALC) <200 cells/mm3: Consider interruption until ALC is ≥200 cells/mm3.
Absolute neutrophil count (ANC) <500 cells/mm3: Consider interruption until ANC ≥500 cells/mm3.
COVID-19, treatment:
Acute kidney injury: Children ≥2 years and Adolescents: Not recommended (Ref).
Altered kidney function (Ref):
Children 2 to <9 years: Oral:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: 1 mg once daily.
eGFR <30 mL/minute/1.73 m2: Not recommended.
Children ≥9 years and Adolescents: Oral:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: 2 mg once daily.
eGFR 15 to <30 mL/minute/1.73 m2: 1 mg once daily.
eGFR <15 mL/minute/1.73 m2: Not recommended.
Hemodialysis: Children ≥2 years and Adolescents: Not recommended (Ref).
Peritoneal dialysis: Children ≥2 years and Adolescents: Not recommended (Ref).
COVID-19, treatment: Children ≥2 years and Adolescents (Ref):
Baseline hepatic impairment:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer-provided information.
Severe impairment: There are no dosage adjustments provided in the manufacturer-provided information (has not been studied); use recommended only if the potential benefit outweighs the potential risk; need for dosage modification is unknown.
Hepatotoxicity during therapy (increases in ALT or AST and drug-induced liver injury is suspected): Discontinue baricitinib until drug-induced liver injury is excluded.
Refer to adult dosing.
Alopecia areata or rheumatoid arthritis:
Infection: If a patient develops a serious infection, interrupt treatment until the infection is controlled.
Lymphopenia:
Lymphopenia (absolute lymphocyte count [ALC] ≥500 cells/mm3): Maintain dose.
Lymphopenia (ALC <500 cells/mm3): Interrupt therapy until ALC ≥500 cells/mm3.
Neutropenia:
Neutropenia (ANC ≥1,000 cells/mm3): Maintain dose.
Neutropenia (ANC <1,000 cells/mm3): Interrupt therapy until ANC ≥1,000 cells/mm3.
Anemia:
Anemia (Hb ≥8 g/dL): Maintain dose.
Anemia (Hb <8 g/dL): Interrupt therapy until Hb ≥8 g/dL.
COVID-19:
Lymphopenia:
Lymphopenia (ALC ≥200 cells/mm3): Maintain dose.
Lymphopenia (ALC <200 cells/mm3): Interrupt therapy until ALC ≥200 cells/mm3.
Neutropenia:
Neutropenia (ANC ≥500 cells/mm3): Maintain dose.
Neutropenia (ANC <500 cells/mm3): Interrupt therapy until ANC ≥500 cells/mm3.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Olumiant: 1 mg, 2 mg, 4 mg [contains soybean lecithin]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Olumiant: 2 mg [contains soybean lecithin]
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Olumiant: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s006lbl.pdf#page=26
Oral: May be administered with or without food. For patients unable to swallow tablets whole, tablets may be dispersed in water. Place required number of tablets to achieve desired dose in a container with ~10 mL (minimum: 5 mL) of room temperature water; gently swirl the tablet(s) to disperse. Ensure tablets are sufficiently dispersed and immediately administer. Rinse container with an additional 5 to 10 mL of room temperature water and swallow. Tablets may be crushed to facilitate dispersion. According to the manufacturer, since it is not known if powder from the crushed tablets may pose a reproductive hazard to the preparer, if tablets are crushed, use proper control measures (eg, ventilated enclosure) or personal protective equipment (ie, N95 respirator).
Gastrostomy feeding tube (G tube): Place required number of tablets to achieve desired dose in a container with ~15 mL (minimum: 10 mL) of room temperature water. Gently swirl the tablet(s) to disperse; ensure tablets are sufficiently dispersed to pass through syringe tip. Withdraw entire contents of container into an appropriate syringe and immediately administer through G tube. Rinse container with an additional ~15 mL (minimum: 10 mL) of room temperature water, withdraw contents into the syringe, and administer through G tube.
Nasogastric or orogastric feeding tube (NG or OG tube): Place required number of tablets to achieve desired dose in a container with ~30 mL of room temperature water. Gently swirl the tablet(s) to disperse; ensure tablets are sufficiently dispersed to pass through syringe tip. Withdraw entire contents of container into an appropriate syringe and immediately administer through enteral tube. For small tubes (<12 French), hold the syringe horizontally and shake during administration to avoid clogging of tube. Rinse container with a minimum of 15 mL of room temperature water, withdraw contents into the syringe, and administer through enteral tube.
Oral: Administer with or without food. If the 1 mg tablet is not available, the 2 mg tablet may be split along the longest diameter using a tablet splitter containing a razor blade; do not administer if tablet portions are unequal after splitting; store other half carefully to ensure breakage does not occur prior to the next dose (Ref). For patients who are unable to swallow whole tablets, tablets may be dispersed and administrated orally or via gastrostomy, nasogastric, or orogastric tube. Tablets may be crushed to facilitate dispersion; however, it is not known if powder from the crushed tablets may pose a reproductive hazard to the preparer; if tablets are crushed, use proper control measures (eg, ventilated enclosure) or personal protective equipment (ie, N95 respirator). After preparation, dispersed tablets should be administered immediately; however, the manufacturer indicates that dispersed tablets are stable in water for up to 4 hours.
For patients unable to swallow tablets: Place required number of tablets to achieve desired dose (up to 4 mg) in a container with ~10 mL (minimum: 5 mL) of room temperature water. Gently swirl the tablet(s) to disperse; immediately administer orally. Rinse container with an additional 10 mL (minimum: 5 mL) of room temperature water and administer entire contents orally to ensure entire dose is administered.
Gastrostomy tube (G tube) administration: Place required number of tablets to achieve desired dose (up to 4 mg) in a container with ~15 mL (minimum: 10 mL) of room temperature water. Gently swirl the tablet(s) to disperse; ensure tablets are sufficiently dispersed to pass through syringe tip. Withdraw entire contents of container into an appropriate syringe and immediately administer through G tube. Rinse container with an additional ~15 mL (minimum: 10 mL) of room temperature water, withdraw contents into the syringe, and administer through G tube.
Nasogastric or orogastric tube (NG or OG tube) administration: Place required number of tablets to achieve desired dose (up to 4 mg) in a container with ~30 mL of room temperature water. Gently swirl the tablet(s) to disperse; ensure tablets are sufficiently dispersed to pass through syringe tip. Withdraw entire contents of container into an appropriate syringe and immediately administer through tube. For small tubes (<12 French), hold the syringe horizontally and shake during administration to avoid clogging of tube. Rinse container with a minimum of 15 mL of room temperature water, withdraw contents into the syringe, and administer through tube.
Alopecia areata: Treatment of severe alopecia areata in adults.
COVID-19, hospitalized patients: Treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
Rheumatoid arthritis: Treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor blockers.
Limitation of use: Use of baricitinib in combination with other Janus kinase inhibitors, biologic disease-modifying antirheumatic drugs, biologic immunomodulators, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
COVID-19, treatment :
>10%: Hepatic: Increased serum alanine aminotransferase (≥3 x ULN: 18%), increased serum aspartate aminotransferase (≥3 x ULN: 12%)
1% to 10%:
Cardiovascular: Deep vein thrombosis (2%), pulmonary embolism (2%), septic shock (2%)
Genitourinary: Urinary tract infection (2%)
Hematologic & oncologic: Thrombocythemia (8%)
Respiratory: Pneumonia (3%)
<1%: Respiratory: Tuberculosis
Alopecia areata/rheumatoid arthritis:
>10%:
Infection: Infection (29%; serious infection: 1%)
Respiratory: Upper respiratory tract infection (16% to 21%)
1% to 10%:
Dermatologic: Acne vulgaris (≤6%), folliculitis (1% to 2%)
Endocrine & metabolic: Hyperlipidemia (4% to 6%), weight gain (≤2%)
Gastrointestinal: Abdominal pain (4%), nausea (2% to 3%)
Genitourinary: Genital candidiasis (1% to 2%), urinary tract infection (4%)
Hematologic & oncologic: Anemia (1%), neutropenia (1%)
Hepatic: Increased liver enzymes (≤3%; including increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Infection: Herpes zoster infection (1%)
Nervous system: Fatigue (2%), headache (6% to 7%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (4%)
Respiratory: Lower respiratory tract infection (2%)
<1%:
Cardiovascular: Arterial thrombosis
Dermatologic: Fungal skin infection
Hematologic & oncologic: Lymphocytopenia, malignant lymphoma (B-cell), malignant neoplasm
Frequency not defined (any indication):
Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides
Gastrointestinal: Esophageal candidiasis
Infection: Bacterial infection, BK virus, candidiasis, cryptococcosis, cytomegalovirus disease, fungal infection, histoplasmosis, mycobacterium infection, opportunistic infection, viral infection
Renal: Increased serum creatinine
Respiratory: Infection due to an organism in genus Pneumocystis
Miscellaneous: Reactivation of disease (viral)
Postmarketing (any indication):
Cardiovascular: Acute myocardial infarction (FDA Safety Alert September 1, 2021), thrombosis (FDA Safety Alert September 1, 2021)
Gastrointestinal: Gastrointestinal perforation
Hematologic & oncologic: Skin carcinoma (nonmelanoma)
Hypersensitivity: Angioedema, hypersensitivity reaction
Nervous system: Cerebrovascular accident (FDA Safety Alert September 1, 2021)
Respiratory: Lung carcinoma (FDA Safety Alert September 1, 2021)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to baricitinib or any component of the formulation.
Concerns related to adverse effects :
• GI perforations: Use with caution in patients at increased risk for GI perforation (eg, history of diverticulitis); perforations have been reported in clinical trials. Promptly evaluate new-onset abdominal symptoms in patients taking baricitinib.
• Hematologic toxicity: Hematologic toxicity, including lymphopenia, anemia, and neutropenia, may occur and is generally reversible and managed by treatment interruption. Do not initiate therapy in patients with alopecia areata or rheumatoid arthritis with an absolute lymphocyte count <500 cells/mm3, ANC <1,000 cells/mm3, or Hb<8 g/dL, or in patients with COVID-19 with an absolute lymphocyte count <200 cells/mm3 or ANC <500 cells/mm3. Monitor CBC at baseline and periodically thereafter.
• Hepatic effects: Increased incidence of liver enzyme elevation (≥5 × ULN for ALT and ≥10 × ULN for AST) was observed in patients taking baricitinib. Monitor LFTs as clinically indicated; interrupt therapy if LFTs are increased and drug-induced liver injury is suspected.
• Hypersensitivity: Hypersensitivity reactions (sometimes serious), including angioedema, urticaria, and rash, have occurred; discontinue therapy and evaluate cause for serious reactions.
• Infections: Patients receiving baricitinib are at increased risk for serious infections, which may result in hospitalization and/or fatality. Do not initiate baricitinib in patients with active, serious, or opportunistic infections, including localized infections. The most common serious infections reported included pneumonia, urinary tract infections, and herpes zoster infections, although other serious infections may occur. Reactivation of viral infections (eg, herpes zoster) was observed in clinical trials; the impact of baricitinib on chronic viral hepatitis reactivation is unknown. If a patient develops herpes zoster, interrupt therapy until episode is resolved. Consultation with a hepatologist may be necessary if hepatitis B virus DNA is detected. There are limited data available in patients with COVID-19 and concomitant active serious infections; consider risks and benefits of treatment.
• Lipid abnormalities: Dose-dependent increases in lipid parameters (eg, total, low-density lipoprotein, and high-density lipoprotein cholesterol) were observed in patients receiving baricitinib; maximum lipid increases were typically seen within 12 weeks of initiation. Assess lipids 12 weeks after baricitinib initiation and manage lipid abnormalities accordingly.
• Malignancy and lymphoproliferative disorders: Lymphoma and other malignancies have been observed in patients receiving baricitinib. A higher rate of lung cancers was observed in patients who smoke or have smoked receiving Janus kinase inhibitors, and these patients also had an additional increased risk of overall malignancies. Consider risks versus benefits prior to use or continuing therapy in patients with a known malignancy (other than successfully treated nonmelanoma skin cancers [NMSCs]), when continuing baricitinib in patients who develop a new malignancy, or in patients who smoke or have smoked. NMSCs have been reported.
• Tuberculosis: Tuberculosis (TB) (pulmonary or extrapulmonary) has been reported in patients receiving baricitinib. Use with caution in patients who have resided or traveled in regions where TB is endemic. Consider antituberculosis therapy if an adequate course of treatment cannot be confirmed in patients with a history of latent or active TB or for patients with risk factors despite negative skin test.
Other warnings/precautions:
• Immunizations: Immunization status should be current before initiating therapy in patients with rheumatoid arthritis. Live vaccines should not be given concomitantly with baricitinib; recommended interval between receipt of live vaccines and initiation of immunosuppressive agents such as baricitinib should follow current vaccination clinical guidelines.
Substrate of BCRP/ABCG2, CYP3A4 (minor), OAT1/3, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Baricitinib. Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
COVID-19 Vaccines: Baricitinib may diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Methotrexate: May enhance the immunosuppressive effect of Baricitinib. Management: Concomitant use of baricitinib with high-dose or IV methotrexate is not recommended. Use with antirheumatic doses of methotrexate is permitted, and if combined, patients should be monitored for infection. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Baricitinib. Management: When baricitinib is combined with probenecid, reduce baricitinib 4 mg daily to 2 mg daily or reduce baricitinib 2 mg daily to 1 mg daily. Don't use probenecid if recommended baricitinib dose is only 1 mg daily. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Recommendations for use of baricitinib to treat rheumatic and musculoskeletal diseases in patients planning to become pregnant or who are planning to father a child are not available due to lack of data (ACR [Sammaritano 2020]). Consider discontinuing use 1 month prior to conception (Costanzo 2020).
Placental transfer of baricitinib may be expected based on molecular weight (ACR [Sammaritano 2020]).
Outcome data following baricitinib exposure in pregnancy are limited (Costanzo 2020; NIH 2022).
Recommendations for use of baricitinib in pregnant patients with rheumatic and musculoskeletal diseases are not available due to lack of data (ACR [Sammaritano 2020]).
Baricitinib is a Janus kinase (JAK) inhibitor; use of a JAK inhibitor for the treatment of COVID-19 in pregnancy may be considered as part of a shared decision-making process when considering the potential benefits and possible risks (NIH 2022). The risk of severe illness from COVID-19 infection is increased in pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Pregnant patients with symptoms may require ICU admission, mechanical ventilation, or ventilatory support (ECMO) compared to symptomatic nonpregnant patients. Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2022; NIH 2022). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to baricitinib is ongoing. Patients exposed to baricitinib during pregnancy are encouraged to notify the manufacturer (800-545-5979).
Data collection to monitor maternal and infant outcomes following exposure to COVID-19 during pregnancy is ongoing. Health care providers are encouraged to enroll patients exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/).
It is not known if baricitinib is present in breast milk.
Due to the risk of serious adverse events in the breastfeeding infant, breastfeeding is not recommended by the manufacturer during therapy and for 4 days after the last dose of baricitinib. Recommendations for use of baricitinib in breastfeeding patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Transfer into breast milk may be expected based on molecular weight (ACR [Sammaritano 2020]).
Interim guidance is available from the Centers for Disease Control and Prevention for the care of lactating patients who are diagnosed with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html). Information related to COVID-19 and breastfeeding is also available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).
In all patients: Lymphocyte, neutrophil, platelet counts, and Hb, LFTs, and renal function (baseline and periodically thereafter); signs/symptoms of infections (including tuberculosis) during and after therapy.
In patients with an anticipated long-term duration of therapy (eg, alopecia areata, rheumatoid arthritis): Lipids (12 weeks after therapy initiation and periodically thereafter); viral hepatitis (prior to initiating therapy in accordance with clinical guidelines); latent tuberculosis (prior to initiating therapy); abdominal symptoms (in patients at increased risk for GI perforation); skin examinations (periodically, in patients at increased risk for skin cancer).
Baricitinib inhibits Janus kinase (JAK) enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. In response to extracellular cytokine or growth factor signaling, JAKs activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. Inhibition of JAKs prevents the activation of STATs and reduces serum IgG, IgM, IgA, and C-reactive protein.
Distribution: Vd: 76 L.
Protein binding: ~50% (plasma proteins); 45% (serum proteins).
Metabolism: Hepatic, primarily via CYP3A4.
Bioavailability: ~80%.
Half-life elimination: ~12 to 16 hours.
Time to peak: ~1 hour.
Excretion: Urine: ~75% (69% as unchanged drug); feces: ~20% (15% as unchanged drug).
Altered kidney function: AUC increased by 1.41-, 2.22-, 4.05- and 2.41-fold for mild, moderate, and severe renal impairment, and ESRD (with hemodialysis), respectively.
Hepatic function impairment: For moderate hepatic impairment, AUC and Cmax increased by 1.19- and 1.08-fold, respectively.
Tablets (Olumiant Oral)
1 mg (per each): $99.89
2 mg (per each): $99.89
4 mg (per each): $199.78
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