The FDA has concluded there is an increased risk of serious cardiovascular-related events (eg, heart attack, stroke), cancer (eg, lymphoma, lung cancer), thrombosis, and death with the use of Xeljanz and Xeljanz XR (tofacitinib) based on a review of a large, randomized safety clinical trial. The FDA is requiring revisions to the Xeljanz and Xeljanz XR prescribing information, including updates to the Boxed Warning, to include information about these risks. Additionally, 2 additional Janus kinase (JAK) inhibitors, Olumiant (baricitinib) and Rinvoq (upadacitinib), that are indicated for arthritis will require similar revisions to the prescribing information. Although Olumiant and Rinvoq have not been studied in trials similar to the Xeljanz trial, they share mechanisms of action and may have similar risks. Recommendations for health care providers will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients who are current or past smokers, those with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy other than a successfully treated nonmelanoma skin cancer. In addition, to ensure the benefits of these 3 medicines outweigh the risks, the FDA is limiting all approved uses to certain patients who have not responded to or cannot tolerate 1 or more tumor necrosis factor blockers.
Further information may be found at https://www.fda.gov/media/151936/download.
A similar safety alert has also been reported by Health Canada.
Further information is available at https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2021/75315a-eng.php.
The FDA has updated the emergency use authorization (EUA) for baricitinib, to be used alone for the treatment of COVID-19 in hospitalized adults and pediatric patients 2 years and older requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. The EUA for baricitinib no longer requires baricitinib to be used in combination with Veklury (remdesivir).
Health care provider fact sheet: https://www.fda.gov/media/143823/download
Patient fact sheet: https://www.fda.gov/media/143824/download
Frequently asked questions for baricitinib: https://www.fda.gov/media/143825/download
Further information may be found at:
FDA: https://www.fda.gov/media/143822/download
ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/results?cond=COVID&term=baricitinib&cntry=&state=&city=&dist=&Search=Search
IDSA: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
Patients treated with baricitinib are at risk for developing serious infections that may lead to hospitalization or death. Most patients 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; patients 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.
COVID-19, hospitalized patients (off-label use):
Note: The role of baricitinib in the treatment of COVID-19 is evolving and varies among available guidelines; however, it is generally recommended for use in combination with corticosteroids and/or remdesivir. Avoid use in combination with tocilizumab, except in a clinical trial (IDSA [Bhimraj 2021]; NIH 2021).
Oral: 4 mg once daily as part of an appropriate combination (IDSA [Bhimraj 2021]; NIH 2021). Duration of baricitinib is 14 days or until hospital discharge, whichever is first (FDA 2021; IDSA [Bhimraj 2021]; Kalil 2020; NIH 2021).
Rheumatoid arthritis (monotherapy or in combination with methotrexate or nonbiologic disease-modifying antirheumatic drugs): Note: Baricitinib should not be used in combination with biologic disease-modifying antirheumatic drugs or with strong immunosuppressants such as azathioprine or cyclosporine. Do not initiate therapy in patients with an absolute lymphocyte count <500 cells/mm3, absolute neutrophil count <1,000 cells/mm3, or hemoglobin <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.
COVID-19 (FDA 2021):
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.
Hepatic impairment prior to treatment initiation:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended (has not been studied).
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 role of baricitinib in the treatment of COVID-19 is evolving. The NIH states that data are insufficient to recommend for or against the use of baricitinib in pediatric patients (NIH 2021). Pediatric dosing is based on ongoing clinical trials for other indications (FDA 2020).
Children 2 to <9 years: Oral: 2 mg once daily in combination with remdesivir. Duration of baricitinib is 14 days or until hospital discharge, whichever is first (FDA 2020).
Children ≥9 years and Adolescents: Oral: 4 mg once daily in combination with remdesivir. Duration of baricitinib is 14 days or until hospital discharge, whichever is first (FDA 2020).
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:
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 (FDA 2020).
Altered kidney function (FDA 2020): Oral:
Children 2 to <9 years:
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:
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; use only if the potential benefit outweighs the potential risk.
eGFR <15 mL/minute/1.73 m2: Not recommended.
Hemodialysis: Children ≥2 years and Adolescents: Not recommended (FDA 2020).
Peritoneal dialysis: Children ≥2 years and Adolescents: Not recommended (FDA 2020).
COVID-19, treatment: Children ≥2 years and Adolescents (FDA 2020):
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 not recommended unless the potential benefit outweighs the potential risk.
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.
COVID-19 (FDA 2021):
Lymphopenia (lymphocytes ≥200 cells/mm3): Maintain dose.
Lymphopenia (lymphocytes <200 cells/mm3): Consider interruption until absolute lymphocyte count ≥200 cells/mm3.
Neutropenia (ANC ≥500 cells/mm3): Maintain dose.
Neutropenia (ANC <500 cells/mm3): Consider interruption until ANC ≥500 cells/mm3.
Rheumatoid arthritis:
Infection: If a patient develops a serious infection, interrupt treatment until the infection is controlled.
Lymphopenia (lymphocytes ≥500 cells/mm3): Maintain dose.
Lymphopenia (lymphocytes <500 cells/mm3): Interrupt therapy until absolute lymphocyte count ≥500 cells/mm3.
Neutropenia (ANC ≥1,000 cells/mm3): Maintain dose.
Neutropenia (ANC <1,000 cells/mm3): Interrupt therapy until ANC ≥1,000 cells/mm3.
Anemia (hemoglobin ≥8 g/dL): Maintain dose.
Anemia (hemoglobin <8 g/dL): Interrupt therapy until hemoglobin ≥8 g/dL.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Olumiant: 1 mg, 2 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/2020/207924s002lbl.pdf#page=18
Oral: May be administered with or without food. For patients unable to swallow tablets whole, the tablet may be chewed; ensure entire dose is swallowed. Alternatively, the tablet may be dispersed in a small amount (5 to 10 mL) of liquid (water, whole milk, green tea, miso soup); the tablet will disperse in <5 minutes. A small amount of food may be added to the liquid mixture; the entire mixture should be consumed at one time (manufacturer data on file).
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 gastrostomy tube (FDA 2021).
Nasogastric feeding tube (NG 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 NG 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 NG tube (FDA 2021).
Oral: Administer with or without food. For patients who are unable to swallow whole tablets or who require administration via gastrostomy or nasogastric tube, tablets may be dispersed in water; tablets may be crushed to help with dispersion. After preparation, dispersed tablets should be administered immediately; however, the manufacturer indicates that dispersed tablets are stable in water for up to 4 hours (FDA 2020).
For patients unable to swallow tablets: 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; 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 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 (FDA 2020).
Nasogastric tube (NG tube) administration: 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 NG 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 NG tube (FDA 2020).
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, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
COVID-19, hospitalized patients
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Baricitinib is currently under investigation for use in the treatment of coronavirus disease 2019 (COVID-19) (see ClinicalTrials.gov). Serious or unexpected adverse reactions not previously reported may occur; refer to emergency use authorization (EUA) for information regarding reporting serious adverse reactions (FDA 2021).
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 (1%), venous thrombosis (3%)
Genitourinary: Urinary tract infection (1%)
Hematologic: Thrombocythemia (8%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (>5 x ULN) (4%)
Frequency not defined: Infection: Infection (including serious infection)
Rheumatoid arthritis :
>10%:
Infection: Infection (29%; serious infection: 1%)
Respiratory: Upper respiratory tract infection (16%)
1% to 10%:
Gastrointestinal: Nausea (3%)
Hepatic: Increased serum alanine aminotransferase (≥3 x ULN) (2%), increased serum aspartate aminotransferase (≥3 x ULN) (1%)
Infection: Herpes zoster infection (1%)
<1%:
Cardiovascular: Arterial thrombosis
Dermatologic: Acne vulgaris
Hematologic & oncologic: Malignant lymphoma, malignant neoplasm, neutropenia
Frequency not defined:
Cardiovascular: Venous thrombosis (including deep vein thrombosis and pulmonary embolism)
Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides
Gastrointestinal: Esophageal candidiasis
Genitourinary: Urinary tract infection
Hematologic & oncologic: Anemia
Infection: Bacterial infection, BK virus, candidiasis, cryptococcosis, cytomegalovirus disease, fungal infection, histoplasmosis, mycobacterium infection, opportunistic infection, viral infection
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen
Renal: Increased serum creatinine
Respiratory: Infection due to an organism in genus Pneumocystis, pneumonia, tuberculosis
Miscellaneous: Reactivation of disease (viral)
Postmarketing:
Cardiovascular: Acute myocardial infarction (FDA Safety Alert September 1, 2021), cerebrovascular accident (FDA Safety Alert September 1, 2021), thrombosis (FDA Safety Alert September 1, 2021)
Dermatologic: Skin rash, urticaria
Gastrointestinal: Gastrointestinal perforation
Hematologic & oncologic: Lung carcinoma (FDA Safety Alert September 1, 2021), skin carcinoma
Hypersensitivity: Angioedema, hypersensitivity reaction
There are no contraindications listed in the 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 an absolute lymphocyte count <500 cells/mm3, absolute neutrophil count <1,000 cells/mm3, or hemoglobin <8 g/dL. Monitor complete blood counts 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 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.
• 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: Lymphoma and other malignancies have been observed in patients receiving baricitinib. Consider risks versus benefits prior to use or continuing therapy in patients with a known malignancy (other than successfully treated nonmelanoma skin cancers [NMSCs]) or when continuing baricitinib in patients who develop a new malignancy. 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. 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
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 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Baricitinib may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider holding baricitinib therapy for 1 week after each vaccine dose when possible for patients with stable underlying disease. Additionally, consider administration of a 3rd dose of COVID-19 vaccine in patients 5 years of age or older on baricitinib. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. 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
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
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
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: For rheumatoid arthritis, decrease the baricitinib dose to 1 mg daily when combined with probenecid. For COVID-19, reduce 4 mg daily to 2 mg daily or reduce 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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. 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
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): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated). 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).
Outcome data following baricitinib exposure in pregnancy are limited (Costanzo 2020).
Recommendations for use of baricitinib in pregnant patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Placental transfer may be expected based on molecular weight (ACR [Sammaritano 2020]).
Baricitinib is currently available under FDA emergency use authorization (EUA) for the treatment of COVID-19 (FDA 2021). The risk of severe illness from COVID-19 infection is increased in pregnant patients compared to nonpregnant patients. Patients with severe illness may require hospitalization, ICU admission, mechanical ventilation, or ventilatory support (ECMO). Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of preeclampsia, coagulopathy, emergency cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG FAQ 2022; NIH 2021).
Baricitinib is a Janus kinase (JAK) inhibitor; pregnancy outcome data for this class of drugs when used for other indications are limited. Use of a JAK inhibitor for the treatment of COVID-19 in pregnancy may be considered when the potential benefits outweigh the possible risks (NIH 2021). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have developed an algorithm to aid practitioners in assessing and managing pregnant patients with suspected or confirmed COVID-19 (https://www.acog.org/covid-19; https://www.smfm.org/covid19). Interim guidance is also available from the CDC for pregnant patients who are diagnosed with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html).
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 adverse events in the breastfeeding infant, breastfeeding is not recommended by the manufacturer. 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).
Lymphocyte, neutrophil, platelet counts, and hemoglobin and LFTs (baseline and periodically thereafter); lipids (12 weeks after therapy initiation and periodically thereafter); viral hepatitis (prior to initiating therapy in accordance with clinical guidelines); signs/symptoms of infections (including tuberculosis) during and after therapy; abdominal symptoms; 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 hours
Time to peak: ~1 hour
Excretion: Urine: ~75% (69% as unchanged drug); feces: ~20% (15% as unchanged drug)
Renal function impairment: 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
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