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 upadacitinib are at increased 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 upadacitinib 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 upadacitinib use and during therapy. Treatment for latent infection should be considered prior to upadacitinib use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
The risks and benefits of treatment with upadacitinib 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 upadacitinib, 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 factor (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 upadacitinib. 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 [MI], and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue upadacitinib in patients that have experienced an MI or stroke.
Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. 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 upadacitinib in patients at risk. Patients with symptoms of thrombosis should discontinue upadacitinib and be promptly evaluated.
Note: Do not use in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants (eg, azathioprine, cyclosporine); do not initiate in patients with an absolute lymphocyte count <500/mm3, ANC <1,000/mm3, or Hb <8 g/dL.
Ankylosing spondylitis: Oral: 15 mg once daily.
Atopic dermatitis: Oral: 15 mg once daily; may increase to 30 mg once daily if inadequate response. Discontinue if an adequate response is not achieved with the 30 mg dose; use the lowest effective dose needed to maintain response.
Nonradiographic axial spondyloarthritis: Oral: 15 mg once daily.
Psoriatic arthritis: Oral: 15 mg once daily.
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 DMARD–naive patients with moderate to high disease activity (ACR [Fraenkel 2021]).
Oral: 15 mg once daily.
Ulcerative colitis: Oral: Induction: 45 mg once daily for 8 weeks; maintenance: 15 mg once daily; may increase to 30 mg once daily in patients with refractory, severe, or extensive disease. Discontinue if an adequate response is not achieved with the 30 mg dose; use the lowest effective dose needed to maintain response.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Ankylosing spondylitis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis:
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary for any degree of kidney dysfunction.
Atopic dermatitis:
Altered kidney function:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Ulcerative colitis:
Altered kidney function:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: Induction: 30 mg once daily for 8 weeks; maintenance: 15 mg once daily.
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
Hepatic impairment prior to treatment initiation:
Ankylosing spondylitis, atopic dermatitis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis :
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment is necessary.
Severe impairment (Child-Pugh class C): Use is not recommended.
Ulcerative colitis :
Mild to moderate impairment (Child-Pugh class A or B): Induction: 30 mg once daily for 8 weeks; maintenance: 15 mg once daily.
Severe impairment (Child-Pugh class C): Use is not recommended.
Hepatotoxicity during treatment: Treatment should be interrupted if drug-induced liver injury is suspected.
(For additional information see "Upadacitinib: Pediatric drug information")
Note: Do not initiate therapy in patients with an absolute lymphocyte count (ALC) <500/mm3, ANC <1,000/mm3, or hemoglobin <8 g/dL. Prior to initiation of therapy, patients should be screened for tuberculosis and viral hepatitis; ensure immunizations are up to date.
Atopic dermatitis; moderate to severe; refractory: Children ≥12 years and Adolescents, weighing ≥40 kg: Oral: 15 mg once daily; may increase to 30 mg once daily if inadequate response; in clinical trials, used as either monotherapy or in combination with topical corticosteroids (Katoh 2021; Guttman-Yassky 2021; Reich 2021; Silverberg 2021).
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 ≥12 years and Adolescents, weighing ≥40 kg:
Hematologic:
ALC <500/mm3: Interrupt therapy until ALC ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Hypersensitivity reaction (severe): Discontinue therapy.
Infection (serious), including herpes zoster: Interrupt treatment until the infection is controlled.
Altered kidney function:
Children ≥12 years and Adolescents, weighing ≥40 kg: Oral:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: 15 mg once daily.
Children ≥12 years and Adolescents, weighing ≥40 kg: Oral:
Baseline hepatic impairment:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment is necessary.
Severe impairment (Child-Pugh class C): Use is not recommended.
Hepatotoxicity during treatment: Treatment should be interrupted if drug-induced liver injury is suspected.
Ankylosing spondylitis, nonradiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis, ulcerative colitis : Refer to adult dosing.
Atopic dermatitis: ≥65 years of age: Oral: 15 mg once daily.
Hematologic:
Absolute lymphocyte count (ALC) <500/mm3: Interrupt therapy until ALC ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Hypersensitivity reaction (severe): Discontinue therapy.
Infection (serious), including herpes zoster: Interrupt treatment until the infection is controlled.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Rinvoq: 15 mg, 30 mg, 45 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Rinvoq: 15 mg, 30 mg
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Rinvoq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211675s007lbl.pdf#page=56
Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.
Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Upadacitinib may cause carcinogenicity and teratogenicity.
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets (NIOSH 2016). Facilities may perform assessment of some (non-antineoplastic) hazardous drugs to determine if appropriate for alternative containment strategies and handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2018).
Ankylosing spondylitis: Treatment of active ankylosing spondylitis in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Atopic dermatitis: Treatment of refractory, moderate to severe atopic dermatitis in pediatric patients ≥12 years of age and adults who had an inadequate response or intolerance to other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic immunomodulators, or with other immunosuppressants is not recommended.
Nonradiographic axial spondyloarthritis: Treatment of active nonradiographic axial spondyloarthritis in adults with objective signs of inflammation who had an inadequate response or intolerance to TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.
Psoriatic arthritis: Treatment of active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Rheumatoid arthritis: Treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Ulcerative colitis: Treatment of moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to 1 or more TNF blockers.
Limitation of use: Use of upadacitinib in combination with other Janus-associated kinase inhibitors, biological therapies for ulcerative colitis, 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. Adverse reactions reported in adults and adolescents.
>10%:
Dermatologic: Acne vulgaris (1% to 16%)
Respiratory: Upper respiratory tract infection (9% to 25%)
1% to 10%:
Dermatologic: Folliculitis (2% to 4%), skin rash (4% to 5%)
Endocrine & metabolic: Hypercholesterolemia (2% to 4%), hyperlipidemia (2%), weight gain (2%)
Gastrointestinal: Abdominal pain (2% to 3%), nausea (3% to 4%)
Hematologic & oncologic: Lymphocytopenia (3%), neutropenia (1% to 6%)
Hepatic: Increased liver enzymes (including cholestasis, drug-induced liver injury, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, and increased serum bilirubin: ≤6%)
Hypersensitivity: Hypersensitivity reaction (3%)
Infection: Herpes simplex infection (≤8%), herpes zoster infection (≤4%), influenza (2% to 3%)
Nervous system: Fatigue (2%), headache (3% to 6%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (1% to 8%), myalgia (2%)
Respiratory: Bronchitis (4%), cough (2% to 3%), flu-like symptoms (2%)
Miscellaneous: Fever (1% to 2%)
<1%:
Gastrointestinal: Oral candidiasis, oral herpes simplex infection
Hematologic: Anemia
Ophthalmic: Retinal detachment
Respiratory: Pneumonia
Frequency not defined:
Cardiovascular: Arterial thrombosis, deep vein thrombosis, pulmonary embolism, thrombosis, venous thrombosis
Dermatologic: Cellulitis, eczema (herpeticum), skin carcinoma, varicella-like rash (Kaposi's varicelliform eruption)
Gastrointestinal: Esophageal candidiasis, gastrointestinal perforation
Hematologic & oncologic: Malignant neoplasm
Hypersensitivity: Anaphylaxis, angioedema
Infection: Bacterial infection, cryptococcosis, fungal infection, infection (including serious infection), opportunistic infection, reactivation of HBV, viral infection
Respiratory: Infection due to an organism in genus Pneumocystis, tuberculosis
Postmarketing:
Cardiovascular: Acute myocardial infarction (FDA Safety Alert September 1, 2021)
Hematologic & oncologic: Lymphocytopenia, malignant lymphoma (FDA Safety Alert September 1, 2021)
Nervous system: Cerebrovascular accident (FDA Safety Alert September 1, 2021)
Respiratory: Lung carcinoma (FDA Safety Alert September 1, 2021)
Hypersensitivity to upadacitinib or any component of the formulation.
Concerns related to adverse effects:
• GI perforation: Use with caution in patients at increased risk for GI perforation (eg, history of diverticulitis, concomitant nonsteroidal anti-inflammatory drugs); perforations have been reported in clinical trials. Promptly evaluate new-onset abdominal symptoms in patients taking upadacitinib.
• 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/mm3, ANC <1,000/mm3, or hemoglobin <8 g/dL. Monitor CBC at baseline and periodically thereafter.
• Hepatic effects: Liver enzyme elevation has been observed. Monitor LFTs at baseline and periodically thereafter; interrupt therapy if LFTs increased and drug-induced liver injury is suspected.
• Hypersensitivity reactions: Severe hypersensitivity, including anaphylaxis and angioedema, has been reported.
• Infections: Patients receiving upadacitinib are at increased risk for serious infections, which may result in hospitalization and/or fatality. The most common serious infections reported included pneumonia and cellulitis. Reactivation of viral infections (eg, herpes zoster, hepatitis B) have been observed; the incidence of chronic viral hepatitis reactivation is unknown. If herpes zoster is reported, consider interrupting therapy until herpes zoster has resolved. Consultation with a hepatologist may be necessary if hepatitis B virus DNA is detected.
• Lipid abnormalities: Increased lipid parameters (eg, total, low-density lipoprotein [LDL], and high-density lipoprotein [HDL] cholesterol) have been observed. Mean LDL and HDL increased by ~15 mg/dL and ~8 mg/dL, respectively, 2 months after starting upadacitinib. Assess lipids 12 weeks after upadacitinib initiation and manage lipid abnormalities according to current clinical guidelines.
• Malignancy: Lymphoma and other malignancies have been reported in patients receiving upadacitinib. Consider risks versus benefits prior to use in patients with a known malignancy (other than successfully treated nonmelanoma skin cancers [NMSCs]) or when continuing upadacitinib in patients who develop a new malignancy. NMSCs have been reported.
• Tuberculosis: Tuberculosis (TB) (pulmonary or extrapulmonary) has been reported in patients receiving upadacitinib. Use with caution in patients who have resided or traveled in regions where TB is endemic. Consider anti-TB 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, or immediately prior to, upadacitinib; recommended interval between receipt of live vaccines and initiation of immunosuppressive agents such as upadacitinib should follow current vaccination clinical guidelines.
Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces BCRP/ABCG2, CYP3A4 (weak), OATP1B1/1B3 (SLCO1B1/1B3)
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
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. 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
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. 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 Upadacitinib. Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider therapy modification
COVID-19 Vaccines: Upadacitinib 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
CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive): Upadacitinib may increase the serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Upadacitinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Upadacitinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Upadacitinib. Management: For ulcerative colitis use upadacitinib 30 mg/day for 8 weeks for induction, then 15 mg/day for maintenance. For rheumatoid arthritis, psoriatic arthritis, or atopic dermatitis use upadacitinib 15 mg/day. Monitor for upadacitinib toxicities. 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: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Upadacitinib. 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 Upadacitinib. Management: Concomitant use of upadacitinib 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
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. 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
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
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
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
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
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
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
Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use adequate contraception during treatment and for 4 weeks following the last dose of upadacitinib.
Based on data from animal reproduction studies, in utero exposure to upadacitinib may cause fetal harm.
Data collection to monitor pregnancy and infant outcomes following exposure to upadacitinib is ongoing. Health care providers should report patients exposed to upadacitinib during pregnancy to the manufacture (AbbVie Inc Adverse Event reporting line 1-888-633-9110) or the FDA (1-800-FDA-1088).
It is not known if upadacitinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 6 days following the last dose of upadacitinib.
Lymphocyte count, neutrophil count, hemoglobin, and LFTs (baseline and periodically thereafter); lipids (12 weeks after therapy initiation and periodically thereafter); viral hepatitis (prior to initiating therapy and periodically thereafter); latent and active tuberculosis (TB) screen at baseline; verify pregnancy status (prior to initiating therapy); signs/symptoms of infection (including TB) during and after therapy; skin examinations (periodically, in patients at increased risk for skin cancer); symptoms of thrombosis.
Upadacitinib inhibits Janus kinase (JAK) enzymes, which are intracellular enzymes involved in stimulating hematopoiesis and immune cell function through a signaling pathway. JAKs activate signal transducers and activators of transcription (STATs), which regulate gene expression and intracellular activity. The inhibition of JAKs prevents the activation of STATs.
Protein binding: 52% (plasma proteins)
Metabolism: Hepatic, primarily via CYP3A4
Half-life elimination: Terminal: 8 to 14 hours
Time to peak: 2 to 4 hours
Excretion: Urine (24% as unchanged drug); feces (38% as unchanged drug)
Altered kidney function: AUCinf 18%, 33%, and 44% higher in mild, moderate, and severe renal impairment, respectively, compared to subjects with normal renal function. Cmax similar in subjects with normal and impaired renal function.
Hepatic function impairment: AUCinf 28% and 24% higher in mild and moderate hepatic impairment, respectively, compared to subjects with normal hepatic function. Cmax unchanged in mild hepatic impairment and 43% higher in moderate hepatic impairment compared to subjects with normal hepatic function. Not studied in patients with severe hepatic impairment (Child-Pugh C).
Tablet, 24-hour (Rinvoq Oral)
15 mg (per each): $226.85
30 mg (per each): $226.85
45 mg (per each): $453.70
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