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Upadacitinib: Drug information

Upadacitinib: Drug information
(For additional information see "Upadacitinib: Patient drug information" and see "Upadacitinib: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
JAK Inhibitors Safety Review September 2021

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.

ALERT: US Boxed Warning
Serious infections:

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

Mortality:

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.

Malignancies:

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.

Major adverse cardiovascular events:

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:

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.

Brand Names: US
  • Rinvoq
Brand Names: Canada
  • Rinvoq
Pharmacologic Category
  • Antirheumatic, Disease Modifying;
  • Antirheumatic, Miscellaneous;
  • Janus Kinase Inhibitor
Dosing: Adult

Note: May be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs); use in combination with biologic DMARDS or potent immunosuppressants (eg, azathioprine, cyclosporine) is not recommended. Do not initiate therapy in patients with an absolute lymphocyte count <500/mm3, ANC <1,000/mm3, or hemoglobin <8 g/dL.

Atopic dermatitis: Oral: 15 mg once daily; may increase to 30 mg once daily if inadequate response.

Psoriatic arthritis: Oral: 15 mg once daily.

Rheumatoid arthritis: Oral: 15 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.

Dosing: Kidney Impairment: Adult

Atopic dermatitis:

Altered kidney function:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: 15 mg once daily.

Psoriatic arthritis, rheumatoid arthritis:

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary for any degree of kidney dysfunction.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

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.

Dosing: Pediatric

(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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Dosing: Older Adult

Atopic dermatitis: ≥65 years of age: Oral: 15 mg once daily.

Psoriatic arthritis, rheumatoid arthritis: Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Rinvoq: 15 mg, 30 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Rinvoq: 15 mg, 30 mg

Medication Guide and/or Vaccine Information Statement (VIS)

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/2022/211675s004lbl.pdf#page=45

Administration: Adult

Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.

Administration: Pediatric

Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.

Hazardous Drugs Handling Considerations

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).

Use: Labeled Indications

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.

Psoriatic arthritis: Treatment of active psoriatic arthritis 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.

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.

Adverse Reactions

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 (14% to 25%)

1% to 10%:

Dermatologic: Folliculitis (2% to 3%)

Endocrine & metabolic: Weight gain (2%)

Gastrointestinal: Abdominal pain (2% to 3%), nausea (3% to 4%)

Hematologic & oncologic: Neutropenia (1% to 2%)

Hepatic: Increased serum aspartate aminotransferase (2%)

Hypersensitivity: Hypersensitivity reaction (3%)

Infection: Herpes simplex infection (≤8%), herpes zoster infection (1% to 2%), influenza (2%)

Nervous system: Fatigue (2%), headache (6%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (1% to 6%), 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), varicella-like rash (Kaposi's varicelliform eruption)

Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides

Gastrointestinal: Esophageal candidiasis, gastrointestinal perforation

Hematologic & oncologic: Malignant neoplasm, skin carcinoma

Hypersensitivity: Anaphylaxis, angioedema

Infection: Bacterial infection, cryptococcosis, fungal infection, infection (including serious infection), opportunistic infection, reactivation of HBV, viral infection

Respiratory: Infection due to organism in genus Pneumocystis, tuberculosis

Postmarketing:

Cardiovascular: Acute myocardial infarction (FDA Safety Alert September 1, 2021), cerebrovascular accident (FDA Safety Alert September 1, 2021)

Hematologic & oncologic: Lung carcinoma (FDA Safety Alert September 1, 2021), lymphocytopenia, malignant lymphoma (FDA Safety Alert September 1, 2021)

Contraindications

Hypersensitivity to upadacitinib or any component of the formulation.

Warnings/Precautions

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.

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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

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. 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). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification

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): Upadacitinib may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider holding upadacitinib therapy for 1 week after each vaccine dose when possible for patients with stable underlying disease. Additionally, consider a 3rd dose of COVID-19 vaccine in patients 5 years of age and older on upadacitinib. 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

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: When used together with a strong CYP3A4 inhibitor, the recommended dose of upadacitinib is 15 mg/day. Coadministration of the upadacitinib 30 mg/day dose together with a strong CYP3A4 inhibitor is not recommended. 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

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

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

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

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 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

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

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

Reproductive Considerations

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.

Pregnancy Considerations

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).

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics

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)

Pharmacokinetics: Additional Considerations

Renal function impairment: 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).

Pricing: US

Tablet, 24-hour (Rinvoq Oral)

15 mg (per each): $226.85

30 mg (per each): $226.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Rinvoq (AR, AT, AU, CZ, DE, EE, GB, HR, HU, LT, LV, NL, NO, PT, RO, SK)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2018:84-103.
  2. Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397(10290):2151-2168. doi:10.1016/S0140-6736(21)00588-2 [PubMed 34023008]
  3. Katoh N, Ohya Y, Murota H, et al. A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysis. JAAD Int. 2021;6:27-36. doi:10.1016/j.jdin.2021.11.001 [PubMed 34988493]
  4. Reich K, Teixeira HD, de Bruin-Weller M, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;397(10290):2169-2181. doi:10.1016/S0140-6736(21)00589-4 [PubMed 34023009]
  5. Rinvoq (upadacitinib) [prescribing information]. North Chicago, IL: AbbVie Inc; January 2022.
  6. Silverberg JI, de Bruin-Weller M, Bieber T, et al. Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results. J Allergy Clin Immunol. Published online August 14, 2021. doi:10.1016/j.jaci.2021.07.036 [PubMed 34403658]
  7. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed September 17, 2019.
  8. US Food and Drug Administration (FDA). FDA Safety Alert. MedWatch. Xeljanz, Xeljanz XR (tofacitinib): FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death. Accessed September 2, 2021
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