Upadacitinib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani
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Black Box Warning
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Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events (MACE), and Thrombosis
See full prescribing information for complete Boxed Warning.
Serious Infections: Patients treated with Upadacitinib are at an increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis, bacterial, invasive fungal, viral, and other opportunistic pathogens. Prior to initiating therapy, evaluate for latent or active tuberculosis and monitor patients closely during treatment.
Mortality: A higher rate of all-cause mortality, including sudden cardiovascular death, has been observed in patients treated with another JAK inhibitor for rheumatoid arthritis. This risk may apply to Upadacitinib as it is in the same class. Malignancy: Lymphoma and other malignancies have been observed in patients treated with Upadacitinib. Major Adverse Cardiovascular Events (MACE): An increased risk of major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, has been observed in patients treated with another JAK inhibitor for rheumatoid arthritis. This risk may apply to Upadacitinib. Thrombosis: Deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have occurred in patients treated with Upadacitinib. Many of these adverse events were serious and some resulted in death. Recommendation: Upadacitinib should be reserved for patients who have had an inadequate response or intolerance to one or more TNF blockers. |
Overview
Upadacitinib is a Janus Kinase (JAK) Inhibitor that is FDA approved for the treatment of Moderate to severe active rheumatoid arthritis, Active psoriatic arthritis, Moderate to severe atopic dermatitis, Moderate to severe ulcerative colitis, Moderate to severe active Crohn's disease, Active ankylosing spondylitis, and Active non-radiographic axial spondyloarthritis.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Upper respiratory tract infections (common cold, sinus infections), Nausea, Cough, Fever, Elevated liver enzymes, Hyperlipidemia, Hypertension, Herpes zoster, and Acne..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
FDA-labeled indications and dosing information for adults:
Rheumatoid Arthritis: 15 mg orally once daily. Psoriatic Arthritis: 15 mg orally once daily. Atopic Dermatitis: 15 mg orally once daily; may increase to 30 mg once daily based on response. Ulcerative Colitis: Induction: 45 mg orally once daily for 8 weeks; Maintenance: 15 mg or 30 mg once daily. Crohn's Disease: Induction: 45 mg orally once daily for 12 weeks; Maintenance: 15 mg or 30 mg once daily. Ankylosing Spondylitis: 15 mg orally once daily. Non-radiographic Axial Spondyloarthritis: 15 mg orally once daily.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Upadacitinib in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Upadacitinib in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Atopic Dermatitis (ages 12 and older): 15 mg orally once daily; may increase to 30 mg once daily based on response.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Upadacitinib in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Upadacitinib in pediatric patients.
Contraindications
Hypersensitivity to Upadacitinib or any of its excipients. Active tuberculosis or other severe infections. Severe hepatic impairment (Child-Pugh Class C). Pregnancy.
Warnings
|
Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events (MACE), and Thrombosis
See full prescribing information for complete Boxed Warning.
Serious Infections: Patients treated with Upadacitinib are at an increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis, bacterial, invasive fungal, viral, and other opportunistic pathogens. Prior to initiating therapy, evaluate for latent or active tuberculosis and monitor patients closely during treatment.
Mortality: A higher rate of all-cause mortality, including sudden cardiovascular death, has been observed in patients treated with another JAK inhibitor for rheumatoid arthritis. This risk may apply to Upadacitinib as it is in the same class. Malignancy: Lymphoma and other malignancies have been observed in patients treated with Upadacitinib. Major Adverse Cardiovascular Events (MACE): An increased risk of major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, has been observed in patients treated with another JAK inhibitor for rheumatoid arthritis. This risk may apply to Upadacitinib. Thrombosis: Deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have occurred in patients treated with Upadacitinib. Many of these adverse events were serious and some resulted in death. Recommendation: Upadacitinib should be reserved for patients who have had an inadequate response or intolerance to one or more TNF blockers. |
There is limited information regarding Upadacitinib Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
Serious infection, malignancies, major adverse cardiovascular events (MACE), thrombosis, elevated liver enzymes., neutropenia, and anemia.
Postmarketing Experience
There is limited information regarding Upadacitinib Postmarketing Experience in the drug label.
Drug Interactions
Strong CYP3A4 Inhibitors: Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) can increase Upadacitinib exposure, potentially enhancing the risk of adverse reactions. Patients should avoid consuming grapefruit or grapefruit-containing products during Upadacitinib treatment. ncbi.nlm.nih.gov
Strong CYP3A4 Inducers: Co-administration with strong CYP3A4 inducers (e.g., rifampin) may decrease Upadacitinib exposure, potentially reducing its therapeutic effect. Therefore, co-administration of Upadacitinib with strong CYP3A4 inducers is not recommended. ncbi.nlm.nih.gov
Methotrexate: Co-administration with methotrexate does not have a clinically relevant effect on Upadacitinib plasma exposures.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should use effective contraception during treatment and for 4 weeks after the final dose.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Upadacitinib in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Upadacitinib during labor and delivery.
Nursing Mothers
It is unknown whether Upadacitinib is excreted in human milk. A decision should be made whether to discontinue breastfeeding or to discontinue the drug, considering the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Pediatric Use
The safety and efficacy of Upadacitinib in pediatric patients younger than 12 years of age have not been established.
Geriatic Use
Patients aged 65 years and older are at an increased risk of adverse reactions, including infections, malignancies, and cardiovascular events. Upadacitinib should only be used in these patients if no suitable treatment alternatives are available.
Gender
There is no FDA guidance on the use of Upadacitinib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Upadacitinib with respect to specific racial populations.
Renal Impairment
No dose adjustment is required in patients with mild or moderate renal impairment. Upadacitinib should be used with caution in patients with severe renal impairment.
Hepatic Impairment
No dose adjustment is required in patients with mild or moderate hepatic impairment. Upadacitinib should not be used in patients with severe hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Upadacitinib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Upadacitinib in patients who are immunocompromised.
Administration and Monitoring
Administration
Upadacitinib is administered orally once daily with or without food. Tablets should be swallowed whole and should not be split, crushed, or chewed to ensure the entire dose is delivered correctly.
Monitoring
Infection Surveillance: Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment.
Laboratory Tests: Regular monitoring of blood counts, liver enzymes, and lipid profiles is recommended.
IV Compatibility
Not Applicable: Upadacitinib is administered orally.
Overdosage
In case of overdose, patients should be closely monitored for signs and symptoms of adverse reactions. Treatment should be symptomatic and supportive.
Pharmacology
There is limited information regarding Upadacitinib Pharmacology in the drug label.
Mechanism of Action
Upadacitinib is a selective Janus kinase (JAK) inhibitor, primarily targeting JAK1. By inhibiting JAK1, upadacitinib modulates the signaling pathways of various cytokines involved in the pathogenesis of autoimmune diseases, thereby reducing inflammation.
Structure
There is limited information regarding Upadacitinib Structure in the drug label.
Pharmacodynamics
Upadacitinib inhibits the JAK-STAT signaling pathway, leading to modulation of immune responses.
Pharmacokinetics
Absorption: Peak plasma concentrations (C_max) are reached approximately 2-4 hours after oral administration. Distribution: The volume of distribution (V_d) is approximately 450 L, indicating extensive tissue distribution. Metabolism: Upadacitinib is metabolized primarily by CYP3A4 enzymes. Elimination: The terminal half-life is approximately 8-14 hours. About 20% is excreted in urine and 80% in feces.
Nonclinical Toxicology
There is limited information regarding Upadacitinib Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Upadacitinib Clinical Studies in the drug label.
How Supplied
Upadacitinib is supplied as extended-release tablets for oral administration in the following strengths:
15 mg: Purple, biconvex oblong tablets with "a15" debossed on one side. 30 mg: Red, biconvex oblong tablets with "a30" debossed on one side.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep the bottle tightly closed to protect from moisture.
Images
Drug Images
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Patient Counseling Information
Risk of Serious Infections: Inform patients about the risk of serious infections that may lead to hospitalization or death. Advise them to seek medical attention if they experience symptoms such as fever, fatigue, cough, or painful urination. Mortality: Discuss the observed higher rate of all-cause mortality, including sudden cardiovascular death, in patients treated with another JAK inhibitor for rheumatoid arthritis, and how this risk may apply to upadacitinib. Malignancy and Lymphoproliferative Disorders: Inform patients about the risk of malignancies, including lymphomas and skin cancers. Advise them to perform regular skin examinations and report any suspicious lesions. Major Adverse Cardiovascular Events (MACE): Educate patients about the increased risk of cardiovascular events such as heart attack or stroke. Advise them to seek immediate medical attention if they experience symptoms like chest pain, shortness of breath, or sudden weakness. Thrombosis: Inform patients about the risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Advise them to seek medical attention if they experience symptoms such as leg pain or swelling, or sudden shortness of breath. Laboratory Monitoring: Advise patients that regular blood tests are necessary to monitor for potential adverse reactions, including changes in blood cell counts and liver enzymes. Pregnancy and Lactation: Discuss potential risks to the fetus and advise against breastfeeding during treatment and for at least 6 days after the final dose.
Precautions with Alcohol
There are no specific contraindications regarding alcohol consumption with upadacitinib. However, patients should consult their healthcare provider regarding alcohol use, especially if they have liver disease or are taking other medications that may interact with alcohol.
Brand Names
Upadacitinib is marketed under the brand name RINVOQ.
Look-Alike Drug Names
There is limited information regarding Upadacitinib Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.