Upadacitinib
FDA Drug Information • Also known as: Rinvoq
- Brand Names
- Rinvoq
- Dosage Form
- TABLET
- Product Type
- DRUG FOR FURTHER PROCESSING
⚠ Boxed Warning (Black Box)
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS SERIOUS INFECTIONS Patients treated with RINVOQ /RINVOQ LQ are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ /RINVOQ LQ 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 RINVOQ /RINVOQ LQ use and during therapy. Treatment for latent infection should be considered prior to RINVOQ /RINVOQ LQ 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 RINVOQ /RINVOQ LQ 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 RINVOQ /RINVOQ LQ , including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions ( 5.1 )]. MORTALITY In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one 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 [see Warnings and Precautions ( 5.2 )] . MALIGNANCIES Lymphoma and other malignancies have been observed in patients treated with RINVOQ . In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions ( 5.3 )] . MAJOR ADVERSE CARDIOVASCULAR EVENTS In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (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 RINVOQ /RINVOQ LQ in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions ( 5.4 )] . THROMBOSIS Thrombos e s, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis , have occurred in patients treated for inflammatory conditions with J AK inhibitors , including RINVOQ . Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid RINVOQ /RINVOQ LQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ /RINVOQ LQ and be promptly evaluated [see Warnings and Precautions ( 5.5 )]. WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), and THROMBOSIS See full prescribing information for complete boxed warning. Increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with RINVOQ / RINVOQ LQ if serious infection occurs until the infection is controlled. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative , latent TB test. ( 5.1 ) Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase (JAK) inhibitor vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients. ( 5.2 ) Malignancies have occurred in patients treated with RINVOQ. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.3 ) Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.4 ) Thrombosis has occurred in patients treated with RINVOQ. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. ( 5.5 )
Description
11 DESCRIPTION RINVOQ and RINVOQ LQ are formulated with upadacitinib, a JAK inhibitor. Upadacitinib has the following chemical name: (3 S ,4 R )-3-Ethyl-4-(3 H -imidazo[1,2- a ]pyrrolo[2,3- e ]pyrazin-8-yl)- N -(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide hydrate (2:1). The strength of upadacitinib is based on anhydrous upadacitinib. The solubility of upadacitinib in water is 38 to less than 0.2 mg/mL across a pH range of 2 to 9 at 37 o C. Upadacitinib has a molecular weight of 389.38 g/mol and a molecular formula of C 17 H 19 F 3 N 6 O
What Is Upadacitinib Used For?
1 INDICATIONS AND USAGE RINVOQ/RINVOQ LQ is a Janus kinase (JAK) inhibitor. RINVOQ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers. ( 1.1 ) Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine. ( 1.1 ) RINVOQ/RINVOQ LQ is indicated for the treatment of adults and pediatric patients 2 years of age and older with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers. ( 1.2 ) Limitation s of Use RINVOQ/RINVOQ LQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine. ( 1.2 ) RINVOQ is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies are inadvisable. ( 1.3 ) Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants. ( 1.3 ) RINVOQ is indicated for the treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more TNF blockers. If TNF blockers are clinically inadvisable, patients should have received at least one approved systemic therapy prior to use of RINVOQ. ( 1.4 ) Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for UC, or with potent immunosuppressants such as azathioprine and cyclosporine. ( 1.4 ) RINVOQ is indicated for the treatment of adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more TNF blockers. If TNF blockers are clinically inadvisable, patients should have received at least one approved systemic therapy prior to use of RINVOQ. ( 1.5 ) Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for CD, or with potent immunosuppressants such as azathioprine and cyclosporine. ( 1.5 ) RINVOQ is indicated for the treatment of adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers. ( 1.6 ) Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine. ( 1.6 ) RINVOQ is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets ( 2.2 , 2.10 ). Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the healthcare provider. Prior to treatment update immunizations and consider evaluating for active and latent tuberculosis, viral hepatitis, hepatic function, and pregnancy status ( 2.1 ) Avoid initiation or interrupt RINVOQ/RINVOQ LQ if absolute lymphocyte count is less than 500 cells/mm 3 , absolute neutrophil count is less than 1000 cells/mm 3 , or hemoglobin level is less than 8 g/dL. ( 2.1 , 2.14 ) Rheumatoid Arthritis , Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis Adults: The recommended dosage of RINVOQ is 15 mg once daily. ( 2.3 , 2.8 , 2.9 ) Psoriatic Arthritis Pediatric Patients 2 to less than 18 Years of Age Weighing at Least 10 kg: The recommended dosage is based on body weight ( 2.4 ) Adults: The recommended dosage of RINVOQ is 15 mg once daily. ( 2.4 ) Atopic Dermatitis Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg and Adults Less Than 65 Years of Age : Initiate treatment with RINVOQ 15 mg orally once daily. If an adequate response is not achieved, consider increasing the dosage to 30 mg orally once daily. ( 2.5 ) Adults 65 Years of Age and Older : Recommended dosage of RINVOQ is 15 mg once daily. ( 2.5 ) Severe Renal Impairment : Recommended dosage of RINVOQ is 15 mg once daily. ( 2.12 ) Ulcerative Colitis Adults: The recommended induction dosage of RINVOQ is 45 mg once daily for 8 weeks. The recommended maintenance dosage of RINVOQ is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue RINVOQ if adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response. ( 2.6 ) See the Full Prescribing Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions. ( 2.12 , 2.13 ) Crohn’s D isease Adults: The recommended induction dosage of RINVOQ is 45 mg once daily for 12 weeks. The recommended maintenance dosage of RINVOQ is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue RINVOQ if an adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response. ( 2.7 ) See the Full Prescribing Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions. ( 2.12 , 2.13 ) Polyarticular Juvenile Idiopathic Arthritis The recommended dosage is based on body weight ( 2.10 ) Giant Cell Arteritis The recommended dosage of RINVOQ is 15 mg once daily in combination with a tapering course of corticosteroids. RINVOQ 15 mg once...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions ( 5.1 )] Mortality [see Warnings and Precautions ( 5.2 )] Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions ( 5.3 )] Major Adverse Cardiovascular Events [see Warnings and Precautions ( 5.4 )] Thrombosis [see Warnings and Precautions ( 5.5 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] Gastrointestinal Perforations [see Warnings and Precautions ( 5.7 )] Laboratory Abnormalities [see Warnings and Precautions ( 5.8 )] Rheumatoid arthritis , psoriatic arthritis , ankylosi ng spondylitis , and n on-radiographic a xial s pondyloarthritis : Adverse reactions (≥ 1%) were: upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache. ( 6.1 ) Giant cell arteritis : Adverse reactions (≥ 5%) are upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea. ( 6.1 ) Atopic d ermatitis : Adverse reactions (≥ 1%) are: upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza like illness. ( 6.1 ) Ulcerative colitis : Adverse reactions (≥ 5%) reported during induction or maintenance are: upper respiratory tract infections, increased blood creatine phosphokinase, acne, neutropenia, elevated liver enzymes, pyrexia, and rash. ( 6.1 ) Crohn’s disease : Adverse reactions (≥ 5%) reported during induction or maintenance are: upper respiratory tract infections, anemia, pyrexia, acne, herpes zoster, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Patients with Rheumatoid Arthritis A total of 3833 adult patients with rheumatoid arthritis were treated with RINVOQ 15 mg or upadacitinib 30 mg tablets once daily in the Phase 3 clinical trials of whom 2806 were exposed for at least one year. Patients could advance or switch to RINVOQ 15 mg from placebo, or be rescued to RINVOQ from active comparator or placebo from as early as Week 12 depending on the trial design. A total of 2630 patients received at least 1 dose of RINVOQ 15 mg, of whom 1860 were exposed for at least one year. In trials RA-I, RA-II, RA-III and RA-V, 1213 patients received at least 1 dose of RINVOQ 15 mg, of which 986 patients were exposed for at least one year, and 1203 patients received at least 1 dose of upadacitinib 30 mg, of which 946 were exposed for at least one year. Table 4: Adverse Reactions Reported in ≥ 1% of Rheumatoid Arthritis Patients Treated with RINVOQ 15 mg in Placebo-controlled Trials Adverse Reaction Placebo RINVOQ 15 mg N = 1042 (%) N = 1035 (%) Upper respiratory tract infection (URTI)* 9.5 13.5 Nausea 2.2 3.5 Cough 1.0 2.2 Pyrexia 0 1.2 *URTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection Other adverse reactions reported in less than 1% of patients in the RINVOQ 15 mg group and at a higher rate than in the placebo group through Week 12 included pneumonia, herpes zoster, herpes simplex (includes oral herpes), and oral candidiasis. Four integrated datasets are presented in the Specific Adverse Reaction section: Placebo-controlled Trials: Trials RA-III, RA-IV, and RA-V were integrated to...
Drug Interactions
7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors : See the Full Prescribing Information for dosage modification for patients with atopic dermatitis, ulcerative colitis, and Crohn’s disease. ( 2.13 , 7.1 ) Strong CYP3A4 Inducers : Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. ( 7.2 ) 7.1 Strong CYP3A4 Inhibitors Upadacitinib exposure is increased when it is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and grapefruit), which may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )] . Monitor patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondylarthritis, pJIA, or giant cell arteritis closely for adverse reactions when co-administering RINVOQ/RINVOQ LQ with strong CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided during treatment with RINVOQ/RINVOQ LQ. For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. For patients with ulcerative colitis or Crohn’s disease taking strong CYP3A4 inhibitors, reduce the RINVOQ induction dosage to 30 mg once daily. The recommended maintenance dosage is 15 mg once daily [see Dosage and Administration ( 2.13 )] . 7.2 Strong CYP3A4 Inducers Upadacitinib exposure is decreased when it is co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect [see Clinical Pharmacology ( 12.3 )] . Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended.
Contraindications
4 CONTRAINDICATIONS RINVOQ/RINVOQ LQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients [see Warnings and Precautions ( 5.6 )] . Known hypersensitivity to upadacitinib or any of the excipients in RINVOQ/RINVOQ LQ. ( 4 , 5.6 )
Pregnancy and Breastfeeding
8.1 Pregnancy Pregnancy Surveillance Program There is a pregnancy surveillance program for RINVOQ/RINVOQ LQ that monitors pregnancy outcomes in women exposed to RINVOQ/RINVOQ LQ. If RINVOQ/RINVOQ LQ exposure occurs during pregnancy, healthcare providers or patients should report the pregnancy by calling 1-800-633-9110. Risk Summary Available data from the pharmacovigilance safety database and postmarketing case reports on use of RINVOQ in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. Based on animal studies, RINVOQ/RINVOQ LQ has the potential to adversely affect a developing fetus. Advise patients of reproductive potential and pregnant patients of the potential risk to the fetus. In animal embryo-fetal development studies, oral upadacitinib administration to pregnant rats and rabbits at exposures equal to or greater than approximately 1.6 and 15 times the 15 mg tablet dose, 0.8 and 7.6 times the 30 mg tablet dose, and 0.6 and 5.6 times the maximum recommended human dose (MRHD) of 45 mg (on an AUC basis) resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased post-implantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits. No developmental toxicity was observed in pregnant rats and rabbits treated with oral upadacitinib during organogenesis at exposures approximately 0.29 and 2.2 times the 15 mg dose, 0.15 times and 1.1 times the 30 mg dose, and at 0.11 and 0.82 times the MRHD (on an AUC basis). In a pre- and post-natal development study in pregnant female rats, oral upadacitinib administration at exposures approximately 3 times the 15 mg dose, 1.4 times the 30 mg dose, and the same as the MRHD (on an AUC basis) resulted in no maternal or developmental toxicity ( see Data ) . The background risks of major birth defects and miscarriage for the indicated populations are...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RINVOQ extended-release tablets are supplied as: 15 mg: purple, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a15’ on one side. 30 tablets in a bottle; NDC: 0074-2306-30 30 mg: red, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a30’ on one side. 30 tablets in a bottle; NDC: 0074-2310-30 45 mg: yellow to mottled yellow, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a45’ on one side. 28 tablets in a bottle; NDC: 0074-1043-28 RINVOQ LQ oral solution is supplied as: A 1 mg/mL oral solution in HDPE bottles with a child-resistant cap. Each bottle contains a labeled volume of 180 mL of clear, colorless to light yellow solution. The bottle is packaged in a carton with one press-in bottle adapter and one 10 mL oral dosing syringe; NDC: 0074-2320-01 Storage and Handling RINVOQ extended-release tablets Store at 2˚C to 25˚C (36˚F to 77˚F). Store in the original bottle in order to protect from moisture. RINVOQ LQ oral solution Store between 2°C to 30°C (36°F to 86°F). Discard remaining oral solution 60 days after opening the bottle.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.