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Rinvoq

Rinvoq (Upadacitinib Extended-release Tablets) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Rinvoq Side Effects Center

What Is Rinvoq?

Rinvoq (upadacitinib) is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

What Are Side Effects of Rinvoq?

Common side effects of Rinvoq include:

  • upper respiratory tract infections,
  • nausea,
  • cough, and
  • fever

Dosage for Rinvoq

The recommended dose of Rinvoq is 15 mg once daily. Rinvoq may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.

What Drugs, Substances, or Supplements Interact with Rinvoq?

Rinvoq may interact with strong CYP3A4 inhibitors (e.g., ketoconazole), strong CYP3A4 inducers (e.g., rifampin), and live vaccines. Tell your doctor all medications and supplements you use.

Rinvoq During Pregnancy and Breastfeeding

Rinvoq is not recommended for use during pregnancy; it may harm a fetus. Females of reproductive potential are advised to use effective contraception during treatment with Rinvoq and for 4 weeks following completion of therapy. It is unknown if Rinvoq passes into breast milk. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment with Rinvoq, and for 6 days after the last dose.

Additional Information

Our Rinvoq (upadacitinib) Extended-Release Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Rinvoq Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

  • fever, chills, sweating;
  • skin sores;
  • tiredness, muscle pain;
  • increased urination, pain or burning when you urinate;
  • stomach pain, diarrhea, weight loss; or
  • cough, shortness of breath, coughing up pink or red mucus.

Further doses may be delayed until your infection clears up.

Also call your doctor at once if you have:

  • shingles--burning pain, numbness, tingling, itching, skin rash or blisters;
  • signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
  • signs of a blood clot in your leg--swelling, warmth, or redness in the leg;
  • signs of perforation (a hole or tear) in your stomach or intestines--fever, ongoing stomach pain, change in bowel habits; or
  • signs of tuberculosis: fever, cough, night sweats, loss of appetite, weight loss, and feeling very tired.

Common side effects may include:

  • fever;
  • cough;
  • nausea; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Rinvoq (Upadacitinib Extended-release Tablets)

 

Rinvoq Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Serious Infections [see WARNINGS AND PRECAUTIONS]
  • Malignancy [see WARNINGS AND PRECAUTIONS]
  • Thrombosis [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Perforations [see WARNINGS AND PRECAUTIONS]
  • Laboratory Parameters [see WARNINGS AND PRECAUTIONS]

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.

A total of 3833 patients with rheumatoid arthritis were treated with upadacitinib in the Phase 3 clinical studies 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 study 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 studies 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 2: Adverse Reactions Reported in greater than or equal to 1% of Rheumatoid Arthritis Patients Treated with RINVOQ 15 mg in Placebo-controlled Studies

Adverse Reaction Placebo
n=1042 (%)		 RINVOQ15 mg
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 Studies: Studies RA-III, RA-IV, and RA-V were integrated to represent safety through 12/14 weeks for placebo (n=1042) and RINVOQ 15 mg (n=1035). Studies RA-III and RA-V were integrated to represent safety through 12 weeks for placebo (n=390), RINVOQ 15 mg (n=385), upadacitinib 30 mg (n=384). Study RA-IV did not include the 30 mg dose and, therefore, safety data for upadacitinib 30 mg can only be compared with placebo and RINVOQ 15 mg rates from pooling studies RA-III and RA-V.

MTX-controlled Studies: Studies RA-I and RA-II were integrated to represent safety through 12/14 weeks for MTX (n=530), RINVOQ 15 mg (n=534), and upadacitinib 30 mg (n=529).

12-Month Exposure Dataset: Studies RA-I, II, III, and V were integrated to represent the longterm safety of RINVOQ 15 mg (n=1213) and upadacitinib 30 mg (n=1203).

Exposure adjusted incidence rates were adjusted by study for all the adverse events reported in this section.

Specific Adverse Reactions

Infections

Placebo-controlled Studies: In RA-III, RA-IV, and RA-V, infections were reported in 218 patients (95.7 per 100 patient-years) treated with placebo and 284 patients (127.8 per 100 patient-years) treated with RINVOQ 15 mg. In RA-III and RA-V, infections were reported in 99 patients (136.5 per 100 patient-years) treated with placebo, 118 patients (164.5 per 100 patientyears) treated with RINVOQ 15 mg, and 126 patients (180.3 per 100 patient-years) treated with upadacitinib 30 mg.

MTX-controlled Studies: Infections were reported in 127 patients (119.5 per 100 patient-years) treated with MTX monotherapy, 104 patients (91.8 per 100 patient-years) treated with RINVOQ 15 mg monotherapy, and 128 patients (115.1 per 100 patient-years) treated with upadacitinib 30 mg monotherapy.

12-Month Exposure Dataset: Infections were reported in 615 patients (83.8 per 100 patientyears) treated with RINVOQ 15 mg and 674 patients (99.7 per 100 patient-years) treated with upadacitinib 30 mg.

Serious Infections

Placebo-controlled Studies: In RA-III, RA-IV, and RA-V, serious infections were reported in 6 patients (2.3 per 100 patient-years) treated with placebo, and 12 patients (4.6 per 100 patientyears) treated with RINVOQ 15 mg. In RA-III and RA-V, serious infections were reported in 1 patient (1.2 per 100 patient-years) treated with placebo, 2 patients (2.3 per 100 patient-years) treated with RINVOQ 15 mg, and 7 patients (8.2 per 100 patient-years) treated with upadacitinib 30 mg.

MTX-controlled Studies: Serious infections were reported in 2 patients (1.6 per 100 patientyears) treated with MTX monotherapy, 3 patients (2.4 per 100 patient-years) treated with RINVOQ 15 mg monotherapy, and 8 patients (6.4 per 100 patient-years) treated with upadacitinib 30 mg monotherapy.

12-Month Exposure Dataset: Serious infections were reported in 38 patients (3.5 per 100 patientyears) treated with RINVOQ 15 mg and 59 patients (5.6 per 100 patient-years) treated with upadacitinib 30 mg.

The most frequently reported serious infections were pneumonia and cellulitis.

Tuberculosis

Placebo-controlled Studies and MTX-controlled Studies: In the placebo-controlled period, there were no active cases of tuberculosis reported in the placebo, RINVOQ 15 mg, and upadacitinib 30 mg groups. In the MTX-controlled period, there were no active cases of tuberculosis reported in the MTX monotherapy, RINVOQ 15 mg monotherapy, and upadacitinib 30 mg monotherapy groups.

12-Month Exposure Dataset: Active tuberculosis was reported for 2 patients treated with RINVOQ 15 mg and 1 patient treated with upadacitinib 30 mg. Cases of extra-pulmonary tuberculosis were reported.

Opportunistic Infections (excluding tuberculosis)

Placebo-controlled Studies

In RA-III, RA-IV, and RA-V, opportunistic infections were reported in 3 patients (1.2 per 100 patient-years) treated with placebo, and 5 patients (1.9 per 100 patientyears) treated with RINVOQ 15 mg. In RA-III and RA-V, opportunistic infections were reported in 1 patient (1.2 per 100 patient-years) treated with placebo, 2 patients (2.3 per 100 patient-years) treated with RINVOQ 15 mg, and 6 patients (7.1 per 100 patient-years) treated with upadacitinib 30 mg.

MTX-controlled Studies

Opportunistic infections were reported in 1 patient (0.8 per 100 patientyears) treated with MTX monotherapy, 0 patients treated with RINVOQ 15 mg monotherapy, and 4 patients (3.2 per 100 patient-years) treated with upadacitinib 30 mg monotherapy. 12-Month Exposure Dataset: Opportunistic infections were reported in 7 patients (0.6 per 100 patient-years) treated with RINVOQ 15 mg and 15 patients (1.4 per 100 patient-years) treated with upadacitinib 30 mg.

Malignancy

Placebo-controlled Studies: In RA-III, RA-IV, and RA-V, malignancies excluding NMSC were reported in 1 patient (0.4 per 100 patient-years) treated with placebo, and 1 patient (0.4 per 100 patient-years) treated with RINVOQ 15 mg. In RA-III and RA-V, malignancies excluding NMSC were reported in 0 patients treated with placebo, 1 patient (1.1 per 100 patient-years) treated with RINVOQ 15 mg, and 3 patients (3.5 per 100 patient-years) treated with upadacitinib 30 mg.

MTX-controlled Studies

Malignancies excluding NMSC were reported in 1 patient (0.8 per 100 patient-years) treated with MTX monotherapy, 3 patients (2.4 per 100 patient-years) treated with RINVOQ 15 mg monotherapy, and 0 patients treated with upadacitinib 30 mg monotherapy.

12-Month Exposure Dataset

Malignancies excluding NMSC were reported in 13 patients (1.2 per 100 patient-years) treated with RINVOQ 15 mg and 14 patients (1.3 per 100 patient-years) treated with upadacitinib 30 mg.

Gastrointestinal Perforations

Placebo-controlled Studies

There were no gastrointestinal perforations (based on medical review) reported in patients treated with placebo, RINVOQ 15 mg, and upadacitinib 30 mg.

MTX-controlled Studies

There were no cases of gastrointestinal perforations reported in the MTX and RINVOQ 15 mg group through 12/14 weeks. Two cases of gastrointestinal perforations were observed in the upadacitinib 30 mg group.

12-Month Exposure Dataset

Gastrointestinal perforations were reported in 1 patient treated with RINVOQ 15 mg and 4 patients treated with upadacitinib 30 mg.

Thrombosis

Placebo-controlled Studies

In RA-IV, venous thrombosis (pulmonary embolism or deep vein thrombosis) was observed in 1 patient treated with placebo and 1 patient treated with RINVOQ 15 mg. In RA-V, venous thrombosis was observed in 1 patient treated with RINVOQ 15 mg. There were no observed cases of venous thrombosis reported in RA-III. No cases of arterial thrombosis were observed through 12/14 weeks.

MTX-controlled Studies

In RA-II, venous thrombosis was observed in 0 patients treated with MTX monotherapy, 1 patient treated with RINVOQ 15 mg monotherapy and 0 patients treated with upadacitinib 30 mg monotherapy through Week 14. In RA-II, no cases of arterial thrombosis were observed through 12/14 weeks. In RA-I, venous thrombosis was observed in 1 patient treated with MTX, 0 patients treated with RINVOQ 15 mg and 1 patient treated with upadacitinib 30 mg through Week 24. In RA-I, arterial thrombosis was observed in 1 patient treated with upadacitinib 30 mg through Week 24.

12-Month Exposure Dataset

Venous thrombosis events were reported in 5 patients (0.5 per 100 patient-years) treated with RINVOQ 15 mg and 4 patients (0.4 per 100 patient-years) treated with upadacitinib 30 mg. Arterial thrombosis events were reported in 0 patients treated with RINVOQ 15 mg and 2 patients (0.2 per 100 patient-years) treated with upadacitinib 30 mg.

Laboratory Abnormalities

Hepatic Transaminase Elevations

In placebo-controlled studies (RA-III, RA-IV, and RA-V) with background DMARDs, for up to 12/14 weeks, alanine transaminase (ALT) and aspartate transaminase (AST) elevations ≥ 3 x upper limit of normal (ULN) in at least one measurement were observed in 2.1% and 1.5% of patients treated with RINVOQ 15 mg, and in 1.5% and 0.7% of patients treated with placebo, respectively. In RA-III and RA-V, ALT and AST elevations ≥ 3 x ULN in at least one measurement were observed in 0.8% and 1.0% of patients treated with RINVOQ 15 mg, 1.0% and 0% of patients treated with upadacitinib 30 mg and in 1.3% and 1.0% of patients treated with placebo, respectively.

In MTX-controlled studies, for up to 12/14 weeks, ALT and AST elevations ≥ 3 x ULN in at least one measurement were observed in 0.8% and 0.4% of patients treated with RINVOQ 15 mg, 1.7% and 1.3% of patients treated with upadacitinib 30 mg and in 1.9% and 0.9% of patients treated with MTX, respectively.

Lipid Elevations

Upadacitinib treatment was associated with dose-related increases in total cholesterol, triglycerides and LDL cholesterol. Upadacitinib was also associated with increases in HDL cholesterol. Elevations in LDL and HDL cholesterol peaked by Week 8 and remained stable thereafter. In controlled studies, for up to 12/14 weeks, changes from baseline in lipid parameters in patients treated with RINVOQ 15 mg and upadacitinib 30 mg, respectively, are summarized below:

  • Mean LDL cholesterol increased by 14.81 mg/dL and 17.17 mg/dL.
  • Mean HDL cholesterol increased by 8.16 mg/dL and 9.01 mg/dL.
  • The mean LDL/HDL ratio remained stable.
  • Mean triglycerides increased by 13.55 mg/dL and 14.44 mg/dL.
Creatine Phosphokinase Elevations

In placebo-controlled studies (RA-III, RA-IV, and RA-V) with background DMARDs, for up to 12/14 weeks, dose-related increases in creatine phosphokinase (CPK) values were observed. CPK elevations > 5 x ULN were reported in 1.0%, and 0.3% of patients over 12/14 weeks in the RINVOQ 15 mg and placebo groups, respectively. Most elevations >5 x ULN were transient and did not require treatment discontinuation. In RA-III and RA-V, CPK elevations > 5 x ULN were observed in 0.3% of patients treated with placebo, 1.6% of patients treated with RINVOQ 15 mg, and none in patients treated with upadacitinib 30 mg.

Neutropenia

In placebo-controlled studies (RA-III, RA-IV, and RA-V) with background DMARDs, for up to 12/14 weeks, dose-related decreases in neutrophil counts, below 1000 cells/mm³ in at least one measurement occurred in 1.1% and <0.1% of patients in the RINVOQ 15 mg and placebo groups, respectively. In RA-III and RA-V, decreases in neutrophil counts below 1000 cells/mm³ in at least one measurement occurred in 0.3% of patients treated with placebo, 1.3% of patients treated with RINVOQ 15 mg, and 2.4% of patients treated with upadacitinib 30 mg. In clinical studies, treatment was interrupted in response to ANC less than 1000 cells/mm³.

Lymphopenia

In placebo-controlled studies (RA-III, RA-IV, and RA-V) with background DMARDs, for up to 12/14 weeks, dose-related decreases in lymphocyte counts below 500 cells/mm³ in at least one measurement occurred in 0.9% and 0.7% of patients in the RINVOQ 15 mg and placebo groups, respectively. In RA-III and RA-V, decreases in lymphocyte counts below 500 cells/mm³ in at least one measurement occurred in 0.5% of patients treated with placebo, 0.5% of patients treated with RINVOQ 15 mg, and 2.4% of patients treated with upadacitinib 30 mg.

Anemia

In placebo-controlled studies (RA-III, RA-IV, and RA-V) with background DMARDs, for up to 12/14 weeks, hemoglobin decreases below 8 g/dL in at least one measurement occurred in <0.1% of patients in both the RINVOQ 15 mg and placebo groups. In RA-III and RA-V, hemoglobin decreases below 8 g/dL in at least one measurement were observed in 0.3% of patients treated with placebo, and none in patients treated with RINVOQ 15 mg and upadacitinib 30 mg.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors

Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors (such as ketoconazole) [see CLINICAL PHARMACOLOGY]. RINVOQ should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors.

Strong CYP3A4 Inducers

Upadacitinib exposure is decreased when co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect of RINVOQ [see CLINICAL PHARMACOLOGY]. Coadministration of RINVOQ with strong CYP3A4 inducers is not recommended.

Read the entire FDA prescribing information for Rinvoq (Upadacitinib Extended-release Tablets)

&Copy; Rinvoq Patient Information is supplied by Cerner Multum, Inc. and Rinvoq Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.