RINVOQ 30 mg prolonged-release tablets

Section 4.4

The following has been added:

Medication Residue in Stool

Reports of medication residue in stool or ostomy output have occurred in patients taking upadacitinib. Most reports described anatomic (e.g., ileostomy, colostomy, intestinal resection) or functional gastrointestinal conditions with shortened gastrointestinal transit times. Patients should be instructed to contact their healthcare professional if medication residue is observed repeatedly. Patients should be clinically monitored, and alternative treatment should be considered if there is an inadequate therapeutic response.

Section 10

Date of revision of text updated to 12/2024

Section 4.2

 Change to posology for Atopic Dermatitis, which now reads as follows:

Atopic dermatitis

·      The recommended dose of upadacitinib is 15 mg or 30 mg once daily based on individual patient presentation.

·      A dose of 15 mg is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy (see section 4.4).

·      A dose of 30 mg once daily may be appropriate for patients with high disease burden who are not at higher risk of VTE, MACE and malignancy (see section 4.4) or patients with an inadequate response to 15 mg once daily.

·      In adolescents (12 to 17 years of age) weighing at least 30 kg, a dose of 15 mg is recommended. If the patient does not respond adequately to 15 mg once daily, the dose can be increased to 30 mg once daily.

·      The lowest effective dose to maintain response should be used.

·      For patients 65 years of age and older, the recommended dose is 15 mg once daily (see section 4.4).

Section 4.8

Skin papilloma was added as an adverse drug reaction in the paediatric population sub-section

Section 5.1

Updated to include 30mg adolescent data.

Section 10

Date of revision of text updated to 10/2024

Removal of Black Inverted Triangle statement.

Minor editorial changes to sections 4.2, 4.4, 4.5, 4.6 and 48

The following additional updates were:

Section 4.8

Table 3

"In ulcerative colitis trials, the frequency was common for acne; abdominal pain was less frequent for upadacitinib than for placebo."

amended to:

"In ulcerative colitis trials, the frequency was common for acne."

Hepatic transaminase elevations

"Most cases of hepatic transaminase elevations were asymptomatic and transient."

amended to:

Of the 22 cases of hepatic transaminase elevations, most were asymptomatic and transient.

Section 5.2

Under "Paediatric poulation", the following has been added:

"No clinical exposure data are available in adolescents < 40 kg."

Section 5.1:

Update to ATC code which now reads:Pharmacotherapeutic group: Immunosuppressants, Janus-associated kinase (JAK) inhibitors ATC code: L04AF03

Inclusion of long-term efficacy and safety data in patients with Non-radiographic axial spondyloarthritis and Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)

Section 4.7:

Updated to read:

Upadacitinib may have a minor influence on the ability to drive and use machines because dizziness and vertigo may occur during treatment with RINVOQ (see section 4.8).

Section 4.8

The following adverse reactions have been added to Table 3 (frequency: common):

Dizziness

Vertigo

Section 10

Revision date updated to 05/2024

Section 4.4

The following text has been added:

Hypoglycaemia in patients treated for diabetes

There have been reports of hypoglycaemia following initiation of JAK inhibitors, including upadacitinib, in patients receiving medication for diabetes. Dose adjustment of anti-diabetic medication may be necessary in the event that hypoglycaemia occurs.

Section 4.1

• The following indication has been added:

Crohn’s disease

 RINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Section 4.2

• Dosing information updated to reflect Crohn's disease indication.

Section 4.4

• Information added regarding gastrointestinal perforation

Section 4.5

• The paragraph relating to "Coadministration with CYP3A4 inhibitors" has been updated to include patients with Crohn's disease.

Section 4.8

• Updated to include the most commonly reported adverse reactions in placebo-controlled Crohn's disease induction and maintenance clinical trials.
• Table 3 - Adverse reactions table has been updated as follows:
• Frequency of pneumonia changed from Uncommon to Common
• Gastrointestinal perforation added as an uncommon adverse reaction
• Section added regarding safety information in patients with Crohn's disease (serious infections, gastrointestinal perforation, laboratory abnormalities)

Section 5.1

• Mechanism of action paragraph: ulcerative colitis amended to inflammatory bowel disease.
• Section added regarding clinical efficacy and safety for Crohn's disease indication

Section 5.2

• Minor editorial changes to "Renal impairment" section
• Crohn's disease added to Paediatric population section

Section 5.3

• Updates made to clinical exposure dosing information

Section 10.0

• Date of revision of text updated to 04/2023

Section 4.2

Atopic dermatitis and Ulcerative colitis sections updated.

Section 4.4

The following warning has been added

"Upadacitinib should only be used if no suitable treatment alternatives are available in patients:

65 years of age and older;

patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers);

patients with malignancy risk factors (e.g. current malignancy or history of malignancy)"

Section added regarding use in patients 65 years of age and older

Serious infections section updated.

Malignancy and non-melanoma skin cancer section updated.

Section on Major Adverse cardiovascular events (MACE) added

Venous thromboembolism section updated.

Section 4.8

Non-melanoma skin cancer added as a common Adverse reaction.

Sepsis added an Uncommon adverse reaction.

Section 4.4

The following has been added:

Hypersensitivity reactions

Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving upadacitinib. If a clinically significant hypersensitivity reaction occurs, discontinue upadacitinib and institute appropriate therapy (see sections 4.3 and 4.8).

Section 4.8

Table 3 Adverse Reactions

Urticaria moved to Immune System Disorders (System Organ Class)

Serious hypersensitivity reactions added as an uncommon side effect

Section 10

Date of revision of text updated to 11/2022

Section 4.8

• "Neutropaenia (2.8%) added to the list of the most commonly reported adverse reactions in the placebo-controlled clinical trials for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Section 5.1

• Updated to include 2 year data for bDMARD-inadequate responders & bDMARD-naïve patients (ankylosing spondylitis (AS) indication)

Section 4.5 - Interaction with other medicinal products and other forms of interaction

• Inclusion of grapefruit as a strong CYP3A4 inhibitor

Section 10 - Date of Revision of the Text

• Updated to 06/2022

Summary of changes

Section 4.8

Table 2. Adverse reactions - urinary tract infection added as a common AE

Section 10

Date of revision updated to 05/2022

Section 5.1 (pharmacodynamic properties) of the SmPC updated to include long-term rheumatoid arthritis data , including clinical response, physical function, and health-related outcome measures through Week 156 (3 years) and radiographic response data through Week 96 (2 years) from the SELECT-Compare and SELECT-Early studies

Section 4.4

Updated to include the following:

Diverticulitis

Events of diverticulitis have been reported in clinical trials and from post‑marketing sources. Diverticulitis may cause gastrointestinal perforation. Upadacitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medications associated with an increased risk of diverticulitis: nonsteroidal anti‑inflammatory drugs, corticosteroids, and opioids. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis to prevent gastrointestinal perforation.

Section 4.8

The following has been added as an Uncommon adverse reaction:

Diverticulitis

Section 10

Date of revision of text updated to 12/2021

4.4     Special warnings and precautions for use

..........................................................

Vaccination

No data are available on the response to vaccination with live or inactivated vaccines in patients receiving upadacitinib. Use of live, attenuated vaccines during or immediately prior to upadacitinib therapy is not recommended. Prior to initiating upadacitinib, it is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations, in agreement with current immunisation guidelines. (see section 5.1 for data on inactivated pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) and concomitant use with upadacitinib).

5.1     Pharmacodynamic properties

.................................................................................

hsCRP

In patients with rheumatoid arthritis, treatment with upadacitinib was associated with decreases from baseline in mean hsCRP levels as early as week 1 which were maintained with continued treatment.

Vaccine study

The influence of upadacitinib on the humoral response following the administration of inactivated pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) was evaluated in 111 patients with rheumatoid arthritis under stable treatment with upadacitinib 15 mg (n=87) or 30 mg (n=24). 97% of patients (n=108) were on concomitant methotrexate. The primary endpoint was the proportion of patients with satisfactory humoral response defined as ≥ 2-fold increase in antibody concentration from baseline to Week 4 in at least 6 out of the 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). Results at Week 4 demonstrated a satisfactory humoral response in 67.5% (95% CI: 57.4, 77.5) and 56.5% (95% CI: 36.3, 76.8) of patients treated with upadacitinib 15 mg and 30 mg, respectively.

10.     DATE OF REVISION OF THE TEXT

09/2021