RINVOQ 15 mg prolonged-release tablets

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 10.0

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

Description of changes

The SmPC has been updated to reflect the approval of atopic dermatitis (AD) indication and a new 30 mg tablet.  The SmPC has been revised as follows:

Section 1 – Name of the Medicinal Product

RINVOQ 30 mg prolonged-release tablets added

Section 2 – Qualitative and Quantitative Composition

Updated to reflect addition of  Rinvoq 30 mg prolonged release tablets to the SmPC

Section 3 - Pharmaceutical Form

Updated to reflect addition of  Rinvoq 30 mg prolonged release tablets to the SmPC

Section 4.1 - Therapeutic Indications

Updated to reflect approval of Atopic dermatitis indication:

Section 4.2 – Posology and method of administration

Updated to include dosing for adults and and adolescents (12 to 17 years) with Atopic dermatitis.

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

Sub-section: Coadministration with CYP3A4 inhibitors
The following has been added:
Upadacitinib 30 mg once daily dose is not recommended for patients receiving chronic treatment with strong CYP3A4 inhibitors.

Section 4.6 – Fertility, pregnancy and Lactation
The following has been added:

Female paediatric patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib.

Section 4.8 – Undesirable effects

The summary of safety profile has been updated.

Table 2  (Adverse reactions) has been updated.  Please refer to SmPC for full details.

Information under “Description of selected adverse reactions” has been updated; this includes a new section for Atopic dermatitis.  Please refer to SmPC for full details.

Section 5.1 Pharmacodynamic properties

“Mechanism of action” section has been updated to reflect information for atopic dermatitis.

Clinical Efficacy and Safety section updated to reflect Atopic dermatitis indication.

Section 5.2 - Pharmacokinetic properties

Special Populations:

• “Renal Impairment” and “Paediatric Population” subsections updated.

Section 5.3 – Preclinical Safety Data

• Updated to reflect Rinvoq 30mg dose – please refer to SmPC document for full details

Section 6.3 – Shelf-life

• Updated to include Rinvoq 30mg tablet presentation

Section 6.5 -  Nature and contents of container

• Updated to include Rinvoq 30mg tablet presentation

Section 8 – Marketing Authorisation Numbers

• Updated to reflect MA numbers for Rinvoq 30mg
  
  EU/1/19/1404/006

            EU/1/19/1404/007

            EU/1/19/1404/008

          EU/1/19/1404/009

Section 10 – Date of Revision of the Text

• Updated to 08/2021

Correction to file name 

No change made to actual PIL itself

Change to file name 

No change to actual SmPC itself

Correction to file name 

No change made to PIL tex

File name of previous uploaded document was incorrectly named

Section 4.4 Special warnings and Precautions for Use

• Section 4.4 has been updated with addition of the following sentence: “The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib.”

Section 10 - Date of Revision of Text

• Updated to 05/2021

Updates made to sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and section 10 due to approval of Psoriatic Arthritis and Ankylosing Sponylitis indications

Section 6.3

Shelf life of bottle presentation has changed from 2 years to 3 years
The shelf life of the  blister presentation is unchanged (still 2 years)

Section 10.0
Date of revision: 11/2020

Section 5.1

ATC code added - L04AA44

Section 9 

Date of first authoriastion  - 16 December 2019

Section 10

Date of Revision of Text:  02/2020

New Product

New product