PIL updated following approval of variation to include new indication for Muscle Invasive Bladder Cancer, based on NIAGARA study and to align with updates made to SmPC.

Updates to SmPC are based on approval of variation to include information from NIAGARA study.

4.1 Therapeutic indication:

Muscle Invasive Bladder Cancer (MIBC)

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by IMFINZI as monotherapy adjuvant treatment after radical cystectomy, is indicated for the treatment of adults with resectable muscle invasive bladder cancer (MIBC).

4.2 Posology and method of administration

Addition of dosing for patients with MIBC in Table 1

4.8 Undesirable effects

Update to the IMFINZI + Chemotherapy pooled safety data to include the “IMFINZI + Chemotherapy” ADR data reported in the NIAGARA Study.

Update to Table 3 to revise ADR list for IMFINZI in combination with chemotherapy column as per revised pooled safety data (N=1769)

Update to the laboratory abnormalities section to reflect the revised incidence rates for IMFINZI in combination with chemotherapy, based on the updated data from the NIAGARA Study

5.1 Pharmacodynamic properties

Update to add a clinical study description of the NIAGARA study and include the study data.

Updates also include changes made to Malta reporting website details according to new Annex V , revision date.

Changes to section 1 and 4 of Package leaflet to align with SmPC updates after approval of a Non-Small Cell Lung Cancer indication based on AEGEAN study.

Updates made include:

4.1 Therapeutic indications

Inclusion of new indication for Non-Small Cell Lung Cancer based on the AEGEAN Study:

IMFINZI in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by IMFINZI as monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements (for selection criteria, see section 5.1).

4.2 Posology and method of administration

Addition of dosing for patients with Resectable NSCLC to Table 1.

4.4 Special warnings and precautions for use

Update to the section “Pneumonitis and radiation Pneumonitis”, to include data from the AEGEAN Study.

4.8 Undesirable effects

Update to the IMFINZI + Chemotherapy pooled safety data to include the “IMFINZ I+ Chemotherapy” ADR data reported in the AEGEAN Study.

Update to Table 3 to revise ADR list for IMFINZI in combination with chemotherapy column as per revised pooled safety data (N=1239)

Update to the laboratory abnormalities section to reflect the revised incidence rates for IMFINZI in combination with chemotherapy, based on the updated data from the AEGEAN Study.

Update to include elderly data from the AEGEAN Study.

5.1 Pharmacodynamic properties

Update to add a clinical study description of the AEGEAN study and include the study data.

The updates follow the approval of new indication based on the ADRIATIC study:

Section 4.1 Therapeutic indications

Inclusion of new indication based on the ADRIATIC Study:

IMFINZI as monotherapy is indicated for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy.

4.2 Posology and method of administration

Addition of dosing for patients with LS-SCLC to Table 1.

4.4 Special warnings and precautions for use

Update to the section “Pneumonitis or Radiation Pneumonitis”, to include data from the ADRIATIC Study

4.8 Undesirable effects

• Update to the ADR safety summary and Table 3 for the IMFINZI monotherapy pool safety data (N=4642)
• Update to the “Description of Selected ADRs” section to reflect the IMFINZI monotherapy pool safety data (N=4642)

Update to the section “Immune-mediate pneumonitis”, to include data from the ADRIATIC Study

5.1 Pharmacodynamic properties

Update to add a clinical study description of the ADRIATIC study and include the study data.

Updates to PIL to align with changes to new indication based on Adriatic study.

This revision was based on the PRAC Recommendation for inclusion of Polymyalgia Rheumatica information in the PIL.

This update is based on PRAC recommendation for inclusion of Polymyalgia Rheumatica information in the SmPC.

Update to SmPC after approval of DUO-E study indications.

4.1 Therapeutic indications: Inclusion of new indication

4.2 Posology and method of administration: inclusion of requirement for NMR testing for patients with endometrial cancer. Addition of dosing for endometrial cancer in Table 1. Inclusion of PRCA in Table 2.

4.4 Special warnings and precautions for use: Inclusion of treatment specific precaution for IMFINZI in combination with olaparib in endometrial cancer

4.8 Undesirable effects: Update to Imfinzi + Chemotherapy pooled safety date, Inclusion of ADR safety summary and new column in Table 3, Inclusion of paragraph for incidence of immune pneumonitis and immune mediated rash

observed in patients in the DUO-E study. Inclusion of a paragraph for the incidence of Immune mediated rash observed in patients in the DUO-E study. Inclusion of the incidence of laboratory abnormalities

observed in in patients in the DUO-E study.

5.1 Pharmacodynamic Properties: Update to add a clinical study description of the DUOE study and include the study data data, including sub-sections for dMMR and pMMR data (aligned with the indication).

Date of revision of text updated.

PIL updated after approval of DUO-E study. indication.

Alignment of Section 1, 2, 3 and 4 with the SmPC (inclusion of information for the DUO-E study).

Section 4 has also been revised to list only additional side effects (to those reported when receiving IMFINZI alone), reported in the combination regimen datasets.

Update to section 4: Possible side effects

-Clinical studies with patients receiving IMFINZI alone, in combination with chemotherapy and in combination with tremelimumab and platinum-based chemotherapy.

• Inclusion of text to Rare side effects: coeliac disease (characterized by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
• Inclusion of text to side effects not known: lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency)

-Removal of NI details for AE reporting and local representative

Updates to section 4.8

• Table 3 and 4: Insertion of Coeliac disease as Rare Gastrointestinal adverse drug reactions
• Insertion of text related to Immune Checkpoint inhibitor class effects :There have been cases of the following adverse reactions reported during treatment with other immune checkpoint inhibitors which might also occur during treatment with durvalumab: pancreatic exocrine insufficiency.

Updates to remove NI details from adverse event reporting and

The SPC is updated to include information related to Corticosteroid and Rhabdomyolysis Updates.

Summary of Information – Corticosteroid Update

Section 4.2:

Included clarifying edits within Table 1 footnotes (i.e., references to prescribing information of specific combination therapies when used with IMFINZI/Tremelimumab, timing or method of administration).

Removal of Corticosteroid treatment column in Table 2 and updated footnotes

Section 4.4:

Relocated Corticosteroid treatment information from Table 2 within respective adverse reaction subsections.

Summary of Information – Rhabdomyolysis Update

Section 4.2:

Rhabdomyolysis term added to current myositis/polymyositis row in Table 2.

Section 4.4:

Within “Other Immune Mediated Adverse Reactions”, added rhabdomyolysis to current paragraph that already included myositis/polymyositis.

Section 4.8:

A footnote was added to myositis/polymyositis preferred term row in Table 3 and Table 4; includes rhabdomyolysis 

Other updates

Removal of United Kingdom (NI) Reporting details.

Date of revision of text: 16 February 2024 30 30 May 2024

Re-upload of SmPC uploaded on 2nd Jan 2024, no changes

4.2 Posology and method of administration

• Update to the “Paediatric” section to confirm that there is no paediatric data available for the approved indications. A brief description of the D419EC00001 study population is included along with confirmation that benefit/risk has not been established. A reference is included to the available data in Sections 5.1 and 5.2. 

5.1 Pharmacodynamic properties

• Update to add a “Paediatric” sub-section describing study D419EC00001, including the number of patients enrolled, primary tumour categories, primary objectives and dose received. Statements confirming that the safety and efficacy in this population has not been established are included.

5.2 Pharmacokinetic properties

• Update to add a “Paediatric” sub-section describing study D419EC00001, including number of patients enrolled, dose received and exposure.

4.       CLINICAL PARTICULARS

4.1        Therapeutic indications

[…]

IMFINZI as monotherapy is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).

[…]

4.2        Posology and method of administration

Update to  Table 1. Recommended dose of IMFINZI monotherapy and combination therapy  

[…]

4.8     Undesirable effects

Update to Summary of the safety profile

Update to Tabulated list of adverse reactions

Update to Table 3. Adverse drug reactions in patients treated with IMFINZI

Frequency category for Myocarditis updated from Rare to Uncommon.

Frequency category for Hepatitis updated from Uncommon to Common.

Frequency category for Pemphigoid updated from Rare to Uncommon

[…]

Description of selected adverse reactions updated throughout.

Immunogenicity updated

Elderly updated to include HIMALAYA study

5.       PHARMACOLOGICAL PROPERTIES

5.1        Pharmacodynamic properties

[…]

HCC - HIMALAYA Study updated throughout

[…]

10.     DATE OF REVISION OF THE TEXT

23 June 2023 15 November 2023

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

ONC 23 0025 ONC 23 0044

[…]

1.           What IMFINZI is and what it is used for

[…]

IMFINZI is used alone or in combination with tremelimumab is used to treat a type of liver cancer called advanced or unresectable hepatocellular carcinoma (HCC) in adults. It is used when your HCC:

·            cannot be removed by surgery (unresectable), and

·            may have spread within your liver or to other parts of the body.

[…]

4.       Possible side effects

[…]

Frequency category for ‘inflammation of the liver that can cause nausea or feeling less hungry (hepatitis)’ updated from Uncommon to Common.

Frequency category for ‘inflammation of the heart (myocarditis)’ updated from Rare to Uncommon.

[…]

6.           Contents of the pack and other information

[…]

This leaflet was last revised in 06/202311/2023

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu

ONC 23 0024ONC 23 0043

[…]

6.      Contents of the pack and other information

[...]

Manufacturer

AstraZeneca AB

Gärtunavägen

SE‑151 85152 57 Södertälje

[...]

This leaflet was last revised in 0406/2023.

Addition of date of renewal to section 9

Removal of the black triangle symbol and editorial changes throughout the SPC following approval of the license renewal.

Removal of the black triangle symbol and editorial updates included throughout the text following the approval of the renewal procedure

Update to the product information following the approval of two new indications and a type II variation to update section 4.2 (Table 2).

Update to the product information following the approval of two new indications.

Update to the product information following the approval of a new indication;

IMFINZI is used to treat a type of cancer of the bile ducts (cholangiocarcinoma) and gallbladder that are collectively referred to as biliary tract cancers (BTC). It is used when your BTC:

•  has spread within your bile ducts and gallbladder (or to other parts of the body).

Update to the product information following the approval of a new indication

IMFINZI in combination with gemcitabine and cisplatin is indicated for the first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC)

Update to section 4.2, 4.4 and 4.8 of the SmPC to include Myelitis Transverse as an immune-mediated adverse reaction.

2.      What you need to know before you are given IMFINZI 

[...]

Warnings and precautions 

[...]

If you have any of the following, call or see your doctor straight away. Your doctor may give you other medicines that prevent more severe complications and to help reduce your symptoms. Your doctor may delay the next dose of IMFINZI or stop your treatment with IMFINZI, if you have:

[...]

·           inflammation of the spinal cord (transverse myelitis): symptoms may include pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems including needing to urinate more frequently, urinary incontinence, difficulty urinating and constipation;

[...]

6.      Contents of the pack and other information

[...]

This leaflet was last revised in 0811/2022.

Minor administrative amendment:

5.      PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

[...]

The OS results with the planned long-term OS follow-up analysis (DCO: 22 March 2021) (median follow-up: 39.3 months) are presented in Table 5. IMFINZI + etoposide + platinum (Arm 2) vs. etoposide + platinum (Arm 3) continued to demonstrate sustained improvement in OS. Kaplan-Meier curve for OS is presented in Figure 7.

Minor administrative errors amended in section 5.1, table 5.

Summary of Revisions:

Update to the CASPIAN Study Data to include the long-term follow-up OS analysis from data cut-off 22 March 2021. OS data is added to the Efficacy table and also updated into the KM Curve.

Update to section 4.8 Undesirable effects, Table 3, Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

Addition of Psoriasis as an uncommon ADR

10.    DATE OF REVISION OF THE TEXT

23^rd June22^nd August 2022

4.      Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

When you get IMFINZI, you can have some serious side effects (see section 2).

Talk to your doctor straight away if you get any of the following side effects, that have been reported in clinical trials with patients receiving IMFINZI alone and includes the serious side effects listed in section 2:

[...]

Uncommon (may affect up to 1 in 100 people)

·  inflammation of thyroid gland

·  decreased secretion of hormones produced by the adrenal glands that can cause tiredness

·  scarring of lung tissue

·  inflammation of the liver that can cause nausea or feeling less hungry

·  blistering of the skin

·  inflammation of the gut or intestine (colitis)

·  inflammation of the muscle

·  inflammation of the kidneys (nephritis) that can decrease the amount of your urine

·  inflammation of the pancreas

·  red, itchy, dry, scaly patches of thickened skin (psoriasis)

[...]

The following side effects have been reported in clinical trials in patients taking IMFINZI in combination with chemotherapy: 

[...]

Uncommon (may affect up to 1 in 100 people)

·  fungal infection in the mouth

·  flu-like illness

·  type 1 diabetes mellitus

·  hoarse voice (dysphonia)

·  scarring of lung tissue

·  inflammation of the gut or intestine (colitis)

·  night sweats

·  red, itchy, dry, scaly patches of thickened skin (psoriasis)

6.      Contents of the pack and other information

[...]

This leaflet was last revised in 0308/2022.

Update to the SmPC in order to reflect the change from a manual to programmatic process for characterizing immune-mediated Adverse Event (imAE) rates.

SmPC Section Change

4.2 Posology and method of administration

Update to Table 2 to the management recommendations for immune-mediated myocarditis

4.4 Special warnings and precautions for use

Inclusion of a separate paragraph for immune-mediated myocarditis (and removal from the section of general other immune-mediated adverse reactions)

4.8 Undesirable effects

Update to Table 3 to list the event terms of immune-mediated encephalitis and autoimmune encephalitis as a revision to the footnote “l”

4.8     Undesirable effects

[...]

Table 3. Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies. ATC code: L01XC28PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors. ATC code: L01FF03

10.     DATE OF REVISION OF THE TEXT

28^th February21^st March 2022

4.       Possible side effects

[...]

Very common (may affect more than 1 in 10 people)

• infections of the upper respiratory tract
• underactive thyroid gland that can cause tiredness or weight gain
• cough
• diarrhoea
• stomach pain
• skin rash or itchiness
• fever
• joint pain (arthralgia)

[...]

Common (may affect up to 1 in 10 people)

• diarrhoea
• fever
• low number of white blood cells with signs of fever
• skin rash or itchiness
• underactive thyroid gland; overactive thyroid gland; inflammation of thyroid gland
• serious lung infections (pneumonia)
• tooth and mouth soft tissue infections
• abnormal liver tests (aspartate aminotransferase increased; alanine aminotransferase increased)
• swelling of legs (oedema peripheral)
• stomach pain
• inflammation of the mouth or lips
• muscle pain (myalgia)
• inflammation of the lungs (pneumonitis)
• infection of the upper respiratory tract
• low number of red blood cells, white blood cells, and platelets (Pancytopenia)
• decreased secretion of hormones produced by the adrenal glands that can cause tiredness
• inflammation of the liver that can cause nausea or feeling less hungry
• abnormal kidney function tests (blood creatinine increased)
• painful urination
• reaction to the infusion of the medicine that can cause fever or flushing
• joint pain (arthralgia)

6.       Contents of the pack and other information

[...]

This leaflet was last revised in 0203/2022.

4.4     Special warnings and precautions for use

[...]

Other immune-mediated adverse reactions

Given the mechanism of action of IMFINZI, other potential immune‑mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy: myasthenia gravis, myocarditis, myositis, polymyositis, meningitis, encephalitis, Guillain-Barré syndrome, immune thrombocytopenia and, cystitis noninfective and pancreatitis (see section 4.8). Events of pancreatitis have been reported in patients in the clinical study programme. Patients should be monitored for signs and symptoms and managed as recommended for other immune-mediated adverse reactions, in section 4.2.

4.8     Undesirable effects

[...]

Table 3. Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

10.     DATE OF REVISION OF THE TEXT

17^th28^th February 2022

2.       What you need to know before you are given IMFINZI

[...]

If you have any of the following, call or see your doctor straight away. Your doctor may give you other medicines that prevent more severe complications and to help reduce your symptoms. Your doctor may delay the next dose of IMFINZI or stop your treatment with IMFINZI, if you have:

[...]

• inflammation of glands (especially the thyroid, adrenal, pituitary and pancreas): symptoms may include fast heart rate, extreme tiredness, weight gain or weight loss, dizziness or fainting, hair loss, feeling cold, constipation, headaches that will not go away or unusual headaches, abdominal pain, nausea and vomiting;

[...]

4.       Possible side effects

[...]

Uncommon (may affect up to 1 in 100 people)

• inflammation of thyroid gland
• decreased secretion of hormones produced by the adrenal glands that can cause tiredness
• scarring of lung tissue
• inflammation of the liver that can cause nausea or feeling less hungry
• blistering of the skin
• inflammation of the gut or intestine (colitis)
• inflammation of the muscle
• inflammation of the kidneys (nephritis) that can decrease the amount of your urine
• inflammation of the pancreas

6.       Contents of the pack and other information

[...]

This leaflet was last revised in 10/202102/2022.

Addition of  PACIFIC 5 year follow up Overall Survival (OS) data in Section 5.1 of the SmPC.

10.     DATE OF REVISION OF THE TEXT

19^th October 2021

17^th February 2022

This approval includes the following significant changes:

Section 4.2 Posology and method of administration

Table 2 was revised to align with updated clinical practice, National Comprehensive Cancer Network (NCCN) guidelines and competitor information.

Section 4.4 Special warnings and precautions for use

Imposition by EMA to add additional language that Diabetic ketoacidosis can be the debut-symptom of diabetes without any preceding diagnosis, history, signs or symptoms of diabetes and that fatal cases have been registered.

4.8 Undesirable effects

Addition of footnote ‘^c including fatal outcome’ below the ADR’s table 3

2.       What you need to know before you are given IMFINZI

[...]

If you have any of the following, call or see your doctor straight away. Your doctor may give you other medicines that prevent more severe complications and to help reduce your symptoms. Your doctor may delay the next dose of IMFINZI or stop your treatment with IMFINZI, if you have:

[...]

• type 1 diabetes: symptoms may include high blood sugar, feeling more hungry or thirsty than usual, passing urine more often than usual, fast and deep breathing, confusion, or a sweet smell to your breath, a sweet or metallic taste in your mouth or a different odour to your urine or sweat;

[...]

6.       Contents of the pack and other information

United Kingdom (Northern Ireland)

AstraZeneca UK Ltd

Tel: +44 1582 836 836

This leaflet was last revised 0910/2021.

4.4     Special warnings and precautions for use

[..]

Other immune-mediated adverse reactions

Given the mechanism of action of IMFINZI, other potential immune‑mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy: myasthenia gravis, myocarditis, myositis, polymyositis, meningitis, encephalitis, Guillain-Barré syndrome and, immune thrombocytopenia. and cystitis noninfective (see section 4.8). Events of pancreatitis have been reported in patients in the clinical study programme.

[..]

4.8     Undesirable effects

Addition of cystitis noninfective to table 3. Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

10.     DATE OF REVISION OF THE TEXT

7th July4^th September 2021

4.       Possible side effects

[..]

Rare (may affect up to 1 in 1000 people)

• a condition leading to high blood sugar levels (type 1 diabetes mellitus)
• underactive function of pituitary gland (hypopituitarism including diabetes insipidus) that can cause tiredness, an increase in the amount of your urine
• inflammation of the heart
• a condition in which the muscles become weak and there is a rapid fatigue of the muscles (myasthenia gravis)
• inflammation of the membrane around the spinal cord and brain (meningitis)
• low number of platelets caused by an immune reaction (immune thrombocytopenia)
• Inflammation of the bladder. Signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen.

6.       Contents of the pack and other information

[..]

This leaflet was last revised in 0709/2021.

(Inserted text/ Deleted text)

4.8     Undesirable effects

[...]

Reporting of suspected adverse reactions

[...]

United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

6.3     Shelf life

Unopened vial

3 years.

Diluted solution

If not used immediately, cChemical and physical in-use stability of IMFINZI has been demonstrated for up to 30 daysno more than 24 hours at 2°C to 8°C and for up toor 2412 hours at room temperature (up to 25°C) from the time of preparationvial puncture to the start of administration.

From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C or 12 hours at room temperature (up to 25°C), unless dilution has taken place in controlled and validated aseptic conditions.

10.     DATE OF REVISION OF THE TEXT

11^th February7th July 2021

(Inserted text, Deleted Text)

4.       Possible side effects

[...]

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

[...]

United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

6.       Contents of the pack and other information

[...]

United Kingdom

AstraZeneca UK Ltd

Tel: +44 1582 836 836

This leaflet was last revised in 12/2020.07/2021.

(Inserted Text; Deleted Text)

4.2     Posology and method of administration

...

Table 1. Recommended Dose of IMFINZI

^a Patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to IMFINZI 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 30 kg.

 ^bIt is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

^c Patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to IMFINZI 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 30 kg.

^d Administer IMFINZI prior to chemotherapy on the same day.

^e  When IMFINZI is administered in combination with chemotherapy, refer to the Prescribing Information for etoposide and carboplatin or cisplatin for dosing information.

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

Clinical efficacy and safety

Durvalumab doses of 10 mg/kg every 2 weeks or 1500 mg every 4 weeks were evaluated in NSCLC and ES-SCLC clinical studies. Based on the modeling and simulation of exposure, exposure-safety relationships and exposure-efficacy data comparisons, there are no anticipated clinically significant differences in efficacy and safety between durvalumab doses of 10 mg/kg every 2 weeks or 1500 mg every 4 weeks.

10.     DATE OF REVISION OF THE TEXT

11^th January 2021 10 December 2020

2. What you need to know before you are given IMFINZI

Warnings and Precautions

• low number of platelets: symptoms may include bleeding (nose or gum bleeding) and/or bruising.

4. Possible side effects

Aligned with the SmPC; meningitis was omitted from a previous PRAC imposition (EMEA/H/C/PSUSA/00010723/201910).

Rare (may affect up to 1 in 1000 people)

• • inflammation of the membrane around the spinal cord and brain (meningitis)

low number of platelets caused by an immune reaction (immune thrombocytopenia)

This leaflet was last revised in 0812/2020.

Section 4.4  Special warnings and precautions for use

Other immune-mediated adverse reactions

Given the mechanism of action of IMFINZI, other potential immune‑mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy: myasthenia gravis, myocarditis, myositis, polymyositis, meningitis, encephalitis, and Guillain-Barré syndrome and immune thrombocytopenia. Events of pancreatitis have been reported in patients in the clinical study programme. Patients should be monitored for signs and symptoms and managed as recommended for other immune-mediated adverse reactions, in section 4.2

Section 4.8 Undesirable effects

Table 3. Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

10.     DATE OF REVISION OF THE TEXT

27 Aug 2020

10 December 2020

Section 4.4  Special warnings and precautions for use

Other immune-mediated adverse reactions

Given the mechanism of action of IMFINZI, other potential immune‑mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy: myasthenia gravis, myocarditis, myositis, polymyositis, meningitis, encephalitis, and Guillain-Barré syndrome and immune thrombocytopenia. Events of pancreatitis have been reported in patients in the clinical study programme. Patients should be monitored for signs and symptoms and managed as recommended for other immune-mediated adverse reactions, in section 4.2

Section 4.8 Undesirable effects

Table 3. Adverse drug reactions in patients treated with IMFINZI monotherapy and IMFINZI in combination with chemotherapy

10.     DATE OF REVISION OF THE TEXT

27 August 2020

10 December 2020

Updates to section 4.4, sub-section Other immune-mediated adverse reactions, to include information on encephalitis, meningitis and Guillain-Barre syndrome

Updates made to table 2 in section 4.8 (addition of noninfective encephalitis, meningitis and Guillain-Barre syndrome)

Date of revision of the text updated to 27th July 2020

Green = added text

2. What you need to know before you are given IMFINZI

Warnings and precautions

....

If you have any of the following, call or see your doctor straight away. Your doctor may give you other medicines that prevent more severe complications and to help reduce your symptoms. Your doctor may delay the next dose of IMFINZI or stop your treatment with IMFINZI, if you have:

....

• inflammation of the brain (encephalitis) or inflammation of the membrane around the spinal cord and brain (meningitis): symptoms may include seizures, neck stiffness, headache, fever, chills, vomiting, eye sensitivity to light, confusion and sleepiness.
• inflammation of the nerves: symptoms may include pain, weakness, and paralysis in the extremities (Guillain-Barré syndrome)

....

Date of revision updated to July 2020

New text: Green

Deleted text: Red strikethrough

4.2 Posology and method of administration

Editorial change in Table 1. Recommended treatment modifications for IMFINZI and management recommendations

4.4 Special warnings and precautions for use

Patients should be monitored for signs and symptoms of pneumonitis or radiation pneumonitis. Patients with sSuspected pneumonitis should be evaluatedconfirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in section 4.2.

10. DATE OF REVISION OF THE TEXT

21 February 202016 April 2020

Update to text with information on 'pemphigoid' as an adverse drug reaction

Addition of 'blistering of the skin' as an uncommon side effect

Change to include Myasthenia gravis as a possible side effect

Update to include side effect of Myasthenia gravis