IMFINZI 50 mg/mL concentrate for solution for infusion *

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