Section 2. What you need to know before you use Repatha

Talk to your doctor, pharmacist or nurse before using Repatha if you have:

• liver disease.,
• severe kidney problems.
   
  Date of revision of the text
  November 2019 January 2020

Deleted text with strikethrough, new text in bold

Section 4.2 Posology and method of administration

Patients with renal impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (see section 5.2)., see section 4.4 for patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²).

Section 4.4 Special Warnings and Precautions

Renal impairment

There is limited experience with Repatha in patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m²) (see section 5.2). Repatha should be used with caution in patients with severe renal impairment.

5.2 Pharmacokinetic properties

Renal impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment. Population pharmacokinetic analysis of integrated dData from the Repatha clinical trials did not reveal a difference in pharmacokinetics of evolocumab in patients with mild or moderate renal impairment relative to non-renally impaired patients. There is limited experience with Repatha in patients with severe renal impairment (see section 4.4).

In a clinical trial of 18 patients with either normal renal function (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m², n = 6), severe renal impairment (eGFR 15 to 29 mL/min/1.73 m², n = 6), or end-stage renal disease (ESRD) receiving haemodialysis (n = 6), exposure to unbound evolocumab as assessed by C_max after a single 140 mg subcutaneous dose was decreased by 30% in patients with severe renal impairment and by 45% in patients with ESRD receiving haemodialysis.  Exposure as assessed by AUC_last was decreased by approximately 24% in patients with severe renal impairment and by approximately 45% in patients with ESRD receiving haemodialysis. The exact mechanism of PK differences is unknown; however, differences in body weight could not explain these differences. Some factors including small sample size and large inter-subject variability should be considered when interpreting the results.  The pharmacodynamics and safety of evolocumab in patients with severe renal impairment and ESRD were similar to patients with normal renal function, and there were no clinically meaningful differences in LDL-C lowering.  Therefore, no dose adjustments are necessary in patients with severe renal impairment or ESRD receiving haemodialysis.

Section 10 Date of revision of the text

November 2019 January 2020

Section 4.8 Undesirable Effects - Addition of hypersensitivity as a common Adverse Event

Section 10 Date of revision of the text - Updated to November 2019

Section 4 Side Effects - Updated to state “Allergic reactions including rash” as a common side effect

Date of revision of the text - Updated to November 2019

Section 2 What you need to know before you use Repatha

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.i.e. it is essentially ‘sodium- free’ and should not affect a sodium-controlled diet.

Section 4 Side Effects

Flu like symptoms

Date of revision of the text

September 2019

Section 4.8 Undesirable Effects

Additon of Influenza-like illness as an uncommon adverse reaction

Section 10 Date of revision of teh text

September 2019

Section 5.1 Pharmacodynamic properties - update to information relating to the OSLER trials

Section 10 Date of revision of the text - July 2019

5.1     Pharmacodynamic properties

Information relating to the TAUSSIG trial has been updated.

Information in Tables 5 and 7 relating to the TAUSSIG trial has been updated.

10.     DATE OF REVISION OF THE TEXT

 Date of revision has been updated to June 2019

Addition of new indication "Established atherosclerotic cardiovascular disease" and subsequently changes made to sections 4.2, 5.1 and 5.2

Changes to section 4.4 regarding patients with renal impairment

Changes to section 4.8 injection site reactions

4.1 Therapeutic indications

Addition of new indication Established atherosclerotic cardiovascular disease

 4.2 Posology and method of administration

Update to the posology sub-section with information on Established atherosclerotic cardiovascular disease in adults

4.4 Special Warnings and Precautions

Update to the renal impairment sub-section

4.8 Undesirable Effects

Update to the Summary of the safety profile, Injection site reactions, Elderly population and Immunogenicity sub-sections

5.1 Pharmacodynamic properties

Update to the Clinical efficacy in primary hypercholesterolaemia and mixed dyslipidaemia sub-section

New information - Effect on atherosclerotic disease burden & Cardiovascular risk reduction in adults with established atherosclerotic cardiovascular disease

Section 5.2 Pharmacokinetic properties

Update to sub section renal impairment

10 Date of revision of the text

May 2018

The shelf life of the Repatha^® pre-filled syringe and the Repatha^® pre-filled pen (SureClick^®) has been extended to 3 years. 

Please note that the Repatha^® pre-filled syringe is not marketed in Ireland

Section 6.3 Shelf life

Repatha 140 mg solution for injection in pre-filled syringe
3 years.

Repatha 140 mg solution for injection in pre-filled pen
3 years.

Repatha 420 mg solution for injection in cartridge
2 years.

Section 10. DATE OF REVISION OF THE TEXT

Updated to March 2018

The Repatha Summary of Product Characteristics has been updated to now incorporate three presentations:

1)         Solution for injection in pre-filled syringe

2)         Solution for injection in pre-filled pen (SureClick)

3)         Solution for injection in cartridge (automated mini-doser)

Please note that the Repatha solution for injection in pre-filled syringe and cartridge (automated mini-doser) are not available in Ireland.

The following sections of the SmPC have been updated:

Section 6.4 Special precautions for storage:

Previous text:

If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 week.

New text:

If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 month.

10.    DATE OF REVISION OF THE TEXT

Previous text:

July 2015

New text:

September 2016