Repatha

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection in pre-filled syringe 
Repatha 140 mg solution for injection in pre-filled pen 
Repatha 420 mg solution for injection in cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Repatha 140 mg solution for injection in pre-filled syringe 
 
Each pre-filled syringe contains 140 mg of evolocumab in 1 mL of solution. 
 
Repatha 140 mg solution for injection in pre-filled pen 
 
Each pre-filled pen contains 140 mg of evolocumab in 1 mL of solution. 
 
Repatha 420 mg solution for injection in cartridge 
 
Each cartridge contains 420 mg of evolocumab in 3.5 mL of solution (120 mg/mL). 
 
Repatha is a human IgG2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells by 
recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
Solution for injection (injection) in pre-filled pen (SureClick). 
Solution for injection (injection) (automated mini-doser). 
 
The solution is clear to opalescent, colourless to yellowish, and practically free from particles. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Hypercholesterolaemia and mixed dyslipidaemia 
 
Repatha is indicated in adults with primary hypercholesterolaemia (heterozygous familial and 
non-familial) or mixed dyslipidaemia, as an adjunct to diet: 
 in combination with a statin or statin with other lipid-lowering therapies in patients unable to 

reach LDL-C goals with the maximum tolerated dose of a statin or, 
 alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, 

or for whom a statin is contraindicated. 
 
Homozygous familial hypercholesterolaemia 
 
Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial 
hypercholesterolaemia in combination with other lipid-lowering therapies. 
 



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Established atherosclerotic cardiovascular disease 
 
Repatha is indicated in adults with established atherosclerotic cardiovascular disease (myocardial 
infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C 
levels, as an adjunct to correction of other risk factors: 
 in combination with the maximum tolerated dose of a statin with or without other lipid-lowering 

therapies or, 
 alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, 

or for whom a statin is contraindicated. 
 

For study results with respect to effects on LDL-C, cardiovascular events and populations studied see 
section 5.1. 
 
4.2 Posology and method of administration 
 
Prior to initiating evolocumab, secondary causes of hyperlipidaemia or mixed dyslipidaemia (e.g., 
nephrotic syndrome, hypothyroidism) should be excluded. 
 
Posology 
 
Primary hypercholesterolaemia and mixed dyslipidaemia in adults 
The recommended dose of evolocumab is either 140 mg every two weeks or 420 mg once monthly; 
both doses are clinically equivalent. 
 
Homozygous familial hypercholesterolaemia in adults and adolescents aged 12 years and over 
The initial recommended dose is 420 mg once monthly. After 12 weeks of treatment, dose frequency 
can be up-titrated to 420 mg once every 2 weeks if a clinically meaningful response is not achieved. 
Patients on apheresis may initiate treatment with 420 mg every two weeks to correspond with their 
apheresis schedule. 
 
Established atherosclerotic cardiovascular disease in adults 
The recommended dose of evolocumab is either 140 mg every two weeks or 420 mg once monthly; 
both doses are clinically equivalent. 
 
Special populations 
 
Elderly patients (age ≥ 65 years) 
No dose adjustment is necessary in elderly patients. 
 
Patients with renal impairment 
No dose adjustment is necessary in patients with renal impairment (see section 5.2). 
 
Patients with hepatic impairment 
No dose adjustment is necessary in patients with mild hepatic impairment, see section 4.4 for patients 
with moderate and severe hepatic impairment. 
 
Paediatric population 
The safety and efficacy of Repatha in children aged less than 18 years has not been established in the 
indication for primary hypercholesterolaemia and mixed dyslipidaemia. No data are available. 
 
The safety and efficacy of Repatha in children aged less than 12 years has not been established in the 
indication for homozygous familial hypercholesterolaemia. No data are available. 
 
Method of administration 
 
Subcutaneous use. 
 



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Evolocumab is for subcutaneous injection into the abdomen, thigh or upper arm region. Injection sites 
should be rotated and injections should not be given into areas where the skin is tender, bruised, red, 
or hard. 
 
Evolocumab must not be administered intravenously or intramuscularly. 
 
Repatha 140 mg solution for injection in pre-filled syringe 
The 140 mg dose should be delivered using a single pre-filled syringe. 
The 420 mg dose should be delivered using three pre-filled syringes administered consecutively within 
30 minutes. 
 
Repatha 140 mg solution for injection in pre-filled pen 
The 140 mg dose should be delivered using a single pre-filled pen. 
The 420 mg dose should be delivered using three pre-filled pens administered consecutively within 
30 minutes. 
 
Repatha 420 mg solution for injection in cartridge 
The 420 mg dose should be delivered using a single cartridge with the automated mini-doser. 
 
Repatha is intended for patient self-administration after proper training. Administration of evolocumab 
can also be performed by an individual who has been trained to administer the product. 
 
For single use only. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hepatic impairment 
 
In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed 
that may lead to a reduced effect on LDL-C reduction. Therefore, close monitoring may be warranted 
in these patients. 
 
Patients with severe hepatic impairment (Child-Pugh class C) have not been studied (see section 5.2). 
Evolocumab should be used with caution in patients with severe hepatic impairment. 
 
Dry natural rubber 
 
Repatha 140 mg solution for injection in pre-filled syringe 
The needle cover of the glass pre-filled syringe is made from dry natural rubber (a derivative of latex), 
which may cause severe allergic reactions. 
 
Repatha 140 mg solution for injection in pre-filled pen 
The needle cover of the pre-filled pen is made from dry natural rubber (a derivative of latex), which 
may cause severe allergic reactions. 
 



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Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
The pharmacokinetic interaction between statins and evolocumab was evaluated in the clinical trials. 
An approximately 20% increase in the clearance of evolocumab was observed in patients co-
administered statins. This increased clearance is in part mediated by statins increasing the 
concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) which did not adversely 
impact the pharmacodynamic effect of evolocumab on lipids. No statin dose adjustments are necessary 
when used in combination with evolocumab. 
 
No studies on pharmacokinetic and pharmacodynamics interaction between evolocumab and lipid-
lowering medicinal products other than statins and ezetimibe have been conducted. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of Repatha in pregnant women. 
 
Animal studies do not indicate direct or indirect effects with respect to reproductive toxicity (see 
section 5.3). 
 
Repatha should not be used during pregnancy unless the clinical condition of the woman requires 
treatment with evolocumab. 
 
Breast-feeding 
 
It is unknown whether evolocumab is excreted in human milk. 
 
A risk to breastfed newborns/infants cannot be excluded. 
 
A decision must be made whether to discontinue breast-feeding or discontinue/abstain from Repatha 
therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the 
woman. 
 
Fertility 
 
No data on the effect of evolocumab on human fertility are available. Animal studies did not show any 
effects on fertility endpoints at area under the concentration time curve (AUC) exposure levels much 
higher than in patients receiving evolocumab at 420 mg once monthly (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Repatha has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions at the recommended doses are nasopharyngitis (7.4%), 
upper respiratory tract infection (4.6%), back pain (4.4%), arthralgia (3.9%), influenza (3.2%), and 



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injection site reactions (2.2%). The safety profile in the homozygous familial hypercholesterolaemia 
population was consistent with that demonstrated in the primary hypercholesterolaemia and mixed 
dyslipidaemia population. 
 
Tabulated list of adverse reactions 
 
Adverse reactions reported in pivotal, controlled clinical studies, and spontaneous reporting, are 
displayed by system organ class and frequency in table 1 below using the following convention: very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to 
< 1/1,000) and very rare (< 1/10,000). 
 
Table 1. Adverse reactions 
 
MedDRA system organ class 
(SOC) 

Adverse reactions Frequency category 

Infections and infestations Influenza Common 
Nasopharyngitis Common 
Upper respiratory tract 
infection

Common 

Immune system disorders Hypersensitivity Common 
Rash Common 
Urticaria Uncommon 

Gastrointestinal disorders Nausea Common 
Skin and subcutaneous tissue 
disorders 

Angioedema Rare 

Musculoskeletal and connective 
tissue disorders 

Back pain Common 
Arthralgia Common 

General disorders and 
administration site conditions 

Injection site reactions1 Common 
Influenza-like illness Uncommon 

1 See section Description of selected adverse reactions. 
 
Description of selected adverse reactions 
 
Injection site reactions 
The most frequent injection site reactions were injection site bruising, erythema, haemorrhage, 
injection site pain, and swelling. 
 
Paediatric population 
 
There is limited experience with evolocumab in paediatric patients. Fourteen patients aged ≥ 12 to 
< 18 years with homozygous familial hypercholesterolaemia were included in clinical studies. No 
difference in safety was observed between adolescent and adult patients with homozygous familial 
hypercholesterolaemia. 
 
The safety and effectiveness of evolocumab in paediatric patients with primary hypercholesterolaemia 
and mixed dyslipidaemia has not been established. 
 
Elderly population 
 
Of the 18,546 patients treated with evolocumab in double-blind clinical studies 7,656 (41.3%) were 
≥ 65 years old, while 1,500 (8.1%) were ≥ 75 years old. No overall differences in safety or efficacy 
were observed between these patients and younger patients. 
 
Immunogenicity 
 
In clinical studies, 0.3% of patients (48 out of 17,992 patients) treated with at least one dose of 
evolocumab tested positive for binding antibody development. The patients whose sera tested positive 



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for binding antibodies were further evaluated for neutralising antibodies and none of the patients tested 
positive for neutralising antibodies. The presence of anti-evolocumab binding antibodies did not 
impact the pharmacokinetic profile, clinical response, or safety of evolocumab. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No adverse effects were observed in animal studies at exposures up to 300-fold higher than those in 
patients treated with 420 mg evolocumab once monthly. 
 
There is no specific treatment for evolocumab overdose. In the event of an overdose, the patient 
should be treated symptomatically, and supportive measures instituted as required. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: lipid modifying agents, other lipid modifying agents. ATC code: 
C10AX13 
 
Mechanism of action 
 
Evolocumab binds selectively to PCSK9 and prevents circulating PCSK9 from binding to the low 
density lipoprotein receptor (LDLR) on the liver cell surface, thus preventing PCSK9-mediated LDLR 
degradation. Increasing liver LDLR levels results in associated reductions in serum LDL-cholesterol 
(LDL-C). 
 
Pharmacodynamic effects 
 
In clinical trials, evolocumab reduced unbound PCSK9, LDL-C, TC, ApoB, non-HDL-C, TC/HDL-C, 
ApoB/ApoA1, VLDL-C, TG and Lp(a), and increased HDL-C and ApoA1 in patients with primary 
hypercholesterolaemia and mixed dyslipidaemia. 
 
A single subcutaneous administration of 140 mg or 420 mg evolocumab resulted in maximum 
suppression of circulating unbound PCSK9 by 4 hours followed by a reduction in LDL-C reaching a 
mean nadir in response by 14 and 21 days, respectively. Changes in unbound PCSK9 and serum 
lipoproteins were reversible upon discontinuation of evolocumab. No increase in unbound PCSK9 or 
LDL-C above baseline was observed during the washout of evolocumab suggesting that compensatory 
mechanisms to increase production of PCSK9 and LDL-C do not occur during treatment. 
 
Subcutaneous regimens of 140 mg every 2 weeks and 420 mg once monthly were equivalent in 
average LDL-C lowering (mean of weeks 10 and 12) resulting in -72 to -57% from baseline compared 
with placebo. Treatment with evolocumab resulted in a similar reduction of LDL-C when used alone 
or in combination with other lipid-lowering therapy. 
 
Clinical efficacy in primary hypercholesterolaemia and mixed dyslipidaemia 
 
LDL-C reduction of approximately 55% to 75% was achieved with evolocumab as early as week 1 
and maintained during long-term therapy. Maximal response was generally achieved within 1 to 
2 weeks after dosing with 140 mg every 2 weeks and 420 mg once monthly. Evolocumab was 



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effective in all subgroups relative to placebo and ezetimibe, with no notable differences observed 
between subgroups, such as age, race, gender, region, body-mass index, National Cholesterol 
Education Program risk, current smoking status, baseline coronary heart disease (CHD) risk factors, 
family history of premature CHD, glucose tolerance status, (i.e. diabetes mellitus type 2, metabolic 
syndrome, or neither), hypertension, statin dose and intensity, unbound baseline PCSK9, baseline 
LDL-C and baseline TG. 
 
In 80-85% of all primary hyperlipidaemia patients treated with either dose, evolocumab demonstrated 
a ≥ 50% reduction in LDL-C at the mean of weeks 10 and 12. Up to 99% of patients treated with 
either dose of evolocumab achieved an LDL-C of < 2.6 mmol/L and up to 95% achieved an LDL-C 
< 1.8 mmol/L at the mean of weeks 10 and 12. 
 
Combination with a statin and statin with other lipid-lowering therapies 
 
LAPLACE-2 was an international, multicentre, double-blind, randomised, 12-week study in 
1,896 patients with primary hypercholesterolaemia or mixed dyslipidaemia who were randomised to 
receive evolocumab in combination with statins (rosuvastatin, simvastatin or atorvastatin). 
Evolocumab was compared to placebo for the rosuvastatin and simvastatin groups and compared with 
placebo and ezetimibe for the atorvastatin group. 
 
Repatha significantly reduced LDL-C from baseline to mean of weeks 10 and 12 compared with 
placebo for the rosuvastatin and simvastatin groups and compared with placebo and ezetimibe for the 
atorvastatin group (p < 0.001). Repatha significantly reduced TC, ApoB, non-HDL-C, TC/HDL-C, 
ApoB/ApoA1, VLDL-C, TG and Lp(a) and increased HDL-C from baseline to mean of weeks 10 
and 12 as compared to placebo for the rosuvastatin and simvastatin groups (p < 0.05) and significantly 
reduced TC, ApoB, non-HDL-C, TC/HDL-C, ApoB/ApoA1 and Lp(a), compared with placebo and 
ezetimibe for the atorvastatin group (p < 0.001) (see tables 2 and 3). 
 
RUTHERFORD-2 was an international, multicentre, double-blind, randomised, placebo-controlled, 
12-week study in 329 patients with heterozygous familial hypercholesterolaemia on lipid-lowering 
therapies. Repatha significantly reduced LDL-C from baseline to mean of weeks 10 and 12 compared 
with placebo (p < 0.001). Repatha significantly reduced TC, ApoB, non-HDL-C, TC/HDL-C, 
ApoB/ApoA1, VLDL-C, TG and Lp(a) and increased HDL-C and ApoA1 from baseline to mean of 
weeks 10 and 12 compared to placebo (p < 0.05) (see table 2). 
 
Table 2. Treatment effects of evolocumab compared with placebo in patients with primary 
hypercholesterolaemia and mixed dyslipidaemia - mean percent change from baseline to average 
of weeks 10 and 12 (%, 95% CI) 
 

Study 
 

Dose 
regimen 

LDL-C 
(%) 

Non-
HDL-C

(%) 

ApoB
(%) 

TC 
(%) 

Lp(a)
(%) 

VLDL-
C 

(%) 

HDL-
C 

(%) 

TG 
(%) 

ApoA
1 

(%) 

TC/ 
HDL-C 

ratio 
% 

ApoB/
ApoA1 
ratio 

% 
LAPLACE-2 

(HMD) 
(combined 

rosuvastatin, 
simvastatin, & 

atorvastatin 
groups) 

140 mg 
Q2W 

(N = 555) 
-72b 

(-75,-69) 
-60b 

(-63,-58)
-56b 

(-58,-53)
-41b 

(-43,-39)
-30b 

(-35,-25)
-18b 

(-23,-14)
6b 

(4,8) 
-17b 

(-22,-13) 
3b 

(1,5) 
-45b 

(-47,-42) 
-56b 

(-59,-53) 

420 mg 
QM 

(N = 562) 
-69b 

(-73,-65) 
-60b 

(-63,-57)
-56b 

(-58,-53)
-40b 

(-42,-37)
-27b 

(-31,-24)
-22b 

(-28,-17)
8b 

(6,10)
-23b 

(-28,-17) 
5b 

(3,7) 
-46b 

(-48,-43) 
-58b 

(-60,-55) 

RUTHERFO
RD-2 
(HeFH) 

140 mg 
Q2W 

(N = 110) 
-61b 

(-67,-55) 
-56b 

(-61,-51)
-49b 

(-54,-44)
-42b 

(-46,-38)
-31b 

(-38,-24)
-22b 

(-29,-16)
8b 

(4,12)
-22b 

(-29,-15) 
7a 

(3,12) 
-47b 

(-51,-42) 
-53 

(-58,-48) 

420 mg 
QM 

(N = 110) 
-66b 

(-72,-61) 
-60b 

(-65,-55)
-55b 

(-60,-50)
-44b 

(-48,-40)
-31b 

(-38,-24)
-16b 

(-23,-8) 
9b 

(5,14)
-17b 

(-24,-9) 
5a 

(1,9) 
-49b 

(-54,-44) 
-56b 

(-61,-50) 

Key: Q2W = once every 2 weeks, QM = once monthly, HMD = Primary hypercholesterolaemia and mixed 
dyslipidaemia, HeFH = Heterozygous familial hypercholesterolaemia, a p value < 0.05 when compared with 
placebo, b p value < 0.001 when compared with placebo. 
 



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Statin intolerant patients 
 
GAUSS-2 was an international, multicentre, double-blind, randomised, ezetimibe-controlled, 12-week 
study in 307 patients who were statin-intolerant or unable to tolerate an effective dose of a statin. 
Repatha significantly reduced LDL-C compared with ezetimibe (p < 0.001). Repatha significantly 
reduced TC, ApoB, non-HDL-C, TC/HDL-C, ApoB/ApoA1 and Lp(a), from baseline to mean of 
weeks 10 and 12 compared to ezetimibe (p < 0.001) (see table 3). 
 
Treatment in the absence of a statin 
 
MENDEL-2 was an international, multicentre, double-blind, randomised, placebo and ezetimibe-
controlled, 12-week study of Repatha in 614 patients with primary hypercholesterolaemia and mixed 
dyslipidaemia. Repatha significantly reduced LDL-C from baseline to mean of weeks 10 and 12 
compared with both placebo and ezetimibe (p < 0.001). Repatha significantly reduced TC, ApoB, 
non-HDL-C, TC/HDL-C, ApoB/ApoA1 and Lp(a), from baseline to mean of weeks 10 and 12 
compared with both placebo and ezetimibe (p < 0.001) (see table 3). 
 
Table 3. Treatment effects of evolocumab compared with ezetimibe in patients with primary 
hypercholesterolaemia and mixed dyslipidaemia - mean percent change from baseline to average 
of weeks 10 and 12 (%, 95% CI) 
 

Study 
 

Dose 
regimen 

LDL-C 
(%) 

Non-
HDL-

C 
(%) 

ApoB
(%) 

TC 
(%) 

Lp(a)
(%) 

VLDL
-C 

(%) 

HDL-
C 

(%) 

TG 
(%) 

ApoA1 
(%) 

TC/ 
HDL-

C ratio 
% 

ApoB/ 
ApoA1 
ratio 

% 

LAPLACE-2 
(HMD) 

(combined 
atorvastatin 

groups) 

140 mg 
Q2W 

(N = 219) 
-43c 

(-50, -37)
-34c 

(-39, -30)
-34c 

(-38, -30)
-23c 

(-26, -19)
-30c 

(-35, -25)
-1 

(-7, 5) 
7c 

(4, 10) 
-2 

(-9, 5) 
7c 

(4, 9) 
-27c 

(-30, -23) 
-38c 

(-42, -34) 

420 mg 
QM 

(N = 220) 
-46c 

(-51, -40)
-39c 

(-43, -34)
-40c 

(-44, -36)
-25c 

(-29, -22)
-33c 

(-41, -26)
-7 

(-20, 6)
8c 

(5, 12) 
-8 

(-21, 5)
7c 

(2, 11) 
-30c 

(-34, -26) 
-42c 

(-47, -38) 

GAUSS-2 
(statin-intolerant) 

140 mg 
Q2W 

(N = 103) 
-38b 

(-44, -33) 
-32b 

(-36, -27)
-32b 

(-37, -27)
-24b 

(-28, -20)
-24b 

(-31, -17)
-2 

(-10, 7)
5 

(1, 10) 
-3 

(-11, 6)
5a 

(2, 9) 
-27b 

(-32, -23) 
-35b 

(-40, -30) 

420 mg 
QM 

(N = 102) 
-39b 

(-44, -35) 
-35b 

(-39, -31)
-35b 

(-40, -30)
-26b 

(-30, -23)
-25b 

(-34, -17)
-4 

(-13, 6)
6 

(1, 10) 
-6 

(-17, 4)
3 

(-1, 7) 
-30b 

(-35, -25) 
-36b 

(-42, -31) 

MENDEL-2 
(treatment in the 

absence of a 
statin) 

140 mg 
Q2W 

(N = 153) 
-40b 

(-44, -37) 
-36b 

(-39, -32)
-34b 

(-37, -30)
-25b 

(-28, -22)
-22b 

(-29, -16)
-7 

(-14, 1)
6a 

(3, 9) 
-9 

(-16, -1)
3 

(0, 6) 
-29b 

(-32, -26) 
-35b 

(-39, -31) 

420 mg 
QM 

(N = 153) 

-41b 
(-44, -37) 

-35b 
(-38, -33)

-35b 
(-38, -31)

-25b 
(-28, -23)

-20b 
(-27, -13)

-10 
(-19, -1)

4 
(1, 7) 

-9 
(-18, 0)

4a 
(1, 7) 

-28b 
(-31, -24) 

-37b 
(-41, -32) 

Key: Q2W = once every 2 weeks, QM = once monthly, HMD = Primary hypercholesterolaemia and mixed 
dyslipidaemia, a p value < 0.05 when compared with ezetimibe, b p value < 0.001 when compared with 
ezetimibe, c nominal p value < 0.001 when compared with ezetimibe. 
 
Long-term efficacy in primary hypercholesterolaemia and mixed dyslipidaemia 
 
DESCARTES was an international, multicentre, double-blind, randomised, placebo-controlled, 
52-week study in 901 patients with hyperlipidaemia who received diet alone, atorvastatin, or a 
combination of atorvastatin and ezetimibe. Repatha 420 mg once monthly significantly reduced 
LDL-C from baseline at 52 weeks compared with placebo (p < 0.001). Treatment effects were 
sustained over 1 year as demonstrated by reduction in LDL-C from week 12 to week 52. Reduction in 
LDL-C from baseline at week 52 compared with placebo was consistent across background lipid-
lowering therapies optimised for LDL-C and cardiovascular risk. 
 
Repatha significantly reduced TC, ApoB, non-HDL-C, TC/HDL-C, ApoB/ApoA1, VLDL-C, TG and 
Lp(a), and increased HDL-C and ApoA1 at week 52 compared with placebo (p < 0.001) (see table 4). 
 



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Table 4. Treatment effects of evolocumab compared with placebo in patients with primary 
hypercholesterolaemia and mixed dyslipidaemia - mean percent change from baseline to 
week 52 (%, 95% CI) 
 

Study 
 

Dose 
regimen 

LDL-C 
(%) 

Non-
HDL-

C 
(%) 

ApoB
(%) 

TC 
(%) 

Lp(a)
(%) 

VLDL
-C 

(%) 

HDL-
C 

(%) 

TG 
(%) 

ApoA1 
(%) 

TC/ 
HDL-

C ratio
% 

ApoB/
ApoA1 
ratio

% 

DESCARTES 
420 mg 

QM 
(N = 599) 

-59b 
(-64, -55) 

-50b 
(-54, -46)

-44b 
(-48, -41)

-33b 
(-36, -31)

-22b 
(-26, -19)

-29b 
(-40, -18)

5b 
(3, 8) 

-12b 
(-17, -6) 

3a 
(1, 5) 

-37b 
(-40, -34)

-46b 
(-50, -43)

Key: QM = once monthly, a nominal p value < 0.001 when compared with placebo, b p value < 0.001 when 
compared with placebo. 
 
OSLER and OSLER-2 were two randomised, controlled, open-label extension studies to assess the 
long-term safety and efficacy of Repatha in patients who completed treatment in a ‘parent’ study. In 
each extension study, patients were randomised 2:1 to receive either Repatha plus standard of care 
(evolocumab group) or standard of care alone (control group) for the first year of the study. At the end 
of the first year (week 52 in OSLER and week 48 in OSLER-2), patients entered the all Repatha 
period in which all patients received open-label Repatha for either another 4 years (OSLER) or 2 years 
(OSLER-2). 
 
A total of 1,324 patients enrolled in OSLER. Repatha 420 mg once monthly significantly reduced 
LDL-C from baseline at week 12 and week 52 compared with control (nominal p < 0.001). Treatment 
effects were maintained over 272 weeks as demonstrated by reduction in LDL-C from week 12 in the 
parent study to week 260 in the open-label extension. A total of 3,681 patients enrolled in OSLER-2. 
Repatha significantly reduced LDL-C from baseline at week 12 and week 48 compared with control 
(nominal p < 0.001). Treatment effects were maintained as demonstrated by reduction in LDL-C from 
week 12 to week 104 in the open-label extension. Repatha significantly reduced TC, ApoB, 
non-HDL-C, TC/HDL-C, ApoB/ApoA1, VLDL-C, TG and Lp(a), and increased HDL-C and ApoA1 
from baseline to week 52 in OSLER and to week 48 in OSLER-2 compared with control (nominal 
p < 0.001). LDL-C and other lipid parameters returned to baseline within 12 weeks after 
discontinuation of Repatha at the beginning of OSLER or OSLER-2 without evidence of rebound. 
 
TAUSSIG was a multicentre, open-label, 5-year extension study to assess the long-term safety and 
efficacy of Repatha, as an adjunct to other lipid-lowering therapies, in patients with severe familial 
hypercholesterolaemia (FH), including homozygous familial hypercholesterolaemia. A total of 194 
severe familial hypercholesterolaemia (non-HoFH) patients and 106 homozygous familial 
hypercholesterolaemia patients enrolled in TAUSSIG. All patients in the study were initially treated 
with Repatha 420 mg once monthly, except for those receiving lipid apheresis at enrolment who began 
with Repatha 420 mg once every 2 weeks. Dose frequency in non-apheresis patients could be titrated 
up to 420 mg once every 2 weeks based on LDL-C response and PCSK9 levels. Long-term use of 
Repatha demonstrated a sustained treatment effect as evidenced by reduction of LDL-C in patients 
with severe familial hypercholesterolaemia (non-HoFH) (see table 5). 
 
Changes in other lipid parameters (TC, ApoB, non-HDL-C, TC/HDL-C, and ApoB/ApoA1) also 
demonstrated a sustained effect of long-term Repatha administration in patients with severe familial 
hypercholesterolaemia (non-HoFH). 
 



11 

Table 5. Effect of evolocumab on LDL-C in patients with severe familial hypercholesterolaemia 
(non-HoFH) – mean percent change from baseline to OLE week 216 (and associated 95% CI) 
 

Patient 
Population 

(N) 

OLE 
Week 12 
(n = 191) 

OLE 
Week 24 
(n = 191) 

OLE 
Week 36 
(n = 187) 

OLE 
Week 48 
(n = 187) 

OLE 
Week 96 
(n = 180) 

OLE 
Week 144 
(n = 180) 

OLE 
Week 192 
(n = 147) 

OLE 
Week 216
(n = 96) 

Severe FH 
(non-HoFH) 

(N = 194) 

-54.9 
(-57.4, -52.4) 

-54.1 
(-57.0, -51.3) 

-54.7 
(-57.4, -52.0)

-56.9 
(-59.7, -54.1)

-53.3 
(-56.9, -49.7)

-53.5 
(-56.7, -50.2) 

-48.3 
(-52.9, -43.7) 

-47.2 
(-52.8, -41.5)

Key: OLE = open-label extension, N (n) = Number of evaluable patients (N) and patients with observed LDL-C 
values at specific scheduled visit (n) in the severe familial hypercholesterolaemia (non-HoFH) final analysis set. 
 
The long-term safety of sustained very low levels of LDL-C (i.e. < 0.65 mmol/L [< 25 mg/dL]) has 
not yet been established. Available data demonstrate that there are no clinically meaningful differences 
between the safety profiles of patients with LDL-C levels < 0.65 mmol/L and those with higher 
LDL-C, see section 4.8. 
 
Treatment of homozygous familial hypercholesterolaemia 
 
TESLA was an international, multicentre, double-blind, randomised, placebo-controlled 12-week 
study in 49 homozygous familial hypercholesterolaemia patients aged 12 to 65 years. Repatha 420 mg 
once monthly, as an adjunct to other lipid-lowering therapies (e.g., statins, bile-acid sequestrants), 
significantly reduced LDL-C and ApoB at week 12 compared with placebo (p < 0.001) (see table 6). 
Changes in other lipid parameters (TC, non-HDL-C, TC/HDL-C, and ApoB/ApoA1) also 
demonstrated a treatment effect of Repatha administration in patients with homozygous familial 
hypercholesterolaemia. 
 
Table 6. Treatment effects of evolocumab compared with placebo in patients with homozygous 
familial hypercholesterolaemia - mean percent change from baseline to week 12 (%, 95% CI) 
 

Study 
 

Dose 
regimen 

LDL-C 
(%) 

Non-
HDL-C

(%) 

ApoB
(%) 

TC 
(%) 

Lp(a) 
(%) 

VLDL-
C 

(%) 

HDL-C
(%) 

TG 
(%) 

TC/ 
HDL-C 

ratio 
% 

ApoB/
ApoA1 
ratio 

% 

TESLA 
(HoFH) 

420 mg 
QM 

(N = 33) 

-32b 
(-45, -19) 

-30a 
(-42, -18) 

-23b 
(-35, -11)

-27a 
(-38, -16)

-12 
(-25, 2) 

-44 
(-128, 40)

-0.1 
(-9, 9) 

0.3 
(-15, 16) 

-26a 
(-38, -14) 

-28a 
(-39, -17)

Key: HoFH = homozygous familial hypercholesterolaemia, QM = once monthly, a nominal p value < 0.001 
when compared with placebo, b p value < 0.001 when compared with placebo. 
 
Long-term efficacy in homozygous familial hypercholesterolaemia 
 
In TAUSSIG, long-term use of Repatha demonstrated a sustained treatment effect as evidenced by 
reduction of LDL-C of approximately 20% to 30% in patients with homozygous familial 
hypercholesterolaemia not on apheresis and approximately 10% to 30% in patients with homozygous 
familial hypercholesterolaemia on apheresis (see table 7). Changes in other lipid parameters (TC, 
ApoB, non-HDL-C, TC/HDL-C, and ApoB/ApoA1) also demonstrated a sustained effect of long-term 
Repatha administration in patients with homozygous familial hypercholesterolaemia. Reductions in 
LDL-C and changes in other lipid parameters in 14 adolescent patients (aged ≥ 12 to < 18 years) with 
homozygous familial hypercholesterolaemia are comparable to those in the overall population of 
patients with homozygous familial hypercholesterolaemia. 
 



12 

Table 7. Effect of evolocumab on LDL-C in patients with homozygous familial 
hypercholesterolaemia - mean percent change from baseline to OLE week 216 (and associated 
95% CI) 
 

Patient 
Population (N) 

OLE 
Week 12 

OLE 
Week 24 

OLE 
Week 36 

OLE 
Week 48 

OLE 
Week 96 

OLE 
Week 144 

OLE 
Week 192 

OLE 
Week 216

HoFH 
(N = 106) 

-21.2 
(-26.0, -16.3) 

(n = 104) 

-21.4 
(-27.8, -15.0)

(n = 99) 

-27.0 
(-32.1, -21.9)

(n = 94) 

-24.8 
(-31.4, -18.3)

(n = 93) 

-25.0 
(-31.2, -18.8)

(n = 82) 

-27.7 
(-34.9, -20.5) 

(n = 79) 

-27.4 
(-36.9, -17.8) 

(n = 74) 

-24.0 
(-34.0, -14.0)

(n = 68) 

Non-apheresis 
(N = 72) 

-22.7 
(-28.1, -17.2) 

(n = 70) 

-25.8 
(-33.1, -18.5)

(n = 69) 

-30.5 
(-36.4, -24.7)

(n = 65) 

-27.6 
(-35.8, -19.4)

(n = 64) 

-23.5 
(-31.0, -16.0)

(n = 62) 

-27.1 
(-35.9, -18.3) 

(n = 60) 

-30.1 
(-37.9, -22.2) 

(n = 55) 

-23.4 
(-32.5, -14.2)

(n = 50) 

Apheresis 
(N = 34) 

-18.1 
(-28.1, -8.1) 

(n = 34) 

-11.2 
(-24.0, 1.7) 

(n = 30) 

-19.1 
(-28.9, -9.3) 

(n = 29) 

-18.7 
(-29.5, -7.9) 

(n = 29) 

-29.7 
(-40.6, -18.8)

(n = 20) 

-29.6 
(-42.1, -17.1) 

(n = 19) 

-19.6 
(-51.2, 12.1) 

(n = 19) 

-25.9 
(-56.4, 4.6) 

(n = 18) 

Key: OLE = open-label extension. N (n) = Number of evaluable patients (N) and patients with observed LDL 
values at specific schedule visit (n) in the HoFH final analysis set. 
 
Effect on atherosclerotic disease burden 
 
The effects of Repatha 420 mg once monthly on atherosclerotic disease burden, as measured by 
intravascular ultrasound (IVUS), were evaluated in a 78-week double-blind, randomised, placebo 
controlled study in 968 patients with coronary artery disease on a stable background of optimal statin 
therapy. Repatha reduced both percent atheroma volume (PAV; 1.01% [95% CI 0.64, 1.38], 
p < 0.0001) and total atheroma volume (TAV; 4.89 mm3 [95% CI 2.53, 7.25], p < 0.0001) compared 
with placebo. Atherosclerotic regression was observed in 64.3% (95% CI 59.6, 68.7) and 47.3% 
(95% CI 42.6, 52.0) of patients who received Repatha or placebo respectively when measured by 
PAV. When measured by TAV, atherosclerotic regression was observed in 61.5% (95% CI 56.7, 66.0) 
and 48.9% (95% CI 44.2, 53.7) of patients who received Repatha or placebo respectively. The study 
did not investigate the correlation between atherosclerotic disease regression and cardiovascular 
events. 
 
Cardiovascular risk reduction in adults with established atherosclerotic cardiovascular disease 
 
The Repatha Outcomes Study (FOURIER) was a randomised, event-driven, double-blind study of 
27,564 subjects, aged between 40 and 86 years (mean age 62.5 years), with established atherosclerotic 
CV disease; 81% had a prior MI event, 19% had a prior stroke event and 13% had peripheral arterial 
disease. Over 99% of patients were on moderate to high intensity statin and at least one other 
cardiovascular medicine such as anti-platelet agents, beta blockers, Angiotensin-Converting Enzyme 
(ACE) inhibitors, or angiotensin receptor blockers; median (Q1, Q3) baseline LDL-C was 2.4 mmol/L 
(2.1, 2.8). Absolute CV risk was balanced between treatment groups, in addition to the index event all 
patients had at least 1 major or 2 minor CV risk factors; 80% had hypertension, 36% had diabetes 
mellitus, and 28% were daily smokers. Patients were randomised 1:1 to either Repatha (140 mg every 
two weeks or 420 mg once every month) or matching placebo; the mean duration of patient follow-up 
was 26 months. 
 
A substantial reduction of LDL-C was observed throughout the study, with achieved median LDL-C 
ranges of 0.8 to 0.9 mmol/L at each assessment; 25% of patients achieved a LDL-C concentration less 
than 0.5 mmol/L. Despite the very low levels of LDL-C achieved, no new safety issues were observed 
(see section 4.8); the frequencies of new onset diabetes and cognitive events were comparable in 
patients who achieved LDL-C levels < 0.65 mmol/L and those with higher LDL-C. 
 
Repatha significantly reduced the risk of cardiovascular events defined as the composite of time to 
first CV death, MI, stroke, coronary revascularisation, or hospitalisation for unstable angina (see 
table 8); the Kaplan-Meier curves for the primary and key secondary composite endpoints separated at 



13 

approximately 5 months (see figure 1 for the MACE three year Kaplan-Meier curve). The relative risk 
of the MACE composite (CV death, MI, or stroke) was significantly reduced by 20%. The treatment 
effect was consistent across all subgroups (including age, type of disease, baseline LDL-C, baseline 
statin intensity, ezetimibe use, and diabetes) and was driven by a reduction in the risk of myocardial 
infarction, stroke and coronary revascularisation; no significant difference was seen on cardiovascular 
or all-cause mortality however the study was not designed to detect such a difference. 
 
Table 8. Effect of evolocumab on major cardiovascular events 
 

 

Placebo 
(N = 13,780) 

n (%) 

Evolocumab
(N = 13,784) 

n (%) 
Hazard ratioa 

(95% CI) p valueb 
MACE+ (composite of MACE, 
coronary revascularisation, or 
hospitalisation for unstable angina) 

1,563 (11.34) 1,344 (9.75) 0.85 (0.79, 0.92) < 0.0001 

MACE (composite of CV death, MI, or 
stroke) 

1,013 (7.35) 816 (5.92) 0.80 (0.73, 0.88) < 0.0001 

Cardiovascular death 240 (1.74) 251 (1.82) 1.05 (0.88, 1.25) 0.62 
All-cause mortality 426 (3.09) 444 (3.22) 1.04 (0.91, 1.19) 0.54 
Myocardial infarction (fatal/non-fatal) 639 (4.64) 468 (3.40) 0.73 (0.65, 0.82) < 0.0001c 
Stroke (fatal/non-fatal) d 262 (1.90) 207 (1.50) 0.79 (0.66, 0.95) 0.0101c 
Coronary revascularisation 965 (7.00) 759 (5.51) 0.78 (0.71, 0.86) < 0.0001c 
Hospitalisation for unstable anginae 239 (1.7) 236 (1.7) 0.99 (0.82, 1.18) 0.89 
a Based on a Cox model stratified by the randomisation stratification factors collected via Interactive Voice Response System 
(IVRS) 
 b 2-sided log-rank test stratified by randomisation stratification factors collected via IVRS. 
c Nominal significance. 
d The treatment effect on stroke was driven by a reduction in risk of ischaemic stroke; there was no effect on haemorrhagic or 
undetermined stroke. 
e Assessment of time to hospitalisation for unstable angina was ad-hoc. 
 
Figure 1. Time to a MACE event (composite of CV death, MI, or stroke); 3-year Kaplan-Meier 
 

 
 
Effect on LDL-C during acute phase of Acute Coronary Syndromes (ACS) 
 
EVOPACS was a single country, multicenter, double-blind, randomized, placebo-controlled, 8-week 
study on 308 ACS patients with evolocumab initiated in-hospital within 24 to 72 hours of presentation. 
 

Months 
Patients at Risk 

11 

10 

9 

8 

7 

6 

5 

4 

3 

2 

1 

0 

Cu
mu

lat
ive

 In
cid

en
ce

 (%
) 

Placebo 13780 13447 13140 12257 7923 3785 717 
Repatha 13784 13499 13240 12422 8066 3837 713 

 

0 6 12 18 24 30 36 

Placebo 

Repatha 

Hazard Ratio, 0.80 (95% CI, 0.73, 0.88) 
P<0.0001 

GR
H0

46
5 v

1 

3.7 

6.8 

9.9 

3.1 

5.5 

7.9 



14 

If patients were not on a statin or were on statin treatment other than atorvastatin 40 mg prior to 
screening, this was stopped and atorvastatin 40 mg once daily was initiated. Randomisation was 
stratified by study centre and presence of stable statin treatment within ≥ 4 weeks prior to enrolment. 
Most subjects (241 [78%]) were not on stable statin treatment for ≥ 4 weeks prior to screening and 
most (235 [76%]) were not taking a statin at baseline. By week 4, 281 (97%) subjects were receiving 
high-intensity statins. Evolocumab 420 mg once monthly significantly reduced LDL-C from baseline 
to week 8 compared with placebo (p < 0.001). The mean (SD) reduction in calculated LDL-C from 
baseline at week 8 was 77.1% (15.8%) in the evolocumab group and 35.4% (26.6%) in the placebo 
group with a least squares (LS) mean difference (95% CI) of 40.7% (36.2%, 45.2%). Baseline LDL-C 
values were 3.61 mmol/L (139.5 mg/dL) in the evolocumab group and 3.42 mmol/L (132.2 mg/dL) in 
the placebo group. LDL-C reductions in this study were consistent with previous studies where 
evolocumab was added to stable lipid-lowering therapy as demonstrated by on-treatment LDL-C 
levels at week 8 in this study (reflecting steady-state effect of high-intensity statin in both treatment 
arms) of 0.79 mmol/L (30.5 mg/dL) and 2.06 mmol/L (79.7 mg/dL) in the evolocumab plus 
atorvastatin and the placebo plus atorvastatin groups, respectively. 
 
The effects of evolocumab in this patient population were consistent with those observed in previous 
studies in evolocumab clinical development program and no new safety concerns were noted. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Repatha in all subsets of the paediatric population in the treatment of mixed dyslipidaemia (see 
section 4.2 for information on paediatric use). 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Repatha in one or more subsets of the paediatric population in the treatment of elevated cholesterol 
(see section 4.2 for information on paediatric use). 
 
There are limited data available on the use of Repatha in the paediatric population. Fourteen 
adolescent patients aged ≥ 12 to < 18 years with homozygous familial hypercholesterolaemia have 
been included in clinical trials. No overall differences in safety or efficacy were observed between 
adolescent and adult patients with homozygous familial hypercholesterolaemia. 
 
5.2 Pharmacokinetic properties 
 
Absorption and distribution 
 
Following a single subcutaneous dose of 140 mg or 420 mg evolocumab administered to healthy 
adults, median peak serum concentrations were attained in 3 to 4 days. Administration of single 
subcutaneous dose of 140 mg resulted in a Cmax mean (SD) of 13.0 (10.4) μg/mL and AUClast mean 
(SD) of 96.5 (78.7) day•μg/mL. Administration of single subcutaneous dose 420 mg resulted in a Cmax 
mean (SD) of 46.0 (17.2) μg/mL and AUClast mean (SD) of 842 (333) day•μg/mL. Three subcutaneous 
140 mg doses were bioequivalent to a single subcutaneous 420 mg dose. The absolute bioavailability 
after SC dosing was determined to be 72% from pharmacokinetic models. 
 
Following a single 420 mg evolocumab intravenous dose, the mean (SD) steady-state volume of 
distribution was estimated to be 3.3 (0.5) L, suggesting evolocumab has limited tissue distribution. 
 
Biotransformation 
 
Evolocumab is composed solely of amino acids and carbohydrates as native immunoglobulin and is 
unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are 
expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides 
and individual amino acids. 
 



15 

Elimination 
 
Evolocumab was estimated to have an effective half-life of 11 to 17 days. 
 
In patients with primary hypercholesterolaemia or mixed dyslipidaemia on high dose statin, the 
systemic exposure of evolocumab was slightly lower than in subjects on low-to-moderate dose statin 
(the ratio of AUClast 0.74 [90% CI 0.29; 1.9]). An approximately 20% increase in the clearance is in 
part mediated by statins increasing the concentration of PCSK9 which did not adversely impact the 
pharmacodynamic effect of evolocumab on lipids. Population pharmacokinetic analysis indicated no 
appreciable differences in evolocumab serum concentrations in hypercholesterolaemic patients (non-
familial hypercholesterolaemia or familial hypercholesterolaemia) taking concomitant statins. 
 
Linearity/non-linearity 
 
Following a single 420 mg intravenous dose, the mean (SD) systemic clearance was estimated to be 
12 (2) mL/hr. In clinical studies with repeated subcutaneous dosing over 12 weeks, dose proportional 
increases in exposure were observed with dose regimens of 140 mg and greater. An approximate two 
to three-fold accumulation was observed in trough serum concentrations (Cmin (SD) 7.21 (6.6)) 
following 140 mg doses every 2 weeks or following 420 mg doses administered monthly (Cmin (SD) 
11.2 (10.8)), and serum trough concentrations approached steady-state by 12 weeks of dosing. 
 
No time dependent changes were observed in serum concentrations over a period of 124 weeks. 
 
Renal impairment 
 
No dose adjustment is necessary in patients with renal impairment. Data from the evolocumab 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. 
 
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 Cmax 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 AUClast 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. 
 
Hepatic impairment 
 
No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A). 
Single 140 mg subcutaneous doses of evolocumab were studied in 8 patients with mild hepatic 
impairment, 8 patients with moderate hepatic impairment and 8 healthy subjects. The exposure to 
evolocumab was found to be approximately 40-50% lower compared to healthy subjects. However, 
baseline PCSK9 levels and the degree and time course of PCSK9 neutralisation were found to be 
similar between patients with mild or moderate hepatic impairment and healthy volunteers. This 
resulted in similar time course and extent of absolute LDL-C lowering. Evolocumab has not been 
studied in patients with severe hepatic impairment (Child-Pugh class C) (see section 4.4). 
 



16 

Body weight 
 
Body weight was a significant covariate in population PK analysis impacting evolocumab trough 
concentrations, however there was no impact on LDL-C reduction. Following repeat subcutaneous 
administration of 140 mg every 2 weeks, the 12-week trough concentrations were 147% higher and 
70% lower in patients of 69 kg and 93 kg respectively, than that of the typical 81 kg subject. Less 
impact from body weight was seen with repeated subcutaneous evolocumab 420 mg monthly doses. 
 
Other special populations 
 
Population pharmacokinetic analyses suggest that no dose adjustments are necessary for age, race or 
gender. The pharmacokinetics of evolocumab were influenced by body weight without having any 
notable effect on LDL-C lowering. Therefore, no dose adjustments are necessary based on body 
weight. 
 
5.3 Preclinical safety data 
 
Evolocumab was not carcinogenic in hamsters at exposures much higher than patients receiving 
evolocumab at 420 mg once monthly. The mutagenic potential of evolocumab has not been evaluated. 
 
In hamsters and cynomolgus monkeys at exposures much higher than patients receiving 420 mg 
evolocumab once monthly, no effect on male or female fertility was observed. 
 
In cynomolgus monkeys at exposures much higher than patients receiving 420 mg evolocumab once 
monthly, no effects on embryo-foetal or postnatal development (up to 6 months of age) were observed. 
 
Apart from a reduced T-cell Dependent Antibody Response in cynomolgus monkeys immunised with 
keyhole limpet haemocyanin (KLH) after 3 months of treatment with evolocumab, no adverse effects 
were observed in hamsters (up to 3 months) and cynomolgus monkeys (up to 6 months) at exposures 
much higher than patients receiving evolocumab at 420 mg once monthly. The intended 
pharmacological effect of decreased serum LDL-C and total cholesterol were observed in these studies 
and was reversible upon cessation of treatment. 
 
In combination with rosuvastatin for 3 months, no adverse effects were observed in cynomolgus 
monkeys at exposures much higher than patients receiving 420 mg evolocumab once monthly. 
Reductions in serum LDL-C and total cholesterol were more pronounced than observed previously 
with evolocumab alone, and were reversible upon cessation of treatment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Proline 
Glacial acetic acid 
Polysorbate 80 
Sodium hydroxide (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 



17 

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. 
 
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. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
 
Repatha 140 mg solution for injection in pre-filled syringe 
 
Store in the original carton in order to protect from light. 
 
Repatha 140 mg solution for injection in pre-filled pen 
 
Store in the original carton in order to protect from light. 
 
Repatha 420 mg solution for injection in cartridge 
 
Store in the original carton in order to protect from light and moisture. 
 
6.5 Nature and contents of container 
 
Repatha 140 mg solution for injection in pre-filled syringe 
 
One mL solution in a single use pre-filled syringe made from type I glass with stainless steel 27 gauge 
needle. 
 
The needle cover of the pre-filled syringe is made from dry natural rubber (a derivative of latex, see 
section 4.4). 
 
Pack size of one pre-filled syringe. 
 
Repatha 140 mg solution for injection in pre-filled pen 
 
One mL solution in a single use pre-filled pen made from type I glass with stainless steel 27 gauge 
needle. 
 
The needle cover of the pre-filled pen is made from dry natural rubber (a derivative of latex, see 
section 4.4). 
 
Pack sizes of one, two, three pre-filled pens or multipacks containing 6 (3 packs of 2) pre-filled pens. 
 



18 

Repatha 420 mg solution for injection in cartridge 
 
A 3.5 mL solution in a single use cartridge made from cyclic olefin polymer with elastomer septum 
and piston as product-contact materials, and a resin cap. The pre-filled cartridge is assembled with a 
telescopic screw device component. The cartridge assembly is co-packed with an administration 
device. The fluid path within the administration device is made from stainless steel and non-DEHP 
polyvinyl chloride, with a stainless steel 29 gauge needle. The administration device contains silver 
oxide-zinc batteries and includes an adhesive patch made from polyester tape with an acrylate 
adhesive. The administration device is designed for use only with the provided 3.5 mL pre-filled 
cartridge assembly. 
 
Pack sizes of one cartridge/automated mini-doser or multipack of three (3x1) cartridges/automated 
mini-dosers. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before administration, the solution should be inspected. The solution should not be injected if it 
contains particles, or is cloudy or discoloured. To avoid discomfort at the site of injection, the 
medicinal product should be allowed to reach room temperature (up to 25°C) before injecting. The 
entire contents should be injected. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Repatha 140 mg solution for injection in pre-filled syringe 
 
EU/1/15/1016/001 - 1 pre-filled syringe 
 
Repatha 140 mg solution for injection in pre-filled pen 
 
EU/1/15/1016/002 - 1 pre-filled pen 
EU/1/15/1016/003 - 2 pre-filled pens 
EU/1/15/1016/004 - 3 pre-filled pens 
EU/1/15/1016/005 - 6 (3x2) pre-filled pens (multipack) 
 
Repatha 420 mg solution for injection in cartridge 
 
EU/1/15/1016/006 - 1 cartridge with co-packed automated mini-doser 
EU/1/15/1016/007 - 3 (3x1) cartridges with co-packed automated mini-dosers (multipack) 
 
 



19 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 July 2015 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURERS RESPONSIBLE 
FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



21 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Immunex Rhode Island Corporation 
40 Technology Way 
West Greenwich 
Rhode Island, 02817 
United States 
 
Name and address of the manufacturers responsible for batch release 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 



22 

An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection in pre-filled syringe 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 140 mg of evolocumab in 1 mL of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
1 pre-filled syringe. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Contains latex, read the package leaflet before use. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



26 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 140 syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



27 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PRE-FILLED SYRINGE BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection 
evolocumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Repatha 140 mg injection 
evolocumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
 
 
 



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection in pre-filled pen 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 140 mg of evolocumab in 1 mL of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
1 SureClick pre-filled pen. 
2 SureClick pre-filled pens. 
3 SureClick pre-filled pens. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Contains latex, read the package leaflet before use. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



30 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/002 
EU/1/15/1016/003 
EU/1/15/1016/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 140 pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR MULTIPACK (with blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection in pre-filled pen 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 140 mg of evolocumab in 1 mL of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
Multipack: 6 (3 packs of 2) SureClick pre-filled pens. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Contains latex, read the package leaflet before use. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 



32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 140 pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTIPACK (without blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 140 mg solution for injection in pre-filled pen 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 140 mg of evolocumab in 1 mL of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
2 SureClick pre-filled pens. Component of a multi-pack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Contains latex, read the package leaflet before use. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



34 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 140 pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Repatha 140 mg injection 
evolocumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON AUTOMATED MINI-DOSER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 420 mg solution for injection in cartridge 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each cartridge contains 420 mg of evolocumab in 3.5 mL of solution (120 mg/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
1 cartridge and automated mini-doser. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light and moisture. 
 
 



37 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 420 cartridge 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



38 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR MULTIPACK (with blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 420 mg solution for injection in cartridge 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each cartridge contains 420 mg of evolocumab in 3.5 mL of solution (120 mg/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
Multipack: 3 (3 packs of 1) cartridges and automated mini-dosers. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light and moisture. 
 
 



39 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 420 cartridge 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTIPACK (without blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Repatha 420 mg solution for injection in cartridge 
evolocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each cartridge contains 420 mg of evolocumab in 3.5 mL of solution (120 mg/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
1 cartridge and automated mini-doser. Component of a multi-pack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light and moisture. 
 
 



41 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061, 
4817 ZK Breda, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1016/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Repatha 420 cartridge 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



42 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL CARTRIDGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Repatha 420 mg injection 
evolocumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3.5 ml 
 
 
6. OTHER 
 
 
 
 



43 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



44 

Package leaflet: Information for the user 
 

Repatha 140 mg solution for injection in pre-filled syringe 
evolocumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Repatha is and what it is used for 
2. What you need to know before you use Repatha 
3. How to use Repatha 
4. Possible side effects 
5. How to store Repatha 
6. Contents of the pack and other information 
 
 
1. What Repatha is and what it is used for 
 
What Repatha is and how it works 
 
Repatha is a medicine that lowers levels of ‘bad’ cholesterol, a type of fat, in the blood. 
 
Repatha contains the active substance evolocumab, a monoclonal antibody (a type of specialised 
protein designed to attach to a target substance in the body). Evolocumab is designed to attach to a 
substance called PCSK9 that affects the liver’s ability to take in cholesterol. By attaching to, and 
mopping up PCSK9, the medicine increases the amount of cholesterol entering the liver and so lowers 
the level of cholesterol in the blood. 
 
What Repatha is used for 
 
Repatha is used in addition to your cholesterol lowering diet if you are: 
 an adult with a high cholesterol level in your blood (primary hypercholesterolaemia 

[heterozygous familial and non-familial] or mixed dyslipidaemia). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 12 years and older with a high cholesterol level in your blood because of a condition that runs in 

your family (homozygous familial hypercholesterolaemia or HoFH). It is given: 
- together with other cholesterol lowering treatments. 

 an adult with a high cholesterol level in your blood and established atherosclerotic 
cardiovascular disease (a history of heart attack, stroke or blood vessel problems). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 



45 

Repatha is used in patients who cannot control their cholesterol levels with a cholesterol lowering diet 
alone. You should stay on your cholesterol lowering diet while taking this medicine. Repatha can help 
prevent heart attack, stroke, and certain heart procedures to restore blood flow to the heart due to a 
build-up of fatty deposits in your arteries (also known as atherosclerotic cardiovascular disease). 
 
 
2. What you need to know before you use Repatha 
 
Do not use Repatha if you are allergic to evolocumab or any of the other ingredients of this medicine 
(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Repatha if you have liver disease. 
 
The needle cover of the glass pre-filled syringe is made from dry natural rubber (a derivative of latex), 
which may cause severe allergic reactions. 
 
Children and adolescents 
 
The use of Repatha has not been studied in children under 18 years of age being treated for primary 
hypercholesterolaemia and mixed dyslipidaemia. 
 
The use of Repatha has not been studied in children under 12 years of age being treated for 
homozygous familial hypercholesterolaemia. 
 
Other medicines and Repatha 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Repatha has not been tested in pregnant women. It is not known if Repatha will harm your unborn 
baby. 
 
It is not known whether Repatha is found in breast milk. 
 
It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help 
you decide whether to stop breast-feeding, or whether to stop taking Repatha, considering the benefit 
of breast-feeding to the baby and the benefit of Repatha to the mother. 
 
Driving and using machines 
 
Repatha has no or negligible influence on the ability to drive and use machines. 
 
Repatha contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-
free’. 
 
 



46 

3. How to use Repatha 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The recommended dose depends on the underlying condition: 
 for adults with primary hypercholesterolaemia and mixed dyslipidaemia the dose is either 

140 mg every two weeks or 420 mg once monthly. 
 for adults or adolescents with homozygous familial hypercholesterolaemia the recommended 

starting dose is 420 mg once monthly. After 12 weeks your doctor may decide to increase the 
dose to 420 mg every two weeks. If you also receive apheresis, a procedure similar to dialysis 
where cholesterol and other fats are removed from the blood, your doctor may decide to start 
you on a dose of 420 mg every two weeks to coincide with your apheresis treatment. 

 for adults with established atherosclerotic cardiovascular disease (a history of heart attack, 
stroke or blood vessel problems) the dose is either 140 mg every two weeks or 420 mg once 
monthly. 

 
Repatha is given as an injection under the skin (subcutaneous). 
 
If your doctor prescribes a dose of 420 mg you must use three pre-filled syringes because each 
pre-filled syringe only contains 140 mg of medicine. After reaching room temperature, all injections 
should be given within a 30 minute period. 
 
If your doctor decides that you or a caregiver can give the injections of Repatha, you or your caregiver 
should receive training on how to prepare and inject Repatha correctly. Do not try to inject Repatha 
until you have been shown how to do it by your doctor or nurse. 
 
See the detailed “Instructions for Use” at the end of this leaflet for instructions about how to store, 
prepare, and give your Repatha injections at home. 
 
Before starting Repatha, you should be on a diet to lower your cholesterol. You should keep on this 
cholesterol lowering diet while taking Repatha. 
 
If your doctor has prescribed Repatha along with another cholesterol lowering medicine, follow your 
doctor’s instructions on how to take these medicines together. In this case, please read the dosage 
instructions in the package leaflet of that particular medicine as well. 
 
If you use more Repatha than you should 
 
Contact your doctor or pharmacist immediately. 
 
If you forget to take Repatha 
 
Take Repatha as soon as you can after the missed dose. Then, contact your doctor who will tell you 
when you should schedule your next dose, and follow the new schedule exactly as your doctor has told 
you. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common (may affect up to 1 in 10 people) 
 Flu (high temperature, sore throat, runny nose, cough and chills) 
 Common cold, such as runny nose, sore throat or sinus infections (nasopharyngitis or upper 

respiratory tract infections) 
 Feeling sick (nausea) 



47 

 Back pain 
 Joint pain (arthralgia) 
 Injection site reactions, such as bruising, redness, bleeding, pain or swelling 
 Allergic reactions including rash 
 
Uncommon (may affect up to 1 in 100 people) 
 Hives, red itchy bumps on your skin (urticaria) 
 Flu-like symptoms 
 
Rare (may affect up to 1 in 1,000 people) 
 Swelling of the face, mouth, tongue, or throat (angioedema) 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Repatha 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Store in the original carton in order to protect from light. 
 
Your pre-filled syringe may be left outside the refrigerator to reach room temperature (up to 25°C) 
before injection. This will make the injection more comfortable. After removal 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. 
 
Do not use this medicine if you notice it is discoloured or contains large lumps, flakes or coloured 
particles. 
 
Do not throw away any medicines via wastewater or household waste. 
 
Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Repatha contains 
- The active substance is evolocumab. Each pre-filled syringe contains 140 mg of evolocumab in 

1 mL of solution. 
- The other ingredients are proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water 

for injections. 
 
What Repatha looks like and contents of the pack 
 
Repatha is a solution which is clear to opalescent, colourless to yellowish, and practically free from 
particles.  
 



48 

Each pack contains one single use pre-filled syringe. 
 
Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Manufacturer 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 
 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 
 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 
 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 
 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 
 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 
 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 
 

Norge 
Amgen AB 
Tel: +47 23308000 
 



49 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 
 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 422 06 06 

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 
 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 
 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 
 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 
 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 
 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
__________________________________________________________________________________ 
 
 



50 

Instructions for use: 
Repatha single use pre-filled syringe 
 

Guide to parts 

Before use After use 

Plunger  
rod 

Medicine 

Syringe  
barrel 

Grey  
needle  
cap on 

 

Used 
plunger

 

Used 
syringe 

barrel

Used 
Needle

 

 
Needle is inside. 

 

Grey 
needle 
cap off 



51 

Important 

Before you use a single use Repatha pre-filled syringe, read this important information: 
  Do not freeze or use the Repatha pre-filled syringe if it has been frozen. 
  Do not use the Repatha pre-filled syringe if the packaging is open or damaged. 
  Do not use the Repatha pre-filled syringe if it has been dropped onto a hard surface. Part of the 

syringe may be broken even if you cannot see the break. Use a new Repatha pre-filled syringe. 
  Do not remove the grey needle cap from the Repatha pre-filled syringe until you are ready to 

inject. 
 

Step 1: Prepare
A Remove the Repatha pre-filled syringe carton from the refrigerator and wait 30 minutes. 
Wait at least 30 minutes for the pre-filled syringe in the carton to naturally reach room temperature 
before injecting. 
Check that the name Repatha appears on the carton label.
  Do not try to warm the Repatha pre-filled syringe by using a heat source such as hot water or 

microwave. 
  Do not leave the Repatha pre-filled syringe exposed to direct sunlight. 
  Do not shake the Repatha pre-filled syringe. 
 

 

B Gather all materials needed for your injection. 
Wash your hands thoroughly with soap and water. 
On a clean, well-lit, flat work surface, place: 
  One Repatha pre-filled syringe in its tray. 

  Alcohol wipes. 

  Cotton ball or gauze pad. 

  Plaster. 

  Sharps disposal container. 

  Do not use if expiry date on the Repatha pre-filled syringe carton has passed. 



52 

C Choose your injection site. 

 

Upper arm 

Belly 

 
Thigh 

You can use: 
  Thigh. 

  Belly, except for the 2 inches (5 centimetres) around the belly button. 

  Outer area of upper arm (only if someone else is giving you the injections). 

 Do not choose an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas 
with scars or stretch marks. 

 

Choose a different site each time you give yourself an injection. If you need to use the same 
injection site, just make sure it is not the same spot on that site you used last time. 

 
D Clean your injection site. 

Clean your injection site with an alcohol wipe. Let your skin dry before injecting. 
  Do not touch this area of skin again before injecting. 

 



53 

E Remove the pre-filled syringe from the tray. 
Turn tray over Gently Press 

 
  

 

To remove: 
  Peel the paper off of the tray. 

  Place the tray on your hand. 

  Turn the tray over and gently press the middle of the tray’s back to release the syringe into your 
palm. 

  If the pre-filled syringe does not release from the tray, gently press on the back of tray. 

  Do not pick up or pull the pre-filled syringe by the plunger rod or grey needle cap. This could 
damage the syringe. 

  Do not remove the grey needle cap from the pre-filled syringe until you are ready to inject. 

 
Always hold the pre-filled syringe by the syringe barrel. 

 
F Inspect medicine and syringe. 

Plunger rod  Syringe barrel
 Syringe label with 

expiration date 
Grey needle 
cap on 

Medicine 
Always hold the pre-filled syringe by the syringe barrel. 
Check that: 
  The name Repatha appears on the pre-filled syringe label. 

  The medicine in the pre-filled syringe is clear and colourless to slightly yellow. 

  Do not use the pre-filled syringe if any part of the pre-filled syringe appears cracked or broken. 

  Do not use the pre-filled syringe if the grey needle cap is missing or not securely attached. 

  Do not use the pre-filled syringe if the medicine is discoloured or contains large lumps, flakes or 
coloured particles. 

  Do not use the pre-filled syringe if the expiration date on the pre-filled syringe has passed. 

 



54 

Step 2: Get ready
A Carefully pull the grey needle cap straight out and away from your body. Do not leave the 

grey needle cap off for more than 5 minutes. This can dry out the medicine. 
1. 

 

2.

 

It is normal to see a drop of medicine at the 
end of the needle. 

 Immediately place the cap in the sharps disposal 
container.

  Do not twist or bend the grey needle cap. This can damage the needle. 
  Do not put the grey needle cap back onto the pre-filled syringe. 
 
B Remove the air bubble / gap. 
You may notice an air bubble/gap in the Repatha pre-filled syringe. 
If you notice an air bubble/gap: 
  Hold the pre-filled syringe with the needle facing up. 

  Gently tap the syringe barrel with your fingers until the air bubble/gap rises to the top of the 
syringe. 

  Slowly and gently push the plunger rod up to get the air out of the pre-filled syringe. Be very 
careful not to push out any medicine.

  Do not tap the syringe needle. 
 
C PINCH your injection site to create a firm surface. 

 

Pinch skin firmly between your thumb and fingers, creating an area about 2 inches (5 centimetres) 
wide. 

 It is important to keep the skin pinched while injecting. 



55 

Step 3: Inject
A Hold the PINCH. Insert the needle into the skin using a 45 to 90 degree angle. 

  Do not place your finger on the plunger rod while inserting the needle. 
 
B Using slow and constant pressure, PUSH the plunger rod all the way down until the syringe 

is empty. 

 
 
C When done, RELEASE your thumb, and gently lift the syringe off skin. 

  Do not put the grey needle cap back onto the used syringe. 
 



56 

Step 4: Finish
A Immediately place the used syringe in a sharps disposal container. 

Talk with your healthcare provider about proper disposal. There may be local guidelines for disposal. 
  Do not reuse the used syringe. 

  Do not use any medicine that is left in the used syringe. 

  Do not recycle the syringe or the sharps disposal container or throw it into household rubbish. 

 Keep the used syringe and sharps container out of the sight and reach of children. 

 
B Examine the injection site. 

If there is blood, press a cotton ball or gauze pad on your injection site. Apply a plaster if needed. 
  Do not rub the injection site. 
 



57 

Package leaflet: Information for the user 
 

Repatha 140 mg solution for injection in pre-filled pen 
evolocumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Repatha is and what it is used for 
2. What you need to know before you use Repatha 
3. How to use Repatha 
4. Possible side effects 
5. How to store Repatha 
6. Contents of the pack and other information 
 
 
1. What Repatha is and what it is used for 
 
What Repatha is and how it works 
 
Repatha is a medicine that lowers levels of ‘bad’ cholesterol, a type of fat, in the blood. 
 
Repatha contains the active substance evolocumab, a monoclonal antibody (a type of specialised 
protein designed to attach to a target substance in the body). Evolocumab is designed to attach to a 
substance called PCSK9 that affects the liver’s ability to take in cholesterol. By attaching to, and 
mopping up PCSK9, the medicine increases the amount of cholesterol entering the liver and so lowers 
the level of cholesterol in the blood. 
 
What Repatha is used for 
 
Repatha is used in addition to your cholesterol lowering diet if you are: 
 an adult with a high cholesterol level in your blood (primary hypercholesterolaemia 

[heterozygous familial and non-familial] or mixed dyslipidaemia). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 12 years and older with a high cholesterol level in your blood because of a condition that runs in 

your family (homozygous familial hypercholesterolaemia or HoFH). It is given: 
- together with other cholesterol lowering treatments. 

 an adult with a high cholesterol level in your blood and established atherosclerotic 
cardiovascular disease (a history of heart attack, stroke or blood vessel problems). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 



58 

Repatha is used in patients who cannot control their cholesterol levels with a cholesterol lowering diet 
alone. You should stay on your cholesterol lowering diet while taking this medicine. Repatha can help 
prevent heart attack, stroke, and certain heart procedures to restore blood flow to the heart due to a 
build-up of fatty deposits in your arteries (also known as atherosclerotic cardiovascular disease). 
 
 
2. What you need to know before you use Repatha 
 
Do not use Repatha if you are allergic to evolocumab or any of the other ingredients of this medicine 
(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Repatha if you have liver disease. 
 
The needle cover of the glass pre-filled pen is made from dry natural rubber (a derivative of latex), 
which may cause severe allergic reactions. 
 
Children and adolescents 
 
The use of Repatha has not been studied in children under 18 years of age being treated for primary 
hypercholesterolaemia and mixed dyslipidaemia. 
 
The use of Repatha has not been studied in children under 12 years of age being treated for 
homozygous familial hypercholesterolaemia. 
 
Other medicines and Repatha 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Repatha has not been tested in pregnant women. It is not known if Repatha will harm your unborn 
baby. 
 
It is not known whether Repatha is found in breast milk. 
 
It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help 
you decide whether to stop breast-feeding, or whether to stop taking Repatha, considering the benefit 
of breast-feeding to the baby and the benefit of Repatha to the mother. 
 
Driving and using machines 
 
Repatha has no or negligible influence on the ability to drive and use machines. 
 
Repatha contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-
free’. 
 
 



59 

3. How to use Repatha 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The recommended dose depends on the underlying condition: 
 for adults with primary hypercholesterolaemia and mixed dyslipidaemia the dose is either 

140 mg every two weeks or 420 mg once monthly. 
 for adults or adolescents with homozygous familial hypercholesterolaemia the recommended 

starting dose is 420 mg once monthly. After 12 weeks your doctor may decide to increase the 
dose to 420 mg every two weeks. If you also receive apheresis, a procedure similar to dialysis 
where cholesterol and other fats are removed from the blood, your doctor may decide to start 
you on a dose of 420 mg every two weeks to coincide with your apheresis treatment. 

 for adults with established atherosclerotic cardiovascular disease (a history of heart attack, 
stroke or blood vessel problems) the dose is either 140 mg every two weeks or 420 mg once 
monthly. 

 
Repatha is given as an injection under the skin (subcutaneous). 
 
If your doctor prescribes a dose of 420 mg you must use three pre-filled pens because each pre-filled 
pen only contains 140 mg of medicine. After reaching room temperature, all injections should be 
given within a 30 minute period. 
 
If your doctor decides that you or a caregiver can give the injections of Repatha, you or your caregiver 
should receive training on how to prepare and inject Repatha correctly. Do not try to inject Repatha 
until you have been shown how to do it by your doctor or nurse. 
 
See the detailed “Instructions for Use” at the end of this leaflet for instructions about how to store, 
prepare, and give your Repatha injections at home. If using the pre-filled pen, place the correct 
(yellow) end of the pen on the skin before injecting. 
 
Before starting Repatha, you should be on a diet to lower your cholesterol. You should keep on this 
cholesterol lowering diet while taking Repatha. 
 
If your doctor has prescribed Repatha along with another cholesterol lowering medicine, follow your 
doctor’s instructions on how to take these medicines together. In this case, please read the dosage 
instructions in the package leaflet of that particular medicine as well. 
 
If you use more Repatha than you should 
 
Contact your doctor or pharmacist immediately. 
 
If you forget to take Repatha 
 
Take Repatha as soon as you can after the missed dose. Then, contact your doctor who will tell you 
when you should schedule your next dose, and follow the new schedule exactly as your doctor has told 
you. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common (may affect up to 1 in 10 people) 
 Flu (high temperature, sore throat, runny nose, cough and chills) 
 Common cold, such as runny nose, sore throat or sinus infections (nasopharyngitis or upper 

respiratory tract infections) 



60 

 Feeling sick (nausea) 
 Back pain 
 Joint pain (arthralgia) 
 Injection site reactions, such as bruising, redness, bleeding, pain or swelling 
 Allergic reactions including rash 
 
Uncommon (may affect up to 1 in 100 people) 
 Hives, red itchy bumps on your skin (urticaria) 
 Flu-like symptoms 
 
Rare (may affect up to 1 in 1,000 people) 
 Swelling of the face, mouth, tongue, or throat (angioedema) 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Repatha 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Store in the original carton in order to protect from light. 
 
Your pre-filled pen may be left outside the refrigerator to reach room temperature (up to 25°C) before 
injection. This will make the injection more comfortable. After removal 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. 
 
Do not use this medicine if you notice it is discoloured or contains large lumps, flakes or coloured 
particles. 
 
Do not throw away any medicines via wastewater or household waste. 
 
Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Repatha contains 
- The active substance is evolocumab. Each SureClick pre-filled pen contains 140 mg of 

evolocumab in 1 mL of solution. 
- The other ingredients are proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water 

for injections. 
 
What Repatha looks like and contents of the pack 
 
Repatha is a solution which is clear to opalescent, colourless to yellowish, and practically free from 
particles.  



61 

 
Each pack contains one, two, three or six single use SureClick pre-filled pens. 
 
Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Manufacturer 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 
 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 
 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 
 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 
 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 
 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 
 

Norge 
Amgen AB 
Tel: +47 23308000 



62 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 
 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 422 06 06 

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 
 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 
 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 
 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 
 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 
 

 
This leaflet was last revised in. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
__________________________________________________________________________________ 
 



63 

Instructions for use: 
Repatha single use SureClick pre-filled pen 

 

Guide to parts 

Before use After use 

Grey start button 

Expiry date 

Window 

Medicine 

Orange cap on 
 

   
 
 
 
Expiry date 
 

Yellow window 
(injection complete)

Yellow safety guard 

Orange cap off 
 

Important: Needle is inside 

 
 



64 

Important 

Before you use the Repatha pre-filled pen, read this important information: 

  Do not freeze or use the Repatha pre-filled pen if it has been frozen. 

  Do not remove the orange cap from the Repatha pre-filled pen until you are ready to inject. 

  Do not use the Repatha pre-filled pen if it has been dropped on a hard surface. Part of the 
Repatha pre-filled pen may be broken even if you cannot see the break. 

 
Step 1: Prepare

A Remove one Repatha pre-filled pen from the package. 
1. Carefully lift the pre-filled pen straight up out of the box. 
2. Put the original package with any unused pre-filled pens back in the refrigerator. 
3. Wait at least 30 minutes for the pre-filled pen to naturally reach room temperature before 

injecting. 
  Do not try to warm the pre-filled pen by using a heat source such as hot water or microwave. 
  Do not leave the pre-filled pen in direct sunlight. 
  Do not shake the pre-filled pen.
  Do not remove the orange cap from the pre-filled pen yet.
 
B Inspect the Repatha pre-filled pen. 

Orange cap on Window Medicine 
Make sure the medicine in the window is clear and colourless to slightly yellow. 
Check the expiration date. 
   Do not use the pre-filled pen if medicine is cloudy or discoloured or contains large lumps, 

flakes, or particles. 
   Do not use the pre-filled pen if any part appears cracked or broken. 
   Do not use if the pre-filled pen has been dropped. 
   Do not use the pre-filled pen if the orange cap is missing or not securely attached. 
   Do not use the pre-filled pen if the expiration date has passed. 
In all cases, use a new pre-filled pen. 
 



65 

C Gather all materials needed for your injection. 
Wash your hands thoroughly with soap and water. 
On a clean, well-lit work surface, place the: 
  New pre-filled pen. 
  Alcohol wipes. 
  Cotton ball or gauze pad. 
  Plaster. 
  Sharps disposal container. 
 

 

 
D Prepare and clean your injection site. 

Upper arm 

Belly 

Thigh 

You can use: 
  Thigh. 
  Belly, except for a 2 inch (5 centimetres) area around your belly button. 
  Outer area of upper arm (only if someone else is giving you the injection). 
Clean the injection site with an alcohol wipe. Let your skin dry. 
  Do not touch this area again before injecting. 
  Choose a different site each time you give yourself an injection. If you need to use the same 

injection site, just make sure it is not the same spot on that site you used last time. 
  Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into 

areas with scars or stretch marks. 
 



66 

Step 2: Get ready
A Pull the orange cap straight off, only when you are ready to inject. Do not leave the orange cap 

off for more than 5 minutes. This can dry out the medicine. 

 

It is normal to see a drop of liquid at the end of the needle or yellow safety guard. 
   Do not twist, bend or wiggle the orange cap. 
   Do not put the orange cap back onto the pre-filled pen. 
   Do not put fingers into the yellow safety guard. 

 Important: Do not remove the orange cap from the pre-filled pen until you are ready to 
inject. 

 
B Stretch or pinch your injection site to create a firm surface. 
Stretch method 

 

Stretch skin firmly by moving your thumb and fingers in the opposite direction, creating an area about 
2 inches (5 centimetres) wide. 

OR
Pinch method 

 

Pinch skin firmly between your thumb and fingers, creating an area about 2 inches (5 centimetres) 
wide. 
 Important: It is important to keep skin stretched or pinched while injecting. 
 



67 

Step 3: Inject
A Hold the stretch or pinch to create a firm surface. With the cap off, place the yellow end of 

the pre-filled pen on the skin at 90 degrees. 

Yellow safety guard

Correct Incorrect 
Do not touch the grey start button

 

 
B Firmly PUSH down the pre-filled pen onto the skin until it stops moving. 

PUSH DOWN

 

 Important: You must push all the way down but do not touch the grey start button until 
you are ready to inject. 

 
C When you are ready to inject, press the grey start button. You will hear a click. 

 
“Click” 

 

 



68 

D Keep PUSHING down on the skin. Then LIFT thumb. Your injection could take 
about 15 seconds. 

 

 
“Click” 

 

15 Seconds 

 

Window turns yellow 
when the injection is 
done 

 NOTE: After you remove the pre-filled pen from your skin, the needle will be automatically covered. 

 
Step 4: Finish

A Discard the used pre-filled pen and orange needle cap.

 

Discard the used pre-filled pen and the orange cap in a sharps disposal container. 
Talk with your healthcare provider about proper disposal. There may be local guidelines for disposal. 
Keep the pre-filled pen and the sharps disposal container out of the sight and reach of children. 
   Do not reuse the pre-filled pen. 
   Do not recap the pre-filled pen or put fingers into the yellow safety guard. 
   Do not recycle the pre-filled pen or sharps disposal container or throw them into 

household rubbish. 
 
B Examine the injection site. 
If there is blood, press a cotton ball or gauze pad on your injection site. DO NOT rub the injection site. 
Apply a plaster if needed. 
 



69 

Package leaflet: Information for the user 
 

Repatha 420 mg solution for injection in cartridge 
evolocumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Repatha is and what it is used for 
2. What you need to know before you use Repatha 
3. How to use Repatha 
4. Possible side effects 
5. How to store Repatha 
6. Contents of the pack and other information 
 
 
1. What Repatha is and what it is used for 
 
What Repatha is and how it works 
 
Repatha is a medicine that lowers levels of ‘bad’ cholesterol, a type of fat, in the blood. 
 
Repatha contains the active substance evolocumab, a monoclonal antibody (a type of specialised 
protein designed to attach to a target substance in the body). Evolocumab is designed to attach to a 
substance called PCSK9 that affects the liver’s ability to take in cholesterol. By attaching to, and 
mopping up PCSK9, the medicine increases the amount of cholesterol entering the liver and so lowers 
the level of cholesterol in the blood. 
 
What Repatha is used for 
 
Repatha is used in addition to your cholesterol lowering diet if you are: 
 an adult with a high cholesterol level in your blood (primary hypercholesterolaemia 

[heterozygous familial and non-familial] or mixed dyslipidaemia). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 12 years and older with a high cholesterol level in your blood because of a condition that runs in 

your family (homozygous familial hypercholesterolaemia or HoFH). It is given: 
- together with other cholesterol lowering treatments. 

 an adult with a high cholesterol level in your blood and established atherosclerotic 
cardiovascular disease (a history of heart attack, stroke or blood vessel problems). It is given: 
- together with a statin or other cholesterol lowering medication, if the maximum dose of a 

statin does not lower levels of cholesterol sufficiently. 
- alone or together with other cholesterol lowering medications when statins do not work 

well or cannot be used. 
 



70 

Repatha is used in patients who cannot control their cholesterol levels with a cholesterol lowering diet 
alone. You should stay on your cholesterol lowering diet while taking this medicine. Repatha can help 
prevent heart attack, stroke, and certain heart procedures to restore blood flow to the heart due to a 
build-up of fatty deposits in your arteries (also known as atherosclerotic cardiovascular disease). 
 
 
2. What you need to know before you use Repatha 
 
Do not use Repatha if you are allergic to evolocumab or any of the other ingredients of this medicine 
(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before using Repatha if you have liver disease. 
 
Children and adolescents 
 
The use of Repatha has not been studied in children under 18 years of age being treated for primary 
hypercholesterolaemia and mixed dyslipidaemia. 
 
The use of Repatha has not been studied in children under 12 years of age being treated for 
homozygous familial hypercholesterolaemia. 
 
Other medicines and Repatha 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Repatha has not been tested in pregnant women. It is not known if Repatha will harm your unborn 
baby. 
 
It is not known whether Repatha is found in breast milk. 
 
It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help 
you decide whether to stop breast-feeding, or whether to stop taking Repatha, considering the benefit 
of breast-feeding to the baby and the benefit of Repatha to the mother. 
 
Driving and using machines 
 
Repatha has no or negligible influence on the ability to drive and use machines. 
 
Repatha contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-
free’. 
 
 
3. How to use Repatha 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 



71 

The recommended dose depends on the underlying condition: 
 for adults with primary hypercholesterolaemia and mixed dyslipidaemia the dose is either 

140 mg every two weeks or 420 mg once monthly. 
 for adults or adolescents with homozygous familial hypercholesterolaemia the recommended 

starting dose is 420 mg once monthly. After 12 weeks your doctor may decide to increase the 
dose to 420 mg every two weeks. If you also receive apheresis, a procedure similar to dialysis 
where cholesterol and other fats are removed from the blood, your doctor may decide to start 
you on a dose of 420 mg every two weeks to coincide with your apheresis treatment. 

 for adults with established atherosclerotic cardiovascular disease (a history of heart attack, 
stroke or blood vessel problems) the dose is either 140 mg every two weeks or 420 mg once 
monthly. 

 
Repatha is given as an injection under the skin (subcutaneous). 
 
If your doctor decides that you or a caregiver can give the injections of Repatha using the automated 
mini-doser, you or your caregiver should receive training on how to prepare and inject Repatha 
correctly. Do not try to use the automated mini-doser until you have been shown how to do it by your 
doctor or nurse. It is recommended that 12 and 13 year olds are supervised by an adult when they are 
using the automated mini-doser. 
 
See the detailed “Instructions for Use” at the end of this leaflet for instructions about how to store, 
prepare, and use your Repatha automated mini-doser at home. 
 
Before starting Repatha, you should be on a diet to lower your cholesterol. You should keep on this 
cholesterol lowering diet while taking Repatha. 
 
If your doctor has prescribed Repatha along with another cholesterol lowering medicine, follow your 
doctor’s instructions on how to take these medicines together. In this case, please read the dosage 
instructions in the package leaflet of that particular medicine as well. 
 
If you use more Repatha than you should 
 
Contact your doctor or pharmacist immediately. 
 
If you forget to take Repatha 
 
Take Repatha as soon as you can after the missed dose. Then, contact your doctor who will tell you 
when you should schedule your next dose, and follow the new schedule exactly as your doctor has told 
you. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common (may affect up to 1 in 10 people) 
 Flu (high temperature, sore throat, runny nose, cough and chills) 
 Common cold, such as runny nose, sore throat or sinus infections (nasopharyngitis or upper 

respiratory tract infections) 
 Feeling sick (nausea) 
 Back pain 
 Joint pain (arthralgia) 
 Injection site reactions, such as bruising, redness, bleeding, pain or swelling 
 Allergic reactions including rash 
 



72 

Uncommon (may affect up to 1 in 100 people) 
 Hives, red itchy bumps on your skin (urticaria) 
 Flu-like symptoms 
 
Rare (may affect up to 1 in 1,000 people) 
 Swelling of the face, mouth, tongue, or throat (angioedema) 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Repatha 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Store in the original carton in order to protect from light and moisture. 
 
Your medicine (cartridge and automated mini-doser) may be left outside the refrigerator to reach room 
temperature (up to 25°C) before injection. This will make the injection more comfortable. After 
removal 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. 
 
Do not use this medicine if you notice it is discoloured or contains large lumps, flakes or coloured 
particles. 
 
Do not throw away any medicines via wastewater or household waste. 
 
Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Repatha contains 
- The active substance is evolocumab. Each cartridge contains 420 mg of evolocumab in 3.5 mL 

of solution (120 mg/mL). 
- The other ingredients are proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water 

for injections. 
 
What Repatha looks like and contents of the pack 
 
Repatha is a solution which is clear to opalescent, colourless to yellowish, and practically free from 
particles.  
 
Each pack contains one single use cartridge co-packed with a single use automated mini-doser. 
 



73 

Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Manufacturer 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 
 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 
 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 
 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 
 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 
 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 
 

Norge 
Amgen AB 
Tel: +47 23308000 
 



74 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 
 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 422 06 06 

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 
 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 
 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 
 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 
 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 
 

 
This leaflet was last revised in. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



75 

 
Instructions for use: 
Repatha single use automated mini-doser and cartridge

 
Guide to parts 

Cartridge
 

White plunger
 Cartridge top 

(Do not rotate) 

Cartridge bottom 

Medicine 
 

 
 

 

 

Cartridge label 

 

Automated mini-doser 
Front view 

Skin 
adhesive

Status 
light 

Start button 
(Do not press until  
ready to inject) 

 

Cartridge door  
(do not close without 

cartridge) 

 

 

 

Medicine 
window 
Pull tabs 

 

Back view Needle cover Adhesive paper 
 

 

Battery  
strip 

Left pull tab 

 

 

 

Needle inside 
(under cover) 

Right pull tab 
 

Important: Needle is inside. 



76 

Important 

Before you use the automated mini-doser and cartridge for use with Repatha, read this important 
information: 
Storing your automated mini-doser and cartridge 

  Keep the automated mini-doser and cartridge out of the sight and reach of children. 

  Do not store the automated mini-doser and cartridge in extreme heat or cold. For example, avoid 
storing in your vehicle’s glove box or boot. Do not freeze. 

Using your automated mini-doser and cartridge 

  Do not shake the automated mini-doser or cartridge. 

  Do not remove the automated mini-doser and cartridge from the box or clear tray until you are 
ready to inject. 

  Do not touch the start button until you place the loaded automated mini-doser and cartridge onto 
your skin and are ready to inject.

  You can only press the start button once. If an error occurs, the automated mini-doser cannot be 
used. 

  Do not use the automated mini-doser and cartridge if either have been dropped onto a hard 
surface. Part of the automated mini-doser and cartridge may be broken even if you cannot see 
the break. Use a new automated mini-doser and cartridge. 

  Do not reuse the automated mini-doser and cartridge. The automated mini-doser and cartridge 
are for single use only. 

  Do not let the automated mini-doser get wet from water or any other liquids. It contains 
electronics that should not get wet. 

  The single use automated mini-doser for subcutaneous injection is intended only for use with the 
cartridge. 

In any above cases, use a new automated mini-doser and cartridge. A healthcare provider familiar with 
Repatha should be able to answer your questions. 
 



77 

Step 1: Prepare
A Remove the automated mini-doser and cartridge carton from the refrigerator. Wait 

45 minutes. 
Important: Wait at least 45 minutes for the automated mini-doser and cartridge to naturally reach room 
temperature in the carton, before you inject.
  Do not try to warm the cartridge by using a heat source such as hot water or a microwave. 
  Do not shake the automated mini-doser and cartridge. 
  Do not use if any part of the cartridge appears cracked or broken. 
  Do not use if the expiration date printed on the carton label has passed. 
In any above cases, use a new automated mini-doser and cartridge.
 

B Open the carton and peel away the white paper cover. Remove the automated mini-doser 
cover from the clear tray. 

 

Clear tray 

Cartridge 

 

  

Automated  
mini-doser 
Plastic cover 

 

Leave the automated mini-doser and cartridge in the clear tray until you are ready to inject.  
  Do not touch the start button until the automated mini-doser is on your skin and you are ready 

to inject. 
  Do not use if the white paper cover is missing or damaged. 
 

C Gather all materials needed for your injection and then wash your hands thoroughly with 
soap and water. 

On a clean, well-lit work surface, place the: 
 Clear tray containing the automated mini-doser and cartridge 
 Alcohol wipes 
 Cotton ball or gauze pad 
 Plaster 
 Sharps disposal container 

 

 
 

 

 

 



78 

D Choose your automated mini-doser placement. Only use the outer arm if someone else is 
giving the injection.  

 
You can use: 
 Your thigh 
 Belly, except for a 2-inch 

(5 centimetre) area around your 
belly button 

 Outer area of upper arm (only if 
someone else is giving the 
injection) 

 

 

Upper arm 

Belly 

Thigh 

 

Clean your injection site with an alcohol wipe. Let your skin dry. 
  Do not touch this area again before injecting. 
  Do not inject into areas where the skin is tender, bruised, red or hard. Avoid injecting into areas 

with wrinkles, skin folds, scars, stretch marks, moles and excessive hair. 
If you want to use the same injection site, make sure it is not the same spot on the injection site you 
used for a previous injection. 
Important: To attach the automated mini-doser securely, it is important to use a firm and flat 
skin surface. 
 

Step 2: Get ready
E Open the automated mini-doser by swinging the cartridge door to the right. Then, leave the 

door open.  

Do not press the start button 
until you are ready to inject. 

 

 

 



79 

F Inspect the cartridge. 
 

Cartridge bottom Medicine 

Cartridge label Cartridge top (do not rotate)

White plunger
 

Expiration date  
 

 

Make sure the medicine in the cartridge is clear and colourless to slightly yellow. 
  Do not use if the medicine is cloudy or discoloured or contains flakes or particles. 
  Do not use if any part of the cartridge appears cracked or broken. 
  Do not use if pieces of the cartridge are missing or not securely attached. 
  Do not use if the expiration date on the cartridge has passed. 
In any above cases, use a new automated mini-doser and cartridge. 

 
G Clean the cartridge bottom. 

 

Grab here
With one hand, hold the cartridge barrel and clean the cartridge bottom with an alcohol wipe. 
  Do not touch the bottom of the cartridge after cleaning with alcohol wipe. 
  Do not remove or rotate the cartridge top or bottom. 
 



80 

H Load the cleaned cartridge into the automated mini-doser and firmly press on the top until 
it is secured in place. 

Load the 
cartridge 
straight 

 

 

Press 
down 
firmly 

 

Insert the cartridge bottom first. 
  Do not insert the cartridge more than 5 minutes before injection. This can dry out the medicine. 
  Do not touch the start button until you have placed the loaded automated mini-doser on your 

skin. 
 

I Swing the door to the left. Then, squeeze firmly until it snaps shut. 

 Squeeze  tight  

 
snap 

  

Make sure the cartridge fits securely in the automated mini-doser before you close the door. 
  Do not close the door if the cartridge is missing or not fully inserted. 
  Do not touch the start button until you have placed the loaded automated mini-doser on your 

skin. 
Important: After you load the automated mini-doser, proceed to the next step without delay. 
 



81 

Step 3: Inject
J Peel away both green pull tabs to show the adhesive. The automated mini-doser is on when the 

blue status light flashes. 
Right pull tab 

 

Flashing Light 
 

Left 
pull 
tab 

 

 

 Skin adhesive 
 

 

 
Beep-beep-beep 

 

 

You must remove both green pull tabs to turn the loaded automated mini-doser on. You will hear 
beeping and see a flashing blue status light. 
  Do not touch the skin adhesive. 
  Do not touch the start button until you have placed the loaded automated mini-doser on your skin. 
  Do not touch or contaminate the needle cover area. 
  Do not place the loaded automated mini-doser on your body if the red status light flashes for more 

than 5 seconds. 
  Do not pull the skin adhesive backing off of the automated mini-doser. 
  Do not fold the skin adhesive over onto itself. 

 
K To securely attach the automated mini-doser, prepare and clean an injection site that is 

less likely to have body hair, or you can trim the area. Use a firm and flat skin surface. 
Belly area placement  Thigh placement 

 

 

OR 
 

 

 

Stretch method for belly  Do not stretch for thigh 
Important: Adjust your body posture to avoid skin folds and bulges. 
 



82 

L When the blue light flashes, the automated mini-doser is ready. Keep the stretch (belly area 
method only). Hold the loaded automated mini-doser with the blue light visible, and place it on 
your skin. You may hear beeps. 

 

 

OR 

 

Flashing Light 

 
beep-beep-beep 

 

 
The loaded automated mini-doser will lay flat on your body. Make sure the entire adhesive is attached to 
your skin. Run a finger around the adhesive edges to secure it. 
Make sure clothing does not get in the way of the loaded automated mini-doser, and you can see the blue 
light at all times. 
  Do not try to reposition the loaded automated mini-doser after it has been placed onto your skin. 
 

M Firmly press and release the start button. A flashing green light and a click signals the injection 
has started.  

 
 

Flashing Light 

 
 

beep-beep-beep 

 

 
 You may hear a pumping sound. 
 You may feel a needle pinch. 
 Make sure you see a green, flashing status light. 
 You may hear beeps indicating your injection has started. 
 
Important: If medication leaks from the loaded automated mini-doser contact your doctor or 
pharmacist. 
 
 



83 

N Injection takes about 5 minutes. The status light turns solid green, and the device beeps, 
when done. 

 
It is okay to hear a pumping sound start and stop during injection. 
 
 Moderate physical activities can be performed during the injection 

process, such as walking, reaching and bending. 
 

Flashing Light 

 

5 min 

 
 
 

Solid Light 

 

Injection is complete when: 
 The status light changes to solid green. 
 You hear several beeps. 

beep-beep-beep 

 

 

 
Step 4: Finish

O When the injection is done, grab the skin adhesive to carefully peel the automated mini-
doser off your skin. After removal, check the medicine window. The green light should now 
be off. 

Used plunger 

 

 

Light Off 

 

beep-beep-beep 

 

Check to see that the used plunger completely fills the medicine window, and the green solid light turns 
off, letting you know all medicine has been injected. If the plunger did not fill the window, contact your 
doctor. 
  The used automated mini-doser will beep when removed from your skin. 
  It is normal to see a few drops of fluid on your skin after you remove the used automated mini-

doser. 
 
 



84 

P Discard the used automated mini-doser in a sharps container.
 The automated mini-doser contains batteries, electronics, and a needle. 
 Put the used automated mini-doser in sharps disposal container right 

away after use. Do not throw away (dispose of) the automated mini-
doser in your household waste. 

 Talk with your healthcare provider about proper disposal. There may be 
local guidelines for disposal. 

 Do not remove the used cartridge from the automated mini-doser. 
 Do not reuse the automated mini-doser. 
 Do not recycle the automated mini-doser or sharps disposal container or 

throw them into household waste. 
 
Important: Always keep the sharps disposal container out of the sight and 
reach of children. 

 

 
Q Examine the injection site. 
If there is blood, press a cotton ball or gauze pad on your injection site. Do not rub the injection site. 
Apply a plaster if needed. 
 

Troubleshooting
What to do if the loaded automated mini-doser status light continuously flashes red and you hear beeps.

 

Flashing Warning Light 

 
 
beep-beep-beep-beep-beep 

 

 
Stop using the loaded automated mini-doser. If the automated mini-doser is attached to your body, 
carefully remove it.  
 

Additional environmental conditions
Relative humidity range is 15% to 85%.
Altitude range is -300 metres to 3,500 metres (-984 feet to 11,483 feet).
During injection, keep the automated mini-doser a minimum of 30 cm (12 inches) away from other 
electronics such as mobile phones. 
Warning: Do not modify the device. 
Automated mini-doser operating temperature range is 15°C to 40°C.
www.devicepatents.com  
 



85 

SYMBOL TABLE 

    

Do not use if 
packaging is 

damaged 

Keep dry Refer to 
Instructions for 

Use

Type BF 
Applied Part 

Single use Sterilised 
using ethylene 

oxide 
 
 

 0344 

 
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, U.S.A. 

 Amgen Europe B.V., Minervum 7061, 4817 ZK, Breda, The Netherlands 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET