Praluent

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Praluent 75 mg solution for injection in pre-filled pen 
Praluent 150 mg solution for injection in pre-filled pen 
Praluent 75 mg solution for injection in pre-filled syringe 
Praluent 150 mg solution for injection in pre-filled syringe 
Praluent 300 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Praluent 75 mg solution for injection in pre-filled pen 
 
Each single-use pre-filled pen contains 75 mg alirocumab in 1 ml solution. 
 
Praluent 75 mg solution for injection in pre-filled syringe 
 
Each single-use pre-filled syringe contains 75 mg alirocumab in 1 ml solution. 
 
Praluent 150 mg solution for injection in pre-filled pen 
 
Each single-use pre-filled pen contains 150 mg alirocumab in 1 ml solution. 
 
Praluent 150 mg solution for injection in pre-filled syringe 
 
Each single-use pre-filled syringe contains 150 mg alirocumab in 1 ml solution. 
 
Praluent 300 mg solution for injection in pre-filled pen 
 
Each single-use pre-filled pen contains 300 mg alirocumab in 2 ml solution. 
 
Alirocumab is a human IgG1 monoclonal antibody produced in Chinese Hamster Ovary cells by 
recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection)  
 
Clear, colourless to pale yellow solution. 
 
pH: 5.7 – 6.3 
 
Osmolality: 
 
Praluent 75 mg solution for injection 
293 - 439 mOsm/kg 
 
Praluent 150 mg solution for injection 
383 - 434 mOsm/kg 
 
Praluent 300 mg solution for injection 
383 – 434 mOsm/kg 
 



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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Primary hypercholesterolaemia and mixed dyslipidaemia  
 
Praluent 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. 

 
Established atherosclerotic cardiovascular disease  
 
Praluent is indicated in adults with established atherosclerotic cardiovascular 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  
 
Posology 
 
Prior to initiating alirocumab secondary causes of hyperlipidaemia or mixed dyslipidaemia (e.g., nephrotic 
syndrome, hypothyroidism) should be excluded. 
 
The usual starting dose for alirocumab is 75 mg administered subcutaneously once every 2 weeks. Patients 
requiring larger LDL-C reduction (>60%) may be started on 150 mg once every 2 weeks, or 300 mg once 
every 4 weeks (monthly), administered subcutaneously. 
 
The dose of alirocumab can be individualised based on patient characteristics such as baseline LDL-C level, 
goal of therapy, and response. Lipid levels can be assessed 4 to 8 weeks after treatment initiation or titration, 
and dose adjusted accordingly (up-titration or down-titration). If additional LDL-C reduction is needed in 
patients treated with 75 mg once every 2 weeks or 300 mg once every 4 weeks (monthly), the dosage may be 
adjusted to the maximum dosage of 150 mg once every 2 weeks.  
 
If a dose is missed, the patient should administer the injection as soon as possible and thereafter resume 
treatment on the original schedule. 
 
Special populations 
 
Elderly  
 
No dose adjustment is needed for elderly patients.  
 
Hepatic impairment 
 
No dose adjustment is needed for patients with mild or moderate hepatic impairment. No data are available 
in patients with severe hepatic impairment (see section 5.2). 



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Renal impairment 
 
No dose adjustment is needed for patients with mild or moderate renal impairment. Limited data are 
available in patients with severe renal impairment (see section 5.2). 
 
Body weight 
 
No dose adjustment is needed in patients based on weight.  
 
Paediatric population 
 
The safety and efficacy of Praluent in children and adolescents less than 18 years of age have not been 
established. Currently available data are described in sections 4.8, 5.1, and 5.2 but no recommendation on a 
posology can be made. Alirocumab has not been studied in paediatric patients less than 8 years of age. 
 
Method of administration  
 
Subcutaneous use. 
 
Alirocumab is injected as a subcutaneous injection into the thigh, abdomen or upper arm. 
 
Each pre-filled pen or pre-filled syringe is for single use only. 
 
To administer the 300 mg dose, either one 300 mg injection or two 150 mg injections should be given 
consecutively at two different injection sites. 
 
It is recommended to rotate the injection site with each injection. 
 
Alirocumab should not be injected into areas of active skin disease or injury such as sunburns, skin rashes, 
inflammation, or skin infections. 
 
Alirocumab must not be co-administered with other injectable medicinal products at the same injection site.  
 
The patient may either self-inject alirocumab, or a caregiver may administer alirocumab, after guidance has 
been provided by a healthcare professional on proper subcutaneous injection technique. 
 
Precautions to be taken before handling or administering the medicinal product 
The solution should be allowed to warm to room temperature prior to use (see section 6.6). 
 
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. 
 
Allergic reactions 
 
General allergic reactions, including pruritus, as well as rare and sometimes serious allergic reactions such as 
hypersensitivity, nummular eczema, urticaria, and hypersensitivity vasculitis have been reported in clinical 
studies. Angioedema has been reported in the postmarketing setting (see section 4.8). If signs or symptoms 



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of serious allergic reactions occur, treatment with alirocumab must be discontinued and appropriate 
symptomatic treatment initiated (see section 4.3).  
 
Renal impairment 
 
In clinical studies, there was limited representation of patients with severe renal impairment (defined as 
eGFR < 30 ml/min/1.73 m2) (see section 5.2). Alirocumab should be used with caution in patients with 
severe renal impairment. 
 
Hepatic impairment 
 
Patients with severe hepatic impairment (Child-Pugh C) have not been studied (see section 5.2). Alirocumab 
should be used with caution in patients with severe hepatic impairment. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Effects of alirocumab on other medicinal products   
 
Since alirocumab is a biological medicinal product, no pharmacokinetic effects of alirocumab on other 
medicinal products and no effect on cytochrome P450 enzymes are anticipated.  
 
Effects of other medicinal products on alirocumab 
 
Statins and other lipid-modifying therapy are known to increase production of PCSK9, the protein targeted by 
alirocumab. This leads to the increased target-mediated clearance and reduced systemic exposure of 
alirocumab. Compared to alirocumab monotherapy, the exposure to alirocumab is about 40%, 15%, and 35% 
lower when used concomitantly with statins, ezetimibe, and fenofibrate, respectively. However, reduction of 
LDL-C is maintained during the dosing interval when alirocumab is administered every two weeks. 
 
4.6 Fertility, pregnancy and lactation  
 
Pregnancy 
 
There are no data from the use of Praluent in pregnant women. Alirocumab is a recombinant IgG1 antibody, 
therefore it is expected to cross the placental barrier (see section 5.3).  
Animal studies do not indicate direct or indirect harmful effects with respect to maintenance of pregnancy or 
embryo-foetal development; maternal toxicity was noted in rats, but not in monkeys at doses in excess of the 
human dose, and a weaker secondary immune response to antigen challenge was observed in the offspring of 
monkeys (see section 5.3).  
The use of Praluent is not recommended during pregnancy unless the clinical condition of the woman 
requires treatment with alirocumab. 
 
Breast-feeding 
 
It is not known whether alirocumab is excreted in human milk. Human immunoglobulin G (IgG) is excreted 
in human milk, in particular in colostrum; the use of Praluent is not recommended in breast-feeding women 
during this period. For the remaining duration of breast-feeding, exposure is expected to be low.  
Since the effects of alirocumab on the breast-fed infant are unknown, a decision should be made whether to 
discontinue nursing or to discontinue Praluent during this period. 
 
Fertility 
 
In animal studies, there were no adverse effects on surrogate markers of fertility (see section 5.3). There are 
no data on adverse effects on fertility in humans. 
 



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4.7 Effects on ability to drive and use machines  
 
Praluent has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects  
 
Summary of the safety profile 
 
The most common adverse reactions, at recommended doses, are local injection site reactions (6.1%), upper 
respiratory tract signs and symptoms (2.0%), and pruritus (1.1%). Most common adverse reactions leading to 
treatment discontinuation in patients treated with alirocumab were local injection site reactions.  
The safety profile in ODYSSEY OUTCOMES was consistent with the overall safety profile described in the 
phase 3 controlled trials. 
 
No difference in the safety profile was observed between the two doses (75 mg and 150 mg) used in the 
phase 3 program. 
 
Tabulated list of adverse reactions  
 
The following adverse reactions were reported in patients treated with alirocumab in pooled controlled 
studies and/or post-marketing use (see Table 1). 
 
Frequencies for all adverse reactions identified from clinical trials have been calculated based on their 
incidence in pooled phase 3 clinical trials. Adverse reactions are presented by system organ class. Frequency 
categories are defined as: 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); very rare (<1/10,000) and not known (cannot be estimated from the 
available data).  
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they are 
derived from spontaneous reports. Consequently, the frequency of these adverse reactions is qualified as "not 
known". 
 
Table 1 – Adverse reactions  
System organ class Common Rare Not known 

Immune system disorders  Hypersensitivity, 
hypersensitivity 
vasculitis 

 

Respiratory, thoracic and 
mediastinal disorders 

Upper respiratory 
tract signs and 
symptoms* 

  

Skin and subcutaneous tissue 
disorders 

Pruritus Urticaria, 
eczema nummular 

Angioedema 

General disorders and 
administration site conditions 

Injection site 
reactions** 

 Flu-like illness 

*   including mainly oropharyngeal pain, rhinorrhea, sneezing 
** including erythema/redness, itching, swelling, pain/tenderness 
 



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Description of selected adverse reactions 
 
Local injection site reactions  
 
Local injection site reactions, including erythema/redness, itching, swelling, and pain/tenderness, were 
reported in 6.1% of patients treated with alirocumab versus 4.1% in the control group (receiving placebo 
injections). Most injection site reactions were transient and of mild intensity. The discontinuation rate due to 
local injection site reactions was comparable between the two groups (0.2% in the alirocumab group versus 
0.3% in the control group). In the cardiovascular outcomes study (ODYSSEY OUTCOMES), injection site 
reactions also occurred more frequently in alirocumab-treated patients than in placebo-treated patients (3.8% 
alirocumab versus 2.1% placebo). 
 
General allergic reactions  
 
General allergic reactions were reported more frequently in the alirocumab group (8.1% of patients) than in 
the control group (7.0% of patients), mainly due to a difference in the incidence of pruritus. The observed 
cases of pruritus were typically mild and transient. In addition, rare and sometimes serious allergic reactions 
such as hypersensitivity, nummular eczema, urticaria, and hypersensitivity vasculitis have been reported in 
controlled clinical studies (see section 4.4). In the cardiovascular outcomes study (ODYSSEY 
OUTCOMES), general allergic reactions were similar in alirocumab-treated patients and placebo-treated 
patients (7.9% alirocumab, 7.8% placebo). No difference was seen in the incidence of pruritus. 
 
Special populations 
 
Elderly 
 
Although no safety issues were observed in patients over 75 years of age, data are limited in this age group. 
In the phase 3 primary hypercholesterolemia and mixed dyslipidaemia controlled studies, 1,158 patients 
(34.7%) treated with alirocumab were ≥65 years of age and 241 patients (7.2%) treated with alirocumab were 
≥75 years of age. In the cardiovascular outcomes controlled study, 2,505 patients (26.5%) treated with 
alirocumab were ≥65 years of age and 493 patients (5.2%) treated with alirocumab were ≥75 years of age. 
There were no significant differences observed in safety and efficacy with increasing age. 
 
Paediatric population 
 
The experience of alirocumab in paediatric patients is limited to 18 patients aged 8 to 17 years with 
homozygous familial hypercholesterolaemia (HoFH). No new safety finding was observed compared to the 
known adult safety profile. 
 
Every 4 week dosing study  
 
The safety profile in patients treated with a 300 mg once every 4 week (monthly) dosing regimen was similar 
to the safety profile as described for the clinical studies program using a 2 week dosing regimen, except for a 
higher rate of local injection site reactions. Local injection site reactions were reported overall at a frequency 
of 16.6% in the 300 mg once every 4 weeks treatment group and 7.9% in the placebo group. Patients in the 
alirocumab 300 mg every 4 weeks treatment group received alternating placebo injections to maintain 
blinding in regard to injection frequency. Excluding injection site reactions (ISRs) that occurred after these 
placebo injections, the frequency of ISRs was 11.8%. The discontinuation rate due to injection site reactions 
was 0.7% in the 300 mg once every 4 weeks treatment group and 0% in the placebo group. 
 
LDL-C values <25 mg/dL (<0.65 mmol/L) 
 
In all clinical studies background lipid lowering therapies could not be adjusted by trial design. The 
percentage of patients who reached LDL-C values <25 mg/dL (<0.65 mmol/L) depended both on the 
baseline LDL-C and the dose of alirocumab. 
 



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In a pool of controlled studies using a 75 mg every 2 week (Q2W) starting dose and in which the dose was 
increased to 150 mg Q2W if the patient’s LDL-C was not <70 mg/dL or < 100 mg/dL (1.81 mmol/L or 2.59 
mmol/L), 29.3% of patients with baseline LDL-C <100 mg/dL and 5.0% of patients with baseline LDL-C 
≥100 mg/dL treated with alirocumab had two consecutive values of LDL-C <25 mg/dL (<0.65 mmol/L). In 
the ODYSSEY OUTCOMES study, in which the starting alirocumab dose was 75 mg Q2W and the dose 
was increased to 150 mg Q2W if the patient’s LDL-C was not <50 mg/dL (1.29 mmol/L), 54.8% of patients 
with baseline LDL-C <100 mg/dL and 24.2% of patients with baseline LDL-C ≥100 mg/dL treated with 
alirocumab had two consecutive values of LDL-C <25 mg/dL (<0.65 mmol/L). 
 
Although adverse consequences of very low LDL-C were not identified in alirocumab trials, the long-term 
effects of very low levels of LDL-C are unknown. In published genetic studies as well as clinical and 
observational trials with lipid lowering therapies an increased risk of new onset of diabetes has been 
associated with lower levels of LDL-C. 
 
Immunogenicity/ Anti-drug-antibodies (ADA)  
 
In the ODYSSEY OUTCOMES trial, 5.5% of patients treated with alirocumab 75 mg and/or 150 mg every 
2 weeks (Q2W) had anti-drug antibodies (ADA) detected after initiating treatment compared with 1.6% of 
patients treated with placebo, most of these were transient responses. Persistent ADA responses were 
observed in 0.7% of patients treated with alirocumab and 0.4% of patients treated with placebo. Neutralising 
antibody (NAb) responses were observed in 0.5% of patients treated with alirocumab and in <0.1% of 
patients treated with placebo.  
 
Anti-drug antibody responses, including NAb, were low titer and did not appear to have a clinically 
meaningful impact on the efficacy or safety of alirocumab, except for a higher rate of injection site reactions 
in patients with treatment emergent ADA compared to patients who were ADA negative (7.5% vs 3.6%). 
The long-term consequences of continuing alirocumab treatment in the presence of ADA are unknown. 
In a pool of ten placebo-controlled and active-controlled trials of patients treated with alirocumab 75 mg 
and/or 150 mg Q2W as well as in a separate clinical study of patients treated with alirocumab 75 mg Q2W or 
300 mg every 4 weeks (including some patients with dose adjustment to 150 mg Q2W), the incidence of 
detecting ADA and NAb was similar to the results from the ODYSSEY OUTCOMES trial described above. 
 
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  
 
There is no specific treatment for alirocumab 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: C10AX14. 
 
Mechanism of action 
 
Alirocumab is a fully human IgG1 monoclonal antibody that binds with high affinity and specificity to 
proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptors 
(LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. LDLR is the primary 
receptor that clears circulating LDL, therefore the decrease in LDLR levels by PCSK9 results in higher blood 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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levels of LDL-C. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs 
available to clear LDL, thereby lowering LDL-C levels.  
 
The LDLR also binds triglyceride-rich VLDL remnant lipoproteins and intermediate-density lipoprotein 
(IDL). Therefore, alirocumab treatment can produce reductions in these remnant lipoproteins as evidenced 
by its reductions in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C) and 
triglycerides (TG). Alirocumab also results in reductions in lipoprotein (a) [Lp(a)], which is a form of LDL 
that is bound to apolipoprotein (a). However, the LDLR has been shown to have a low affinity for Lp(a), 
therefore the exact mechanism by which alirocumab lowers Lp(a) is not fully understood. 
 
In genetic studies in humans, PCSK9 variants with either loss-of-function or gain-of-function mutations have 
been identified. Individuals with single allele PCSK9 loss-of-function mutation have lower levels of LDL-C, 
which correlated with a significantly lower incidence of coronary heart disease. A few individuals have been 
reported, who carry PCSK9 loss-of-function mutations in two alleles and have profoundly low LDL-C 
levels, with HDL-C and TG levels in the normal range. Conversely, gain-of-function mutations in the 
PCSK9 gene have been identified in patients with increased LDL-C levels and a clinical diagnosis of familial 
hypercholesterolaemia. 
 
In a multicenter, double-blind, placebo-controlled, 14 week study, 13 patients with heterozygous familial 
hypercholesterolaemia (heFH) due to gain-of-function mutations in the PCSK9 gene were randomised to 
receive either alirocumab 150 mg Q2W or placebo. Mean baseline LDL-C was 151.5 mg/dL (3.90 mmol/L). 
At week 2, the mean reduction from baseline in LDL-C was 62.5% in the alirocumab-treated patients as 
compared to 8.8% in the placebo patients. At week 8, the mean reduction in LDL-C from baseline with all 
patients treated with alirocumab was 72.4%.  
  
Pharmacodynamic effects 
 
In in vitro assays, alirocumab did not induce Fc-mediated effector function activity (antibody-dependent 
cell-mediated toxicity and complement-dependent cytotoxicity) either in the presence or absence of PCSK9 
and no soluble immune complexes capable of binding complement proteins were observed for alirocumab 
when bound to PCSK9.  
 
Clinical efficacy and safety in primary hypercholesterolaemia and mixed dyslipidaemia 
 
Summary of the Phase 3 Clinical Trials Program - 75 mg and/or 150 mg every 2 weeks (Q2W) dosing 
regimen 
 
The efficacy of alirocumab was investigated in ten phase 3 trials (five placebo-controlled and five 
ezetimibe-controlled studies), involving 5,296 randomised patients with hypercholesterolaemia 
(heterozygous familial and non-familial) or mixed dyslipidaemia, with 3,188 patients randomised to 
alirocumab. In the phase 3 studies, 31% of patients had type 2 diabetes mellitus, and 64% of patients had a 
history of coronary heart disease. Three of the ten studies were conducted exclusively in patients with 
heterozygous familial hypercholesterolaemia (heFH). The majority of patients in the phase 3 program were 
taking background lipid-modifying therapy consisting of a maximally tolerated dose of statin, with or 
without other lipid-modifying therapies, and were at high or very high cardiovascular (CV) risk. Two studies 
were conducted in patients who were not concomitantly treated with a statin, including one study in patients 
with documented statin intolerance.  
 
Two studies (LONG TERM and HIGH FH), involving a total of 2,416 patients, were performed with a 
150 mg every 2 weeks (Q2W) dose only. Eight studies were performed with a dose of 75 mg Q2W, and 
criteria-based up-titration to 150 mg Q2W at week 12 in patients who did not achieve their pre-defined target 
LDL-C based on their level of CV risk at week 8.  
 
The primary efficacy endpoint in all of the phase 3 studies was the mean percent reduction from baseline in 
LDL-C at week 24 as compared to placebo or ezetimibe. All of the studies met their primary endpoint. In 
general, administration of alirocumab also resulted in a statistically significant greater percent reduction in 



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total cholesterol (Total-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (Apo 
B), and lipoprotein (a) [Lp(a)] as compared to placebo/ ezetimibe, whether or not patients were 
concomitantly being treated with a statin. Alirocumab also reduced triglycerides (TG), and increased 
high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (Apo A-1) as compared to placebo. 
For detailed results see Table 2 below. Reduction in LDL-C was seen across age, gender, body mass index 
(BMI), race, baseline LDL-C levels, patients with heFH and non-heFH, patients with mixed dyslipidaemia, 
and diabetic patients. Although similar efficacy was observed in patients over 75 years, data are limited in 
this age group. LDL-C reduction was consistent regardless of concomitantly used statins and doses. A 
significantly higher proportion of patients achieved an LDL-C of ˂70 mg/dL (˂1.81 mmol/L) in the 
alirocumab group as compared to placebo or ezetimibe at week 12 and week 24. In studies using the criteria-
based up-titration regimen, a majority of patients achieved the pre-defined target LDL-C (based on their 
level of CV risk) on the 75 mg Q2W dose, and a majority of patients maintained treatment on the 75 mg 
Q2W dose. The lipid-lowering effect of alirocumab was observed within 15 days after the first dose reaching 
maximum effect at approximately 4 weeks. With long-term treatment, efficacy was sustained over the 
duration of the studies (up to 2 years). Following discontinuation of alirocumab, no rebound in LDL-C was 
observed, and LDL-C levels gradually returned to baseline levels.  
 
In pre-specified analyses before possible up-titration at week 12 in the 8 studies in which patients started 
with the 75 mg every 2 weeks dosing regimen, mean reductions in LDL-C ranging from 44.5% to 49.2% 
were achieved. In the 2 studies in which patients were started and maintained on 150 mg every 2 weeks, the 
achieved mean reduction of LDL-C at week 12 was 62.6%. In analyses of pooled phase 3 studies that 
allowed up-titration, among the subgroup of patients up-titrated, an increase from 75 mg Q2W to 150 mg 
Q2W alirocumab at week 12 resulted in an additional 14% mean reduction in LDL-C in patients on a 
background statin. In patients not on a background statin, up-titration of alirocumab resulted in an additional 
3% mean reduction in LDL-C, with the majority of the effect seen in approximately 25% of patients who 
achieved at least an additional 10% LDL-C lowering after up-titration. Patients up-titrated to 150 mg Q2W 
had a higher mean baseline LDL-C. 
 
Evaluation of cardiovascular (CV) events  
 
In pre-specified analyses of pooled phase 3 studies, treatment-emergent CV events confirmed by 
adjudication, consisting of coronary heart disease (CHD) death, myocardial infarction, ischemic stroke, 
unstable angina requiring hospitalisation, congestive heart failure hospitalisation, and revascularisation, were 
reported in 110 (3.5%) patients in the alirocumab group and 53 (3.0%) patients in the control group (placebo 
or active control) with HR=1.08 (95% CI, 0.78 to 1.50). Major adverse cardiovascular events (“MACE-
plus”, i.e.: CHD death, myocardial infarction, ischemic stroke, and unstable angina requiring hospitalisation) 
confirmed by adjudication were reported in 52 of 3,182 (1.6%) patients in the alirocumab group and 33 of 
1,792 (1.8%) patients in the control group (placebo or active control); HR=0.81 (95% CI, 0.52 to 1.25). 
 
In pre-specified final analyses of the LONG TERM study, treatment-emergent CV events confirmed by 
adjudication occurred in 72 of 1,550 (4.6%) patients in the alirocumab group and in 40 of 788 (5.1%) 
patients in the placebo group; MACE-plus confirmed by adjudication were reported in 27 of 1,550 (1.7%) 
patients in the alirocumab group and 26 of 788 (3.3%) patients in the placebo group. Hazard ratios were 
calculated post-hoc; for all CV events, HR=0.91 (95% CI, 0.62 to 1.34); for MACE-plus, HR=0.52 (95% CI, 
0.31 to 0.90). 
 
All-cause mortality 
 
All-cause mortality in phase 3 studies was 0.6% (20 of 3,182 patients) in the alirocumab group and 0.9% (17 
of 1,792 patients) in the control group. The primary cause of death in the majority of these patients was CV 
events. 

Combination therapy with a statin 
 
Placebo-controlled phase 3 studies (on background statin) in patients with primary hypercholesterolaemia 
or mixed dyslipidaemia 
 



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LONG TERM study  
 
This multicenter, double-blind, placebo-controlled, 18-month study included 2,310 patients with primary 
hypercholesterolaemia at high or very high CV risk and on a maximally tolerated dose of statin, with or 
without other lipid-modifying therapy. Patients received either alirocumab at a dose of 150 mg Q2W or 
placebo in addition to their existing lipid-modifying therapy. The LONG TERM study included 17.7% heFH 
patients, 34.6% with type 2 diabetes mellitus, and 68.6% with a history of coronary heart disease. At week 
24, the mean treatment difference from placebo in LDL-C percent change from baseline was -61.9% (95% 
CI: -64.3%, -59.4%; p-value: ˂0.0001). For detailed results see Table 2. At week 12, 82.1% of patients in the 
alirocumab group reached an LDL-C ˂70 mg/dL (˂1.81 mmol/L) compared to 7.2% of patients in the 
placebo group. Difference versus placebo was statistically significant at week 24 for all lipids/lipoproteins. 
 
COMBO I study 
 
A multicenter, double-blind, placebo-controlled, 52 week study included 311 patients categorised as very 
high CV risk and not at their pre-defined target LDL-C on a maximally tolerated dose of statin, with or 
without other lipid-modifying therapy. Patients received either 75 mg alirocumab Q2W or placebo in 
addition to their existing lipid-modifying therapy. Dose up-titration of alirocumab to 150 mg Q2W occurred 
at week 12 in patients with LDL-C ≥70 mg/dL (≥1.81 mmol/L). At week 24, the mean treatment difference 
from placebo in LDL-C percent change from baseline was -45.9% (95% CI: -52.5%, -39.3%; p-value: 
˂0.0001). For detailed results see Table 4. At week 12 (before up-titration), 76.0% of patients in the 
alirocumab group reached an LDL-C of ˂70 mg/dL (˂ 1.81 mmol/L) as compared to 11.3% in the placebo 
group. The dose was up-titrated to 150 mg Q2W in 32 (16.8%) patients treated beyond 12 weeks. Among the 
subgroup of patients up-titrated at week 12, an additional 22.8% mean reduction in LDL-C was achieved at 
week 24. The difference versus placebo was statistically significant at week 24 for all lipids/ lipoproteins 
except TG and Apo A-1. 
 
Placebo-controlled phase 3 studies (on background statin) in patients with heterozygous familial 
hypercholesterolaemia (heFH) 
 
FH I and FH II studies  
 
Two multicenter, placebo-controlled, double-blind 18-month studies included 732 patients with heFH 
receiving a maximally tolerated dose of statin, with or without other lipid-modifying therapy. Patients 
received either alirocumab 75 mg Q2W or placebo in addition to their existing lipid-modifying therapy. Dose 
up-titration of alirocumab to 150 mg Q2W occurred at week 12 in patients with LDL-C 
≥70 mg/dL (≥1.81 mmol/L). At week 24, the mean treatment difference from placebo in LDL-C percent 
change from baseline was -55.8% (95% CI: -60.0%, -51.6%; p-value: ˂ 0.0001). For detailed results see 
Table 2. At week 12 (before up-titration), 50.2% of patients reached an LDL-C of 
˂70 mg/dL (˂1.81 mmol/L) as compared to 0.6% in the placebo group. Among the subgroup of patients 
up-titrated at week 12, an additional 15.7% mean reduction in LDL-C was achieved at week 24. Difference 
versus placebo was statistically significant at week 24 for all lipids/ lipoproteins. 
 
HIGH FH study 
 
A third multicenter, double-blind, placebo-controlled 18-month study included 106 heFH patients on a 
maximally tolerated dose of statin, with or without other lipid-modifying therapies, and a baseline LDL-C 
≥160 mg/dL (≥4.14 mmol/L). Patients received either alirocumab at a dose of 150 mg Q2W or placebo in 
addition to their existing lipid-modifying therapy. At week 24, the mean treatment difference from placebo in 
LDL-C percent change from baseline was -39.1% (95% CI: -51.1%, -27.1%; p-value: ˂0.0001). For detailed 
results see Table 2. Mean changes for all other lipids/ lipoproteins were similar to the FH I and FH II studies, 
however statistical significance was not reached for TG, HDL-C and Apo A-1.  
 
Ezetimibe-controlled phase 3 study (on background statin) in patients with primary hypercholesterolaemia 
or mixed dyslipidaemia  
 



12 

COMBO II study  
 
A multicenter, double-blind, ezetimibe-controlled 2 year study included 707 patients categorised as very high 
CV risk and not at their pre-defined target LDL-C on a maximally tolerated dose of statin. Patients received 
either alirocumab 75 mg Q2W or ezetimibe 10 mg once daily in addition to their existing statin therapy. 
Dose up-titration of alirocumab to 150 mg Q2W occurred at week 12 in patients with LDL-C 
≥70 mg/dL (≥1.81 mmol/L). At week 24, the mean treatment difference from ezetimibe in LDL-C percent 
change from baseline was -29.8% (95% CI: -34.4%, -25.3%; p-value: ˂0.0001). For detailed results see 
Table 2. At week 12 (before up-titration), 77.2% of patients reached an LDL-C of 
˂70 mg/dL (˂1.81 mmol/L) as compared to 46.2% in the ezetimibe group. Among the subgroup of patients 
up-titrated at week 12, an additional 10.5% mean reduction in LDL-C was achieved at week 24. Difference 
versus ezetimibe was statistically significant at week 24 for all lipids/ lipoproteins except for TG, and Apo 
A-1. 

Monotherapy or as add-on to non-statin lipid-modifying therapy 
 
Ezetimibe-controlled phase 3 trials in patients with primary hypercholesterolaemia (without a background 
statin) 
 
ALTERNATIVE study  
 
A multicentre, double-blind, ezetimibe-controlled, 24 week study included 248 patients with documented 
statin intolerance due to skeletal muscle-related symptoms. Patients received either alirocumab 75 mg Q2W 
or ezetimibe 10 mg once daily, or atorvastatin 20 mg once daily (as a re-challenge arm). Dose up-titration of 
alirocumab to 150 mg Q2W occurred at week 12 in patients with LDL-C ≥70 mg/dL (≥1.81 mmol/L) or 
≥100 mg/dL (≥2.59 mmol/L), depending on their level of CV risk. At week 24, the mean treatment 
difference from ezetimibe in LDL-C percent change from baseline was -30.4% (95% CI: -36.6%, -24.2%; p-
value: ˂0.0001). For detailed results see Table 2. At week 12 (before up-titration), 34.9% of patients reached 
an LDL-C of ˂70 mg/dL (˂1.81 mmol/L) as compared to 0% in the ezetimibe group. Among the subgroup of 
patients up-titrated at week 12, an additional 3.6% mean reduction in LDL-C was achieved at week 24. 
Difference versus ezetimibe was statistically significant at week 24 for LDL-C, Total-C, Non-HDL-C, Apo 
B, and Lp(a). 
 
This trial evaluated patients who did not tolerate at least two statins (at least one at the lowest approved 
dose), In these patients, musculo-skeletal adverse events occurred at a lower rate in the alirocumab group 
(32.5%) as compared to the atorvastatin group (46.0%) (HR= 0.61 [95% CI, 0.38 to 0.99]), and a lower 
percentage of patients in the alirocumab group (15.9%) discontinued study treatment due to musculo-skeletal 
adverse events as compared to the atorvastatin group (22.2%). In the five placebo-controlled trials in patients 
on a maximally tolerated dose of statin (n=3752), the discontinuation rate due to musculo-skeletal adverse 
events was 0.4% in the alirocumab group and 0.5% in the placebo group.  
 
MONO study  
 
A multicenter, double-blind, ezetimibe-controlled, 24-week study included 103 patients with a moderate CV 
risk, not taking statins or other lipid-modifying therapies, and a baseline LDL-C between 
100 mg/dL (2.59 mmol/L) to 190 mg/dL (4.91 mmol/L). Patients received either alirocumab 75 mg Q2W or 
ezetimibe 10 mg once daily. Dose up-titration of alirocumab to 150 mg Q2W occurred at week 12 in patients 
with LDL-C ≥70 mg/dL (≥1.81 mmol/L). At week 24, the mean treatment difference from ezetimibe in 
LDL-C percent change from baseline was -31.6% (95% CI: -40.2%, -23.0%; p-value: ˂0.0001). For detailed 
results see Table 2. At week 12 (before up-titration), 57.7% of patients reached an LDL-C of 
˂70 mg/dL (˂1.81 mmol/L) as compared to 0% in the ezetimibe group. The dose was up-titrated to 150 mg 
Q2W in 14 (30.4%) patients treated beyond 12 weeks. Among the subgroup of patients up-titrated at week 
12, an additional 1.4 % mean reduction in LDL-C was achieved at week 24. The difference versus ezetimibe 
was statistically significant at week 24 for LDL-C, Total-C, Non-HDL-C and Apo B. 



13 

Table 2: Mean percent change from baseline in LDL-C and other lipids/ lipoproteins in placebo-
controlled and ezetimibe-controlled studies – 75 mg and/or 150 mg Q2W dosing regimen 

 
Mean Percent Change from Baseline in Placebo-Controlled Studies on Background Statin 

 LONG TERM 
(N=2310) 

FHI and FHII 
(N=732) 

High FH (N=106) COMBO I (N=311) 

 Placeb
o  

Alirocuma
b 

Placeb
o 

Alirocuma
b 

Placeb
o 

Alirocuma
b 

Placeb
o 

Alirocuma
b 

Number 
of 
patients 

780 1530 244 488 35 71 106 205 

Mean 
Baseline 
LDL-C in 
mg/dL 
(mmol/L) 

122.0 
(3.16) 

122.8 
(3.18) 

140.9 
(3.65) 

141.3 
(3.66) 

201.0 
(5.21) 

196.3 
(5.10) 

104.6 
(2.71) 

100.3 
(2.60) 

Week 12  
LDL-C 
(ITT)a 

1.5 -63.3 5.4 -43.6 -6.6 -46.9 1.1 -46.3 

LDL-C 
(on 
treatment
)b 

1.4 -64.2 5.3 -44.0 -6.6 -46.9 1.7 -47.6 

Week 24 
LDL-C 
(ITT)a 

0.8 -61.0c 7.1 -48.8d -6.6 -45.7e -2.3 -48.2f 

LDL-C 
(on 
treatment
)b 

0.7 -62.8 6.8 -49.3 -6.6 -45.5 -0.8 -50.7 

Non-
HDL-C 

0.7 -51.6 7.4 -42.8 -6.2 -41.9 -1.6 -39.1 

Apo B 1.2 -52.8 1.9 -41.7 -8.7 -39.0 -0.9 -36.7 
Total-C -0.3 -37.8 5.5 -31.2 -4.8 -33.2 -2.9 -27.9 
Lp(a) -3.7 -29.3 -8.5 -26.9 -8.7 -23.5 -5.9 -20.5 
TG 1.8 -15.6 4.3 -9.8 -1.9 -10.5 -5.4 -6.0 
HDL-C -0.6 4.0 0.2 7.8 3.9 7.5 -3.8 3.5 
Apo A-1 1.2 4.0 -0.4 4.2 2.0 5.6 -2.5 3.3 

Mean percent change from baseline in ezetimibe-controlled studies 
 On background statin Without background statin 

 COMBO II (N=707) ALTERNATIVE (N=248) MONO (N=103) 
 Ezetimibe Alirocumab Ezetimibe Alirocumab Ezetimibe Alirocumab 
Number of 
patients 

240 467 122 126 51 52 

Mean baseline 
LDL-C in mg/dL 
(mmol/L) 

104.5 
(2.71) 

108.3 
(2.81) 

194.2 
(5.03) 

191.1 
(5.0) 

138.3 
(3.58) 

141.1  
(3.65) 

Week 12 
LDL-C (ITT )a -21.8 -51.2 -15.6 -47.0 -19.6 -48.1 
LDL-C (on 
treatment)b 

-22.7 -52.4 -18.0 -51.2 -20.4 -53.2 

Week24 
LDL-C (ITT)a -20.7 -50.6g -14.6 -45.0h -15.6 -47.2i 

LDL-C (on 
treatment)b 

-21.8 -52.4 -17.1 -52.2 -17.2 -54.1 



14 

Non-HDL-C -19.2 -42.1 -14.6 -40.2 -15.1 -40.6 
Apo B -18.3 -40.7 -11.2 -36.3 -11.0 -36.7 
Total-C -14.6 -29.3 -10.9 -31.8 -10.9 -29.6 
Lp(a) -6.1 -27.8 -7.3 -25.9 -12.3 -16.7 
TG -12.8 -13.0 -3.6 -9.3 -10.8 -11.9 
HDL-C 0.5 8.6 6.8 7.7 1.6 6.0 
Apo A-1 -1.3 5.0 2.9 4.8 -0.6 4.7 

a ITT analysis – intent-to-treat population, includes all lipid data throughout the duration of the study irrespective of 
adherence to the study treatment. 
b On-treatment analysis – analysis restricted to the time period that patients actually received treatment.  
The % LDL-C reduction at week 24 corresponds to a mean absolute change of: 
c -74.2 mg/dL (-1.92 mmol/L); d -71.1 mg/dL (-1.84 mmol/ml); e -90.8 mg/dL (-2.35 mmol/L); f -50.3 mg/dL (-
1.30 mmol/L); g -55.4 mg/dL (1.44 mmol/L); h -84.2 mg/dL (-2.18 mmol/L); i -66.9 mg/dL (-1.73 mmol/L) 
 
Every 4 week (Q4W) dosing regimen 
 
CHOICE I study  
 
A multicenter, double-blind, placebo-controlled, 48 week study included 540 patients on a maximally 
tolerated dose of a statin, with or without other lipid-modifying therapy (308 in the alirocumab 300 mg Q4W 
group, 76 in the alirocumab 75 mg Q2W group, and 156 in the placebo group), and 252 patients not treated 
with a statin (144 in the alirocumab 300 mg Q4W group, 37 in the alirocumab 75 mg Q2W group, and 71 in 
the placebo group). Patients received either alirocumab 300 mg Q4W, alirocumab 75 mg Q2W, or placebo in 
addition to their existing lipid-modifying therapy (statin, non-statin therapy or diet alone). Patients in the 
alirocumab 300 mg every 4 weeks treatment group received alternating placebo injections to maintain 
blinding in regard to injection frequency. Overall, 71.6% of patients were categorized at high or very high 
CV risk and not at their LDL-C target. Dose adjustment in the alirocumab groups to 150 mg Q2W occurred 
at week 12 in patients with LDL-C ≥70 mg/dL or ≥100 mg/dL, depending on their level of CV risk, or in 
patients who did not have at least a 30% reduction of LDL-C from baseline. 
 
In the cohort of patients on background statin, the mean baseline LDL-C was 112.7 mg/dL. At week 12, the 
mean percent change from baseline with alirocumab 300 mg Q4W in LDL-C (ITT analysis) was -55.3% 
compared to +1.1% for placebo. At week 12 (before dose adjustment), 77.3% of patients treated with 
alirocumab 300 mg Q4W reached an LDL-C of ˂70 mg/dL as compared to 9.3% in the placebo group. At 
week 24, the mean percent change from baseline with alirocumab 300 mg Q4W/150 mg Q2W in LDL-C 
(ITT analysis) was -58.8% compared to -0.1% for placebo. At week 24, the mean treatment difference for 
alirocumab 300 mg Q4W/150 mg Q2W from placebo in LDL-C percent change from baseline was -58.7% 
(97.5% CI: -65.0%, -52.4%; p-value: ˂ 0.0001). In patients treated beyond 12 weeks, the dose was adjusted 
to 150 mg Q2W in 56 (19.3%) of 290 patients in the alirocumab 300 mg Q4W arm. Among the subgroup of 
patients dose adjusted to 150 mg Q2W at week 12, an additional 25.4% reduction in LDL-C was achieved at 
week 24. 
 
In the cohort of patients not treated with a concomitant statin, the mean baseline LDL-C was 142.1 mg/dL. 
At week 12, the mean percent change from baseline with alirocumab 300 mg Q4W in LDL-C (ITT analysis) 
was -58.4% compared to +0.3% for placebo. At week 12 (before dose adjustment), 65.2% of patients treated 
with alirocumab 300 mg Q4W reached an LDL-C of ˂70 mg/dL as compared to 2.8% in the placebo group. 
At week 24, the mean percent change from baseline with alirocumab 300 mg Q4W/150 mg Q2W in LDL-C 
(ITT analysis) was -52.7% compared to -0.3% for placebo. At week 24, the mean treatment difference for 
alirocumab 300 mg Q4W/150 mg Q2W from placebo in LDL-C percent change from baseline was -52.4% 
(97.5% CI: -59.8%, -45.0%; p-value: ˂ 0.0001). In patients treated beyond 12 weeks, the dose was adjusted 
to 150 mg Q2W in 19 (14.7%) of 129 patients in the alirocumab 300 mg Q4W arm. Among the subgroup of 
patients dose adjusted to 150 mg Q2W at week 12, an additional 7.3% mean reduction in LDL-C was 
achieved at week 24. 
 
In both cohorts, the difference vs placebo was statistically significant at week 24 for all lipid parameters, 
except for Apo A-1 in the subgroup of patients on background statin. 



15 

 
Clinical efficacy and safety in prevention of cardiovascular events   
 
ODYSSEY OUTCOMES study  
 
A multicentre, double-blind, placebo-controlled trial included 18,924 adult patients (9,462 alirocumab; 9,462 
placebo) followed for up to 5 years. Patients had experienced an acute coronary syndrome (ACS) event 4 to 
52 weeks prior to randomization and were treated with a lipid-modifying-therapy (LMT) regimen that was 
statin-intensive (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) or at maximally tolerated 
dose of those statins, with or without other LMT. Patients were randomized 1:1 to receive either alirocumab 
75 mg once every two weeks (Q2W) or placebo Q2W. At month 2, if additional LDL-C lowering was 
required based on pre-specified LDL-C criteria (LDL-C ≥50 mg/dL or 1.29 mmol/L), alirocumab was 
adjusted to 150 mg Q2W. For patients who had their dose adjusted to 150 mg Q2W and who had two 
consecutive LDL-C values below 25 mg/dL (0.65 mmol/L), down-titration from 150 mg Q2W to 75 mg 
Q2W was performed. Patients on 75 mg Q2W who had two consecutive LDL-C values below 15 mg/dL 
(0.39 mmol/L) were switched to placebo in a blinded fashion. Approximately 2,615 (27.7%) of 9,451 
patients treated with alirocumab required dose adjustment to 150 mg Q2W. Of these 2615 patients, 805 
(30.8%) were down-titrated to 75 mg Q2W. Overall, 730 (7.7%) of 9,451 patients switched to placebo. A 
total of 99.5% of patients were followed for survival until the end of the trial. The median follow-up duration 
was 33 months. 

The index ACS event was a myocardial infarction in 83.2% of patients (34.6% STEMI, 48.6% NSTEMI) 
and an episode of unstable angina in 16.8% of patients. Most patients (88.8%) were receiving high intensity 
statin therapy with or without other LMT at randomization. The mean LDL-C value at baseline was 92.4 
mg/dL (2.39 mmol/L). 

Alirocumab significantly reduced the risk for the primary composite endpoint of the time to first occurrence 
of Major Adverse Cardiovascular Events (MACE-plus) consisting of coronary heart disease (CHD) death, 
non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, or unstable angina (UA) requiring 
hospitalization (HR 0.85, 95% CI: 0.78, 0.93; p-value=0.0003). Alirocumab also significantly reduced the 
following composite endpoints: risk of CHD event; major CHD event; cardiovascular event; and the 
composite of all-cause mortality, non-fatal MI, and non-fatal ischemic stroke. A reduction of all-cause 
mortality was also observed, with only nominal statistical significance by hierarchical testing (HR 0.85, 95% 
CI: 0.73, 0.98). The results are presented in Table 3.  



16 

Table 3: Efficacy of alirocumab in ODYSSEY OUTCOMES (overall population) 
Endpoint Number of events  

Hazard ratio 
(95% CI) 
p-value 

Alirocumab 
N=9,462 

n (%) 

Placebo 
N=9,462 

n (%) 

Primary endpoint (MACE-
plusa) 903 (9.5%) 1052 (11.1%) 0.85 (0.78, 0.93) 

0.0003 

 
 
 

CHD death 205 (2.2%) 222 (2.3%) 0.92 (0.76, 1.11) 
0.38 

Non-fatal MI 626 (6.6%) 722 (7.6%) 0.86 (0.77, 0.96) 
 0.006f 

Ischemic stroke 111 (1.2%) 152 (1.6%) 0.73 (0.57, 0.93) 
0.01f 

Unstable anginab 37 (0.4%) 60 (0.6%) 0.61 (0.41, 0.92) 
0.02f 

Secondary endpoints 
 

CHD eventc 1199 (12.7%) 1349 (14.3%) 0.88 (0.81, 0.95) 
0.0013 

Major CHD eventd 793 (8.4%) 899 (9.5%) 0.88 (0.80, 0.96) 
0.0060 

Cardiovascular evente 1301 (13.7%) 1474 (15.6%) 0.87 (0.81, 0.94) 
0.0003 

All-cause mortality, non-fatal 
MI, non-fatal ischemic stroke 973 (10.3%) 1126 (11.9%) 0.86 (0.79, 0.93) 

0.0003 

CHD death 205 (2.2%) 222 (2.3%) 0.92 (0.76, 1.11) 
0.3824 

CV death 240 (2.5%) 271 (2.9%) 0.88 (0.74, 1.05) 
0.1528 

All-cause mortality 334 (3.5%) 392 (4.1%) 0.85 (0.73, 0.98) 
0.0261f 

 

a MACE-plus defined as a composite of: coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), 
fatal and non-fatal ischemic stroke, or unstable angina (UA) requiring hospitalization 
b Unstable angina requiring hospitalization 
c CHD event defined as: major CHD eventd, unstable angina requiring hospitalization, ischemia-driven coronary 
revascularization procedure 
d Major CHD event defined as: CHD death, non-fatal MI 
e Cardiovascular event defined as follows: CV death, any non-fatal CHD event, and non-fatal ischemic stroke 
f Nominal significance 

The Kaplan-Meier estimates of the cumulative incidence of the primary endpoint for the overall patient 
population over time are presented in Figure 1.  

 

Favours Alirocumab     Favours Placebo 



17 

Figure 1 Primary composite endpoint cumulative incidence over 4 years in ODYSSEY OUTCOMES 
 

Overall population 

 
 

 
Paediatric population 
 
A 48-week, open-label study was conducted to evaluate the efficacy and safety of alirocumab 75 mg Q2W 
(if body weight (BW) < 50 kg) or 150 mg Q2W (if BW ≥ 50 kg) in 18 paediatric patients (8 to 17 years of 
age) with HoFH on top of background treatments. Patients received alirocumab 75 or 150 mg Q2W without 
dose adjustment up to week 12. 
 
The mean baseline LDL-C was 9.6 mmol/l (373 mg/dL). The mean percent change from baseline in LDL-C 
to week 12 was -4.1% (95% CI: -23.1% to 14.9%) in the ITT population (N=18) and was associated with a 
high variability in the response with regard to the decrease in LDL-C. Responders achieving ≥15% reduction 
from baseline at weeks 12, 24, and 48 were 50%, 50% and 39% respectively (see section 4.2). 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Praluent in 
one or more subsets of the paediatric population in the treatment of elevated cholesterol (see section 4.2 for 
information on paediatric use). 
 
The European Medicines Agency has waived the obligation to submit the results of studies with Praluent in 
all subsets of the paediatric population in the treatment of mixed dyslipidaemia (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties  
 
Absorption 
 
After subcutaneous administration of 50 mg to 300 mg alirocumab, median times to maximum serum 
concentration (tmax) were 3-7 days. The pharmacokinetics of alirocumab after single subcutaneous 
administration of 75 mg into the abdomen, upper arm or thigh were similar. The absolute bioavailability of 
alirocumab after subcutaneous administration was about 85% as determined by population pharmacokinetic 
analysis. Monthly exposure with 300 mg every 4 weeks treatment was similar to that of 150 mg every 
2 weeks. The fluctuations between Cmax and Ctrough were higher for the every 4 weeks dosage regimen. Steady 
state was reached after 2 to 3 doses with an accumulation ratio up to a maximum of about 2-fold.  
 
Distribution 
 
Following intravenous administration, the volume of distribution was about 0.04 to 0.05 L/kg indicating that 
alirocumab is distributed primarily in the circulatory system.  
 
Biotransformation 
 

Hazard Ratio: 0.85 
95% CI (0.78, 0.93) 

Placebo 

Alirocumab 

Cu

mu

lati

ve 

inci

den

ce 

 

 Time (months) 



18 

Specific metabolism studies were not conducted, because alirocumab is a protein. Alirocumab is expected to 
degrade to small peptides and individual amino acids. 
 
Elimination 
 
Two elimination phases were observed for alirocumab. At low concentrations, the elimination is 
predominately through saturable binding to target (PCSK9), while at higher concentrations the elimination of 
alirocumab is largely through a non-saturable proteolytic pathway.  
 
Based on a population pharmacokinetic analysis, the median apparent half-life of alirocumab at steady state 
was 17 to 20 days in patients receiving alirocumab as monotherapy at subcutaneous doses of either 75 mg 
Q2W or 150 mg Q2W. When co-administered with a statin, the median apparent half-life of alirocumab was 
12 days.  
 
Linearity/non-linearity 
 
A slightly greater than dose proportional increase was observed, with a 2.1- to 2.7-fold increase in total 
alirocumab concentrations for a 2-fold increase in dose from 75 mg to 150 mg Q2W. 
 
Special populations 
 
Elderly 
 
Based on a population pharmacokinetic analysis, age was associated with a small difference in alirocumab 
exposure at steady state, with no impact on efficacy or safety. 
 
Gender 
 
Based on a population pharmacokinetic analysis, gender has no impact on alirocumab pharmacokinetics. 
 
Race 
 
Based on a population pharmacokinetic analysis, race had no impact on alirocumab pharmacokinetics. 
Following single-dose subcutaneous administration of 100 mg to 300 mg alirocumab, there was no 
meaningful difference in exposure between Japanese and Caucasian healthy subjects. 
 
Body weight 
 
Body weight was identified as one significant covariate in the final population PK model impacting 
alirocumab pharmacokinetics. Alirocumab exposure (AUC0-14d) at steady state at both the 75 and 150 mg 
Q2W dosing regimen was decreased by 29% and 36% in patients weighing more than 100 kg as compared to 
patients weighing between 50 kg and 100 kg. This did not translate into a clinically meaningful difference in 
LDL-C lowering. 
 
Hepatic impairment 
 
In a phase 1 study, after administration of a single 75 mg subcutaneous dose, alirocumab pharmacokinetic 
profiles in subjects with mild and moderate hepatic impairment were similar as compared to subjects with 
normal hepatic function. No data are available in patients with severe hepatic impairment. 
 
Renal impairment  
 
Since monoclonal antibodies are not known to be eliminated via renal pathways, renal function is not 
expected to impact the pharmacokinetics of alirocumab. Population pharmacokinetic analyses showed that 
alirocumab exposure (AUC0-14d) at steady state at both the 75 and 150 mg Q2W dosing regimen was 
increased by 22%-35%, and 49%-50% in patients with mild and moderate renal impairment, respectively, 



19 

compared to patients with normal renal function. The distribution of body weight and age, two covariates 
impacting alirocumab exposure, were different among renal function categories and most likely explain the 
observed pharmacokinetic differences. Limited data are available in patients with severe renal impairment; in 
these patients the exposure to alirocumab was approximately 2-fold higher compared with subjects with 
normal renal function. 
 
Paediatric population 
  
Limited pharmacokinetic data are available in 18 paediatric patients (8 to 17 years of age) with HoFH. The 
steady-state mean Ctrough alirocumab concentrations was reached at or before Week 12 in both alirocumab 
75 mg Q2W and 150 mg Q2W groups. No studies with alirocumab have been performed in paediatric 
patients less than 8 years of age (see section 5.1). 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
 
The pharmacodynamic effect of alirocumab in lowering LDL-C is indirect, and mediated through the binding 
to PCSK9. A concentration-dependent reduction in free PCSK9 and LDL-C is observed until target 
saturation is achieved. Upon saturation of PCSK9 binding, further increases in alirocumab concentrations do 
not result in a further LDL-C reduction, however an extended duration of the LDL-C lowering effect is 
observed. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology 
and repeated dose toxicity. 
 
Reproductive toxicology studies in rats and monkeys indicated that alirocumab, like other IgG antibodies, 
crosses the placental barrier. 
 
There were no adverse effects on surrogate markers of fertility (e.g. estrous cyclicity, testicular volume, 
ejaculate volume, sperm motility, or total sperm count per ejaculate) in monkeys, and no alirocumab-related 
anatomic pathology or histopathology findings in reproductive tissues in any rat or monkey toxicology study. 
 
There were no adverse effects on foetal growth or development in rats or monkeys. Maternal toxicity was not 
evident in pregnant monkeys at systemic exposures that were 81 times the human exposure at the 150 mg 
Q2W dose. However, maternal toxicity was noted in pregnant rats at systemic exposures estimated to be 
approximately 5.3 times greater than the human exposure at the 150 mg Q2W dose (based on exposure 
measured in non-pregnant rats during a 5-week toxicology study). 
 
The offspring of monkeys that received high doses of alirocumab weekly throughout pregnancy had a 
weaker secondary immune response to antigen challenge than did the offspring of control animals. There was 
no other evidence of alirocumab-related immune dysfunction in the offspring.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Histidine  
Sucrose  
Polysorbate 20 
Water for injections 
 



20 

6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
6.3 Shelf life  
 
Praluent 75 mg solution for injection in pre-filled pen  
 
3 years. 
 
Praluent 75 mg solution for injection in pre-filled syringe  
 
3 years. 
 
Praluent 150 mg solution for injection in pre-filled pen  
 
2 years. 
 
Praluent 150 mg solution for injection in pre-filled syringe  
 
2 years. 
 
Praluent 300 mg solution for injection in pre-filled pen  
 
2 years. 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2°C to 8°C). Do not freeze.  
Praluent can be stored outside the refrigerator (below 25 °C) protected from light for a single period not 
exceeding 30 days. After removal from the refrigerator, the medicinal product must be used within 30 days 
or discarded. 
 
Keep the pen or syringe in the outer carton in order to protect from light. 
 
6.5 Nature and contents of container  
 
1 ml or 2 ml solution in a siliconised Type 1 clear glass syringe, equipped with a stainless steel staked 
needle, a styrene-butadiene rubber soft needle shield, and an ethylene tetrafluoroethylene -coated bromobutyl 
rubber plunger stopper. 
 
75 mg solution for injection in pre-filled pen 
 
The syringe components are assembled into a single-use pre-filled pen with a blue cap and a light green 
activation button. 
 
Pack size:  
1, 2 or 6 pre-filled pens.  
 
Or 
 
The syringe components are assembled into a single-use pre-filled pen with a blue cap and without activation 
button. 
 



21 

Pack size:  
1, 2 or 6 pre-filled pens without activation button.  
 
150 mg solution for injection in pre-filled pen 
 
The syringe components are assembled into a single-use pre-filled pen with a blue cap and a dark grey 
activation button. 
 
Pack size:  
1, 2 or 6 pre-filled pens.  
 
Or 
 
The syringe components are assembled into a single-use pre-filled pen with a blue cap and without activation 
button. 
 
Pack size:  
1, 2 or 6 pre-filled pens without activation button.  
 
300 mg solution for injection in pre-filled pen 
 
The syringe components are assembled into a single-use pre-filled pen with a blue cap and without activation 
button. 
 
Pack size:  
1 or 3 pre-filled pens without activation button.  
 
75 mg solution for injection in pre-filled syringe 
 
The syringe is equipped with a light green polypropylene plunger rod. 
 
Pack size:  
1, 2 or 6 pre-filled syringes. 
 
150 mg solution for injection in pre-filled syringe 
 
The syringe is equipped with a dark grey polypropylene plunger rod. 
 
Pack size:  
1, 2 or 6 pre-filled syringes. 
 
Not all presentations and pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling  
 
After use, the pre-filled pen/ pre-filled syringe should be placed into a puncture resistant container. The 
container should not be recycled.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 



22 

7. MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe  
54, rue La Boétie 
F – 75008 Paris 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1031/001 
EU/1/15/1031/002 
EU/1/15/1031/003 
EU/1/15/1031/004 
EU/1/15/1031/005 
EU/1/15/1031/006 
EU/1/15/1031/007 
EU/1/15/1031/008 
EU/1/15/1031/009 
EU/1/15/1031/010 
EU/1/15/1031/011 
EU/1/15/1031/012 
EU/1/15/1031/013 
EU/1/15/1031/014 
EU/1/15/1031/015 
 
EU/1/15/1031/016 
EU/1/15/1031/017 
EU/1/15/1031/018 
 
EU/1/15/1031/019 
EU/1/15/1031/020 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 September 2015 
Date of latest renewal: 2 June 2020 
 
 
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. 
 

  

http://www.ema.europa.eu/


23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE 
AND MANUFACTURER 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 
 

 



24 

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

Name and address of the manufacturers of the biological active substance  

Regeneron Pharmaceuticals, Inc. 
81 Columbia Turnpike 
Rensselaer, NY 12144 
United States 
 
Regeneron Ireland DAC  
Raheen Business Park 
Limerick 
Ireland 
 
SANOFI CHIMIE 
9 Quai Jules Guesde 
94403 Vitry-sur-Seine  
France 
 
Name and address of the manufacturers responsible for batch release 

For pre-filled syringes 
Sanofi Winthrop Industrie 
1051 Boulevard Industriel  
76580 Le Trait 
France 
 
For pre-filled pens 
Sanofi-Aventis Deutschland GmbH 
Industriepark Hoechst 
Brüningstraße 50 
65926 Frankfurt am Main 
Germany 
 
Or 
 
Genzyme Ireland Ltd 
IDA Industrial Park 
Old Kilmeaden Road 
Waterford 
Ireland 
 
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. 
 
 



25 

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. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 months 
following authorisation. 
 
 
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. 
 
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.  

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III  
 

LABELLING AND PACKAGE LEAFLET  
  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – Pre-filled pen 75 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 75 mg solution for injection in pre-filled pen 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled pen contains 75 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection  
 
1 pre-filled pen  
2 pre-filled pens  
6 pre-filled pens  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Open here 
 
 
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 
 
 



29 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the pen in the outer 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  
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1031/001 1 pre-filled pen  
EU/1/15/1031/002 2 pre-filled pens 
EU/1/15/1031/003 6 pre-filled pens   
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 75 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – Pre-filled pen 75 mg (without activation button) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Praluent 75 mg solution for injection in pre-filled pen 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 75 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
1 pre-filled pen without activation button 
2 pre-filled pens without activation button 
6 pre-filled pens without activation button 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Open here 
 
1 pre-filled pen without activation button 
2 pre-filled pens without activation button 
6 pre-filled pens without activation button 
Read “Instructions for use” leaflet before using the pen 
 
 
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 
 
 



31 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the pen in the outer 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 
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1031/013 1 pre-filled pen 
EU/1/15/1031/014 2 pre-filled pen 
EU/1/15/1031/015 6 pre-filled pen 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 75 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



32 

PC  
SN 
NN  
  



33 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL – 75 mg 
PEN LABEL – 75 mg (without activation button)  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Praluent 75 mg injection 
alirocumab 
Subcutaneous use 
 
 
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  
 
 
  



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – Pre-filled pen 150 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 150 mg solution for injection in pre-filled pen 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled pen contains 150 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection  
 
1 pre-filled pen  
2 pre-filled pens  
6 pre-filled pens  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Open here 
 
 
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 
 
 



35 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the pen in the outer 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  
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1031/007 1 pre-filled pen  
EU/1/15/1031/008 2 pre-filled pens 
EU/1/15/1031/009 6 pre-filled pens   
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 150 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – Pre-filled pen 150 mg (without activation button) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Praluent 150 mg solution for injection in pre-filled pen 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 150 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
1 pre-filled pen without activation button 
2 pre-filled pens without activation button 
6 pre-filled pens without activation button 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Open here 
 
1 pre-filled pen without activation button 
2 pre-filled pens without activation button 
6 pre-filled pens without activation button 
Read “Instructions for use” leaflet before using the pen 
 
 
 
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 
 
 



37 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the pen in the outer 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 
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1031/016 1 pre-filled pens   
EU/1/15/1031/017 2 pre-filled pens   
EU/1/15/1031/018 6 pre-filled pens   
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 150 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



38 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



39 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL – 150 mg  
PEN LABEL – 150 mg (without activation button)  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Praluent 150 mg injection 
alirocumab 
Subcutaneous use 
 
 
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  
 
 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – Pre-filled pen 300 mg  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Praluent 300 mg solution for injection in pre-filled pen 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 300 mg alirocumab in 2 ml solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
1 pre-filled pen without activation button  
3 pre-filled pens without activation button 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Open here  
 
1 pre-filled pen without activation button  
3 pre-filled pens without activation button 
Read “Instructions for use” leaflet before using the pen 
 
 
 
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 



41 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the pen in the outer 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 
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1031/019 1 pre-filled pen 
EU/1/15/1031/020 3 pre-filled pen 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 300 mg 
 
 
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 
 
PEN LABEL – 300 mg  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Praluent 300 mg injection 
alirocumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
150 mg/ml 
2 ml 
 
 
6. OTHER 
  



43 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON – Pre-filled syringe 75 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 75 mg solution for injection in pre-filled syringe 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 75 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
1 pre-filled syringe  
2 pre-filled syringes  
6 pre-filled syringes  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
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  
 
 
8. EXPIRY DATE  
 
EXP 
 
 



44 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the syringe in the outer 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  
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1031/004 1 pre-filled syringe  
EU/1/15/1031/005 2 pre-filled syringes  
EU/1/15/1031/006 6 pre-filled syringes  
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 75 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



45 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER – Pre-filled syringe 75 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 75 mg solution for injection in pre-filled syringe 
alirocumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe 
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. OTHER  
 
 
  



46 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL – 75 mg   
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Praluent 75 mg injection 
alirocumab 
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  
 
 



47 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON – Pre-filled syringe 150 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 150 mg solution for injection in pre-filled syringe 
alirocumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 150 mg alirocumab in 1 ml solution. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: histidine, sucrose, polysorbate 20, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection  
 
1 pre-filled syringe  
2 pre-filled syringes  
6 pre-filled syringes  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
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  
 
 
8. EXPIRY DATE  
 
EXP 
 
 



48 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Can be stored outside the refrigerator below 25 °C for a single period up to 30 days protected from light.  
Keep the syringe in the outer 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  
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1031/010 1 pre-filled syringe  
EU/1/15/1031/011 2 pre-filled syringes  
EU/1/15/1031/012 6 pre-filled syringes  
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Praluent 150 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



49 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER – Pre-filled syringe 150 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Praluent 150 mg solution for injection in pre-filled syringe 
alirocumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe 
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. OTHER  
 
 
  



50 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL – 150 mg   
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Praluent 150 mg injection 
alirocumab 
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  
 
 
  



51 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



52 

Package leaflet: Information for the user  
 

Praluent 75 mg solution for injection in a pre-filled pen  
Praluent 150 mg solution for injection in a pre-filled pen  
Praluent 300 mg solution for injection in a pre-filled pen 

alirocumab 
 
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 Praluent is and what it is used for  
2. What you need to know before you use Praluent  
3. How to use Praluent  
4. Possible side effects  
5. How to store Praluent  
6. Contents of the pack and other information 
 
 
1. What Praluent is and what it is used for 
 
What Praluent is 
• Praluent contains the active substance alirocumab.  
• Praluent is a monoclonal antibody (a type of specialised protein designed to attach to a target 

substance in the body). Monoclonal antibodies are proteins that recognise and bind to other unique 
proteins. Alirocumab binds to PCSK9. 

 
How Praluent works 
Praluent helps lower your levels of “bad” cholesterol (also called “LDL cholesterol”). Praluent blocks a 
protein called PCSK9. 
• PCSK9 is a protein secreted by liver cells. 
• “Bad” cholesterol is normally removed from your blood by binding to specific “receptors” (docking 

stations) in your liver.  
• PCSK9 lowers the number of these receptors in the liver – this causes your “bad” cholesterol to be 

higher than it should.  
• By blocking PCSK9, Praluent increases the number of receptors available to help remove the “bad” 

cholesterol – this lowers your “bad” cholesterol levels. 
 
What Praluent is used for 
• Adults with high cholesterol levels in their blood (hypercholesterolaemia [heterozygous familial and 

non-familial] or mixed dyslipidaemia).  
• Adults with high cholesterol levels in their blood and with cardiovascular disease to reduce 

cardiovascular risk.  
 

It is given:  
- together with a statin (a commonly used medicine that treats high cholesterol) or other cholesterol 
lowering medicines, if the maximum dose of a statin does not lower levels of cholesterol sufficiently 
or, 
- alone or together with other cholesterol lowering medicines when statins are not tolerated or cannot 
be used. 

Continue to follow your cholesterol-lowering diet while taking this medicine. 



53 

 
 
2. What you need to know before you use Praluent  
 
Do not use Praluent  
• if you are allergic to alirocumab 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 Praluent.  
 
If you develop a serious allergic reaction, stop using Praluent, talk to your doctor right away. Sometimes 
serious allergic reactions such as hypersensitivity, including angioedema (difficulties breathing, or swelling 
of the face, lips, throat or tongue), nummular eczema (reddish skin spots sometimes with blisters), and 
hypersensitivity vasculitis (which is a specific form of a hypersensitivity reaction with symptoms such as 
diarrhoea, with a rash, or purple-coloured skin spots on the skin) have occurred. For allergic reactions that 
may occur while taking Praluent, see section 4. 
 
Tell your doctor if you have kidney or liver disease before using this medicine, because Praluent has been 
studied in few patients with severe kidney disease and not in patients with severe liver disease. 
 
Children and adolescents 
Praluent should  not be given  to children and adolescents under 18 years old because there is limited  
experience of using the medicine in these age groups.  
 
Other medicines and Praluent 
Tell your doctor, pharmacist or nurse if you are using, have recently used or might use 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 using this medicine. 
Praluent is not recommended during pregnancy or breast-feeding. 
 
Driving and using machines 
This medicine is not expected to have any effect on your ability to drive or use machines. 
 
 
3. How to use Praluent 
 
Always use this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your doctor, 
pharmacist or nurse if you are not sure.  
 
How much to inject 
Your doctor will tell you which dose is right for you and how often to inject (75 mg or 150 mg once every 2 
weeks, or 300 mg once every 4 weeks/monthly)). Your doctor will check your cholesterol levels and may 
adjust the dose (up or down) during treatment.  
Always check the label of your pen to make sure you have the right medicine and the right strength. 
 
When to inject 
Inject Praluent once every 2 weeks (for the 75 mg or 150 mg dose), or once every 4 weeks/monthly (for the 
300 mg dose). To give the 300 mg dose, one 300 mg injection or two 150 mg injections should be given in a 
row at two different injection sites. 
 
Before you inject 
Praluent should be allowed to warm to room temperature prior to use. 
Read the detailed instructions for use leaflet before you inject Praluent.  
 



54 

Where to inject 
Praluent is injected under your skin into the thigh, abdomen or upper arm. 
Read the detailed instructions for use leaflet on where to inject. 
 
Learning how to use the pre-filled pen 
Before you use the pen for the first time, your doctor, pharmacist or nurse will show you how to inject 
Praluent.  

• Always read the "Instructions for Use" provided in the box.  
• Always use the pen as described in the “Instructions for Use”.  

 
If you use more Praluent than you should  
If you use more Praluent than you should, talk to your doctor, pharmacist or nurse.  
 
If you forget to use Praluent  
If you miss a dose of Praluent, inject your missed dose as soon as you can. Then take your next dose at your 
regular scheduled time. This will keep you on the original schedule. If you are not sure when to inject 
Praluent, call your doctor, pharmacist or nurse. 
 
If you stop using Praluent  
Do not stop using Praluent without talking with your doctor. If you stop using Praluent, your cholesterol 
levels can increase. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you develop a serious allergic reaction, stop using Praluent, talk to your doctor right away. Sometimes 
serious allergic reactions such as hypersensitivity (difficulties breathing), nummular eczema (reddish skin 
spots sometimes with blisters), and hypersensitivity vasculitis (which is a specific form of a hypersensitivity 
reaction with symptoms such as diarrhoea, with a rash, or purple-coloured skin spots on the skin) have 
occurred (may affect up to 1 in 1,000 people).  
 
Other side effects are: 
 
Common (may affect up to 1 in 10 people) 
• redness, itching, swelling, pain/tenderness where the medicine was injected (local injection site 

reactions) 
• upper respiratory tract signs or symptoms such as sore throat, running nose, sneezing 
• itching (pruritus). 
 
Rare (may affect up to 1 in 1,000 people) 
• red and itchy raised bumps or hives (urticaria) 
 
Not Known 
 
The following side effects have been reported since the marketing of Praluent, but how often they occur is 
not known: 
• flu-like illness 
• difficulties breathing, or swelling of the face, lips, throat or tongue (angioedema)  
 



55 

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 Praluent 
 
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 to 8°C). Do not freeze.  
Keep the pen in the outer carton in order to protect from light.  
 
If needed, individual pre-filled pens may be kept outside the refrigerator below 25°C for a maximum of 30 
days. Protect from light. After removal from the refrigerator, Praluent must be used within 30 days or 
discarded.  
 
Do not use this medicine if it looks discoloured or cloudy, or if it contains visible flakes or particles. 
 
After use put the pen into a puncture-resistant container. Ask your doctor, pharmacist or nurse how to throw 
away the container. Do not recycle the container.  
 
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 Praluent contains  
• The active substance is alirocumab. 

 
Praluent 75 mg solution for injection in pre-filled pen 
Each pre-filled pen contains 75 milligrams of alirocumab. 
 
Praluent 150 mg solution for injection in pre-filled pen 
Each pre-filled pen contains 150 milligrams of alirocumab. 
 
Praluent 300 mg solution for injection in pre-filled pen 
Each pre-filled pen contains 300 milligrams of alirocumab. 
 

• The other ingredients are histidine, sucrose, polysorbate 20 and water for injections. 
 
What Praluent looks like and contents of the pack 
Praluent is a clear, colourless to pale yellow solution for injection that comes in a pre-filled pen.  
 
Praluent 75 mg solution for injection in pre-filled pen 
Each pre-filled pen with green button contains 1 ml of solution, delivering one single dose of 75 milligrams 
of alirocumab.  
It is available in pack size of 1, 2 or 6 pre-filled pens. 
 
Each pre-filled pen without activation button contains 1 ml of solution, delivering one single dose of 
75 milligrams.  
It is available in pack size of 1, 2 or 6 pre-filled pens without activation button. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


56 

 
Praluent 150 mg solution for injection in pre-filled pen 
Each pre-filled pen with grey button contains 1 ml of solution, delivering one single dose of 150 milligrams 
of alirocumab.  
It is available in pack size of 1, 2 or 6 pre-filled pens. 
 
Each pre-filled pen without activation button contains 1 ml of solution, delivering one single dose of 
150 milligrams.  
It is available in pack size of 1, 2 or 6 pre-filled pens without activation button. 
 
Praluent 300mg solution for injection in pre-filled pen 
Each pre-filled pen without activation button contains 2 ml of solution, delivering one single dose of 
300 milligrams.  
It is available in pack size of 1 or 3 pre-filled pens without activation button. 
 
Not all presentations and pack sizes may be marketed. 
 
Marketing Authorisation Holder  
sanofi-aventis groupe  
54, rue La Boétie 
F – 75008 Paris 
France 
 
Manufacturer 
Sanofi-Aventis Deutschland GmbH 
Industriepark Hoechst 
Brüningstraße 50 
65926 Frankfurt am Main 
Germany 
 
Manufacturer 
Genzyme Ireland Ltd 
IDA Industrial Park 
Old Kilmeaden Road 
Waterford 
Ireland 
 
  



57 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB “SANOFI-AVENTIS LIETUVA” 
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt.  
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 
 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 52 52 010 
Tel. aus dem Ausland: +49 69 305 21 131 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 



58 

Italia 
Sanofi S.r.l. 
Tel: 800 131212 (domande di tipo tecnico)  
        800 536389 (altre domande)  
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

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



59 

Praluent pre-filled pen  
 
Instructions for use 
 
The parts of the Praluent pen are shown in this picture.  
 

 
 
 
Important information  
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• This pen can only be used for one single injection, and must be thrown away after use. 
 
Do 
 Keep the Praluent pen out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent pen. 
 Follow these instructions every time you use a Praluent pen. 

 
Do not 
 Do not touch the yellow safety cover. 
 Do not use the pen if it has been dropped or damaged.  
 Do not use the pen if the blue cap is missing or not securely attached. 
 Do not re-use a pen. 
 Do not shake the pen. 
 Do not freeze the pen. 
 Do not expose the pen to direct sunlight. 
 
 

 

 
For single 
use only 

Body 

Window 

Yellow safety cover 
Needle inside 

Blue cap 

Green Button 



60 

Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent pen  
• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B, 8). 
 
 Look at the label on the pen. 

• Check that you have the correct product and the correct dose. 
• Check the use by date: do not use if this date has passed. 

 

 
 
 Look at the window. 
• Check the liquid is clear, colourless to pale yellow and free from particles - if not, do not use (see 

picture A). 
• You may see an air bubble. This is normal. 
• Do not use if the window appears solid yellow (see picture B). 

 
 
 Let the pen warm up at room temperature for 30 to 40 minutes. 
• Do not heat the pen, let it warm up on its own. 
• Do not put the pen back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into your: 

o thigh 
o belly (except for the 5 cm area around your navel)   
o outer side of your upper arm  
(See picture). 



61 

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein. 
• Use a different spot each time you inject. 
• Do not inject Praluent with other injectable medicines at the same spot. 

 

 
 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the blue cap  
• Do not pull off the cap until you are ready to inject. 
• Do not put the blue cap back on. 
 

 
 
Hold the Praluent pen like this. 
• Do not touch the yellow safety cover. 
• Make sure you can see the window. 
 

 
 
Press the yellow safety cover on your skin at roughly a 90° angle. 
• Press and firmly hold the pen against your body until the yellow safety cover is no longer visible. The 

pen will not work if the yellow safety cover is not depressed fully.  
• If needed, pinch the skin to make sure the injection site is firm. 

 

Blue cap 



62 

 
 
 
 Push and immediately release the green button with your thumb.  
• You will hear a click. Your injection has now started. 
• The window will start to turn yellow. 

 
 
 Keep holding the pen against your skin after releasing the button 
• The injection may take up to 20 seconds. 

 
 
 Check if the window has turned yellow, before removing the pen. 
• Do not remove the pen until the entire window has turned yellow.  
• Your injection is complete, when the window has turned completely yellow, you may hear a second 

click. 
• If the window does not turn completely yellow, call sanofi-aventis for help. Do not give yourself a 

second dose without speaking to your doctor, pharmacist or nurse. 

Release the button 
immediately 

Click 



63 

 
 
 Pull pen away from your skin. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 
 

 
 
 
Throw away pen and cap 
• Do not put the blue cap back on.  
• Throw away pen and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 

 
 



64 

Praluent pre-filled pen  
 
Instructions for use 
 
The parts of the Praluent pen are shown in this picture.  
 

  
 
 
Important information  
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• This pen can only be used for one single injection, and must be thrown away after use. 
 
Do 
 Keep the Praluent pen out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent pen. 
 Follow these instructions every time you use a Praluent pen. 

 
Do not 
 Do not touch the yellow safety cover. 
 Do not use the pen if it has been dropped or damaged.  
 Do not use the pen if the blue cap is missing or not securely attached. 
 Do not re-use a pen. 
 Do not shake the pen. 
 Do not freeze the pen. 
 Do not expose the pen to direct sunlight. 
 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 

 

Body 

 

 

 

 

Grey button 

 

Window 

Yellow safety cover 
Needle inside 

Blue cap 

For single 
use only 



65 

STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent pen  
• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B, 8). 
 
 Look at the label on the pen. 
• Check that you have the correct product and the correct dose. 
• Check the use by date: do not use if this date has passed. 
 

 
 
 Look at the window. 
• Check the liquid is clear, colourless to pale yellow and free from particles - if not, do not use (see 

picture A). 
• You may see an air bubble. This is normal. 
• Do not use if the window appears solid yellow (see picture B). 

 
 
 Let the pen warm up at room temperature for 30 to 40 minutes. 
• Do not heat the pen, let it warm up on its own. 
• Do not put the pen back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into your: 

o thigh 
o belly (except for the 5 cm area around your navel)   
o outer side of your upper arm  
(See picture). 

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein.  
• Use a different spot each time you inject. 



66 

• Do not inject Praluent with other injectable medicines at the same spot. 

 
 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the blue cap  
• Do not pull off the cap until you are ready to inject. 
• Do not put the blue cap back on. 
 

 
 
 
Hold the Praluent pen like this. 
• Do not touch the yellow safety cover. 
• Make sure you can see the window. 
 

 
 
 
Press the yellow safety cover on your skin at roughly a 90° angle. 
• Press and firmly hold the pen against your body until the yellow safety cover is no longer visible. The 

pen will not work if the yellow safety cover is not depressed fully.  
• If needed, pinch the skin to make sure the injection site is firm. 

Blue cap 



67 

 
 
 Push and immediately release the grey button with your thumb.  
• You will hear a click. Your injection has now started. 
• The window will start to turn yellow. 

 

 
 

 
 Keep holding the pen against your skin after releasing the button 
• The injection may take up to 20 seconds. 

 

 
 
 Check if the window has turned yellow, before removing the pen. 
• Do not remove the pen until the entire window has turned yellow.  
• Your injection is complete, when the window has turned completely yellow, you may hear a second 

click. 
• If the window does not turn completely yellow, call sanofi-aventis for help. Do not give yourself a 

second dose without speaking to your doctor, pharmacist or nurse. 

Release the button 
immediately 
 

Click 



68 

 
 
 Pull pen away from your skin. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 

 

 
 
 
Throw away pen and cap 
• Do not put the blue cap back on.  
• Throw away pen and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 

 



69 

Praluent pre-filled pen  
 
Instructions for use 
 
The parts of the Praluent pen are shown in this picture. 
 
 

 
 
 
Important information 
 
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• It is important that you do not try to give yourself or someone else the injection unless you have 

received training from your healthcare provider. 
• This pen can only be used for one single injection, and must be thrown away after use. 
 
Do 
 Keep the Praluent pen out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent pen. 

 

 
Yellow safety 
cover 
Needle inside 

Body 

Window 

Blue cap 

For single 
use only 

Medication 
Label 



70 

 Follow these instructions every time you use a Praluent pen. 

 
Do not 
 Do not touch the yellow safety cover. 
 Do not use the pen if it has been dropped or damaged.  
 Do not use the pen if the blue cap is missing or not securely attached. 
 Do not re-use a pen. 
 Do not shake the pen. 
 Do not freeze the pen. 
 Do not expose the pen to extreme heat. 
 Do not expose the pen to direct sunlight. 
 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent pen  
• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B7). 
 
 Look at the label on the pen. 

• Check that you have the correct product and the correct dose. 
• Check the expiration date: do not use if this date has passed. 
• Do not use the Praluent pen if it has been dropped on a hard surface or damaged. 

 

 
 
 Look at the window. 
• Check the liquid is clear, colourless to pale yellow and free from particles (see picture A). 
• Do not use this medicine if the solution is discoloured or cloudy, or if it contains visible flakes or 

particles. 
• You may see an air bubble. This is normal. 
• Do not use if the window appears solid yellow (see picture B). 

 

  A  B 



71 

 
 Let the pen warm up at room temperature for 30 to 40 minutes. 
• This is important for administering the entire dose and helps minimize discomfort. 
• Do not heat the pen, let it warm up on its own. 
• Do not put the pen back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into (see PICTURE): 

o the top of your thighs 
o your belly (except for the 5 cm area around your navel)   
o outer side of your upper arm (to be given by your caregiver only)  

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein. 
• Change (rotate) your injection site each time you give yourself an injection. 
• If you need to use the same injection site, make sure it is not the same spot on the site you used last 

time. 
• Do not inject Praluent with other injectable medicines at the same spot. 

 

 
 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the blue cap  
• Do not pull off the cap until you are ready to inject. 
• Do not put the blue cap back on. 
• Do not use the pen if the blue cap is missing or not securely attached. 
 

 
 
Hold the Praluent pen like this. 
• Do not touch the yellow safety cover. The needle is inside the yellow safety cover. 
• Make sure you can see the window. 
• Do not press the pen down against your skin until you are ready to inject. 

Blue cap 

Recommended injection sites: 

Injection by 
caregiver only 

Self-injection 
or by caregiver 

 

Pull the blue cap 
straight off 



72 

 

 
 
Press the yellow safety cover on your skin at roughly a 90° angle. 
• Pinch the skin to make sure the injection site is firm. 
• Press the pen straight down against your skin until the yellow safety cover is pushed all the way into 

the pen and hold (see picture). 
• The injection will not start until the yellow safety cover is fully depressed. 
• There will be a click when the injection starts. The window will start to turn yellow. 

 

 
 
 
 Keep holding the pen against your skin 
• You may hear a second click. 
• Check that the entire window has turned yellow. 
• Then, slowly count to 5. 

 
 
 Check again that the window has turned yellow, before removing the pen. 
• If the window has not turned completely yellow, remove the pen and call sanofi-aventis for help.  
• Do not give yourself a second injection without speaking to your doctor, pharmacist or nurse. 

 
 

Click 

Do not touch the 
yellow safety cover 

Correct 

Incorrect 

Check Yellow 
Window Then slowly 

count to 5. 
1…2…3…4…5. 



73 

 Pull pen away from your skin. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 
 

 
 
 
Throw away pen and cap 
• Do not put the blue cap back on.  
• Throw away pen and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 

 
 



74 

Praluent pre-filled pen  
 
Instructions for use 
 
The parts of the Praluent pen are shown in this picture. 
 

  
 
 
Important information 
 
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• It is important that you do not try to give yourself or someone else the injection unless you have 

received training from your healthcare provider. 
• This pen can only be used for one single injection and must be thrown away after use. 
 
Do 
 Keep the Praluent pen out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent pen. 
 Follow these instructions every time you use a Praluent pen. 

 

 

 

 

 

Window 

Yellow safety 
cover 
Needle inside 

Blue 
 

For single 
use only 

Medication 
Label 

Body 



75 

 
Do not 
 Do not touch the yellow safety cover. 
 Do not use the pen if it has been dropped or damaged.  
 Do not use the pen if the blue cap is missing or not securely attached. 
 Do not re-use a pen. 
 Do not shake the pen. 
 Do not freeze the pen. 
 Do not expose the pen to extreme heat. 
 Do not expose the pen to direct sunlight. 
 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent pen  
• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B7). 
 
 Look at the label on the pen. 
• Check that you have the correct product and the correct dose. 
• Check the expiration date: do not use if this date has passed. 
• Do not use the Praluent pen if it has been dropped on a hard surface or damaged. 
 

 
 
 Look at the window. 
• Check the liquid is clear, colourless to pale yellow and free from particles (see picture A). 
• Do not use this medicine if the solution is discoloured or cloudy, or if it contains visible flakes or 

particles. 
• You may see an air bubble. This is normal. 
• Do not use if the window appears solid yellow (see picture B). 

 
 
 Let the pen warm up at room temperature for 30 to 40 minutes. 

A B 



76 

• This is important for administering the entire dose and helps minimize discomfort. 
• Do not heat the pen, let it warm up on its own. 
• Do not put the pen back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into (see PICTURE): 

o the top of your thighs 
o your belly (except for the 5 cm area around your navel)   
o outer side of your upper arm (to be given by your caregiver only)  

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein.  
• Change (rotate) your injection site each time you give yourself an injection. 
• If you need to use the same injection site, make sure it is not the same spot on the site you used last 

time. 
• Do not inject Praluent with other injectable medicines at the same spot. 

 

 
 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the blue cap  
• Do not pull off the cap until you are ready to inject. 
• Do not put the blue cap back on. 
• Do not use the pen if the blue cap is missing or not securely attached. 
 

 
 
 
Hold the Praluent pen like this. 
• Do not touch the yellow safety cover. The needle is inside the yellow safety cover. 
• Make sure you can see the window. 
• Do not press the pen down against your skin until you are ready to inject. 

Blue cap 

Recommended injection sites: 

Injection by 
caregiver only 

Self-injection 
or by caregiver 

 

Pull the blue cap 
straight off 



77 

 
 
 
Press the yellow safety cover on your skin at roughly a 90° angle. 
• Pinch the skin to make sure the injection site is firm. 
• Press the pen straight down against your skin until the yellow safety cover is pushed all the way into 

the pen and hold (see picture). 
• The injection will not start until the yellow safety cover is fully depressed. 
• There will be a click when the injection starts. The window will start to turn yellow. 

 
 
 Keep holding the pen against your skin 
• You may hear a second click. 
• Check that the entire window has turned yellow. 
• Then, slowly count to 5. 

 

 
 
 Check if the window has turned yellow, before removing the pen. 
• If the window has not turned completely yellow, remove the pen and call sanofi-aventis for help.  
• Do not give yourself a second injection without speaking to your doctor, pharmacist or nurse. 

Click 

Do not touch the yellow 
safety cover 

Correct 

Incorrect 

Check Yellow 
Window 

Then slowly 
count to 5. 
1…2…3…4…5. 



78 

 
 
 Pull pen away from your skin. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 

 

 
 
 
Throw away pen and cap 
• Do not put the blue cap back on.  
• Throw away pen and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 

 
 



79 

Praluent pre-filled pen  
 
Instructions for use 
 
The parts of the Praluent pen are shown in this picture. 
 
 

 
 
 
Important information 
 
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• It is important that you do not try to give yourself or someone else the injection unless you have 

received training from your healthcare provider. 
• This pen can only be used for one single injection and must be thrown away after use. 
 
Do 
 Keep the Praluent pen out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent pen. 
 Follow these instructions every time you use a Praluent pen. 

 

 
Yellow safety 
cover 
Needle inside 

Body 

Window 

Blue cap 

For single 
use only 

Medication 
Label 



80 

 
Do not 
 Do not touch the yellow safety cover. 
 Do not use the pen if it has been dropped or damaged.  
 Do not use the pen if the blue cap is missing or not securely attached. 
 Do not re-use a pen. 
 Do not shake the pen. 
 Do not freeze the pen. 
 Do not expose the pen to extreme heat. 
 Do not expose the pen to direct sunlight. 
 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent pen  
• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B7). 
 
 Look at the label on the pen. 

• Check that you have the correct product and the correct dose. 
• Check the expiration date: do not use if this date has passed. 
• Do not use the Praluent pen if it has been dropped on a hard surface or damaged. 

 

 
 
 Look at the window. 
• Check the liquid is clear, colourless to pale yellow and free from particles (see picture A). 
• Do not use this medicine if the solution is discoloured or cloudy, or if it contains visible flakes or 

particles. 
• You may see an air bubble. This is normal. 
• Do not use if the window appears solid yellow (see picture B). 

 
 
 Let the pen warm up at room temperature for 45 minutes. 

  A  B 



81 

• This is important for administering the entire dose and helps minimize discomfort. 
• Do not heat the pen, let it warm up on its own. 
• Do not put the pen back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into (see PICTURE): 

o the top of your thighs 
o your belly (except for the 5 cm area around your navel)   
o outer side of your upper arm (to be given by your caregiver only)  

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein. 
• Change (rotate) your injection site each time you give yourself an injection. 
• If you need to use the same injection site, make sure it is not the same spot on the site you used last 

time. 
• Do not inject Praluent with other injectable medicines at the same spot. 

 

 
 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the blue cap  
• Do not pull off the cap until you are ready to inject. 
• Do not put the blue cap back on. 
• Do not use the pen if the blue cap is missing or not securely attached. 
 

 
 
Hold the Praluent pen like this. 
• Do not touch the yellow safety cover. The needle is inside the yellow safety cover. 
• Make sure you can see the window. 
• Do not press the pen down against your skin until you are ready to inject. 

Blue cap 

Recommended injection sites: 

Injection by 
caregiver only 

Self-injection 
or by caregiver 

 

Pull the blue cap 
straight off 



82 

 

 
 
Press the yellow safety cover on your skin at roughly a 90° angle. 
• Pinch the skin to make sure the injection site is firm. 
• Press the pen straight down against your skin until the yellow safety cover is pushed all the way into 

the pen and hold (see picture). 
• The injection will not start until the yellow safety cover is fully depressed. 
• There will be a click when the injection starts. The window will start to turn yellow. 

 

 
 
 
 Keep holding the pen against your skin 
• You may hear a second click. 
• Check that the entire window has turned yellow. 
• Then, slowly count to 5. 

 
 
 Check again that the window has turned yellow, before removing the pen. 
• If the window has not turned completely yellow, remove the pen and call sanofi-aventis for help.  
• Do not give yourself a second injection without speaking to your doctor, pharmacist or nurse. 

 
 

Click 

Do not touch the 
yellow safety cover 

Correct 

Incorrect 

Check Yellow 
Window Then slowly 

count to 5. 
1…2…3…4…5. 



83 

 Pull pen away from your skin. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 
 

 
 
 
Throw away pen and cap 
• Do not put the blue cap back on.  
• Throw away pen and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 

 
  



84 

Package leaflet: Information for the user  
 

Praluent 75 mg solution for injection in a pre-filled syringe  
Praluent 150 mg solution for injection in a pre-filled syringe  

alirocumab 
 
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 Praluent is and what it is used for  
2. What you need to know before you use Praluent  
3. How to use Praluent  
4. Possible side effects  
5. How to store Praluent  
6. Contents of the pack and other information 
 
 
1. What Praluent is and what it is used for 
 
What Praluent is 
• Praluent contains the active substance alirocumab.  
• Praluent is a monoclonal antibody (a type of specialised protein designed to attach to a target 

substance in the body). Monoclonal antibodies are proteins that recognise and bind to other unique 
proteins. Alirocumab binds to PCSK9. 

 
How Praluent works 
Praluent helps lower your levels of “bad” cholesterol (also called “LDL cholesterol”). Praluent blocks a 
protein called PCSK9. 
• PCSK9 is a protein secreted by liver cells. 
• “Bad” cholesterol is normally removed from your blood by binding to specific “receptors” (docking 

stations) in your liver.  
• PCSK9 lowers the number of these receptors in the liver – this causes your “bad” cholesterol to be 

higher than it should.  
• By blocking PCSK9, Praluent increases the number of receptors available to help remove the “bad” 

cholesterol – this lowers your “bad” cholesterol levels. 
 
What Praluent is used for 
• Adults with high cholesterol levels in their blood (hypercholesterolaemia, heterozygous familial and 

non-familial, or mixed dyslipidaemia).  
• Adults with high cholesterol levels in their blood and with cardiovascular disease to reduce 

cardiovascular risk.  
 

It is given: 
 - together with a statin (a commonly used medicine that treats high cholesterol) or other cholesterol 
lowering medicines, if the maximum dose of a statin does not lower levels of cholesterol sufficiently 
or, 
- alone or together with other cholesterol lowering medicines when statins are not tolerated or cannot 
be used. 

Continue to follow your cholesterol-lowering diet while taking this medicine. 
 



85 

 
2. What you need to know before you use Praluent  
 
Do not use Praluent  
• if you are allergic to alirocumab 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 Praluent. 
 
If you develop a serious allergic reaction, stop using Praluent, talk to your doctor right away. Sometimes 
serious allergic reactions such as hypersensitivity, including angioedema (difficulties breathing, or swelling 
of the face, lips, throat or tongue), nummular eczema (reddish skin spots sometimes with blisters), and 
hypersensitivity vasculitis (which is a specific form of a hypersensitivity reaction with symptoms such as 
diarrhoea, with a rash, or purple-coloured skin spots on the skin) have occurred. For allergic reactions that 
may occur while taking Praluent, see section 4. 
 
Tell your doctor if you have kidney or liver disease before using this medicine, because Praluent has been 
studied in few patients with severe kidney disease and not in patients with severe liver disease. 
 
Children and adolescents 
Praluent should not be given to children and adolescents under 18 years old because there is limited 
experience of using the medicine in these age groups.  
 
Other medicines and Praluent 
Tell your doctor, pharmacist or nurse if you are using, have recently used or might use 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 using this medicine. 
Praluent is not recommended during pregnancy or breast-feeding. 
 
Driving and using machines  
This medicine is not expected to have any effect on your ability to drive or use machines.  
 

 

3. How to use Praluent 
 
Always use this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your doctor, 
pharmacist or nurse if you are not sure.  
 
How much to inject 
Your doctor will tell you which dose is right for you and how often to inject (75 mg or 150 mg once every 2 
weeks, or 300 mg once every 4 weeks/monthly). Your doctor will check your cholesterol levels and may 
adjust the dose (up or down) during treatment.   
Always check the label of your syringe to make sure you have the right medicine and the right strength. 
 
When to inject 
Inject Praluent once every 2 weeks (for the 75 mg or 150 mg dose), or once every 4 weeks/monthly (for the 
300 mg dose). To give the 300 mg dose, two 150 mg injections should be given in a row at two different 
injection sites. 
 
Before you inject 
Praluent should be allowed to warm to room temperature prior to use. 
Read the detailed instructions for use leaflet before you inject Praluent.  
 
Where to inject 
Praluent is injected under your skin into the thigh, abdomen or upper arm. 



86 

Read the detailed instructions for use leaflet on where to inject. 
 
Learning how to use the pre-filled syringe 
Before you use the syringe for the first time, your doctor, pharmacist or nurse will show you how to inject 
Praluent.  

• Always read the "Instructions for Use" provided in the box.  
• Always use the syringe as described in the “Instructions for Use”.  

 
If you use more Praluent than you should  
If you use more Praluent than you should, talk to your doctor, pharmacist or nurse.  
 
If you forget to use Praluent  
If you miss a dose of Praluent, inject your missed dose as soon as you can. Then take your next dose at your 
regular scheduled time. This will keep you on the original schedule. If you are not sure when to inject 
Praluent, call your doctor, pharmacist or nurse. 
 
If you stop using Praluent  
Do not stop using Praluent without talking with your doctor. If you stop using Praluent, your cholesterol 
levels can increase. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you develop a serious allergic reaction, stop using Praluent , talk to your doctor right away. Sometimes 
serious allergic reactions such as hypersensitivity (difficulties breathing), nummular eczema (reddish skin 
spots sometimes with blisters), and hypersensitivity vasculitis (which is a specific form of a hypersensitivity 
reaction with symptoms such as diarrhoea, with a rash, or purple-coloured skin spots on the skin) have 
occurred (may affect up to 1 in 1,000 people).  
 
Other side effects are: 
Common (may affect up to 1 in 10 people) 
• redness, itching, swelling, pain/tenderness where the medicine was injected (local injection site 

reactions) 
• upper respiratory tract signs or symptoms such as sore throat, running nose, sneezing 
• itching (pruritus). 
 
Rare (may affect up to 1 in 1,000 people) 
• red and itchy raised bumps or hives (urticaria) 
 
Not Known 
 
The following side effects have been reported since the marketing of Praluent, but how often they occur is 
not known: 
 
• flu-like illness 
• difficulties breathing, or swelling of the face, lips, throat or tongue (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. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


87 

 
5. How to store Praluent 
 
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 to 8°C). Do not freeze.  
Keep the syringe in the outer carton in order to protect from light.  
 
If needed, individual pre-filled syringes may be kept outside the refrigerator below 25°C for a maximum of 
30 days. Protect from light. After removal from the refrigerator, Praluent must be used within 30 days or 
discarded. 
 
Do not use this medicine if it looks discoloured or cloudy, or if it contains visible flakes or particles. 
 
After use put the syringe into a puncture-resistant container. Ask your doctor, pharmacist or nurse how to 
throw away the container. Do not recycle the container.  
 
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 Praluent contains  
• The active substance is alirocumab. 

 
Praluent 75 mg solution for injection in pre-filled syringe 
Each single-use syringe contains 75 milligrams of alirocumab. 
 
Praluent 150 mg solution for injection in pre-filled syringe 
Each single-use syringe contains 150 milligrams of alirocumab. 
 

• The other ingredients are histidine, sucrose, polysorbate 20 and water for injections. 
 
What Praluent looks like and contents of the pack 
Praluent is a clear, colourless to pale yellow solution for injection that comes in a pre-filled syringe.  
 
Praluent 75 mg solution for injection in pre-filled syringe 
Each pre-filled syringe with green plunger contains 1 ml of solution, delivering one single dose of 
75 milligrams of alirocumab.  
It is available in pack size of 1, 2 or 6 pre-filled syringes. 
 
Praluent 150 mg solution for injection in pre-filled syringe 
Each pre-filled syringe with grey plunger contains 1 ml of solution, delivering one single dose of 
150 milligrams of alirocumab.  
It is available in pack size of 1, 2 or 6 pre-filled syringes. 
 
Not all presentations and pack sizes may be marketed. 
 



88 

Marketing Authorisation Holder  
sanofi-aventis groupe  
54, rue La Boétie 
F – 75008 Paris 
France 
 
Manufacturer 
Sanofi Winthrop Industrie 
1051 Boulevard Industriel 
76580 Le Trait 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB “SANOFI-AVENTIS LIETUVA” 
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt.  
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 52 52 010 
Tel. aus dem Ausland: +49 69 305 21 131 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 



89 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l. 
Tel: 800 131212 (domande di tipo tecnico)  
        800 536389 (altre domande) 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

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



90 

Praluent pre-filled syringe  
 
Instructions for use 
 
The parts of the Praluent syringe are shown in this picture.  
 

   
 
 
Important information  
• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• This syringe can only be used for one single injection, and must be thrown away after use. 
 
Do  
 Keep the Praluent syringe out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent syringe. 
 Follow these instructions every time you use a Praluent syringe. 
 
Do not  
 Do not touch the needle. 
 Do not use the syringe if it has been dropped or damaged. 
 Do not use the syringe if the grey needle cap is missing or not securely attached. 
 Do not re-use a syringe. 
 Do not shake the syringe. 
 Do not freeze the syringe. 
 Do not expose syringe to direct sunlight. 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent syringe  
• alcohol wipes  

  

Syringe body 

Needle  
cap 

Needle  

Green plunger 



91 

• cotton ball or gauze  
• a puncture-resistant container (see Step B, 6). 
 
 Before you start.  
• Take the syringe out of the packaging by holding the syringe body. 

 
 
 Look at the label on the syringe. 
• Check that you have the correct product and the correct dose (green plunger for 75 mg/ml). 
• Check the use by date and do not use if this date has passed. 
• Check the liquid is clear, colourless to pale yellow and free from particles; if not, do not use. 
• Check that the syringe is not open or damaged. 
 
 Let the syringe warm up at room temperature for 30 to 40 minutes. 
• Do not heat the syringe, let it warm up on its own. 
• Do not put the syringe back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into your:  

o thigh 
o belly (except for the 5 cm area around your navel) 
o outer side of your upper arm  
(See picture). 

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein.  
• Use a different spot each time you inject. 
• Do not inject Praluent with other injectable medicines at the same spot. 

 



92 

 
STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the needle cap.  
• Do not pull off the cap until you are ready to inject. 
• Hold the syringe in the middle of the syringe body with the needle pointing away from you. 
• Keep your hand away from the plunger.  
• You may see an air bubble. This is normal. Do not get rid of any air bubbles in the syringe before the 

injection.  
• Do not put the grey cap back on. 

 
 
 If needed pinch the skin. 
• Use your thumb and first finger to pinch a fold of skin at the injection site. 
• Hold the skin like this for the whole injection. 

 
 
 Insert the needle into the fold of skin with a quick dart-like motion. 
• Use a 90º angle if you can pinch 5 cm of skin.  
• Use a 45° angle if you can only pinch 2 cm of skin. 

 

 
 

Needle 
cap 

Plunger 



93 

 
 Push the plunger down.  
• Inject all of the solution by slowly and steadily pushing down the plunger. 

 

 
 
 
 Before you remove the needle check the syringe is empty. 
• Do not remove the syringe until it is completely empty.  
• Pull the needle out of the skin at the same angle as it was inserted. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 
 

 
 
 Throw away syringe and cap 
• Do not put the grey needle cap back on.  
• Do not re-use the syringe. 
• Throw away syringe and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 
 

 
 



94 

  
Praluent pre-filled syringe  
 
Instructions for use 
 
The parts of the Praluent syringe are shown in this picture.  
 

 
 
 
Important information  

• The medicine is injected under your skin and can be given by yourself or someone else (caregiver).  
• This syringe can only be used for one single injection, and must be thrown away after use. 

 
Do  
 Keep the Praluent syringe out of the sight and reach of children. 
 Read all of the instructions carefully before using the Praluent syringe. 
 Follow these instructions every time you use a Praluent syringe. 
 
Do not  
 Do not touch the needle. 
 Do not use the syringe if it has been dropped or damaged. 
 Do not use the syringe if the grey needle cap is missing or not securely attached. 
 Do not re-use a syringe. 
 Do not shake the syringe. 
 Do not freeze the syringe. 
 Do not expose syringe to direct sunlight. 
 
Keep this leaflet. If you have questions, ask your doctor, pharmacist or nurse or call the sanofi-aventis 
number on the package leaflet.  
 
 
STEP A: Getting ready for an injection 
 
Before you start you will need:  
• the Praluent syringe  

Grey plunger 

Syringe body 

Needle  
cap 

Needle 



95 

• alcohol wipes  
• cotton ball or gauze  
• a puncture-resistant container (see Step B, 6). 
 
 
 Before you start.  
• Take the syringe out of the packaging by holding the syringe body. 

 
 
 Look at the label on the syringe. 
• Check that you have the correct product and the correct dose (grey plunger for 150 mg/ml). 
• Check the use by date and do not use if this date has passed. 
• Check the liquid is clear, colourless to pale yellow and free from particles; if not, do not use. 
• Check that the syringe is not open or damaged. 
 
 Let the syringe warm up at room temperature for 30 to 40 minutes. 
• Do not heat the syringe, let it warm up on its own. 
• Do not put the syringe back in the refrigerator. 
 
 Prepare the injection site. 
• Wash your hands with soap and water and dry with a towel. 
• You can inject into your:  

o thigh 
o belly (except for the 5 cm area around your navel) 
o outer side of your upper arm  
(See picture). 

• You can stand or sit to give yourself an injection. 
• Clean skin in the injection area with an alcohol wipe. 
• Do not use skin that is tender, hard, red or hot. 
• Do not use any area near a visible vein. 
• Use a different spot each time you inject. 
• Do not inject Praluent with other injectable medicines at the same spot. 
 

 
 



96 

STEP B: How to inject 
 
 After completing all steps in “Step A: Getting ready for an injection”, pull off the needle cap.  
• Do not pull off the cap until you are ready to inject. 
• Hold the syringe in the middle of the syringe body with the needle pointing away from you. 
• Keep your hand away from the plunger.  
• You may see an air bubble. This is normal. Do not get rid of any air bubbles in the syringe before the 

injection.  
• Do not put the grey cap back on. 

 
 
 If needed pinch the skin. 
• Use your thumb and first finger to pinch a fold of skin at the injection site. 
• Hold the skin like this for the whole injection. 

 
 
 Insert the needle into the fold of skin with a quick dart-like motion. 
• Use a 90º angle if you can pinch 5 cm of skin.  
• Use a 45° angle if you can only pinch 2 cm of skin. 

 

 
 

Needle 
cap 

Plunger 



97 

 
 Push the plunger down.  
• Inject all of the solution by slowly and steadily pushing down the plunger. 

 

 
 
 
 Before you remove the needle check the syringe is empty. 
• Do not remove the syringe until it is completely empty.  
• Pull the needle out of the skin at the same angle as it was inserted. 
• Do not rub the skin after the injection. 
• If you see any blood, press a cotton ball or gauze on the site until the bleeding stops. 
 

 
 
 
 Throw away syringe and cap 
• Do not put the grey needle cap back on.  
• Do not re-use the syringe. 
• Throw away syringe and cap into a puncture-resistant container immediately after use. 
• Ask your doctor, pharmacist or nurse how to throw away the container. 
• Always keep the container out of the sight and reach of children. 
 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET