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PRALUENT®
Rx Only
(alirocumab) injection, for subcutaneous use
Brief Summary of Prescribing Information
1
INDICATIONS AND USAGE
1.1 Primary
Hyperlipidemia
PRALUENT® is indicated as an adjunct to diet and maximally tolerated statin therapy for the
treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic
cardiovascular disease, who require additional lowering of LDL-C.
1.2 Limitations of Use
The effect of PRALUENT on cardiovascular morbidity and mortality has not been determined.
4
CONTRAINDICATIONS
PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to
PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions
requiring hospitalization. [See Warnings and Precautions (5.1)]
5
WARNINGS AND PRECAUTIONS
5.1 Allergic Reactions
Hypersensitivity reactions (e.g., pruritus, rash, urticaria), including some serious events (e.g.,
hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization), have been
reported with PRALUENT treatment. If signs or symptoms of serious allergic reactions occur,
discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until
signs and symptoms resolve [see Contraindications (4)].
6
ADVERSE REACTIONS
The following adverse reactions are also discussed in the other sections of the labeling:
• Allergic Reactions [See Warnings and Precautions (5.1).]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug and may not reflect the rates observed in practice.
The safety of PRALUENT was evaluated in 9 placebo-controlled trials that included 2476
patients treated with PRALUENT, including 2135 exposed for 6 months and 1999 exposed for
more than 1 year (median treatment duration of 65 weeks). The mean age of the population
was 59 years, 40% of the population were women, 90% were Caucasians, 4% were Black or
African American, and 3% were Asians. At baseline, 37% of patients had a diagnosis of
heterozygous familial hypercholesterolemia and 66% had clinical atherosclerotic cardiovascular
disease.
Adverse reactions reported in at least 2% of PRALUENT-treated patients, and more frequently
than in placebo-treated patients, are shown in Table 1.

Adverse reactions led to discontinuation of treatment in 5.3% of patients treated with
PRALUENT and 5.1% of patients treated with placebo. The most common adverse reactions
leading to treatment discontinuation in patients treated with PRALUENT were allergic reactions
(0.6% versus 0.2% for PRALUENT and placebo, respectively) and elevated liver enzymes (0.3%
versus <0.1%).
Local Injection Site Reactions
Local injection site reactions including erythema/redness, itching, swelling, and pain/tenderness
were reported more frequently in patients treated with PRALUENT (7.2% versus 5.1% for
PRALUENT and placebo, respectively). Few patients discontinued treatment because of these
reactions (0.2% versus 0.4% for PRALUENT and placebo, respectively), but patients receiving
PRALUENT had a greater number of injection site reactions, had more reports of associated
symptoms, and had reactions of longer average duration than patients receiving placebo.
Allergic Reactions
Allergic reactions were reported more frequently in patients treated with PRALUENT than in
those treated with placebo (8.6% versus 7.8%). The proportion of patients who discontinued
treatment due to allergic reactions was higher among those treated with PRALUENT (0.6%
versus 0.2% ). Serious allergic reactions, such as hypersensitivity, nummular eczema, and
hypersensitivity vasculitis were reported in patients using PRALUENT in controlled clinical trials
[see Warnings and Precautions (5.1)].
Neurocognitive Events
Neurocognitive events were reported in 0.8% of patients treated with PRALUENT and 0.7% of
patients treated with placebo. Confusion or memory impairment were reported more frequently
by those treated with PRALUENT (0.2% for each) than in those treated with placebo (<0.1%
for each).
Liver Enzyme Abnormalities
Liver-related disorders (primarily related to abnormalities in liver enzymes) were reported in
2.5% of patients treated with PRALUENT and 1.8% of patients treated with placebo, leading to
treatment discontinuation in 0.4% and 0.2% of patients, respectively. Increases in serum

transaminases to greater than 3 times the upper limit of normal occurred in 1.7% of patients
treated with PRALUENT and 1.4% of patients treated with placebo.
Low LDL-C Values
In a pool of both placebo- and active-controlled clinical trials, 796 PRALUENT-treated patients
had two consecutive calculated LDL-C values <25 mg/dL, and 288 had two consecutive
calculated LDL-C values <15 mg/dL. Changes to background lipid-altering therapy (e.g.,
maximally tolerated statins) were not made in response to low LDL-C values, and PRALUENT
dosing was not modified or interrupted on this basis. Although adverse consequences of very
low LDL-C were not identified in these trials, the long-term effects of very low levels of LDL-C
induced by PRALUENT are unknown.
6.2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity with PRALUENT. In a
pool of ten placebo- and active-controlled trials, 4.8% of patients treated with PRALUENT had
anti-drug antibodies (ADA) newly detected after initiating treatment as compared with 0.6% of
patients treated with control.
Patients who developed ADA had a higher incidence of injection site reactions compared with
patients who did not develop ADA (10.2% vs 5.9%).
A total of 1.2% of patients treated with PRALUENT developed neutralizing antibodies (NAb) on
at least one occasion as compared with no patients treated with control, and 0.3% of patients
both tested positive for NAb and exhibited transient or prolonged loss of efficacy. The long-term
consequences of continuing PRALUENT treatment in the presence of persistent NAb are
unknown.
Immunogenicity data are highly dependent on the sensitivity and specificity of the assay as well
as other factors. Additionally, the observed incidence of antibody positivity in an assay may be
influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of
antibodies to PRALUENT with the incidence of antibodies to other products may be misleading.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary: There are no available data on use of PRALUENT in pregnant women to inform
a drug-associated risk. In animal reproduction studies, there were no effects on embryo-fetal
development when rats were subcutaneously administered alirocumab during organogenesis at
dose exposures up to 12-fold the exposure at the maximum recommended human dose of 150
mg every two weeks. In monkeys, suppression of the humoral immune response was observed
in infant monkeys when alirocumab was dosed during organogenesis to parturition at dose
exposures 13-fold the exposure at the maximum recommended human dose of 150 mg every
two weeks. No additional effects on pregnancy or neonatal/infant development were observed
at dose exposures up to 81-fold the maximum recommended human dose of 150 mg every two
weeks. Measurable alirocumab serum concentrations were observed in the infant monkeys at
birth at comparable levels to maternal serum, indicating that alirocumab, like other IgG
antibodies, crosses the placental barrier. FDA’s experience with monoclonal antibodies in
humans indicates that they are unlikely to cross the placenta in the first trimester; however, they
are likely to cross the placenta in increasing amounts in the second and third trimester. Consider
the benefits and risks of PRALUENT and possible risks to the fetus before prescribing
PRALUENT to pregnant women.
In the U.S. general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Data; Animal Data - In Sprague Dawley rats, no effects on embryo-fetal development were
observed when alirocumab was dosed at up to 75 mg/kg/dose by the subcutaneous route on
gestation days 6 and 12 at exposures 12-fold the maximum recommended human dose of 150
mg every two weeks, based on serum AUC.
In cynomolgus monkeys, suppression of the humoral immune response to keyhole limpet
hemocyanin (KLH) antigen was observed in infant monkeys at 4 to 6 months of age when
alirocumab was dosed during organogenesis to parturition at 15 mg/kg/week and 75 mg/kg/week
by the subcutaneous route, corresponding to 13- and 81-fold the human exposure at the
maximum recommended human dose of 150 mg every two weeks, based on serum AUC. The
lowest dose tested in the monkey resulted in humoral immune suppression; therefore it is
unknown if this effect would be observed at clinical exposure. No study designed to challenge
the immune system of infant monkeys was conducted. No additional embryo-fetal, prenatal or
postnatal effects were observed in infant monkeys, and no maternal effects were observed,
when alirocumab was dosed at up to 75 mg/kg/week by the subcutaneous route, corresponding
to maternal exposure of 81-fold the exposure at the maximum recommended human dose of
150 mg every two weeks, based on serum AUC.
8.2 Lactation
Risk Summary: There is no information regarding the presence of alirocumab in human milk,
the effects on the breastfed infant, or the effects on milk production. The development and health
benefits of breastfeeding should be considered along with the mother’s clinical need for
PRALUENT and any potential adverse effects on the breastfed infant from PRALUENT or from
the underlying maternal condition. Human IgG is present in human milk, but published data
suggest that breastmilk IgG antibodies do not en ter the neonatal and infant circulation in
substantial amounts.
8.4 Pediatric Use
Safety and efficacy in pediatric patients have not been established.
8.5 Geriatric Use
In controlled studies, 1158 patients treated with PRALUENT were ≥65 years of age and 241
patients treated with PRALUENT were ≥75 years of age. No overall differences in safety or
effectiveness were observed between these subjects and younger subjects, and other reported
clinical experience has not identified differences in responses between the elderly and younger
patients, but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
No dose adjustment is needed for patients with mild or moderately impaired renal function. No
data are available in patients with severe renal impairment. [See Clinical Pharmacology (12.3)
in the full prescribing information.]
8.7 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 Clinical Pharmacology (12.3) in
the full prescribing information.]
Manufactured by:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY
U.S. License # 1752
Marketed by sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)
and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
PRALUENT is a registered trademark of Sanofi
©2015 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC
Revised: October 2015
ALI-BPLR-SA-OCT15

©2016, Sanofi and Regeneron Pharmaceuticals, Inc.
03/2016 US-PRB-1976 US.ALI.16.02.081

Reference: 1. PRALUENT® (alirocumab) Prescribing Information.
Sanofi/Regeneron Pharmaceuticals, 2015.

Table 1 Adverse Reactions Occurring in Greater Than or Equal to 2% of
PRALUENT-Treated Patients and More Frequently Than with Placebo
Placebo
(N=1276)

PRALUENT*
(N=2476)

11.1%

11.3%

Injection site reactions

5.1%

7.2%

Influenza

4.6%

5.7%

Urinary tract infection

4.6%

4.8%

Diarrhea

4.4%

4.7%

Bronchitis

3.8%

4.3%

Myalgia

3.4%

4.2%

Muscle spasms

2.4%

3.1%

Sinusitis

2.7%

3.0%

Cough

2.3%

2.5%

Contusion

1.3%

2.1%

Adverse Reactions
Nasopharyngitis
†

Musculoskeletal pain
1.6%
*75 mg every 2 weeks and 150 mg every 2 weeks combined
†includes erythema/redness, itching, swelling, pain/tenderness

2.1%