Praluent

PRALUENT- alirocumab injection, solution
Sanofi US Corporation

1 INDICATIONS AND USAGE

PRALUENT^® is indicated:

• To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
• As an adjunct to diet, alone or in combination with other low density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.
• ​ As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

• In adults with established cardiovascular disease or with primary hyperlipidemia, including HeFH:
  • The recommended starting dose of PRALUENT is either 75 mg once every 2 weeks or 300 mg once every 4 weeks administered subcutaneously [see Dosage and Administration (2.3)].
  • For patients receiving PRALUENT 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, because LDL-C can vary between doses in some patients [see Clinical Studies (14)].
  • If the LDL-C response is inadequate, the dosage may be adjusted 150 mg subcutaneously every 2 weeks.
• In adults with HeFH undergoing LDL apheresis or in adults with HoFH:
  • ​The recommended dose of PRALUENT is 150 mg once every 2 weeks administered subcutaneously [see Dosage and Administration (2.3)].
  • ​PRALUENT can be administered without regard to the timing of LDL apheresis.
• ​ Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation.

2.2 Missed Doses

If a dose is missed:

• Within 7 days from the missed dose, instruct the patient to administer PRALUENT and resume the patient’s original schedule.
• More than 7 days after the missed dose:
  • For every 2 week dose, instruct the patient to wait until the next dose on the original schedule.
  • For every 4 week dose, instruct the patient to administer the dose and start a new schedule based on this date.

2.3 Important Administration Instructions

• Train patients and/or caregivers on how to prepare and administer PRALUENT, according to the Instructions for Use and instruct them to read and follow the Instructions for Use each time they use PRALUENT.
• Prior to use, allow PRALUENT to warm to room temperature for 30 to 40 minutes if PRALUENT has been refrigerated [see How Supplied/Storage and Handling (16)].
• Visually inspect PRALUENT prior to administration. PRALUENT is a clear, colorless to pale yellow solution. Do not use if the solution is cloudy, discolored, or contains particles.
• ​ Administer PRALUENT subcutaneously into areas of the thigh, abdomen, or upper arm that are not tender, bruised, red, or indurated. Rotate injection sites for each administration.
• ​ To administer the 300 mg dose, give two 150 mg PRALUENT injections consecutively at two different injection sites.

3 DOSAGE FORMS AND STRENGTHS

PRALUENT injection is a clear, colorless to pale yellow solution available as follows:

• 75 mg/mL single-dose pre-filled pen
• 150 mg/mL single-dose pre-filled pen

4 CONTRAINDICATIONS

​ PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any of the excipients in PRALUENT. Hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalization have occurred [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including hypersensitivity vasculitis, angioedema, and other hypersensitivity reactions requiring hospitalization, have been reported with PRALUENT treatment. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with PRALUENT, treat according to the standard of care, and monitor until signs and symptoms resolve. PRALUENT is contraindicated in patients with a history of a serious hypersensitivity reaction to alirocumab or any excipient in PRALUENT [see Contraindications (4)].

6 ADVERSE REACTIONS

The following adverse reactions are also discussed in the other sections of the labeling:

• Hypersensitivity 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 data in Table 1 are derived from 9 primary hyperlipidemia placebo-controlled trials that included 2476 patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks, 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 White, 4% were Black or African American, and 3% were Asian.

Adverse reactions reported in at least 2% of PRALUENT-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1.

Table 1: Adverse Reactions Occurring in >2% of PRALUENT-Treated Patients and More Frequently Than with Placebo

Adverse Reactions	Placebo(N=1276)%	PRALUENT *(N=2476)%
* 75 mg every 2 weeks and 150 mg every 2 weeks combined † Includes erythema/redness, itching, swelling, pain/tenderness
Nasopharyngitis	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
Musculoskeletal pain	1.6	2.1

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%).

In an analysis of ezetimibe-controlled trials in which 864 patients were exposed to PRALUENT for a median of 27 weeks and 618 patients were exposed to ezetimibe for a median of 24 weeks, the types and frequencies of common adverse reactions were similar to those listed above.

In a cardiovascular outcomes trial in which 9451 patients were exposed to PRALUENT for a median of 31 months and 9443 patients were exposed to placebo for a median of 32 months, common adverse reactions (greater than 5% of patients treated with PRALUENT and occurring more frequently than placebo) included non-cardiac chest pain (7.0% PRALUENT, 6.8% placebo), nasopharyngitis (6.0% PRALUENT, 5.6% placebo), and myalgia (5.6% PRALUENT, 5.3% placebo).

In the HoFH placebo-controlled trial in which 45 patients were exposed to PRALUENT for a median of 12 weeks and 24 patients were exposed to placebo for a median of 12 weeks, no additional adverse reactions were identified.

Local Injection Site Reactions

In a pool of placebo-controlled trials evaluating PRALUENT 75 mg and/or 150 mg administered every 2 weeks, 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.

In a 48-week placebo-controlled trial evaluating PRALUENT 300 mg every 4 weeks and 75 mg every 2 weeks, in which all patients received an injection of drug or placebo every 2 weeks, local injection site reactions were reported more frequently in patients treated with PRALUENT 300 mg every 4 weeks as compared to those receiving PRALUENT 75 mg every 2 weeks or placebo (16.6%, 9.6%, and 7.9%, respectively). Three patients (0.7%) treated with PRALUENT 300 mg every 4 weeks discontinued treatment due to local injection site reactions versus no patients (0%) in the other 2 treatment groups.

In a cardiovascular outcomes trial, local injection site reactions were reported in 3.8% of patients treated with PRALUENT versus 2.1% patients treated with placebo, and led to permanent discontinuation in 26 patients (0.3%) versus 3 patients (<0.1%), respectively.

Hypersensitivity Reactions

Hypersensitivity reactions were reported more frequently in patients treated with PRALUENT than in those treated with placebo (8.6% versus 7.8%). The most common hypersensitivity reaction was pruritus (1.1% versus 0.4% for PRALUENT and placebo, respectively). 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.

Liver Enzyme Abnormalities

In the primary hyperlipidemia trials, 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.