Alirocumab

FDA Drug Information • Also known as: Praluent

Brand Names: Praluent
Drug Class: PCSK9 Inhibitor [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Alirocumab is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). Alirocumab is a PCSK9 inhibitor produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Alirocumab consists of two disulfide-linked human heavy chains, each covalently linked through a disulfide bond to a human kappa light chain. A single N-linked glycosylation site is located in each heavy chain within the CH2 domain of the Fc constant region of the molecule. The variable domains of the heavy and light chains combine to form the PCSK9 binding site within the antibody. Alirocumab has an approximate molecular weight of 146 kDa. PRALUENT is a sterile, preservative-free, clear, colorless to pale yellow solution for subcutaneous use. PRALUENT 75 mg/mL or 150 mg/mL solution for subcutaneous injection in a single-dose pre-filled pen is supplied in a siliconized 1 mL Type-1 clear glass syringe. Each 75 mg/mL pre-filled pen contains 75 mg alirocumab, histidine (8 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0. Each 150 mg/mL pre-filled pen contains 150 mg alirocumab, histidine (6 mM), polysorbate 20 (0.1 mg), sucrose (100 mg), and Water for Injection USP, to pH 6.0.

What Is Alirocumab Used For?

1 INDICATIONS AND USAGE PRALUENT ® is indicated: To reduce the risk of major adverse cardiovascular (CV) events (coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization) in adults at increased risk for these events . As an adjunct to diet and exercise to reduce low- density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia. adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). adults with homozygous familial hypercholesterolemia (HoFH). PRALUENT is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor indicated: To reduce the risk of major adverse cardiovascular (CV) events (coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization) in adults at increased risk for these events. ( 1 ) As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in : adults with hypercholesterolemia ( 1 ) adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). ( 1 ) adults with homozygous familial hypercholesterolemia (HoFH). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION In adults with hypercholesterolemia, including HeFH ( 2.1 ): The recommended starting dosage of PRALUENT is either 75 mg once every 2 weeks or 300 mg once every 4 weeks administered subcutaneously. For patients receiving PRALUENT 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dosage, because LDL-C can vary between dosages in some patients. 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 ( 2.1 ): The recommended dosage of PRALUENT is 150 mg once every 2 weeks administered subcutaneously. PRALUENT can be administered without regard to the timing of LDL apheresis. In pediatric patients with HeFH ( 2.2 ): The recommended dosage of PRALUENT for patients with a body weight less than 50 kg is 150 mg once every 4 weeks administered subcutaneously. The recommended dosage of PRALUENT for patients with a body weight of 50 kg or more is 300 mg once every 4 weeks administered subcutaneously. If the LDL-C response is inadequate, the dosage may be adjusted for patients with a body weight less than 50 kg to 75 mg subcutaneously once every 2 weeks or for patients with a body weight of 50 kg or more to 150 mg subcutaneously once every 2 weeks. Assess LDL-C when clinically appropriate. The LDL-lowering effect of PRALUENT may be measured as early as 4 weeks after initiation. ( 2.1 ) 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. ( 2.4 ) To administer the 300 mg dosage, give two 150 mg PRALUENT injections consecutively at two different injection sites. ( 2.4 ) 2.1 Recommended Dosage in Adults Hypercholesterolemia, including HeFH: The recommended starting dosage of PRALUENT is either 75 mg once every 2 weeks or 300 mg once every 4 weeks administered subcutaneously [see Dosage and Administration (2.4) ] . 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 to 150 mg subcutaneously every 2 weeks. HeFH undergoing LDL apheresis or with HoFH: The recommended dosage of PRALUENT is 150 mg once every 2 weeks administered subcutaneously [see Dosage and Administration (2.4) ] . 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 Recommended Dosage in Pediatric Patients Aged 8 years and Older With HeFH The recommended dosage of PRALUENT for patients with a body weight less than 50 kg is 150 mg once every 4 weeks administered subcutaneously [see Dosage and Administration (2.4) ] . If the LDL-C lowering response is...

Side Effects (Adverse Reactions)

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) ] Common (>5% of patients treated with PRALUENT and more frequently than placebo) adverse reactions in adults with: Primary hypercholesterolemia : injection site reactions, and influenza. ( 6 ) Established CV disease: myalgia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-844-734-6643 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. Adverse Reactions in Adults with Hypercholesterolemia The data in Table 1 are derived from 9 primary hypercholesterolemia placebo-controlled trials that included 2,476 adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks, including 2,135 exposed for 6 months and 1,999 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 female, 90% were White, 4% were Black or African American, 3% were Asian, and 3% other races; 6% identified as Hispanic or Latino ethnicity. 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 Adult Patients and ≥1% More Frequently Than with Placebo Adverse Reactions Placebo (N=1,276) % PRALUENT 75 mg every 2 weeks and 150 mg every 2 weeks combined (N=2,476) % Injection site reactions Includes erythema/redness, itching, swelling, pain/tenderness 5 7 Influenza 5 6 Diarrhea 4 5 Myalgia 3 4 Muscle spasms 2 3 Contusion 1 2 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. Adverse Reactions in a Cardiovascular Outcomes Trial in Adults In a CV outcomes trial in which 9,451 patients were exposed to PRALUENT for a median of 31 months and 9,443 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 myalgia (6% PRALUENT, 5% placebo). Adverse Reactions in Pediatric Patients with HeFH In a 24-week placebo-controlled clinical trial in which 101 pediatric patients aged 8 to 17 years with HeFH were exposed to PRALUENT and 52 pediatric patients with HeFH were exposed to placebo [see Clinical Studies (14.3) ], the safety profile of PRALUENT observed in this population was consistent with the safety profile observed in adults with HeFH. Other Adverse Reactions Local Injection Site Reactions In a pool of placebo-controlled trials evaluating PRALUENT 75 mg and/or 150 mg administered every 2 weeks in adults, 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...

Contraindications

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) ]. History of a serious hypersensitivity reaction to alirocumab or any of the excipients in PRALUENT. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available data from clinical trials and postmarketing reports on PRALUENT use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. 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. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, alirocumab has the potential to be transmitted from the mother to the developing fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. 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. There is a pregnancy safety study for PRALUENT. If PRALUENT is administered during pregnancy, healthcare providers should report PRALUENT exposure by contacting Regeneron at 1-844-734-6643. 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...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING PRALUENT injection is a clear, colorless to pale yellow solution, supplied as follows: Pack Size 75 mg/mL Pre-filled Pen 150 mg/mL Pre-filled Pen Pack of 1 pen NDC 0024-5901-01 NDC 0024-5902-01 The needle shield is not made with natural rubber latex. Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. Do not shake. PRALUENT may be kept at room temperature up to 77°F (25°C) in the original carton for 30 days. If not used within the 30 days, discard PRALUENT.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.