Praluent

Yes

There is no data on the use of alirocumab in pregnant women.

It is not known if alirocumab can enter human milk or cause harm to the nursing infant.

1-10%

Allergic reactions (8.6%)

Injection site reactions (7.2%)

Influenza (5.7%)

Antidrug antibodies (4.8%)

Myalgia (4.2%)

Muscle spasms (3.1%)

Contusion (2.1%)

Musculoskeletal pain (2.1%)

Praluent comes as a prefilled syringe or prefilled dosing pen to inject under the skin.

You may be shown how to administer this medicine at home. Follow your doctor's instructions carefully.

Praluent is typically given once every two weeks. Try to inject this medicine around the same time every two weeks.

Your doctor may increase your dose after four to eight weeks of treatment.

Each dosing pen or syringe contains enough medicine for one dose only. Discard the device after using it.

It may take up to 20 seconds to inject Praluent.

You can inject Praluent into your thighs, upper arms, or stomach area — but not the two-inch area around your navel.

Use a different spot each time you inject the drug.

Don't give yourself an injection into an area of the skin that's red, bruised, sore, sunburned, or infected. Avoid locations with scars, rashes, stretch marks, or visible veins.

Don't inject more or less Praluent than is recommended.

Continue to use this medicine even if you feel well. Don't stop taking it without first talking to your doctor.

Never mix Praluent with other medicines.

Don't shake the prefilled syringe or dosing pen.

Praluent should be clear or pale yellow and free of floating particles. Look at the solution carefully before injecting it to ensure that it's the correct color and consistency.

Praluent should be stored in the refrigerator, away from light and heat.

Allow the syringe or dosing pen to warm to room temperature for about 30 to 40 minutes before using it.

Don't use this medicine if it's been at room temperature for 24 hours or longer.

Never put the syringe or dosing pen back in the refrigerator after it's been warmed to room temperature.

Praluent Overdose

If you suspect an overdose of Praluent, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Praluent

If you miss a dose of Praluent, give yourself an injection as soon as you remember, as long as it's been seven days or less since the medicine was supposed to be given.

Then, return to your normal dosing schedule.

Skip the missed dose entirely if it's been more than seven days since you were supposed to administer the injection.

Don't give yourself extra medicine to make up for a missed dose.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Praluent is excreted in human breast milk or if it will harm your nursing baby. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Praluent, nursing is not recommended. You and your healthcare provider should decide if you will take Praluent or breastfeed. You should not do both without talking to your healthcare provider first.

Antilipemic agent; fully human monoclonal antibody to human proprotein convertase subtilisin kexin type 9 (PCSK9).1 2 3 4 7 10 11 12 17 19

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Difficulty with breathing or swallowing
• fever
• hives
• nausea
• reddening of the skin, especially around the ears
• swelling of the eyes, face, or inside of the nose
• unusual tiredness or weakness

• Cough producing mucus
• tightness in the chest

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Chills
• cough
• diarrhea
• general feeling of discomfort or illness
• headache
• joint pain
• loss of appetite
• muscle aches and pains
• redness, itching, swelling, pain at the injection site
• shivering
• sore throat
• stuffy or runny nose
• sweating
• trouble sleeping
• vomiting

• Bladder pain
• bloody or cloudy urine
• difficult, burning, or painful urination
• difficulty with moving
• frequent urge to urinate
• lower back or side pain
• muscle pains or stiffness
• muscle spasms
• pain or tenderness around the eyes and cheekbones
• swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to lower cholesterol.
• It is used in some people with hard arteries in the heart.

• If you have an allergy to Praluent (alirocumab) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Praluent with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Mechanism of Action

Alirocumab is a human monoclonal antibody that binds 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 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.

Pharmacodynamics

Alirocumab reduced free PCSK9 in a concentration-dependent manner. Following a single subcutaneous administration of alirocumab 75 or 150 mg, maximal suppression of free PCSK9 occurred within 4 to 8 hours. Free PCSK9 concentrations returned to baseline when alirocumab concentrations decreased below the limit of quantitation.

Pharmacokinetics

Absorption

After subcutaneous (SC) administration of 75 mg to 300 mg alirocumab, median times to maximum serum concentrations (tmax) were 3–7 days. The pharmacokinetics of alirocumab after single SC administration of 75 mg into the abdomen, upper arm, or thigh were similar. The absolute bioavailability of alirocumab after SC administration was about 85% as determined by population pharmacokinetics analysis. 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 every 2 weeks to 150 mg every 2 weeks. Monthly dose normalized exposure with 300 mg every 4 weeks treatment was similar to that of 150 mg every 2 weeks. Steady state was reached after 2 to 3 doses with an accumulation ratio up to a maximum of about 2-fold.

Distribution

Following IV administration, the volume of distribution was about 0.04 to 0.05 L/kg indicating that alirocumab is distributed primarily in the circulatory system.

Metabolism and Elimination

Specific metabolism studies were not conducted, because alirocumab is a protein. Alirocumab is expected to degrade to small peptides and individual amino acids. In clinical studies where alirocumab was administered in combination with atorvastatin or rosuvastatin, no relevant changes in statin concentrations were observed in the presence of repeated administration of alirocumab, indicating that cytochrome P450 enzymes (mainly CYP3A4 and CYP2C9) and transporter proteins such as P-gp and OATP were not affected by alirocumab.

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 at subcutaneous doses of 75 mg Q2W or 150 mg Q2W.

Specific Populations

A population pharmacokinetic analysis was conducted on data from 2799 subjects. Age, body weight, gender, race, and creatinine clearance were found not to significantly influence alirocumab pharmacokinetics. No dose adjustments are recommended for these demographics.

Pediatric

Praluent has not been studied in pediatric patients [see Use in Specific Populations (8.4)].

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.

No data are available in patients with severe renal impairment.

Hepatic Impairment

Following administration of a single 75 mg SC dose, alirocumab pharmacokinetic profiles in subjects with mild and moderate hepatic impairment were similar to those in subjects with normal hepatic function.

No data are available in patients with severe hepatic impairment.

Drug-Drug Interactions

The median apparent half-life of alirocumab is reduced to 12 days when administered with a statin; however, this difference is not clinically meaningful and does not impact dosing recommendations.

NDC 0024-5904-02
Rx ONLY

Praluent®
alirocumab
Injection
150 mg/mL

Two Pre-filled Syringes

For subcutaneous injection only. Single-dose.

Carton contains: Two single-dose pre-filled syringes,
the Package Insert, Patient Information, and Instructions for Use.

150 mg/mL

▶ OPEN

REGENERON
SANOFI

Praluent (alirocumab) is a human monoclonal antibody. It works by helping the liver reduce levels of "bad" cholesterol (low-density lipoprotein, or LDL) circulating in your blood.

Praluent is used together with a low-fat diet and a "statin" medication in people with heterozygous familial hypercholesterolemia (an inherited type of high cholesterol). This condition can cause high blood levels of LDL cholesterol, and can also cause plaque to build up inside your arteries.

Praluent is also used to treat heart disease with plaque build-up in the arteries (atherosclerosis, sometimes called hardening of the arteries).

You should not use Praluent if you are allergic to alirocumab.

To make sure Praluent is safe for you, tell your doctor about all your medical conditions or allergies.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether alirocumab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using Praluent.

Praluent is not approved for use by anyone younger than 18 years old.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.