Alirocumab

Name: Alirocumab

What Is Praluent (Alirocumab)?

Praluent is the brand name of the injectable medicine alirocumab.

It's used along with diet and statins (cholesterol-lowering drugs) to treat people with heterozygous familial hypercholesterolemia (an inherited type of high cholesterol).

Praluent is also sometimes given to treat certain types of heart disease.

It's not known whether this drug can reduce the risk of heart attack, stroke, or death.

Praluent is a human monoclonal antibody. It works by blocking the production of low-density lipoprotein (LDL, or "bad") cholesterol in the body.

The Food and Drug Administration (FDA) approved Praluent in 2015. It's marketed by Sanofi-Aventis U.S. and Regeneron Pharmaceuticals, Inc.

Praluent Warnings

Your healthcare provider will probably recommend that you adopt a specific diet and exercise plan while taking Praluent. Follow these instructions carefully.

Before starting on Praluent, let your healthcare provider know about any medical conditions you have, especially allergies to medications.

Your doctor will probably want to perform frequent tests to check your body's response to Praluent.

Keep all appointments with your doctor and laboratory.

Pregnancy and Praluent

It's not known whether Praluent could harm a fetus if taken during pregnancy.

Tell your doctor if you're pregnant, or might become pregnant, while using this drug.

It's also not known whether Praluent passes into breast milk. Don't breastfeed a baby while taking this medicine.

Praluent Dosage

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.

What is alirocumab, and how does it work (mechanism of action)?

Alirocumab is a man-made injectable drug that reduces cholesterol levels in the blood. It is the first member of a new class of drugs called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. Cholesterol is carried in the blood to a large extent by particles of low density lipoproteins that are removed from the blood by liver cells. The particles are removed from the blood by low-density lipoprotein receptors (LDLR) on liver cells. PCSK9 is a protein on liver cells that promotes the destruction of LDLR. Therefore, a decrease in LDLR levels by PCSK9 results in higher blood levels of LDL cholesterol.

Alirocumab is an antibody, which means that it is a protein that binds to another protein and inactivates it. Alirocumab binds to the PCSK9 protein and prevents it from destroying LDLR. By inhibiting PCSK9, Alirocumab increases the number of LDLRs available to remove LDL cholesterol and consequently reduces LDL cholesterol levels in blood. The FDA approved alirocumab in July 2015.

Administration

SC Preparation

Provide proper training to patients and/or caregivers on preparation and administration prior to use

Allow prefilled syringe or pen to warm to room temperature for 30-40 minutes prior injection; administer as soon as possible after it has warmed up

Do not use if it has been at room temperature [77°F (25°C)] for ≥24 hr

Visually inspect for particulate matter and discoloration before administration; discard if the solution is discolored or contains visible particulate matter

Follow aseptic injection technique for every administration time

Missed dose

  • Administer the injection within 7 days from the missed dose and then resume the original schedule
  • If the missed dose is not administered within 7 days, instruct the patient to wait until the next dose on the original schedule

SC Administration

Administer by SC injection into the thigh, abdomen, or upper arm using a single-dose prefilled pen or syringe

Rotate the injection site with each injection

Do not inject into areas of active skin disease or injury (eg, sunburns, rashes, inflammation, infections)

Do not coadminister with other injectable drugs at the same injection site

Missed dose

  • Every 2 week dose
    • Administer the injection within 7 days from the missed dose and then resume the original schedule
    • If the missed dose is not administered within 7 days, instruct the patient to wait until the next dose on the original schedule
  • Every 4 week dose
    • Administer the injection within 7 days from the missed dose and then resume the original schedule
    • If the missed dose is not administered within 7 days, instruct the patient to administer the dose, starting a new 4-week schedule based on this date

Storage

Refrigerate at 36-46°F (2-8°C) in the outer carton in order to protect from light

If needed, may store up to 30 days at room temperature not exceeding 77°F (25°C) in original container

Do not freeze

Do not expose to extreme heat

Do not shake

Alirocumab Overview

Alirocumab is a prescription medication used to lower cholesterol in certain patients. 

Alirocumab belongs to a new class of drugs called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. These work to block a naturally occurring protein called PCSK9 that prevents the liver from removing LDL from the blood.

Alirocumab is available as an injection. It is usually injected subcutaneously (under the skin) once every two weeks or once every four weeks. 

Common side effects of alirocumab include itching, swelling, and pain at the injection site. 

 

Alirocumab Precautions

Serious side effects have been reported with alirocumab including the following:

  • Allergic reactions. Alirocumab may cause allergic reactions that can be severe and require treatment in a hospital. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, severe itching, a swollen face, or trouble breathing. 
  Do not take alirocumab if you are allergic to alirocumab or any of its ingredients. 

What other drugs will affect alirocumab?

Other drugs may interact with alirocumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Actions

  • Fully human IgG1 monoclonal antibody that binds to PCSK9.1 2 3 4 7 10 11 12 17 19 Produced by recombinant DNA technology.1

  • PCSK9 is a serine protease produced principally in the liver.7 9 11 12 Major function of PCSK9 is to promote degradation of LDL receptors, the primary receptors responsible for clearing circulating LDL cholesterol.1 9 11 25

  • Alirocumab binds specifically and with high affinity to PCSK9; inhibition of PCSK9 increases number of receptors available to clear LDL cholesterol, and consequently reduces plasma concentrations of LDL cholesterol.1 7 10 17

  • Reductions in lipoprotein (a), apolipoprotein B, and other lipid fractions also demonstrated.1 2 3 24 32

Advice to Patients

  • Importance of patients reading the manufacturer’s patient information and instructions for use prior to starting therapy and each time the prescription is refilled.1 13 15 16

  • Importance of discontinuing alirocumab and promptly seeking medical attention if any signs or symptoms of serious hypersensitivity (e.g., severe pruritus, rash, or redness; swollen face; difficulty breathing) occur.1 13 (See Sensitivity Reactions under Cautions.)

  • Importance of instructing patients and/or caregivers regarding proper preparation and sub-Q administration of alirocumab, including use of aseptic technique and safe disposal of the prefilled pens and syringes in a puncture-resistant container.1 13 Importance of informing patients that injection of alirocumab may take up to 20 seconds.1

  • Importance of instructing patients on proper storage of the drug.1

  • Importance of instructing patients not to reuse the prefilled pens and syringes.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 13 (See Pregnancy in Cautions.)

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Alirocumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

75 mg/mL

Praluent (available as single-dose prefilled injection pens and syringes)

Sanofi-Aventis and Regeneron

150 mg/mL

Praluent (available as single-dose prefilled injection pens and syringes)

Sanofi-Aventis and Regeneron

If OVERDOSE is suspected

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.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about alirocumab, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about alirocumab. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using alirocumab.

Review Date: October 4, 2017

Brand Names U.S.

  • Praluent

Pharmacologic Category

  • Antilipemic Agent, PCSK9 Inhibitor
  • Monoclonal Antibody

Onset of Action

Peak effect: Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 to 8 hours

Time to Peak

SubQ: 3 to 7 days

Half-Life Elimination

SubQ: Steady-state: 17 to 20 days; reduced to 12 days when administered with a statin

Contraindications

Serious hypersensitivity to alirocumab or any component of the formulation.

Documentation of allergenic cross-reactivity for PCSK9 inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing Adult

Hyperlipidemia, primary: SubQ: Initial: 75 mg every 2 weeks or 300 mg every 4 weeks; for both regimens, if an adequate LDL-C response is not achieved, may increase or modify dosing regimen to a maximum of 150 mg every 2 weeks.

Switching regimens: When switching from the monthly regimen to an every 2 week regimen, start the new dose on the next scheduled dosing date; reassess LDL-C 4 to 8 weeks after dosing change.

Missed dose: If a dose is missed ≤7 days from the usual day of administration, administer the dose as soon as possible and then resume the original schedule; otherwise, if beyond 7 days, skip the missed dose and resume the normal dosing schedule, or if dosage is monthly, start a new schedule based on this date.

Dosing Geriatric

Refer to adult dosing.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions, including some severe reactions requiring hospitalization (eg, hypersensitivity vasculitis), have been reported. Discontinue treatment and initiate supportive treatment in patients who develop serious allergic reaction. Other hypersensitivity reactions, including pruritus, rash, and urticaria, have been reported.

Alirocumab Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.

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