HIGHLIGHTS OF PRESCRIBING INFORMATION

 

These highlights do not include all the information needed to use

PRALUENT safely and effectively. See full prescribing information for PRALUENT. ® PRALUENT (alirocumab) injection, for subcutaneous use

 

Initial U.S. Approval: 2015

 

RECENT MAJOR CHANGES

 Dosage and Administration  07/2017

 

 

INDICATIONS AND USAGE

 

 PRALUENT is a PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody indicated as 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-cholesterol (LDL-C). 

 

Limitations of Use -

The effect of PRALUENT on cardiovascular morbidity and mortality has not been determined. 

 

 

NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL

 

PRODUCTS APPROVED FOR 2015

 

Certain drugs are classified as New molecular Emtities- NME- for FDA review 

Many of these products contain active moieties that have not been approved

by FDA  previously, either as a single ingredient or as part of a combination

products; these products frequently provide important new therapies for the

patients.

 

Some drugs are characterized as NMEs for administrative purposes ,but 

nonetheless contain certain active moieties in products that have been 

previously approved by FDA. For example, CDER  classifies biological 

products submitted in an application under section 351(a) of the Public

Service Act as NME for purposes of FDA review, regardless of whether 

the agency previously  approved a related active moiety in  a different 

product. 

 

FDAs classification of a drug as an -NME- for review purposes is distinct

from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-

within the meaning of the Federal Food,Drug, and  Cosmetic Act

 

 

No.18

 

Drug Name -   Alirocumab

 

Active Ingredient-  Praluent

 

Date of approval -  7/24/2015

 

FDA-approved use -  To treat patients with high chloesterol                   

                                                                                                                                                                                                                              

Approved by US FDA  on 7/24/2015-   (Ref- FDA approved List- 2015)

 

ADVERSE REACTIONS

 

The most commonly occurring adverse reactions (=5% of patients treated with PRALUENT and occurring more frequently than with placebo) are nasopharyngitis, injection site reactions, and influenza. 

 

CONTRAINDICATIONS

 

History of a serious hypersensitivity reaction to PRALUENT. 

 

WARNINGS AND PRECAUTIONS

 

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.

 

 

 

 

INDICATIONS AND USAGE

 

 PRALUENT is a PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody indicated as 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-cholesterol (LDL-C). 

 

Limitations of Use -

The effect of PRALUENT on cardiovascular morbidity and mortality has not been determined. 

 

DOSAGE AND ADMINISTRATION

The recommended starting dose of PRALUENT is 75 mg once every 2 weeks administered subcutaneously, since the majority of patients achieve sufficient LDL-C reduction with this dosage. 

 

An alternative starting dosage for patients who prefer less frequent dosing is 300 mg once every 4 weeks (monthly). 

If the LDL-C response is inadequate, the dosage may be adjusted to the maximum dosage of 150 mg administered every 2 weeks. 

 PATIENT COUNSELING INFORMATION

 

See FDA-Approved Patient Labeling (Patient Information and Instructions for Use).

 

Pregnancy Registry -

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PRALUENT during pregnancy. Encourage participation in the registry 

      

 

 

                       

   

 

   

 

 

 

 

              

Allergic Reactions ? Advise patients to discontinue PRALUENT and seek prompt medical attention if any signs or symptoms of serious allergic reactions occur. Instructions for Administration ? Instruct patients and caregivers to read the Patient Information and Instructions For Use (IFU) before the patient starts using PRALUENT, and each time the patient gets a refill as there may be new information they need to know. ? Provide guidance to patients and caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the pre-filled pen or pre-filled syringe correctly (see Instructions for Use leaflet). Inform patients that it may take up to 20 seconds to inject PRALUENT. ? The pre-filled pen or pre-filled syringe should be allowed to warm to room temperature for 30 to 40 minutes prior to use. ? Patients and caregivers should be cautioned that the pre-filled pen or pre-filled syringe must not be re-used and instructed in the technique of proper pen and syringe disposal in a puncture-resistant container. Do not recycle the container. 

 

 

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 ©2018 Regeneron Pharmaceuticals

 CLINICAL PHARMACOLOGY

 

1. 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. 

 

2. 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. 

 

3. 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.

 

 

 

       

 

 

 

  

 

 

 

 

            

 

  

 

  

  

 

           

  

 

  

 

    

 

 

USE IN SPECIFIC POPULATIONS 

 

1. Pregnancy-

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PRALUENT during pregnancy. Please contact 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/praluent/ to enroll in or to obtain information about the registry.

 

Risk Summary-

There are no available data on use of PRALUENT in pregnant women to inform a drugassociated 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.

 

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.

 

 

 

 

  

  

 

  

  

 

 

 

 

 

      

           

  

   

 

     

   

      

  

 

     

 

  

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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.

 

3.Pediatric Use-

 Safety and efficacy in pediatric patients have not been established. 

 

4. 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. 

 

5. 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. 

 

6.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.