Dosing & Uses
Dosage Forms & Strengths
SC injection
- 75mg/mL
- 150mg/mL
Hyperlipidemia Treatment and/or CV Risk Reduction
Indications
-
Primary hyperlipidemia (including heterozygous familial hypercholesterolemia)
- Indicated as an adjunct to diet, alone or in combination with other lipid-lowering therapies (eg, statins, ezetimibe), for treatment of adults with primary hyperlipidemia to reduce low-density lipoprotein cholesterol (LDL-C)
-
Prevention of cardiovascular events
- Indicated to reduce the risk of MI, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease
Every 2 week schedule
- Recommended starting dose: 75 mg SC q2Weeks
- Measure CLC-C levels within 4-8 week of initiating; if inadequate response, may increase to 150 mg SC q2Weeks; reassess LDL-C within 4-8 weeks
- Not to exceed 150 mg SC q2Weeks
Every 4 week schedule
- Recommended starting dose: 300 mg SC q4Weeks (ie, two 150-mg injections consecutively at 2 different injection sites)
- Measure LDL-C just prior to the next scheduled dose; if inadequate response, may adjust dose to 150 mg q2Weeks, starting the new dose on the next scheduled dosing date; reassess LDL-C within 4-8 weeks
Patients with HeFH undergoing apheresis
- 150 mg SC q2Weeks
- May be administered without regard to timing of apheresis
Dosage Modifications
Renal impairment
- Mild or moderate: No dose adjustment required
- Severe: Not studied
Hepatic impairment
- Mild or moderate: No dose adjustment required
- Severe: Not studied
Dosing Considerations
Limitation of use: Effect on cardiovascular morbidity and mortality not determined
Homozygous Familial Hypercholesterolemia (Orphan)
Orphan designation for treatment of homozygous familial hypercholesterolemia
Sponsor
- Sanofi-Aventis US, LLC; 55 Corporate Drive; Bridgewater, New Jersey 08807
Safety and efficacy not established
Adverse Effects
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%)
Postmarketing Reports
Angioedema
Vasculitis
Warnings
Contraindications
History of serious hypersensitivity reaction to alirocumab; reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization
Cautions
Hypersensitivity reactions (eg, pruritus, rash, urticaria), including some serious events (eg, hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization), have been reported; discontinue and treat if signs or symptoms of serious allergic reactions occur
Pregnancy
Pregnancy
No available data on use in pregnant women; pregnancy exposure registry (1-877-311-8972 or https://mothertobaby.org/ongoing-study/praluent/) monitors pregnancy outcomes in women exposed to drug during pregnancy
Animal studies
- Studies in rats have not shown effects on embryo-fetal development when given during organogenesis up to 12-fold the human exposure
- 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 q2wk
Lactation
Unknown if distributed in human breast milk
The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant
Human IgG is present in human milk, but published data suggest that breastmilk IgG antibodies do not enter the neonatal and infant circulation in substantial amounts
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9)
LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway
PCSK9 is a serine protease that destroys LDLR in the liver, resulting in decreased LDL-C clearance and increased plasma LDL-C
PCSK9 inhibitors decrease LDLR degradation by PCSK9, and thereby improve LDL-C clearance and lower plasma LDL-C
Absorption
Absolute bioavailability: 85%
Peak plasma time: 3-7 days
Distribution
Vd: 0.04-0.05 L/kg
Distributed primarily in circulatory system
Metabolism
Specific metabolism studies were not conducted because alirocumab is a protein and is expected to degrade to small peptides and individual amino acids
Does not affect P450 enzymes, P-gp, and OATP
Elimination
Half-life: 17-20 days
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
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
Images
Patient Handout
Formulary
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