Alirocumab

Primary hyperlipidemia (including heterozygous familial hypercholesterolemia), Prevention of cardiovascular events, Homozygous familial hypercholesterolemia To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C. As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.

Subcutaneous In adults with established cardiovascular disease or with primary hyperlipidemia, including HeFH Every 2-week schedule Recommended starting dose: 75 mg SC once every 2 weeks Measure CLC-C levels within 4-8 weeks of initiating; if inadequate response, may increase to 150 mg SC once every 2 weeks; reassess LDL-C within 4-8 weeks Not to exceed 150 mg SC once every 2 weeks Every 4-week schedule Recommended starting dose: 300 mg SC every 4 weeks (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 the dose to 150 mg every 2 weeks, starting the new dose on the next scheduled dosing date; reassess LDL-C within 4-8 weeks In adults with HeFH undergoing LDL apheresis or in adults with HoFH The recommended dose of Alirocumab is 150 mg once every 2 weeks administered subcutaneously. Alirocumab can be administered without regard to the timing of LDL apheresis.

Heterozygous Familial Hypercholesterolemia Indicated as an adjunct to diet and other LDL-C-lowering therapies in children aged >8 years with heterozygous familial hypercholesterolemia (HeFH) to reduce LDL-C <50 kg 150 mg SC q4Weeks If inadequate LDL-C lowering response, may adjust the dose to 75 mg SC q2Weeks >50 kg 300 mg SC q4Weeks If inadequate LDL-C lowering response, may adjust the dose to 150 mg SC q2Weeks

Renal impairment Mild or moderate: No dose adjustment required Severe: Not studied

No overall differences in safety or effectiveness were observed between these patients and younger patients, 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.

Hepatic impairment Mild or moderate: No dose adjustment required Severe: Not studied

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

History of serious hypersensitivity reaction to alirocumab; reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization

Discontinue if symptoms of allergic reactions occur. Exclude secondary causes of hyperlipidaemia or mixed dyslipidaemia (eg, nephrotic syndrome, hypothyroidism) prior to initiating therapy. Severe renal & hepatic impairment. Pregnancy & lactation. Childn & adolescents <18 yr. 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

Not Classi Pregnancy No available data on use in pregnant women; 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

Increased target-mediated clearance & reduced systemic exposure w/ statins & other lipid-modifying therapy.

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%)

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