Alirocumab
Indications
Alirocumab is used for:
Hypercholesterolemia, Indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol (LDL-C)
Adult Dose
Hypercholesterolemia
Indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol (LDL-C)
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
Hepatic impairment
Mild or moderate: No dose adjustment required
Severe: Not studied
Child Dose
Renal Dose
Renal impairment
Mild or moderate: No dose adjustment required
Severe: Not studied
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
Contra Indications
History of serious hypersensitivity reaction to alirocumab; reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization
Precautions
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
Pregnancy-Lactation
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
Interactions
Increased target-mediated clearance & reduced systemic exposure w/ statins & other lipid-modifying therapy.
Adverse Effects
Side effects of Alirocumab :
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%)
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