Praluent

Antilipemic Monoclonal Antibodies Targeting PCSK9

Visually inspect for particulate matter and discoloration prior to administration. Solution is clear, colorless to pale yellow. Do not use if discolored or if particulate matter is present.

Warm to room temperature for 30 to 40 minutes before use.
Do not shake.
Alirocumab is provided as a single use system; discard after use.
Give by subcutaneous injection into the thigh, abdomen, or upper arm. Rotate injection site with each injection.
Do NOT inject into areas of active skin disease or injury (e.g., sunburns, skin rashes, inflammation, or skin infections).
To administer the 300 mg dose, give two 150-mg injections consecutively at 2 different injection sites.
Do NOT administer with other injectable drugs at the same injection site.
Missed dose: If a dose is missed, administer the injection within 7 days from the missed dose and then resume original schedule. If an every 2 weeks dose is not administered within 7 days, instruct the patient to wait until the next dose on the original schedule, and if an every 4 weeks dose is not administered within 7 days, administer the dose, starting a new schedule based on current date.
Storage: Store in refrigerator at 2 to 8 degrees C (36 to 46 degrees F) in the original carton to protect from light. Do not freeze. If needed, may keep at room temperature up to 25 degrees C (77 degrees F) for a maximum of 30 days in the original carton to protect from light. After removal from the refrigerator, use within 30 days or discard. Do not store above 77 degrees F.[60003]

vasculitis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

chest pain (unspecified) / Early / 7.0-7.0
antibody formation / Delayed / 4.8-5.5
elevated hepatic enzymes / Delayed / 1.7-1.7
memory impairment / Delayed / 0.2-0.2
confusion / Early / 0.2-0.2
edema / Delayed / Incidence not known
erythema / Early / Incidence not known

pharyngitis / Delayed / 6.0-11.3
injection site reaction / Rapid / 3.8-7.2
influenza / Delayed / 5.7-5.7
infection / Delayed / 4.8-4.8
diarrhea / Early / 4.7-4.7
myalgia / Early / 4.2-4.2
sinusitis / Delayed / 3.0-3.0
cough / Delayed / 2.5-2.5
ecchymosis / Delayed / 2.1-2.1
musculoskeletal pain / Early / 2.1-2.1
pruritus / Rapid / 1.1-1.1

Praluent

Rx

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor
For use in heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, and reduction of myocardial infarction, stroke, or hospitalization for unstable angina in adults with established cardiovascular disease
Reports of serious hypersensitivity reactions including hypersensitivity vasculitis

75 mg subcutaneously every 2 weeks or 300 mg subcutaneously every 4 weeks. Monitor LDL-C as clinically appropriate; the LDL-lowering effect may be measured as early as 4 weeks after starting therapy. Measure LDL-C just before next dose in persons receiving 300 mg subcutaneously every 4 weeks. May adjust dose to 150 mg subcutaneously every 2 weeks if response is inadequate.

150 mg subcutaneously every 2 weeks. Monitor LDL-C as clinically appropriate; the LDL-lowering effect may be measured as early as 4 weeks after starting therapy.

150 mg subcutaneously every 2 weeks. Monitor LDL-C as clinically appropriate; the LDL-lowering effect may be measured as early as 4 weeks after starting therapy.

75 mg subcutaneously every 2 weeks or 300 mg subcutaneously every 4 weeks. Measure LDL-C prior to next dose for persons receiving 300 mg subcutaneously every 4 weeks and otherwise as clinically appropriate. May adjust dose to 150 mg subcutaneously every 2 weeks for inadequate LDL-C response.

No dosage adjustment is needed for mild or moderate hepatic impairment. Specific guidelines for dosage adjustments in severe hepatic impairment are not available.

No dosage adjustment is needed for mild or moderate renal impairment. Specific guidelines for dosage adjustments in severe renal impairment are not available.

There are no drug interactions associated with Alirocumab products.

Alirocumab/Praluent Subcutaneous Inj Sol: 1mL, 75mg, 150mg

300 mg subcutaneously once every month.

300 mg subcutaneously once every month.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Alirocumab is a human monoclonal IgG1 antibody that binds to and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein receptors (LDLR). PCSK9 binds to LDLR on the hepatocyte surface to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; with alirocumab inhibiting the binding of PCSK9 to LDLR, the number of LDLRs available to clear LDL increases and LDL-C concentrations decrease.

Alirocumab is administered subcutaneously. Alirocumab is a protein and is expected to degrade to small peptides and amino acids. At low concentrations, elimination is through saturable biding to proprotein convertase subtilisin/kexin type 9 (PCSK9). At higher concentrations, elimination is mainly through a non-saturable proteolytic pathway. The median apparent half-life of alirocumab at steady state is 17—20 days.
 
Affected cytochrome P450 isoenzymes: none

The median time to maximum serum alirocumab concentration (Tmax) following administration of doses of 75—150 mg is 3—7 days. Alirocumab reduces free PCSK9 in a concentration-dependent manner; maximal suppression of PCSK9 occurs within 4—8 hours of a single subcutaneous dose of alirocumab 75 or 150 mg and returns to baseline once alirocumab concentrations are undetectable. The pharmacokinetics of alirocumab following injection into different anatomical sites (i.e., abdomen, upper arm, thigh) are similar. Steady state is reached after 2—3 doses. The absolute bioavailability after subcutaneous administration was approximately 85%.

There are no available human data examining drug-associated risks with alirocumab use during pregnancy. Animal data indicate that alirocumab crosses the placental barrier. Like other IgG antibodies, it is unlikely that alirocumab crosses the placenta in the first trimester, but it is likely that alirocumab crosses the placenta in the second and third trimester. In animal reproduction studies, there were no embryo-fetal adverse effects with dose exposures up to 12 times the exposure at the maximum recommended human dose (MRHD) of 150 mg every 2 weeks. In monkeys, suppression of the humoral immune response occurred in infant monkeys when alirocumab was dosed during organogenesis to birth at dose exposures 13-fold the exposure at the MRHD. No additional effects on pregnancy or neonatal/infant development were ob served at dose exposures up to 81-fold the MRHD. Consider the benefits and risks of alirocumab prior to exposure during pregnancy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to alirocumab; information about the registry can be obtained by calling 1-877-311-8972.

There is no information regarding the presence of alirocumab in human milk, the effects on the breastfed infant, or the effects on milk production. Data suggest that IgG antibodies that are present in human milk do not enter the neonatal and infant circulation in substantial amounts. Consider the development and health benefits of breast-feeding along with the mother's clinical need for alirocumab and any potential side effects on the breastfed infant from alirocumab or from the underlying maternal condition.