Dosing & Uses
Dosage Forms & Strengths
injection, solution
- Single-dose vial
- 345mg/2.3mL (150mg/mL)
- 1200mg/8mL (150mg/mL)
Hypercholesterolemia
Indicated as an adjunct to other LDL-C lowering therapies for homozygous familial hypercholesterolemia (HoFH) in adults and children aged ≥5 years
15 mg/kg IV once monthly
Dosage Modifications
Renal impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Not studied
Hepatic impairment
- Data are not available
Dosing Considerations
Assess LDL-C when clinically appropriate; LDL lowering may be measured as early as 2 weeks after initiation
Consider pregnancy testing in females who may become pregnant before starting treatment
Limitations of use
- Safety and efficacy not established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia
- Effects on cardiovascular morbidity and mortality not determined
Dosage Forms & Strengths
injection, solution
- Single-dose vial
- 345mg/2.3mL (150mg/mL)
- 1200mg/8mL (150mg/mL)
Hypercholesterolemia
Indicated as an adjunct to other LDL-C lowering therapies for homozygous familial hypercholesterolemia (HoFH) in adults and children aged ≥5 years
<5 years: Safety and efficacy not established
≥5 years: 15 mg/kg IV once monthly
Dosage Modifications
Renal impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Not studied
Hepatic impairment
- Data are not available
Dosing Considerations
Assess LDL-C when clinically appropriate; LDL lowering may be measured as early as 2 weeks after initiation
Consider pregnancy testing in females who may become pregnant before starting treatment
Limitations of use
- Safety and efficacy not established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia
- Effects on cardiovascular morbidity and mortality not determined
Adverse Effects
>10%
Nasopharyngitis (16%)
1-10%
Influenzalike illness (7%)
Infusion-related reactions (7%)
Dizziness (6%)
Rhinorrhea (5%)
Nausea (5%)
Pain in extremity (4%)
Asthenia (4%)
Constipation (<3%)
Upper respiratory tract infection (<3%)
Nasal congestion (<3%)
Abdominal pain (<3%)
Serious anaphylaxis (1%)
Frequency Not Defined
Decreased diastolic blood pressure (transient, mild-to-moderate)
Increased heart rate
Warnings
Contraindications
History of serious hypersensitivity to drug or any of its excipients
Cautions
Serious hypersensitivity reactions, including anaphylaxis, reported; if serious reaction occurs, discontinue infusion and treat according to standard of care
May cause fetal harm based on animal reproduction studies
Pregnancy & Lactation
Pregnancy
Based on animal studies, may cause fetal harm
Consider pregnancy testing in females who may become pregnant before starting treatment
Available human data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Evinacumab is a human IgG4 monoclonal antibody, and human IgG is known to cross the placental barrier; therefore, evinacumab may potentially transmit from mother to developing fetus
Advise pregnant females of potential fetal risk
If patient becomes pregnant during treatment, report exposure by calling 1-833-385-3392
Animal data
- SC administration to pregnant rabbits during organogenesis resulted in fetal malformations (domed head, hydrocephalus, and flexed limbs) at doses below the maximum recommended human dose
- These malformations were not observed in pregnant rats
Contraception
- Females of reproductive potential should use effective contraception during treatment and for at least 5 months following last dose
Lactation
Data are unavailable regarding presence in human milk or animal milk, effects on breastfed infants, or effects on milk production
Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in breastfed infants are unknown
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
Recombinant human monoclonal antibody that binds to and inhibits angiopoietin-like 3 (ANGPTL3)
ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, thereby, reducing lipid metabolism; evinacumab inhibits ANGPTL3 and results in increased lipid metabolism, leading to decreased LDL-C, HDL-C, and triglycerides (TG)
Inhibition of ANGPTL3 induces accelerated hydrolysis of very low-density lipoprotein particles by up-regulating clearance pathways; up-regulation of apolipoprotein-B–containing lipoprotein clearance occurs before reaching the size of LDL
Absorption
Steady-state reached after 4 doses
Trough concentration (steady-state): 241 mg/L
Peak plasma concentration (end of infusion): 157 mg/L
Distribution
Vd: 4.8 L
Metabolism
Not characterized
As an IgG4 antibody, expected to be degraded into small peptides and amino acids via catabolic pathways, similar to endogenous IgG
Elimination
Mediated via parallel linear and nonlinear pathways; at high concentrations, elimination primarily through nonsaturable proteolytic pathway; at lower concentrations, nonlinear, saturable ANGPTL3 target-mediated elimination predominates
Half-life: Function of concentrations and is not a constant
Excretion: Not likely to undergo renal excretion
Administration
IV Compatability
0.9% NaCl
D5W
IV Preparation
Calculate dose (mg) and total volume (mL) required to determine number of vials required
Visually inspect solution for cloudiness, discoloration, and particulate matter; should appear clear to slightly opalescent, colorless to pale-yellow
Do not administer if solution is cloudy or discolored or contains particulate matter
Withdraw dosage volume from vial(s) and transfer into an IV infusion bag containing maximum volume of 250 mL of 0.9% NaCl or D5W
Mix diluted solution by gentle inversion; do not shake
Final concentration of diluted solution should be 0.5-20 mg/mL depending on patient weight
Administer diluted solution immediately after preparation and discard any unused portion left in vial; if unable to use immediately, may store briefly (see Storage)
IV Administration
If refrigerated, allow diluted solution to come to room temperature before administration
Infuse IV over 60 minutes through an IV line containing a sterile, in-line or add-on, 0.2- to 5-micron filter
Do not mix with other medications or administer other medications concomitantly via the same IV line
Infusion may be slowed, interrupted, or discontinued if signs of adverse reactions occur, including infusion-related reactions or hypersensitivity
May administer without regard to timing of lipoprotein apheresis
Missed dose
- Administer as soon as possible
- Thereafter, schedule monthly from date of last dose
Storage
Does not contain preservative
Do not shake
Do not freeze
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
Diluted solution
- Refrigerate at 2-8ºC (36-46ºF) for no more than 24 hr from time of preparation to end of infusion, OR
- Room temperature up to 25ºC (77ºF) for no more than 6 hr from time of preparation to end of infusion
Images
Formulary
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