EVKEEZA™ (evinacumab-dgnb) injection
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Must use an add-on or inline filter during administration (see below).
*The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions
.- The recommended dose of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion over 60 minutes once monthly (every 4 weeks).
- Calculate the dose (mg), total volume (mL) of EVKEEZA required, and the number of vials required based on the patient's current body weight.
- Visually inspect the solution for cloudiness, discoloration, and particulate matter prior to administration. EVKEEZA is a clear to slightly opalescent, colorless to pale-yellow solution. Do not administer if the solution is cloudy or discolored or contains particulate matter.
- EVKEEZA vials are single-dose containers and do not contain a preservative. Observe aseptic technique when preparing EVKEEZA.
- Do not shake the vial. Withdraw the required volume from the vial(s) of EVKEEZA and transfer into an IV infusion bag containing a maximum volume of 250 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix the diluted solution by gentle inversion; do not shake.
- Administer the diluted solution immediately after preparation and discard any unused portion left in the vial.
- If not used immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of infusion preparation to the end of the infusion. Do not freeze the diluted solution.
Evinacumab-dgnb is an angiopoietin-like protein 3 (ANGPTL3) inhibitor monoclonal antibody (IgG4 isotype) produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Evinacumab-dgnb has an approximate molecular weight of 146 kDa.
EVKEEZA (evinacumab-dgnb) injection is a sterile, preservative-free solution for intravenous use. The solution is clear to slightly opalescent, colorless to pale-yellow, and free from visible particles.
Each vial contains 345 mg/2.3 mL or 1,200 mg/8 mL. Each mL contains 150 mg of evinacumab-dgnb, and L-arginine hydrochloride (14.8 mg), L-histidine (0.74 mg), L-histidine monohydrochloride monohydrate (1.1 mg), L-proline (30 mg), polysorbate 80 (1 mg) and Water for Injection, USP. The pH is 6.
Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to reduction in LDL-C, HDL-C, and triglycerides (TG). Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.
EVKEEZA is indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult and pediatric patients, aged 12 years and older, with homozygous familial hypercholesterolemia (HoFH).
Limitations of Use:
- The safety and effectiveness of EVKEEZA have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH).
- The effects of EVKEEZA on cardiovascular morbidity and mortality have not been determined.
EVKEEZA is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb or to any of the excipients in EVKEEZA. Serious hypersensitivity reactions, including anaphylaxis, have occurred.
5.1 Serious Hypersensitivity Reactions
Serious hypersensitivity reactions have occurred with EVKEEZA. In clinical trials, 1 (1%) EVKEEZA-treated patient experienced anaphylaxis versus 0 (0%) patients who received placebo. If signs or symptoms of serious hypersensitivity reactions occur, discontinue EVKEEZA infusion, treat according to the standard-of-care, and monitor until signs and symptoms resolve. EVKEEZA is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb [see CONTRAINDICATIONS].
5.2 Embryo-Fetal Toxicity
Based on the findings in animal reproduction studies, EVKEEZA may cause fetal harm when administered to pregnant patients. Administration of evinacumab to rabbits during organogenesis caused increases in fetal malformations at doses below the human exposure. Advise patients who may become pregnant of the risk to a fetus. Consider obtaining a pregnancy test prior to initiating treatment with EVKEEZA. Advise patients who may become pregnant to use effective contraception during treatment with EVKEEZA and for at least 5 months following the last dose of EVKEEZA
Common adverse reactions (≥ 5%) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-833-385-3392 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
2.1 Recommended Dosage
- The recommended dose of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion over 60 minutes once monthly (every 4 weeks).
- If a dose of EVKEEZA is missed, administer as soon as possible. Thereafter, EVKEEZA should be scheduled monthly from the date of the last dose.
- Assess LDL-C when clinically appropriate. The LDL-lowering effect of EVKEEZA may be measured as early as 2 weeks after initiation.
2.2 Preparation Instructions for Intravenous Infusion
- Calculate the dose (mg), total volume (mL) of EVKEEZA required, and the number of vials required based on the patient's current body weight.
- Visually inspect the solution for cloudiness, discoloration, and particulate matter prior to administration. EVKEEZA is a clear to slightly opalescent, colorless to pale-yellow solution. Do not administer if the solution is cloudy or discolored or contains particulate matter.
- EVKEEZA vials are single-dose containers and do not contain a preservative. Observe aseptic technique when preparing EVKEEZA.
- Do not shake the vial. Withdraw the required volume from the vial(s) of EVKEEZA and transfer into an IV infusion bag containing a maximum volume of 250 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix the diluted solution by gentle inversion; do not shake.
- The final concentration of the diluted solution should be between 0.5 mg/mL and 20 mg/mL depending on the patient's current body weight.
- Administer the diluted solution immediately after preparation and discard any unused portion left in the vial.
- If not used immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of infusion preparation to the end of the infusion. Do not freeze the diluted solution.
2.3 Administration Instructions for Intravenous Infusion
- If refrigerated, allow the diluted solution to come to room temperature prior to administration.
- Administer EVKEEZA diluted solution via IV infusion over 60 minutes through an IV line containing a sterile, in-line or add-on, 0.2-micron to 5-micron filter.
- Do not mix other medications with EVKEEZA or administer other medications concomitantly via the same infusion line.
- The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions [see WARNINGS AND PRECAUTIONS (5.1) and ADVERSE REACTIONS (6.1)].
- EVKEEZA can be administered without regard to the timing of lipoprotein apheresis.
Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single-dose vials.
EVKEEZA (evinacumab-dgnb) injection is a clear to slightly opalescent, colorless to pale yellow solution. It is supplied as one single-dose vial per carton.
- 345 mg/2.3 mL (150 mg/mL) NDC 61755-013-01
- 1,200 mg/8 mL (150 mg/mL) NDC 61755-010-01
Storage
Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Store the vial in the original carton to protect from light. Do not freeze. Do not shake.
EVKEEZA does not contain a preservative. If not used immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of infusion preparation to the end of the infusion
