TY - JOUR
AB - Evinacumab-dgnb is an antilipemic agent. Class: 24:06.92 • Antilipemic Agents, Miscellaneous (AHFS primary) Brands: Evkeeza® Uses Evinacumab-dgnb has the following uses: Evinacumab-dgnb is an angiopoietin-like protein 3 (ANGPTL3) inhibitor 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). Evinacumab-dgnb has the following limitations of use: The safety and effectiveness of evinacumab-dgnb have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The effects of evinacumab-dgnb on cardiovascular morbidity and mortality have not been determined. Dosage and Administration General. Evinacumab-dgnb is available in the following dosage form(s) and strength(s): Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single- dose vials. Dosage. It isessentialthat the manufacturer’s labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary: Pediatric Patients. Dosage and Administration. The recommended dose of evinacumab-dgnb is 15 mg/kg administered by intravenous (IV) infusion once monthly (every 4 weeks). See the Full Prescribing Information for preparation instructions for the IV infusion. Administer the 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 evinacumab-dgnb 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. Adults. Dosage and Administration. The recommended dose of evinacumab-dgnb is 15 mg/kg administered by IV infusion once monthly (every 4 weeks). See the Full Prescribing Information for preparation instructions for the IV infusion. Administer the 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 evinacumab-dgnb 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. Cautions Contraindications. History of serious hypersensitivity reactions to evinacumab-dgnb or to any of the excipients in evinacumab-dgnb. Warnings/Precautions. Serious Hypersensitivity Reactions. Serious hypersensitivity reactions have occurred with evinacumab-dgnb. In clinical trials, 1 (1%) evinacumab-dgnb-treated patient experienced anaphylaxis versus 0 (0%) patients who received placebo. If signs or symptoms of serious hypersensitivity reactions occur, discontinue evinacumab-dgnb infusion, treat according to the standard-of-care, and monitor until signs and symptoms resolve. Evinacumab-dgnb is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb. Embryo-fetal Toxicity. Based on the findings in animal reproduction studies, evinacumab-dgnb 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 evinacumab-dgnb. Advise patients who may become pregnant to use effective contraception during treatment with evinacumab-dgnb and for at least 5 months following the last dose of evinacumab-dgnb. Specific Populations. Pregnancy Risk Summary: Based on data from animal reproduction studies, evinacumab-dgnb may cause fetal harm when administered to pregnant patients. Available human data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Evinacumab-dgnb is a human IgG4 monoclonal antibody and human IgG is known to cross the placental barrier; therefore, evinacumab-dgnb has the potential to be transmitted from the mother to the developing fetus. Subcutaneous administration of evinacumab-dgnb to pregnant rabbits during the period of organogenesis resulted in fetal malformations (domed head, hydrocephalus, and flexed limbs) at doses below the maximum recommended human dose (MRHD). No adverse embryofetal effects were observed with subcutaneous administration of evinacumab-dgnb to pregnant rats during the period of organogenesis at doses below the MRHD. Measurable evinacumab-dgnb serum concentrations were observed in fetal rabbit and rat sera at birth, indicating that evinacumab- dgnb, like other IgG antibodies, crosses the placental barrier. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. If a patient becomes pregnant while receiving evinacumab-dgnb, healthcare providers should report evinacumab-dgnb exposure by calling 1-833-385-3392. Animal Data: In an embryo-fetal development study in pregnant rabbits, evinacumab-dgnb was administered subcutaneously at doses of 1, 5, 10 and 30 mg/kg every 3 days during the period of organogenesis from gestation day 7 to day 19. Evinacumab-dgnb was teratogenic in rabbits, causing domed head, dilation of the lateral and third ventricles of the brain, and flexed fore/hind paws at maternal evinacumab-dgnb exposures below human exposure at the MRHD of 15 mg/kg every 4 weeks, based on AUC. Other fetal malformations, consisting of irregular and abnormal ossification in the skull, palate, and metacarpal, and enlarged anterior and/or posterior fontanelles occurred and were consistent with significant maternal toxicity (including early deaths due to abortion and premature delivery at all doses, reduction in maternal body weight gains, and reduced maternal food consumption). Increased incidences of post-implantation losses, resorptions (total, early, and late), and decreased fetal body weight were also consistent with maternal toxicity. Evinacumab-dgnb was present in the sera of fetuses born from mothers at 10 and 30 mg/kg every 3 days at levels higher than in maternal serum. In an embryo-fetal development study in pregnant rats, evinacumab-dgnb was administered subcutaneously at doses of 5, 10, 30 and 100 mg/kg every 3 days during the period of organogenesis from gestation day 6 to day 18. Maternal exposures to evinacumab-dgnb were below the human exposure measured at the MRHD. Evinacumab-dgnb resulted in unexplained maternal deaths at 100 mg/kg every 3 days. Evinacumab-dgnb crossed the placenta and was present at ratios (CFetal/CMaternal) ranging from 0.42 to 0.65. No adverse effects on embryofetal development were observed at any dose. In a combined fertility, embryofetal, and pre- and postnatal development study, female rats were administered evinacumab-dgnb via subcutaneous injection at doses of 30 and 100 mg/kg every 3 days beginning 2 weeks prior to mating and continuing to gestation day 21 or lactation day 21. Mean maternal systemic exposures were below the human exposure at the MRHD throughout the study. No maternal or developmental toxicity was observed. Lactation Risk Summary: There are no data on the presence of evinacumab-dgnb in human milk or animal milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to evinacumab-dgnb are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for evinacumab-dgnb and any potential adverse effects on the breastfed infant from evinacumab-dgnb or from the underlying maternal condition. Females and Males of Reproductive Potential Consider pregnancy testing in patients who may become pregnant prior to starting treatment with evinacumab-dgnb. Based on animal studies, evinacumab-dgnb may cause fetal harm when administered to pregnant patients. Patients who may become pregnant should use effective contraception during treatment with evinacumab-dgnb and for at least 5 months following the last dose of evinacumab-dgnb. Pediatric Use The safety and effectiveness of evinacumab-dgnb as an adjunct to other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 12 years and older. Use of evinacumab-dgnb for this indication is supported by evidence from adequate and well-controlled trials in adults with additional efficacy and safety data in pediatric patients aged 12 years and older. The safety and effectiveness of evinacumab-dgnb have not been established in pediatric patients with HoFH who are younger than 12 years old. Geriatric Use Clinical studies of evinacumab-dgnb did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. Common Adverse Effects. Common adverse reactions (≥ 5%) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. Interactions Specific Drugs. It isessentialthat the manufacturer’s labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights: Please see product labeling for drug interaction information. Actions Mechanism of Action. 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. Advice to Patients Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Reactions. Inform patients that hypersensitivity reactions have occurred with evinacumab-dgnb. Advise patients to contact their healthcare provider immediately if they experience signs or symptoms of a hypersensitivity reaction. Embryofetal Toxicity. Advise pregnant patients and patients that may become pregnant of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise patients who may become pregnant to use effective contraception during treatment with evinacumab-dgnb and for 5 months after the final dose. Encourage patients who become pregnant to report their pregnancy to 1-833-385-3392. Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Open in new tabDownload slide Open in new tabDownload slide © Copyright, March 8, 2021, American Society of Health-System Pharmacists, Inc. Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2021. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Evinacumab-dgnb
JF - American Journal of Health-System Pharmacy
DO - 10.1093/ajhp/zxab140
DA - 2021-04-21
UR - https://www.deepdyve.com/lp/oxford-university-press/evinacumab-dgnb-ZoaGuW09DM
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -