Eptinezumab-jjmr (Monograph)

Brand name: Vyepti
Drug class: Calcitonin Gene-related Peptide (CGRP) Antagonists
- Anti-Calcitonin Gene-related Peptide Monoclonal Antibodies
- Anti-CGRP Monoclonal Antibodies
- Calcitonin Gene-related Peptide Antagonists
- CGRP Antagonists
Molecular formula: C₆₃₅₂H₉₈₃₈N₁₆₉₄O₁₉₉₂S₄₆
CAS number: 1644539-04-7

Medically reviewed by Drugs.com on Mar 21, 2024. Written by ASHP.

Introduction

Antimigraine agent; recombinant humanized IgG₁ monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand.

Uses for Eptinezumab-jjmr

Preventive Treatment of Migraine

Preventive treatment of migraine in adults.

Substantially reduces monthly migraine days in patients with episodic or chronic migraine when compared with placebo.

The American Headache Society (AHS) states that eptinezumab and other anti-CGRP monoclonal antibodies offer a number of advantages over some oral migraine preventive therapies, including no need for dosage escalation, rapid onset of therapeutic activity, minimal risk of adverse drug reactions, favorable overall tolerability profiles, and demonstrated efficacy after failure of prior preventive treatments or in combination with oral preventive treatments. However, the potential benefit of using newer therapies such as the anti-CGRP monoclonal antibodies over established therapies should be considered on an individual basis.

AHS has established a criteria for initiating treatment with anti-CGRP monoclonal antibodies based on a balance of cost-effective considerations and access to care; according to this criteria, use of anti-CGRP monoclonal antibodies may be appropriate when patients with migraine are unable to tolerate and/or have an inadequate response to an 8-week trial of at least 2 oral preventive therapies (e.g., topiramate, valproate, β-adrenergic blocking agents, tricyclic antidepressants, selective serotonin- and norepinephrine-reuptake inhibitors).

Eptinezumab-jjmr Dosage and Administration

Administration

IV Administration

Administer by IV infusion only. Do not administer by rapid IV injection (e.g., IV push or bolus). Do not mix eptinezumab with or administer simultaneously through the same IV line with other drugs.

Must be diluted prior to IV infusion.

Administer diluted solution through a separate IV line using a 0.2- or 0.22-µm inline or add-on sterile filter.

After completion of IV infusion, flush IV line with 20 mL of 0.9% sodium chloride injection.

Single-dose vials are intended for single use only and contain no preservatives; discard any unused portion in the vial.

Dilution

Prior to dilution, eptinezumab injection concentrate should be clear or slightly opalescent and colorless to brownish-yellow; do not use if solution appears cloudy or discolored or contains visible particles.

Must be diluted in polyvinyl chloride (PVC), polyethylene, or polyolefin infusion bags.

To prepare a 100-mg dose, withdraw 1 mL of injection concentrate from a single-dose vial (containing 100 mg/mL of eptinezumab) and add to an infusion bag containing 100 mL of 0.9% sodium chloride injection. Mix by gentle inversion; do not shake.

To prepare a 300-mg dose, withdraw a total of 3 mL of injection concentrate from 3 single-dose vials (containing 100 mg/mL of eptinezumab) and add to an infusion bag containing 100 mL of 0.9% sodium chloride injection. Mix by gentle inversion; do not shake.

Administer within 8 hours following dilution. (See Storage under Stability.)

Rate of Administration

Administer by IV infusion over approximately 30 minutes.

Dosage

Adults

Migraine

Preventive Treatment

100 mg by IV infusion every 3 months. May consider 300 mg every 3 months in some patients. Gradual dosage titration not necessary; may initiate therapy with either the 100- or 300-mg dose.

When initiating therapy with eptinezumab or another anti-CGRP monoclonal antibody in patients already receiving a preventive treatment for migraine, AHS recommends adding the anti-CGRP monoclonal antibody to the existing antimigraine regimen and avoiding making other changes until the clinical efficacy of the anti-CGRP monoclonal antibody is determined.

Some patients who do not experience a response to anti-CGRP monoclonal antibody therapy following the first dose may experience a response within 4 weeks after the second dose or within 4–8 weeks after the third dose. AHS recommends assessing clinical efficacy of eptinezumab 6 months after initiating treatment; continue therapy only if treatment benefits have been observed by that time.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Eptinezumab-jjmr

Contraindications

Serious hypersensitivity to eptinezumab-jjmr or any excipients in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including angioedema, urticaria, facial flushing, and rash, reported during clinical trials. Most reactions reported to date occurred during IV infusion and were not serious, but often led to discontinuance of therapy or required treatment. However, serious hypersensitivity reactions may occur.

If a hypersensitivity reaction occurs, consider discontinuing the drug and initiate appropriate therapy.

Manufacturer states that the vial stoppers of eptinezumab-jjmr vials are not made with natural rubber latex.

Immunogenicity

Potential for immunogenicity. Antibodies to eptinezumab, including neutralizing antibodies to the drug, reported. Available data do not demonstrate an effect of anti-eptinezumab antibody development on efficacy or safety of the drug; however, data are too limited to make definitive conclusions.

Specific Populations

Pregnancy

No adequate data on the developmental risk associated with use of eptinezumab in pregnant women. No adverse developmental effects observed when pregnant rats and rabbits received the drug IV at dosages resulting in systemic exposures greater than those expected clinically.

Estimated rates of major birth defects and miscarriage among deliveries to women with migraine (2.2–2.9 and 17%, respectively) are similar to rates reported in women without migraine.

Possible increased risk of preeclampsia and gestational hypertension in women with migraine.

Lactation

Not known whether distributed into human milk. Effects on breast-fed infants and on milk production also unknown. Consider developmental and health benefits of breast-feeding, mother's clinical need for eptinezumab, and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Manufacturer states that safety and efficacy not established in pediatric patients.

Pending further clinical experience with anti-CGRP monoclonal antibodies in pediatric patients, the Pediatric and Adolescent Headache special interest group of the AHS recommends limiting use of anti-CGRP monoclonal antibodies mainly to postpubertal adolescents^{† [off-label]} with relatively frequent migraines (i.e., ≥8 headache days per month) who have moderate to severe disability associated with migraine (e.g., PedMIDAS score ≥30) and in whom ≥2 preventive therapies have failed. For younger pediatric patients^{† [off-label]} with severe chronic migraine that is refractory to multiple preventive therapies, consider anti-CGRP monoclonal antibodies only in carefully selected patients with close monitoring (e.g., pubertal status, bone health, linear growth, weight, body mass index [BMI], infectious complications).

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Hepatic impairment not expected to substantially affect pharmacokinetics.

Renal Impairment

Renal impairment not expected to substantially affect pharmacokinetics.

Common Adverse Effects

Nasopharyngitis, hypersensitivity reactions.

Drug Interactions

Not metabolized by CYP isoenzymes. In addition, eptinezumab is unlikely to affect drug-metabolizing enzymes or drug transporters.

Risk of adverse drug interactions appears minimal.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes: Pharmacokinetic interactions unlikely.

Substrates of CYP isoenzymes: Pharmacokinetic interactions unlikely.

Drugs Affected by Drug Transport Systems

Substrates of various drug transport systems: Pharmacokinetic interactions unlikely.

Specific Drugs

Drug	Interaction
Sumatriptan	No clinically important pharmacokinetic interaction

Eptinezumab-jjmr Pharmacokinetics

Absorption

Bioavailability

Exhibits linear and dose-proportional pharmacokinetics over IV dosages of 100 and 300 mg.

Peak plasma concentrations occur at the end of IV infusion.

Mean accumulation ratio is 1.2 following IV administration every 3 months.

Steady-state plasma concentrations achieved after the first dose.

Special Populations

Age, sex, race, body weight, and body mass index (BMI) do not have clinically important effects on the pharmacokinetics of eptinezumab.

Not formally studied in renal or hepatic impairment. Population pharmacokinetic analysis indicates that pharmacokinetics not affected by renal or hepatic impairment.

Distribution

Extent

Due to large molecule size, unlikely to cross the blood-brain barrier in substantial amounts.

Not known whether distributed into human milk.

Elimination

Elimination Route

Expected to undergo proteolytic degradation to small peptides and amino acids.

Half-life

Approximately 27 days.

Stability

Storage

Parenteral

Injection, for IV infusion

2–8°C in original carton to protect from light until time of use. Do not freeze or shake.

Diluted solutions should be stored at room temperature (20–25°C) and must be infused within 8 hours. Do not freeze.

Compatibility

Parenteral

Solution Compatibility

Compatible
Sodium chloride 0.9%

Actions

A humanized IgG₁ monoclonal antibody that binds to the CGRP ligand and blocks its binding to the receptor. Produced using recombinant DNA technology in Pichia pastoris yeast cells.
CGRP is a potent vasodilator and pain-signaling neuropeptide associated with migraine pathophysiology. CGRP and its receptors are located at sites that are relevant to migraine development (e.g., trigeminal neurons); they also are widely distributed throughout the central and peripheral nervous systems as well as in nonneuronal tissues throughout the body.
Increased serum CGRP concentrations observed in individuals during acute migraine attacks (with or without aura). IV infusion of CGRP induces migraines in patients with a history of migraines.
Because of its large molecular size, unlikely to cross the blood-brain barrier; probably antagonizes CGRP function peripherally rather than centrally within the nervous system.

Advice to Patients

Importance of advising patients to read the manufacturer's patient information.
Importance of informing patients that hypersensitivity reactions, including angioedema, urticaria, facial flushing, and rash, may occur. Patients should immediately contact their healthcare provider if signs or symptoms of a hypersensitivity reaction occur.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.