Eptinezumab is an injectable calcitonin gene-related peptide (CGRP) receptor antagonist indicated for migraine prophylaxis in adults. In a clinical trial of patients with episodic migraine, monthly migraine days were significantly reduced by 3.9 to 4.3 days from baseline at 3 months in eptinezumab-treated patients in comparison to 3.2 days for placebo. At month 3, eptinezumab-treated chronic migraine patients experienced a significant 7.7 to 8.2-day reduction in monthly migraine days from baseline in comparison to 5.6 days for placebo. A 50% or greater reduction in monthly migraine days was achieved by 49.8% to 56.3% of episodic migraineurs and 57.6% to 61.4% of chronic migraineurs who were treated with eptinezumab compared to 37.4% of episodic migraineurs and 39.3% of chronic migraineurs given placebo.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Dilution
-Dilute the dose in 100 mL of 0.9% Sodium Chloride Injection. Infusion bags must be made of polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO).
-Gently invert the bag to mix completely. Do not shake.
-Storage: Single-dose vials contain no preservatives and must be discarded after use. After dilution, infuse within 8 hours; store the diluted solution at room temperature of 20 to 25 degrees C (68 to 77 degrees F) during this time. Do not freeze.
Intravenous Infusion
-Infuse intravenously over approximately 30 minutes.
-Use an intravenous infusion set with a 0.2 or 0.22 micron in-line or add-on sterile filter. Flush the line with 20 mL of 0.9% Sodium Chloride Injection after the infusion is complete.
-Do not administer other medications through the infusion set or mixed with eptinezumab.
Hypersensitivity reactions, including angioedema, urticaria, facial flushing, and rash occurred in 1% of patients who received eptinezumab 100 mg, 2% of patients who received eptinezumab 300 mg, and 0% of patients who received placebo in clinical trials. Most hypersensitivity reactions occurred during infusion and were not serious, but often led to discontinuation or required treatment. Serious hypersensitivity reactions may occur; anaphylactoid reactions (anaphylaxis) and dyspnea have been reported during postmarketing experience. If a hypersensitivity reaction occurs, institute appropriate therapy and consider discontinuing eptinezumab.
Naso-pharyngitis occurred in 6% of patients who received eptinezumab 100 mg, 8% of patients who received eptinezumab 300 mg, and 6% of patients who received placebo in clinical trials.
As with all therapeutic proteins, there is the potential for immunogenicity and antibody formation. In a clinical trial of eptinezumab for episodic migraine (up to 56 weeks), anti-eptinezumab antibodies developed in 20.6% (92/447) of patients who received 100 or 300 mg every 3 months; anti-eptinezumab neutralizing antibodies developed in 41.3% (38/92) of those patients. In a clinical trial of eptinezumab for chronic migraine (up to 32 weeks), anti-eptinezumab antibodies developed in 18.3% (129/706) of patients who received 100 or 300 mg every 3 months; anti-eptinezumab neutralizing antibodies developed in 34.9% (45/129) of patients. In an open-label study (84 weeks), anti-eptinezumab antibodies developed in 18% (23/128) of patients, and anti-eptinezumab neutralizing antibodies developed in 39% (9/23) of those patients. Although the study results did not demonstrate an impact of anti-eptinezumab antibody development on the efficacy or safety of eptinezumab, data are too limited to make definitive conclusions.
Fatigue was reported with eptinezumab in postmarketing surveillance.
Eptinezumab is contraindicated in patients with serious hypersensitivity to eptinezumab or any of its excipients. Hypersensitivity reactions, including angioedema, urticaria, facial flushing, and rash, occurred with eptinezumab treatment during clinical trials. Anaphylaxis and dyspnea have been reported during postmarketing experience. If a hypersensitivity reaction occurs, institute appropriate therapy and consider discontinuing eptinezumab.
There are no adequate data on the developmental risk associated with eptinezumab use during human pregnancy. No adverse developmental effects on offspring were observed when rats and rabbits were given eptinezumab throughout pregnancy at doses 30 times the maximum recommended human dose of 300 mg, on a body weight basis (mg/kg). Women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.
There are no data on the presence of eptinezumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for eptinezumab and any potential adverse effects on the breast-fed infant from eptinezumab or the underlying maternal condition.
Guideline indications for initiating migraine prevention with monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor:
-Migraine with or without aura (4 to 7 monthly headache days) and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments and at least moderate disability defined by Migraine Disability Assessment Score (MIDAS) more than 11 or Headache Impact Test Score (HIT-6) more than 50
-Migraine with or without aura (8 to 14 monthly headache days) and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments
-Chronic migraine and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments or inability to tolerate or inadequate response to a minimum of 2 quarterly injections (6 months) of onabotulinumtoxinA
Evidence-based migraine preventative treatments with established or probable efficacy include:
-Topiramate
-Divalproex sodium/valproate sodium
-Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
-Tricyclic antidepressant: amitriptyline, nortriptyline
-Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
Guideline criteria for continuation of migraine prevention with monoclonal antibodies to CGRP or its receptor after 6 months or more (quarterly dosing):
-Reduction in mean monthly headache days of 50% or more relative to pretreatment baseline (diary documentation or healthcare provider attestation) or
-Clinically meaningful improvement, defined by MIDAS reduction of 5 points or more with a baseline score of 11 to 20 or reduction of 30% or more with baseline score more than 20, HIT-6 reduction of 5 points or more, or Migraine Physical Function Impact Diary (MPFID) reduction of 5 points or more
For migraine prophylaxis:
Intravenous dosage:
Adults: 100 mg IV every 3 months. Some persons may benefit from a dose of 300 mg IV every 3 months. Guidelines classify eptinezumab as having established efficacy for migraine prophylaxis.
Maximum Dosage Limits:
-Adults
300 mg/every 3 months IV.
-Geriatric
300 mg/every 3 months IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Eptinezumab products.
Eptinezumab is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. CGRP is distributed throughout the nervous system, and it is concentrated at anatomical sites, such as the trigeminovascular system, which are involved in migraine pathophysiology. Centrally, CGRP is involved in nociceptive transmission through second and third order neurons and pain modulation in the brainstem. Peripherally, CGRP mediates vasodilation through smooth muscle receptors. CGRP concentrations are elevated during acute migraine attacks and may be chronically elevated in chronic migraineurs.
Eptinezumab is administered intravenously. Steady-state is achieved after the first dose with an every 3 months dosing schedule. Eptinezumab has an approximate central volume of distribution of 3.7 L. Eptinezumab is degraded by enzymatic proteolysis into small peptides and amino acids. Eptinezumab apparent clearance is 0.006 L/hour. The half-life of eptinezumab is approximately 27 days.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
Eptinezumab exhibits linear pharmacokinetics after intravenous administration. Eptinezumab exposure increases proportionally with doses from 100 to 300 mg.
-Special Populations
Hepatic Impairment
Hepatic impairment is not expected to affect the pharmacokinetics of eptinezumab. A population pharmacokinetic analysis of integrated data from eptinezumab clinical studies did not reveal clinically significant impact on pharmacokinetics of patients with hepatic impairment.
Renal Impairment
Renal impairment is not expected to affect the pharmacokinetics of eptinezumab. A population pharmacokinetic analysis of integrated data from eptinezumab clinical studies did not reveal clinically significant impact on pharmacokinetics of patients with renal impairment.
Geriatric
A population pharmacokinetic analysis did not suggest any clinically significant impact of age on eptinezumab exposures.
Gender Differences
A population pharmacokinetic analysis did not suggest any clinically significant impact of gender on eptinezumab exposures.
Ethnic Differences
A population pharmacokinetic analysis did not suggest any clinically significant impact of race on eptinezumab exposures.
Obesity
A population pharmacokinetic analysis did not suggest any clinically significant impact of body weight on eptinezumab exposures.