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Erenumab-aooe

Class: Calcitonin Gene-related Peptide (CGRP) Antagonists
- Anti-CGRP Monoclonal Antibodies
- Calcitonin Gene-related Peptide Receptor Antagonists
- CGRP Antagonists
- CGRP Receptor Antagonists
Chemical Name: Disulfide with human monoclonal light chain, anti-(human calcitonin gene-related peptide receptor) (human monoclonal heavy chain) immunoglobulin G, dimer
Molecular Formula: C6472H9964N1728O2018S50
CAS Number: 1582205-90-0
Brands: Aimovig

Medically reviewed by Drugs.com. Last updated on July 15, 2019.

Introduction

Antimigraine agent; recombinant fully human IgG2 monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP) receptor function.1 8 9

Uses for Erenumab-aooe

Preventive Treatment of Migraine

Preventive treatment of migraine.1 2 3 4 7

Substantially reduces monthly migraine days and acute antimigraine agent-use days in patients with episodic or chronic migraine (with or without aura) when compared with placebo.1 2 3 4

The American Headache Society (AHS) states that erenumab and other CGRP antagonists offer a number of advantages over some oral migraine preventive therapies, including no need for dosage escalation, rapid onset of therapeutic activity, demonstrated efficacy in patients after prior preventive treatments have failed as well as in those concurrently receiving oral preventive treatments, minimal risk of adverse drug interactions, and favorable overall tolerability profiles.12 However, because of the relatively high cost of CGRP antagonists, AHS recommends that CGRP antagonists be considered for use only in patients who are unable to tolerate oral preventive therapies and/or who have an inadequate response to a 6-week trial of ≥2 oral preventive therapies (e.g., topiramate, valproate, β-adrenergic blocking agents, tricyclic antidepressants, selective serotonin- and norepinephrine-reuptake inhibitors).12

Erenumab-aooe Dosage and Administration

Administration

Administer by sub-Q injection only.1

Commercially available in single-dose prefilled auto-injectors (i.e., injection pens) and single-dose prefilled syringes, which both contain 70 or 140 mg of the drug1 17 and are intended for patient self-administration.1

Some packaging components contain dry natural rubber, which may cause allergic reactions in individuals sensitive to latex.1 (See Latex Sensitivity under Cautions.)

Sub-Q Administration

Administer by sub-Q injection into the abdomen, thigh, or outer area of upper arm; avoid injections within 2 inches of the navel.1 Use upper arm only if someone other than the patient (e.g., caregiver, healthcare professional) is administering the injection.1 Avoid injection into areas where the skin is tender, bruised, erythematous, or indurated.1

Prior to use, provide patients and/or caregivers with proper training on how to prepare and administer erenumab-aooe sub-Q using the prefilled auto-injectors or syringes, including aseptic technique.1 Consult manufacturer's labeling for detailed instructions.1

Prior to sub-Q administration, remove prefilled auto-injector or syringe from carton and allow to sit at room temperature for ≥30 minutes; avoid exposure to direct sunlight.1 Do not warm auto-injectors and syringes using a heat source (e.g., microwave, hot water).1 Do not use if the solution is cloudy or discolored or contains flakes or particles.1

Prefilled auto-injectors and syringes are intended for single-use only; discard any unused portions.1

Dosage

Adults

Migraine
Preventive Treatment
Sub-Q

70 mg once monthly.1 May consider 140 mg once monthly in some patients.1 Gradual dosage titration not necessary; may initiate therapy with either the 70- or 140-mg dose.12

If a dose is missed, administer the missed dose as soon as possible.1 May then schedule subsequent doses once monthly from the date of the last administered dose.1

When initiating therapy with erenumab or another CGRP antagonist in patients already receiving a preventive treatment for migraine, AHS recommends adding the CGRP antagonist to the existing antimigraine regimen and avoiding making other changes until the clinical efficacy of the CGRP antagonist is determined.12 The risk of adverse drug interactions with erenumab-aooe appears minimal (see Interactions).1 12

Patients who respond to erenumab therapy usually respond following the first 3 monthly doses.12 Therefore, AHS recommends assessing clinical efficacy after 3 months of treatment; continue therapy only if treatment benefits have been observed by that time.12

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Geriatric Patients

Select dosage carefully, usually starting at the low end of the dosage range.1 (See Geriatric Use under Cautions.)

Cautions for Erenumab-aooe

Contraindications

  • Serious hypersensitivity to erenumab-aooe or any excipient in the formulation.1 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, reported during postmarketing experience.1 Most hypersensitivity reactions were not serious and occurred within hours of administration; however, some reactions occurred >1 week following administration.1

If a serious or severe hypersensitivity reaction occurs, discontinue administration of the drug and initiate appropriate therapy.1 (See Contraindications under Cautions and see also Advice to Patients.)

Latex Sensitivity

Some packaging components (e.g., needle shield within cap of the prefilled auto-injector, needle cap of the prefilled syringe) of erenumab-aooe contain natural rubber (a latex derivative),1 which may cause allergic reactions in individuals sensitive to latex.1 14 15 16

Some individuals may be hypersensitive to natural latex proteins;14 15 16 rarely, hypersensitivity reactions to natural latex proteins have been fatal.14 16

Immunogenicity

Potential for immunogenicity.1 Antibodies to erenumab, including neutralizing antibodies to the drug, reported.1 Available data do not demonstrate an effect of anti-erenumab antibody development on efficacy or safety of the drug; however, data are too limited to make definitive conclusions.1

Specific Populations

Pregnancy

No adequate data on the developmental risk associated with use of erenumab in pregnant women.1 No adverse effects on offspring observed when pregnant monkeys received the drug sub-Q at dosages resulting in systemic exposures approximately 20 times the exposure from the maximum recommended human dosage.1

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.1 Possible increased risk of preeclampsia during pregnancy in women with migraine.1

Lactation

Not known whether distributed into human milk.1 Effects on the breast-fed infant or on milk production also unknown.1 Consider developmental and health benefits of breast-feeding, mother's clinical need for erenumab, and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.1

Pediatric Use

Manufacturer states that safety and efficacy not established in pediatric patients <18 years of age.1

Pending further clinical experience with CGRP antagonists in pediatric patients, the Pediatric and Adolescent Headache special interest group of the AHS recommends limiting use of CGRP antagonists (e.g., erenumab, fremanezumab, galcanezumab) mainly to postpubertal adolescents 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.11 For younger pediatric patients with severe chronic migraine that is refractory to multiple preventive therapies, consider CGRP antagonists only in carefully selected patients with close monitoring (e.g., pubertal status, bone health, linear growth, weight, body mass index [BMI], infectious complications).11

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Select dosage with caution, usually starting at the low end of the dosage range.1 Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy when selecting dosage in geriatric patients.1

Hepatic Impairment

Hepatic impairment not expected to affect pharmacokinetics.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Renal impairment not expected to affect pharmacokinetics.1 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Injection site reactions (e.g., pain, erythema, pruritus; usually mild and transient),1 5 17 constipation.1 5 17

Interactions for Erenumab-aooe

Not metabolized by CYP isoenzymes.1 Unlikely to affect drug-metabolizing enzymes or drug transporters.5

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes: Pharmacokinetic interactions unlikely.1

Substrates of major CYP isoenzymes: Pharmacokinetic interactions unlikely.1 5

Drugs Affected by Drug Transport Systems

Substrates of various drug transport systems: Pharmacokinetic interactions unlikely.5

Specific Drugs

Drug

Interaction

Contraceptives, oral (ethinyl estradiol with norgestimate)

Pharmacokinetics of the oral contraceptive not affected1

Sumatriptan

Pharmacokinetics of sumatriptan not affected1 5 19

Concomitant administration of erenumab-aooe (single 140-mg IV dose) and sub-Q sumatriptan (given as two 6-mg sub-Q doses 1 hour apart) in healthy individuals did not result in increased mean arterial pressure and resting BP compared with sumatriptan administered alone1 5 19

Concomitant administration is well tolerated19

Erenumab-aooe Pharmacokinetics

Absorption

Bioavailability

Following single-dose, sub-Q administration, estimated absolute bioavailability is 82%.1

Peak concentrations achieved in approximately 6 days following a single sub-Q dose.1

Steady-state trough concentrations approached in 3 months following once-monthly sub-Q administration; systemic accumulation is less than twofold.1

Exhibits nonlinear pharmacokinetics due to binding to the CGRP receptor;1 17 however, at clinically relevant dosages, pharmacokinetics following once-monthly sub-Q administration are predominantly linear because of saturation of binding to the CGRP receptor.1 5 17

Onset

Antimigraine effects usually evident following 1–3 monthly sub-Q injections in responding patients.12

Special Populations

Not formally studied in renal or hepatic impairment; renal or hepatic impairment not expected to affect pharmacokinetics.1 Population pharmacokinetic analysis indicates that pharmacokinetics not affected by mild or moderate renal impairment.1 Not studied in patients with severe renal impairment (estimated GFR <30 mL/minute per 1.73 m2).1

Age, sex, race, or subtype of migraine spectrum (e.g., episodic or chronic migraine) does not affect pharmacokinetics.1

Distribution

Extent

Due to large molecule size, unlikely to cross the blood-brain barrier.11 13 18

Not known whether distributed into human milk.1

Elimination

Elimination Route

At low concentrations, predominantly eliminated through saturable binding to the CGRP receptor; at higher concentrations, predominantly eliminated through a nonspecific, nonsaturable proteolytic pathway.1

Half-life

Effective half-life: 28 days.1

Stability

Storage

Parenteral

Injection

2–8°C in original carton to protect from light until time of use; do not freeze.1 Do not shake.1

If removed from the refrigerator, store at room temperature (≤25°C) in the original carton; use within 7 days.1 Discard if stored at room temperature for >7 days.1

Actions

  • A fully human IgG2 immunoglobulin that binds to the CGRP receptor and antagonizes CGRP receptor function.1 8 9 Produced using recombinant DNA technology in Chinese hamster ovary cells.1

  • CGRP is a potent vasodilator and pain-signaling neuropeptide associated with migraine pathophysiology.8 9 10 17 18 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 non-neuronal tissues throughout the body.8 9 10 11 17 18

  • Increased serum CGRP concentrations observed in individuals during acute migraine attacks (with or without aura).8 9 10 17 18 IV infusion of CGRP induces migraines in patients with a history of migraines.8 9 10 17 18

  • Potently and selectively binds to the extracellular binding site of the CGRP receptor and competitively blocks its interaction with CGRP.5 8 9 10 17

  • Because of its large molecular size, unlikely to cross the blood-brain barrier; probably antagonizes CGRP receptor function peripherally rather than centrally within the nervous system.11 13 18

Advice to Patients

  • Importance of advising patients to read the manufacturer's patient information and instructions for use.1

  • Importance of providing guidance to patients and/or caregivers on proper sub-Q administration of erenumab-aooe, including the use of aseptic technique, and use of the single-dose auto-injectors or syringes.1 Importance of instructing patients and/or caregivers to read and follow the instructions for use each time they use erenumab-aooe.1

  • If a dose is missed, administer the missed dose as soon as possible.1 Schedule subsequent doses monthly from the date of the last administered dose.1

  • Some packaging components of erenumab-aooe (e.g., needle shield within cap of the prefilled auto-injector, needle cap of the prefilled syringe) contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex.1 Importance of alerting clinician if allergy to rubber or latex exists.1

  • Importance of advising patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions.1

  • 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.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 (See Pregnancy under Cautions.)

  • Importance of informing patients of other important precautionary information.1 (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.

Erenumab-aooe

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use only

70 mg/1 mL

Aimovig (available as single-dose prefilled auto-injectors [SureClick] and single-dose prefilled syringes)

Amgen , (comarketed with Novartis)

140 mg/1 mL

Aimovig (available as single-dose prefilled auto-injectors [SureClick] and single-dose prefilled syringes)

Amgen , (comarketed with Novartis)

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 15, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Amgen Inc. Aimovig (erenumab-aooe) injection, for subcutaneous use prescribing information. Thousand Oaks, CA; 2019 Mar.

2. Goadsby PJ, Reuter U, Hallström Y et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017; 377:2123-2132. http://www.ncbi.nlm.nih.gov/pubmed/29171821?dopt=AbstractPlus

3. Dodick DW, Ashina M, Brandes JL et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018; 38:1026-1037. http://www.ncbi.nlm.nih.gov/pubmed/29471679?dopt=AbstractPlus

4. Tepper S, Ashina M, Reuter U et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017; 16:425-434. http://www.ncbi.nlm.nih.gov/pubmed/28460892?dopt=AbstractPlus

5. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761077Orig1s000: Summary review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761077Orig1s000SumR.pdf

6. Schwedt T, Reuter U, Tepper S et al. Early onset of efficacy with erenumab in patients with episodic and chronic migraine. J Headache Pain. 2018; 19:92. http://www.ncbi.nlm.nih.gov/pubmed/30276500?dopt=AbstractPlus

7. Ashina M, Dodick D, Goadsby PJ et al. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. Neurology. 2017; 89:1237-1243. http://www.ncbi.nlm.nih.gov/pubmed/28835404?dopt=AbstractPlus

8. Shi L, Lehto SG, Zhu DX et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor. J Pharmacol Exp Ther. 2016; 356:223-31. http://www.ncbi.nlm.nih.gov/pubmed/26559125?dopt=AbstractPlus

9. Edvinsson L, Haanes KA, Warfvinge K et al. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018; 14:338-350. http://www.ncbi.nlm.nih.gov/pubmed/29691490?dopt=AbstractPlus

10. Schuster NM, Rapoport AM. Calcitonin gene-related peptide-targeted therapies for migraine and cluster headache: a review. Clin Neuropharmacol. 2017 Jul/Aug; 40:169-174. http://www.ncbi.nlm.nih.gov/pubmed/28644160?dopt=AbstractPlus

11. Szperka CL, VanderPluym J, Orr SL et al. Recommendations on the use of anti-CGRP monoclonal antibodies in children and adolescents. Headache. 2018; 58:1658-69. http://www.ncbi.nlm.nih.gov/pubmed/30324723?dopt=AbstractPlus

12. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019; 59:1-18. http://www.ncbi.nlm.nih.gov/pubmed/30536394%20?dopt=AbstractPlus

13. Raffaelli B, Reuter U. The biology of monoclonal antibodies: focus on calcitonin gene-related peptide for prophylactic migraine therapy. Neurotherapeutics. 2018; 15:324-35. http://www.ncbi.nlm.nih.gov/pubmed/29616494?dopt=AbstractPlus

14. Food and Drug Administration. Natural rubber-containing medical devices; user labeling. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1997; 62:51021-30.

15. Food and Drug Administration. Amended economic impact analysis of final rule requiring use of labeling on natural rubber containing devices. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1998; 63:50660-704.

16. Food and Drug Administration. Latex-containing devices; user labeling. 21 CFR Part 801. Proposed rule. (Docket No. 96N-0119) Fed Regist. 1996; 61:32617-21.

17. Novartis Europharm Limited. Aimovig (erenumab) injection, solution for injection summary of product characteristics. Dublin, Ireland; 2018 Aug 8.

18. Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache. 2017; 57:47-55. http://www.ncbi.nlm.nih.gov/pubmed/28485848?dopt=AbstractPlus

19. de Hoon J, Van Hecken A, Vandermeulen C et al. Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers. Cephalalgia. 2019; 39:100-110. http://www.ncbi.nlm.nih.gov/pubmed/PMID:%2029783863?dopt=AbstractPlus

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