What You Need to Know About Erenumab for Preventive Treatment of Migraine

In May 2018, erenumab-aooe (Aimovig, Amgen/Novartis) was approved by the FDA for the preventive treatment of migraine in adults.¹

Migraines are ranked the third most prevalent illness and sixth most disabling illness in the world according to Migraine Research Foundation. They are severe throbbing, recurring pain, usually on one side of the head. Patients with migraines do not only have headaches, but also other debilitating symptoms such as nausea, vomiting, dizziness, sensitivity to light, touch and sound. Migraines usually last anywhere between 4 to 72 hours. They affect quality of life, leading to early disability, depression, anxiety, and sleep disturbances.²

Dosing and Administration

Erenumab is administered subcutaneously at a dosage of either 70 mg or 140 mg once monthly in the abdomen, thigh, or upper arm.³ It is self-administered by the patient. Before administering, keep erenumab at room temperature for at least 30 minutes, protected from direct sunlight. Let it warm up naturally, without using other heat sources. Do not shake the solution.

Visually inspect the solution for any discoloration or particulate matters before administering. Do not use if the solution is cloudy or contains particles.

One administration of either the autoinjector or syringe will deliver the entire dose of 70 mg. Two prefilled syringes or autoinjectors will be needed for a 140 mg dose. See instructions for use for full administration directions.

Pharmacology

Erenumab is human monoclonal antibody that is a calcitonin gene-related peptide (CGRP) antagonist.³

Table 1. Method of Supply

Erenumab injection comes as a clear and colorless to light yellow solution. The needle shield from the autoinjector and the needle cap of the syringe contains dry natural rubber, a type of latex.³

Drug Administration/Packaging

NDC Information

Pack of 1 autoinjector 70 mg/ml

Pack of 2 autoinjectors 140 mg/ml (2 x 70 mg/ml)

55513-0841-01

55513-0841-02

Pack of 1 syringe 70 mg/ml

Pack of 2 syringes 140 mg/ml (2 x 70 mg/ml)

55513-0840-01

55513-0840-02

NDC indicates National Drug Code.

Storage

Erenumab is to be refrigerated at 2°C to 8°C (36°F-46°F) in its original container and protected from light. erenumab must be used within 7 days if kept at room temperature, 25°C (77°F), in its original container. Do not store in the freezer and do not shake.³

Drug Interactions/Contraindications

There are no drug interactions or contraindications reported on the packaging label of erenumab. Of note, erenumab is not metabolized by CYP450 enzymes, and does not affect oral contraceptive or sumatriptan pharmacokinetics.³

Belimumab should be not used together with erenumab because erenumab will increase the toxicity of belimumab.⁴

Adverse Reactions

Adverse reactions listed below were observed from placebo-controlled clinical trials from both doses of erenumab (70 mg and 140 mg).³

Table 2. Adverse Reactions Observed From Placebo-controlled Clinical Trials

Adverse Reactions

Percentage

Injection site reactions (pain, erythema, pruritus)

5-6%

Constipation

1-3%

Cramps and muscle spasms

1-2%

Pregnancy and Lactation

There are no data on the effect that erenumab has on human pregnancy or lactation.³ Erenumab did not have any adverse effects on female monkey’s offspring. Studies have shown that women with migraine may be predisposed to an increased risk of preeclampsia during pregnancy.

Pediatric and Geriatric Population

Erenumab has not been tested in pediatrics. Patients 65 years and older should start erenumab treatment at the lower dose (70 mg).³

Clinical Studies

Erenumab was evaluated in 3 different clinical studies, 2 studies in patients with episodic migraine and 1 study in patients with chronic migraine. In the first study evaluating patients with episodic migraine, erenumab 70 mg and 140 mg had significantly lower mean monthly migraine days (3-4 migraine day difference from baseline), increased the proportion of patients with a ≥50% reduction from baseline in mean monthly migraine days (43.3% to 50% responders in erenumab), lowered monthly acute migraine-specific medication days (1-2 day difference from baseline), and saw improvements in migraine physical function impact diary (MPFID), a measurement of the impacts that migraine has on everyday activities and physical impairment.

Similarly, in the second study conducted on patients with episodic migraine, erenumab 70 mg was shown to significantly lower monthly migraine days, increased the proportion of patients with ≥50% reduction from baseline in mean monthly migraine days, and lowered monthly acute migraine-specific medication days. MFPID improvements in scores of at least a 5-point reduction, as a predetermined outcome, was not achieved by erenumab compared to placebo.

The third study on erenumab efficacy was assessed in patients with chronic migraine. erenumab 70 mg and 140 mg had significantly lower mean monthly migraine days (6.6 migraine day difference from baseline), increased proportion of patients with ≥50% reduction from baseline in mean monthly migraine days (39.9% to 41.2% responders in erenumab), and lower monthly acute migraine-specific medication days (approximately 4-day difference from baseline).

Migraine Guidelines

Classification of migraine preventative therapies are done through medications with established efficacy in trials. Level A medications with established efficacy (≥2 Class I trials) include antiepileptic drugs (valproate, topiramate), β-blockers (metoprolol, propranolol, timolol) and frovatriptan. Level B medications with probable efficacy (1 class I or 2 class II studies) include amitriptyline, venlafaxine, β-blockers (atenolol, nadolol) and triptans (naratriptan, zolmitriptan). Level C medications with possible efficacy (1 class II study) include lisinopril, candesartan, α-agonists (clonidine, guanfacine), carbamazepine, β-blockers (nebivolol, pindolol) and cyproheptadine. Selective serotonin reuptake inhibitors, calcium channel blockers and other drugs in the same drug class as the ones listed in Level A to C either have inadequate data to support use or are ineffective.⁵

The most recent update for the prevention of episodic migraines was the 2012 guidelines from the American Headache Society. Because erenumab was just approved in 2018, it does not have a recommendation on usage in this guideline.

Costs and Availability

The cost for erenumab 70-mg and 140-mg autoinjectors are listed below (see TABLE 3). There is a co-pay card that commercially insured patients may be eligible for. There is also a service request form that can be submitted by the clinician to help cover the cost of the drug. Both are available online at www.aimovig.com/co-pay-and-support.⁵

Table 3. Costs of Erenumab from Red Book Online⁶

Drug

NDC

Quantity

Wholesale Acquisition Cost

Average Wholesale Price

Erenumab 70 mg

55513-0841-01

1 autoinjector

70 mg/ml

$575.00

$690.00

Erenumab 140 mg

55513-0841-02

2 autoinjectors 70 mg/ml x 2

$575.00

$690.00

Patient Counseling

Erenumab is a prescription drug used for the preventative treatment of migraine in adults 18 years and older. Inject erenumab subcutaneously once a month in the abdomen, thigh, or upper arm. If the dose taken is 70 mg, use one injection only. If the dose is 140 mg, 2 separate injections will need to be administered at the same body site, or at different locations. If injecting at the same body site, the second injection cannot be the same spot as the first injection. Inform patients to check for discoloration, particulates, and the expiration date prior to use. Missed doses should be taken as soon as the patient remembers. The next dose after the missed dose should be spaced from 1 month of the missed dose. Eerenumab should be stored in the refrigerator in its original container. Erenumab can stay at room temperature in its original container for up to 7 days, then it must be discarded. Patients should be advised not to freeze or shake the medication.³

Common adverse events (AE) include injection site reactions (pain, swelling, redness) and constipation. AEs should be reported to the clinician if they do not go away or if they bother the patient. The needle shield from the autoinjector and the needle cap of the syringe contains latex. Caution should be taken if a patient is allergic to latex.

Instructions for use

Autoinjector

1. Lift the autoinjector straight out of the container.
2. Keep the autoinjector at room temperature for at least 30 minutes prior to injecting. Let the medication warm up naturally (do not use hot water, a microwave, or direct sunlight).
3. Check the window of the autoinjector to make sure that the medication is clear and colorless to slightly yellow. Do not use the medication if it is discolored, there are particles, if it’s dropped, broken, expired, or the white cap covering the hidden needle is missing or not securely attached.
4. Assemble all materials that are needed: autoinjector, alcohol wipes, cotton balls or gauze pads, bandages, and a sharps disposal container.
5. Clean the area of injection (thigh, upper arm- someone else must give the injection, abdomen- 2 inches away from the navel). Do not pick an area where the skin is bruised, red, tender, lesioned, or scarred. If there is a need for two injections (140 mg), the second injection cannot be the same spot as the first.
6. Pull the white cap straight off. The autoinjector must be used within 5 minutes, otherwise, the medicine may dry out. Do not recap, twist or bend the white cap.
7. Stretch or pinch the injection site. Hold the stretch or pinch and place the autoinjector on your skin at a 90-degree angle. Push the autoinjector down onto the skin to make sure that the autoinjector does not move. Press the purple start button. There will a click sound, indicating that the medication is being administered. Hold down the autoinjector for 15 seconds. The window of the medicine will turn yellow when the injection is done.
8. Discard the autoinjector and the white cap into the sharps container afterward.
9. Repeat the steps if a second injection is needed. If the window of the medication does not turn yellow or if the medication is still injecting when it was removed, the full dose may not have been administered and the clinician should be informed.

Syringe

1. For the syringe injection, the steps are very similar to the autoinjector. The syringe should be removed from the container by grabbing the syringe barrel from the tray.
2. Keep the syringe at room temperature for at least 30 minutes prior to injecting. Let the medication warm up naturally (do not use hot water, a microwave, or direct sunlight).
3. Check the syringe to make sure that the medication is clear and colorless to slightly yellow. Do not use the medication if it is discolored, there are particles, if its dropped, broken, expired, or the gray needle cap covering the needle is missing or not securely attached.
4. Assemble all materials that are needed: syringe, alcohol wipes, cotton balls or gauze pads, bandages, and a sharps disposal container.
5. Clean the area of injection (thigh, upper arm- someone else must give the injection, abdomen- 2 inches away from the navel). Do not pick an area where the skin is bruised, red, tender, lesioned, or scarred. If there is a need for two injections (140 mg), the second injection cannot be the same spot as the first.
6. Pull the gray needle cap straight out away from the body. The syringe must be used within 5 minutes, otherwise, the medicine will dry. Do not recap, twist or bend the gray needle cap.
7. Pinch the injection site. Keep pinching and insert the syringe into the skin at a 45- to 90-degree angle. Place a finger on the plunger rod and push it down all the way until the syringe stops moving. Lift the syringe off the skin after finished.
8. Discard the syringe and the gray needle cap into the sharps container afterward.
9. Repeat the steps if a second injection is needed.

REFERENCES

1. FDA approves novel preventive treatment for migraines. FDA website. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm608120.htm?rel=0" . Updated May 17, 2018. Accessed August 23, 2018.

2. Migraine Facts. Migraine Research Foundation. http://migraineresearchfoundation.org/about-migraine/migraine-facts/?rel=0" . Accessed August 23, 2018.

3. Erenumab [prescribing information]. Thousand Oaks, California: Amgen; 2018. https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/erenumab/erenumab_pi_hcp_english.pdf?rel=0" . Accessed August 23, 2018.

4. Erenumab. Lexicomp [online database]. Wolters Kluwer Health, Inc: Riverwoods, IL; 2018. Accessed August 23, 2018.

5. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society [published correction appears in Neurology. 2013;80(9):871. doi:10.1212/WNL.0b013e318287dc4e]. Neurology. 2012;78(17):1337-1345. doi:10.1212/WNL.0b013e3182535d20.

6. Erenumab. Red Book Online. Micromedex Healthcare Series [online database]. Greenwood Village, CO: Truven Health Analytics; 2018. Accessed August 22, 2018.