Erenumab is an injectable selective calcitonin gene-related peptide (CGRP) receptor antagonist indicated for migraine prophylaxis in adults. In clinical trials of patients with episodic migraine, monthly migraine days were significantly reduced by 2.9 to 3.7 days from baseline at 3 to 6 months in erenumab-treated patients in comparison to placebo. At month 3, erenumab-treated chronic migraine patients experienced a significant 6.6-day reduction in monthly migraine days from baseline vs. placebo. A 50% or greater reduction in monthly migraine days was achieved by 39.7% to 50% of episodic migraineurs and 39.9% to 41.2% of chronic migraineurs who were treated with erenumab compared to 26.6% to 29.5% of episodic migraineurs and 23.5% 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. Do not use if the erenumab solution is cloudy or discolored or contains flakes or particles. Erenumab is a clear to opalescent, colorless to light yellow solution.
Subcutaneous Administration
-Erenumab is intended for patient self-administration. Provide proper training to patients and/or caregivers on how to prepare and administer erenumab, including aseptic technique.
-Before administration, allow erenumab to sit at room temperature for at least 30 minutes protected from direct sunlight. Do not warm using a heat source such as hot water or microwave.
-Do not shake.
-Clean injection site on the abdomen, thigh, or upper arm with an alcohol wipe, and allow skin to dry.
-Do not leave cap off the autoinjector or prefilled syringe for more than 5 minutes; this can dry out the medicine.
-Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting directly into raised, thick, red, or scaly skin patch or lesion, or areas with scars or stretch marks.
-If using the same body area for the 2 separate injections needed for the 140 mg dose, ensure the second injection is not at same location used for the first injection.
-Discard the autoinjector or prefilled syringe in a FDA-cleared sharps disposal container. Do not discard in household trash.
-Storage: After removing erenumab from the refrigerator, it can be stored at room temperature between 68 to 77 degrees F (20 to 25 degrees C) for up to 7 days. Do not return erenumab to the refrigerator after it has reached room temperature.
Single-dose, Prefilled SureClick Autoinjector
-Pull white or orange cap straight off autoinjector.
-Do not place fingers into the green or yellow safety guards. The needle is inside the safety guard.
-Stretch or pinch skin to create a firm injection site.
-Firmly push the autoinjector down onto the skin.
-When ready to inject, press the start button; a click will be heard. The injection could take about 15 seconds. When the injection is complete, a click may be heard or felt, and the window will turn yellow.
-Remove the autoinjector from the skin.
Single-dose, Prefilled Syringe
-Always hold syringe by the barrel.
-Pull gray needle cap straight out and away from body.
-Pinch injection site skin firmly between thumb and fingers.
-Hold the pinch, and insert the syringe into skin at 45 to 90 degrees.
-Using slow and constant pressure, push the plunger rod all the way down with thumb until the prefilled syringe stops moving.
-When done, release thumb, and gently lift syringe off the skin.
Constipation was reported during 3 double-blind, placebo-controlled studies of erenumab. Constipation occurred in 1% of patients who received at least 1 dose of 70 mg once monthly (n = 787), 3% of patients who received at least 1 dose of 140 mg once monthly (n = 507), and 1% of placebo-treated patients (n = 890). In a small retrospective study (n = 220) when most patients were specifically asked about constipation, it was reported by 20% of patients. Constipation (n = 1,169) was the most frequently reported adverse event in postmarketing surveillance. Many cases of constipation were managed with laxatives while others required hospitalization, surgery, or treatment discontinuation. Constipation was associated with a serious outcome in 187 cases. In most cases, the onset of constipation was reported after the first dose of erenumab; however, patients have also presented with constipation later during treatment. Erenumab was discontinued in most cases of constipation with serious complications. Monitor patients treated with erenumab for severe constipation and manage as clinically appropriate. Concurrent use of medications that decrease GI motility may increase the risk for more severe constipation and constipation-related complications. Oral ulceration (mucosal) has been reported with the use of erenumab during postmarketing experience.
Muscle cramps or muscle spasms were reported during 3 double-blind, placebo-controlled studies of erenumab. Muscle cramps or spasms occurred in less than 1% of patients who received at least 1 dose of 70 mg once monthly (n = 787), 2% of patients who received at least 1 dose of 140 mg once monthly (n = 507), and less than 1% of placebo-treated patients (n = 890). Muscle spasms (n= 263), arthralgia (n = 173), and myalgia or musculoskeletal pain (n = 121) were reported with erenumab in postmarketing surveillance. Muscle disorders were reported in approximately 3% of patients in a small retrospective study (n = 220).
As with all therapeutic proteins, there is the potential for immunogenicity and antibody formation. In clinical trials of erenumab, anti-erenumab antibodies developed in 6.2% (48/778) of patients who received 70 mg once monthly (2 of whom had in vitro neutralizing activity) and 2.6% (13/504) of patients who received 140 mg once monthly (none of whom had in vitro neutralizing activity). Anti-erenumab antibody development occurred in 11.1% (25/225) of patients who received erenumab 70 or 140 mg (2 of whom had in vitro neutralizing activity) in a long-term study including 12 weeks of double-blind treatment and 256 weeks of open-label treatment. Although the data do not demonstrate an impact of anti-erenumab antibody development on the efficacy or safety of erenumab, data are too limited to make definitive conclusions.
Hypersensitivity reactions, including rash, angioedema, and anaphylaxis or anaphylactoid reactions, have been reported during postmarketing experience with erenumab. Life-threatening cases of anaphylactic shock (n = 35) have been reported. Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than 1 week after administration. Discontinue erenumab and begin appropriate therapy if a serious or severe hypersensitivity reaction occurs.
An injection site reaction, including injection site pain, injection site erythema, or injection site pruritus, was among the most frequent adverse reactions reported during 3 double-blind, placebo-controlled studies of erenumab. Injection site reactions occurred in 6% of patients who received at least 1 dose of 70 mg once monthly (n = 787), 5% of patients who received at least 1 dose of 140 mg once monthly (n = 507), and 3% of placebo-treated patients (n = 890). Injection site erythema (n = 139), swelling (n = 109), rash (n = 123), and pruritus (n = 107) were reported with erenumab in postmarketing surveillance.
Depression (n = 309) was reported with erenumab in postmarketing surveillance.
Alopecia (n= 376) was reported with erenumab in postmarketing surveillance with 17% (n = 64) of the cases classified as serious.
Monitor patients treated with erenumab for new-onset hypertension or worsening of pre-existing hypertension during treatment. If hypertension occurs, consider discontinuing erenumab if an alternative etiology cannot be established. Cases of hypertension and worsening of pre-existing hypertension, some requiring pharmacological treatment and hospitalization, have been reported after erenumab use in the postmarketing setting. Many patients had pre-existing hypertension or risk factors for hypertension. Hypertension may occur at any time during treatment but was most frequently reported within 7 days of administration. In the majority of the cases, the onset or worsening of hypertension was reported after the first dose. Erenumab was discontinued in many of the reported cases. Palpitations (n = 86), heart rate increase (n = 60), arrhythmia exacerbation (n = 225), loss of consciousness (n = 27), cardiac arrest (n = 5), and sudden death (n = 1) were reported with erenumab in postmarketing surveillance.
Erenumab is contraindicated in patients with serious hypersensitivity to erenumab or any of the excipients. Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with erenumab. Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than 1 week after administration. Discontinue erenumab and begin appropriate therapy if a serious or severe hypersensitivity reaction occurs.
Monitor patients treated with erenumab for new-onset hypertension or worsening of pre-existing hypertension during treatment. If hypertension occurs, consider discontinuing erenumab if an alternative etiology cannot be established. Cases of hypertension and worsening of pre-existing hypertension, some requiring pharmacological treatment and/or hospitalization, have been reported after erenumab use in the postmarketing setting. Many patients had pre-existing hypertension or risk factors for hypertension. Hypertension may occur at any time during treatment but was most frequently reported within 7 days of administration. In the majority of the cases, the onset or worsening of hypertension was reported after the first dose. Erenumab was discontinued in many of the reported cases.
There are no adequate data on the developmental risk associated with erenumab use during human pregnancy. Women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. No adverse effects on offspring were observed when monkeys were given erenumab throughout pregnancy at exposures approximately 20 times those in humans at a dose of 140 mg once monthly.
There are no data on the presence of erenumab 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 erenumab and any potential adverse effects on the breast-fed infant from erenumab 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 3 months or more (monthly 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:
Subcutaneous dosage:
Adults: 70 mg subcutaneously once monthly. Some persons may benefit from a dosage of 140 mg subcutaneously once monthly. Guidelines classify erenumab as having established efficacy for migraine prophylaxis.
Maximum Dosage Limits:
-Adults
140 mg/month subcutaneously.
-Geriatric
140 mg/month subcutaneously.
-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 Erenumab products.
Erenumab is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function. 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.
Erenumab is administered subcutaneously. Erenumab exhibits non-linear kinetics. Serum trough concentrations approach steady state by 3 months of dosing. At low concentrations, elimination is predominately through saturable target binding at the calcitonin gene-related peptide (CGRP) receptor; at higher concentrations, elimination is predominantly through a non-specific, non-saturable proteolytic pathway. The half-life of erenumab is 28 days.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Subcutaneous Route
After single doses of 70 or 140 mg, the mean Cmax (SD) of erenumab was 6.1 (2.1) mcg/mL and 15.8 (4.8) mcg/mL, respectively. Median peak serum concentrations occurred in approximately 6 days. The estimated bioavailability was 82%. In patients with episodic migraine, Cmin (SD) was 5.7 (3.1) mcg/mL and 12.8 (6.5) mcg/mL for 70 mg monthly and 140 mg monthly, respectively. In patients with chronic migraine, Cmin was 6.2 (2.9) mcg/mL and 14.9 (6.5) mcg/mL for 70 mg monthly and 140 mg monthly, respectively.
-Special Populations
Hepatic Impairment
Hepatic impairment is not expected to affect the clearance of erenumab.
Renal Impairment
No difference in the pharmacokinetics of erenumab was found among patients with mild or moderate renal impairment compared to those with normal renal function. Patients with severe renal impairment (GFR less than 30 mL/minute/1.73 m2) have not been studied.
Geriatric
The pharmacokinetics of erenumab were not affected by age.
Gender Differences
The pharmacokinetics of erenumab were not affected by gender.
Ethnic Differences
The pharmacokinetics of erenumab were not affected by race.