Drug Monograph
Erenumab (Aimovig)
erenumab-aooe
Pharmacokinetic Profile
Half-Life
28 days (effective)
Metabolism
Proteolytic degradation (not CYP450)
Bioavailability
~82% (SC)
Volume of Distribution
3.86 L (Vz, IV)
Steady State
~12 weeks (3 monthly doses)
Clinical Information
Drug Class
CGRP receptor antagonist (human IgG2 mAb)
Available Doses
70 mg/mL, 140 mg/mL prefilled autoinjector or syringe
Route
Subcutaneous
Renal Adjustment
None required (mild/moderate); severe not studied
Hepatic Adjustment
None expected (mAb; not hepatically metabolised)
Pregnancy
Insufficient human data; no fetal harm in monkey studies
Lactation
Unknown if excreted in breast milk
Schedule / Legal Status
Prescription only (not scheduled)
Generic Available
No (biologic; biosimilar pathway)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Preventive treatment of episodic migraine | Adults (≥18 years) | Preventive (prophylactic) | FDA Approved |
| Preventive treatment of chronic migraine | Adults (≥18 years) | Preventive (prophylactic) | FDA Approved |
Erenumab is the first FDA-approved monoclonal antibody specifically developed for migraine prevention, targeting the CGRP receptor. It is indicated for both episodic migraine (4–14 migraine days per month) and chronic migraine (≥15 headache days per month with ≥8 migraine days). In the pivotal STRIVE trial (Study 1), erenumab 70 mg and 140 mg reduced monthly migraine days by 3.2 and 3.7 respectively, compared with 1.8 for placebo, over months 4–6 (FDA PI). Erenumab is not indicated for acute treatment of migraine attacks.
Off-Label Uses
Cluster headache prevention: Small open-label case series have explored erenumab in episodic cluster headache with mixed results. Evidence quality: Very low (case reports only).
New daily persistent headache (NDPH): Limited retrospective data suggest potential benefit in select NDPH patients. Evidence quality: Very low (retrospective case series).
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Episodic migraine prevention, initial therapy | 70 mg SC once monthly | 70 mg SC once monthly | 140 mg/month | No loading dose required; allow 12 weeks to assess full efficacy Self-administered into abdomen, thigh, or upper arm |
| Episodic migraine, suboptimal response at 70 mg | 140 mg SC once monthly | 140 mg SC once monthly | 140 mg/month | STRIVE: 50% responder rate was 50.0% (140 mg) vs 43.3% (70 mg) Available as single 140 mg/mL autoinjector or two 70 mg injections |
| Chronic migraine prevention | 70 mg SC once monthly | 70–140 mg SC once monthly | 140 mg/month | Phase 2 trial: both 70 mg and 140 mg reduced MMD by 6.6 days vs 4.2 placebo Can be used with or without concomitant oral preventives |
| Patients who failed prior oral preventives | 70 mg SC once monthly | 70–140 mg SC once monthly | 140 mg/month | LIBERTY trial showed benefit in patients who failed 2–4 prior preventives Can be initiated alongside triptans for acute treatment |
| Elderly patients (≥65 years) | 70 mg SC once monthly | 70 mg SC once monthly | 140 mg/month | Limited clinical data in this population; start at low end of dosing range PK not affected by age |
| Missed dose | Give as soon as possible | 140 mg/month | Reschedule monthly dosing from date of last injection No need to restart or re-titrate | |
Clinical Pearl: Administration
Allow erenumab to sit at room temperature for at least 30 minutes before injection (protected from direct sunlight). Do not warm using a heat source. Do not shake. Can be stored at room temperature (up to 25°C / 77°F) for up to 7 days outside the refrigerator. Inspect for particulate matter and discoloration; do not use if the solution is cloudy, discoloured, or contains particles (FDA PI). Rotate injection sites between the abdomen, thigh, and upper arm.
Pharmacology
Mechanism of Action
Erenumab is a fully human immunoglobulin G2 (IgG2) monoclonal antibody that binds with high affinity to the canonical calcitonin gene-related peptide (CGRP) receptor and competitively blocks CGRP from activating it. Unlike other anti-CGRP antibodies (galcanezumab, fremanezumab, eptinezumab) that bind the CGRP ligand itself, erenumab uniquely targets the receptor. CGRP is a potent vasodilator and neuromodulator released from trigeminal sensory neurons during migraine attacks, driving neurogenic inflammation, meningeal vasodilation, and central sensitisation. By blocking CGRP receptor activation, erenumab interrupts these pathophysiological cascades without directly affecting vascular tone at rest. This receptor-level blockade prevents both the peripheral and central effects of CGRP signalling in the trigeminovascular system.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | SC bioavailability ~82%; Tmax ~6 days (median); <2-fold accumulation at steady state | Slow absorption supports once-monthly dosing. No food interaction (injectable). Steady-state concentrations reached by 12 weeks (3 doses). |
| Distribution | Vz 3.86 L (SD 0.77); ~150 kDa molecular weight; largely confined to vascular space | Small volume of distribution consistent with monoclonal antibody (limited extravascular distribution). Does not cross intact blood-brain barrier significantly. |
| Metabolism | Proteolytic degradation to peptides and amino acids; not metabolised by CYP450 enzymes | No CYP-mediated drug interactions. No hepatic dose adjustment needed. No interaction with oral contraceptives or sumatriptan demonstrated in clinical studies. |
| Elimination | Effective t½ 28 days; dual elimination: saturable target-mediated (CGRP-R binding at low concentrations) + non-saturable proteolysis (at higher concentrations) | Long half-life supports monthly dosing. Non-linear PK at sub-therapeutic doses; at approved 70–140 mg doses, receptor saturation is achieved and PK becomes approximately linear. Washout ~4 months after discontinuation. |
Side Effects
≥3%
Common (first 3 months of controlled trials)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Injection site reactions (pain, erythema, pruritus) | 5–6% (vs 3% placebo) | Mild and transient in most cases. Allow solution to warm to room temperature before injection to reduce discomfort. Rotate injection sites. Note: incidence data from trials using prefilled syringe (PI Table 1 footnote). |
| Constipation | 1–3% (vs 1% placebo; up to 3% with 140 mg) | Class effect related to CGRP receptor blockade in the enteric nervous system. Can be serious in post-marketing reports, including cases requiring hospitalisation and surgery. |
≥2%
Common (at either dose and ≥2% greater than placebo)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Muscle cramps / spasms | 2% (140 mg; vs <1% placebo) | More common at the higher dose. Self-limiting; no specific intervention typically needed. |
Serious
Serious Adverse Effects (post-marketing and clinical trials)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Constipation with serious complications | Uncommon (post-marketing) | Often after first dose; can occur later | Monitor; discontinue if severe. Hospitalisation and surgery reported. Concurrent use of drugs that slow GI motility increases risk. |
| Hypertension (new-onset or worsening) | Uncommon (post-marketing) | Most frequently within 7 days of dosing, often after first dose | Monitor BP. Pharmacological treatment and hospitalisation reported. Discontinue if no alternative aetiology identified. |
| Hypersensitivity reactions (rash, angioedema, anaphylaxis) | Rare (post-marketing) | Within hours, but can occur >1 week after injection | Discontinue permanently; initiate appropriate emergency therapy. Contraindicated for re-challenge after serious reaction. |
| Raynaud’s phenomenon (new-onset or worsening) | Rare (post-marketing; class-wide) | Median ~71 days after dosing (mAb CGRP antagonists) | Discontinue erenumab. Evaluate if symptoms do not resolve. Hospitalisation and disability reported. Monitor patients with Raynaud’s history. |
Discontinuation
Discontinuation Rates
Controlled Trials (Studies 1, 2, 3)
1.3% (due to adverse events)
Context: Very low discontinuation reflects favourable tolerability. Most common reason was injection site reactions.
Long-Term Safety (up to 5 years)
2,537 patients (3,040 patient-years)
Observation: No new safety signals emerged during extended follow-up; 216 patients followed through 5 years.
Managing Constipation
Constipation is a class effect of CGRP receptor blockade, as CGRP plays a role in regulating gastrointestinal motility. Post-marketing cases have included hospitalisations and surgeries. Patients should be counselled about this risk at initiation. Those already taking medications that decrease GI motility (e.g., opioids, anticholinergics) are at higher risk. Early intervention with lifestyle measures and osmotic laxatives is recommended if constipation develops (FDA PI, Section 5.2).
Drug Interactions
Erenumab is a monoclonal antibody that is eliminated via proteolytic degradation, not through CYP450 enzymes. This confers a very low potential for pharmacokinetic drug interactions. Formal interaction studies have confirmed the absence of clinically significant interactions with sumatriptan and combined oral contraceptives.
Moderate
Drugs that Decrease GI Motility (opioids, anticholinergics)
MechanismAdditive reduction in gastrointestinal motility (CGRP blockade + pharmacological GI slowing)
EffectIncreased risk of severe constipation and constipation-related complications
ManagementMonitor closely for constipation. Consider prophylactic bowel regimen. Warn patients about the combined risk.
FDA PI · Section 5.2
Minor
Sumatriptan
MechanismPotential pharmacodynamic overlap (both affect CGRP/serotonin pathways)
EffectNo effect on sumatriptan PK. No effect on resting blood pressure when co-administered
ManagementNo dose adjustment needed. Safe to use triptans for acute rescue while on erenumab prevention.
FDA PI · Clinical PK/PD Study
Minor
Oral Contraceptives (ethinyl estradiol / norgestimate)
MechanismNo CYP450-mediated interaction
EffectNo effect on oral contraceptive pharmacokinetics
ManagementNo dose adjustment needed. Contraceptive efficacy maintained.
FDA PI · Interaction Study
Minor
CYP450 Substrates, Inducers, and Inhibitors
MechanismErenumab is not metabolised by CYP450 enzymes
EffectNo CYP-mediated drug interactions expected
ManagementNo dose adjustments required with any concomitant medications metabolised through CYP pathways
FDA PIMonitoring
-
Migraine Frequency
Monthly (headache diary)
Routine Track monthly migraine days to assess treatment response. Full effect may take up to 12 weeks (3 doses) to manifest. A ≥50% reduction in monthly migraine days is considered a clinically meaningful response. Consider discontinuation if no meaningful benefit after 3–6 months. -
Blood Pressure
Baseline, then periodically
Routine New-onset and worsening hypertension reported in post-marketing experience, frequently within 7 days of the first dose. Many patients had pre-existing hypertension or risk factors. Monitor especially after initial doses; consider discontinuation if BP elevation has no alternative cause. -
Constipation
Each visit
Routine Assess bowel habits proactively. Serious complications (hospitalisation, surgery) have been reported. Risk increased with concurrent use of drugs that slow GI motility. Onset often after first dose but can occur at any time during treatment. -
Raynaud’s Symptoms
Each visit (especially if history)
Trigger-based New-onset or worsening Raynaud’s phenomenon is a class-wide concern for CGRP antagonists. Median onset ~71 days. Serious outcomes including hospitalisations reported. Discontinue if signs develop; evaluate if symptoms do not resolve. -
Hypersensitivity Signs
After each injection
Trigger-based Watch for rash, angioedema, or anaphylaxis. Most occur within hours but can be delayed (>1 week). Discontinue permanently if a serious reaction occurs. Contraindicated for re-challenge. -
Injection Site
Each injection
Routine Inspect for redness, swelling, bruising, or induration. Rotate injection sites between abdomen, thigh, and upper arm. Most reactions are mild and self-limiting.
Contraindications & Cautions
Absolute Contraindications
- Serious hypersensitivity to erenumab-aooe or any excipient (anaphylaxis and angioedema have been reported)
Relative Contraindications (Specialist Input Recommended)
- Pre-existing Raynaud’s phenomenon — risk of worsening or recurrence; monitor closely if treatment is initiated, and discontinue if symptoms develop or worsen
- Significant cardiovascular disease — patients with MI, stroke, TIA, or unstable angina within 12 months were excluded from clinical trials; theoretical concern regarding loss of CGRP-mediated protective vasodilation in ischaemic states
- Severe constipation or intestinal obstruction history — CGRP blockade reduces GI motility; serious complications including hospitalisation and surgery reported post-marketing
Use with Caution
- Uncontrolled or labile hypertension — new-onset and worsening hypertension reported, frequently within 7 days of first dose; monitor blood pressure
- Elderly patients (≥65 years) — insufficient clinical trial data; start cautiously
- Severe renal impairment (eGFR <30) — not studied; dose adjustment unlikely necessary for a mAb but data lacking
FDA Safety Communication
Raynaud’s Phenomenon with CGRP Antagonists (March 2025)
The FDA updated the labelling of all CGRP antagonists, including erenumab, to include warnings about new-onset or worsening Raynaud’s phenomenon. Post-marketing reports include serious outcomes such as hospitalisations and disability. CGRP is a potent vasodilator, and its blockade may contribute to peripheral vasospasm. Patients with a history of Raynaud’s should be monitored, and erenumab should be discontinued if symptoms develop (FDA PI, Section 5.4, Revised March 2025).
Patient Counselling
Purpose of Therapy
Erenumab is a preventive medication that aims to reduce the number of migraine days you experience each month. It does not treat an active migraine attack. You will still need a separate acute treatment (e.g., a triptan or NSAID) for breakthrough migraine episodes. The full benefit may take up to 3 months of regular monthly injections to become apparent.
How to Take
Erenumab is given as a self-administered subcutaneous injection once monthly using a prefilled autoinjector or syringe. Remove from the refrigerator and allow to warm at room temperature for at least 30 minutes before injecting. Inject into the abdomen, thigh, or upper arm, rotating sites each month. Each autoinjector or syringe is single-use only.
Constipation
Tell patient
Constipation is a known side effect that can occur with erenumab, especially after the first dose. Stay well hydrated, eat a fibre-rich diet, and consider an over-the-counter stool softener or osmotic laxative if needed.
Call prescriber
Seek medical attention promptly if you experience severe abdominal pain, inability to pass stool for several days, nausea, vomiting, or abdominal bloating, as serious constipation requiring hospitalisation has been reported.
Blood Pressure Changes
Tell patient
Some patients develop high blood pressure or notice worsening of existing high blood pressure, often within the first week after an injection. If you have a home blood pressure monitor, check your readings periodically, especially after your first few injections.
Call prescriber
Contact your doctor if you develop headaches that feel different from your usual migraines, visual changes, chest pain, or if your home blood pressure readings are consistently elevated.
Allergic Reactions
Tell patient
Allergic reactions including rash, swelling of the face/throat, and rarely anaphylaxis can occur. Most happen within hours of injection, but delayed reactions (more than a week later) have also been reported.
Call prescriber
Seek immediate emergency care if you experience difficulty breathing, throat or tongue swelling, severe rash, or dizziness after injection. Do not take another dose until evaluated.
Cold Fingers and Toes (Raynaud’s)
Tell patient
Some patients develop colour changes (white, blue, red) in fingers or toes, especially in cold environments, along with numbness, tingling, or pain. This is called Raynaud’s phenomenon and is related to how the medication affects blood vessel function.
Call prescriber
Notify your prescriber if you notice these symptoms. The medication may need to be stopped. If symptoms cause significant pain or do not resolve with warming, seek medical attention promptly.
Injection Technique and Storage
Tell patient
Store erenumab in the refrigerator (2–8°C / 36–46°F) in its original carton to protect from light. If removed, it can be kept at room temperature (up to 25°C / 77°F) for up to 7 days. Do not freeze, shake, or heat. Let the injection warm for at least 30 minutes before use.
Call prescriber
If the solution appears cloudy, discoloured, or contains particles, do not use it. Contact the pharmacy for a replacement.
Pregnancy and Breastfeeding
Tell patient
There are insufficient data on erenumab use during pregnancy. No fetal harm was observed in animal studies at exposures 20 times the human dose. It is unknown whether erenumab passes into breast milk. Discuss reproductive plans with your prescriber.
Call prescriber
Notify your doctor immediately if you become pregnant. A pregnancy exposure registry (1-833-244-4083 or genesispregnancyregistry.com) is available to monitor outcomes.
Sources
Regulatory (PI / SmPC)
- Aimovig (erenumab-aooe) injection, for subcutaneous use. Full Prescribing Information. Amgen Inc. Revised March 2025. FDA Label (2025) Primary regulatory reference for all dosing, warnings, adverse effect incidence, PK parameters, and clinical study results cited in this monograph.
- Aimovig (erenumab). Summary of Product Characteristics. European Medicines Agency. EMA SmPC European labelling providing additional clinical guidance, including the recommendation to initiate treatment in patients with ≥4 migraine days per month.
Key Clinical Trials
- Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123–2132. doi:10.1056/NEJMoa1705848 STRIVE (Study 1): pivotal 6-month phase 3 RCT in 955 episodic migraine patients demonstrating efficacy of both 70 mg and 140 mg monthly doses.
- Dodick DW, Ashina M, Brandes JL, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026–1037. doi:10.1177/0333102418759786 Study 2: phase 3 RCT of erenumab 70 mg in 577 patients with episodic migraine, confirming efficacy over 3 months.
- 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(6):425–434. doi:10.1016/S1474-4422(17)30083-2 Study 3: phase 2 RCT in 667 chronic migraine patients showing both doses reduced MMD by 6.6 days vs 4.2 days placebo.
- Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280–2287. doi:10.1016/S0140-6736(18)32534-0 LIBERTY trial: demonstrated erenumab 140 mg efficacy in treatment-refractory episodic migraine (patients who failed 2–4 prior preventives).
Guidelines
- American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1–18. doi:10.1111/head.13456 AHS consensus positioning CGRP monoclonal antibodies as options after failure of or intolerance to at least two oral preventive classes.
- Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021–1039. doi:10.1111/head.14153 Updated AHS guidance expanding first-line positioning of CGRP-targeted therapies, including erenumab, in appropriate patients.
Mechanistic / Basic Science
- Shi L, Lehto SG, Zhu DXD, 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(1):223–231. doi:10.1124/jpet.115.227793 Preclinical characterisation of erenumab demonstrating high-affinity competitive antagonism at the canonical CGRP receptor.
- Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies — successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338–350. doi:10.1038/s41582-018-0003-1 Comprehensive review of CGRP biology in migraine and the translational science behind anti-CGRP therapies.
Pharmacokinetics / Special Populations
- Vu T, Ma P, Chen JS, et al. Pharmacokinetic-pharmacodynamic relationship of erenumab (AMG 334) and capsaicin-induced dermal blood flow in healthy and migraine subjects. Pharm Res. 2017;34(9):1784–1795. doi:10.1007/s11095-017-2183-6 PK/PD modelling study establishing the target-mediated drug disposition model and dose-response relationship for CGRP receptor occupancy.
- Schwedt TJ, Kuruppu DK, Engel SS, et al. Erenumab in chronic migraine: patient-reported outcomes in a randomized double-blind study. Neurology. 2019;92(12):e1314–e1323. doi:10.1212/WNL.0000000000007167 Patient-reported outcomes from the chronic migraine phase 2 trial showing improvements in quality of life, disability, and headache impact scores.