Erenumab

• Migraine Prevention
• Chronic Migraine
• Episodic Migraine
• CGRP-Targeted Therapy

Erenumab, marketed as Aimovig, is a fully human monoclonal antibody and the first FDA-approved therapy specifically engineered to prevent migraine by targeting the calcitonin gene-related peptide (CGRP) pathway. Given as a once-monthly subcutaneous injection, it offers an option for patients with episodic or chronic migraine who have not responded to, cannot tolerate, or have contraindications to traditional preventives such as topiramate, beta-blockers, tricyclic antidepressants, or onabotulinumtoxinA. Erenumab does not stop a migraine in progress; it reduces how often attacks occur and, in many patients, also lowers the severity and disability of the attacks that still happen. For patients living with frequent disabling headaches, this class has reshaped expectations for migraine prevention.

Mechanism of Action

CGRP is a 37-amino-acid neuropeptide released from trigeminal sensory nerve endings during a migraine attack. Once released, CGRP triggers cranial vasodilation, plasma protein extravasation, neurogenic inflammation around meningeal vessels, and central sensitization of pain pathways in the trigeminocervical complex. These events together produce the throbbing pain, photophobia, phonophobia, and allodynia that define a migraine. Erenumab binds with high specificity to the canonical CGRP receptor, a heterodimer composed of the calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1). By occupying this receptor, erenumab prevents endogenous CGRP from initiating its signaling cascade.

Unlike the small-molecule gepants such as ubrogepant and rimegepant that block the receptor for hours, erenumab provides sustained receptor blockade across a full month due to the long half-life characteristic of IgG2 monoclonal antibodies (approximately 28 days). Other CGRP-targeted preventives such as galcanezumab and fremanezumab bind the CGRP ligand itself rather than the receptor, but the downstream clinical effect is similar. Because erenumab is a large protein, it does not meaningfully cross the blood-brain barrier, suggesting that its effect arises primarily from peripheral trigeminal nociceptor blockade rather than central CNS action. It is cleared by reticuloendothelial proteolysis, not by hepatic CYP enzymes, which explains why drug-drug interactions with conventional medications are not expected. More background on migraine mechanisms is available from the American Academy of Neurology.

Clinical Use

Erenumab is indicated for the preventive treatment of migraine in adults. Within the prevention algorithm, the American Headache Society now considers CGRP-pathway monoclonal antibodies appropriate first-line preventive options for patients with at least four monthly migraine days plus moderate disability, a position that diverges from older stepwise approaches that required failure of two or three older agents first. In real-world practice, however, insurance coverage often still requires documentation of an inadequate response to traditional preventives such as topiramate, beta-blockers like metoprolol or atenolol, tricyclic antidepressants, or anti-epileptics, before approving erenumab.

Clinical trials including STRIVE (episodic migraine) and ARISE demonstrated approximately a 1- to 2-day reduction in monthly migraine days beyond placebo at the 70 mg dose, with some patients experiencing 50 percent or greater reduction in headache days. The 140 mg dose tends to provide modestly greater benefit and is often chosen for chronic migraine (15 or more headache days per month) or when response to 70 mg plateaus. Patient selection favors those with frequent disabling attacks, prior treatment failures, intolerance to oral preventives, and willingness to perform monthly self-injection. Erenumab is not used for tension-type headache, cluster headache (other CGRP agents have data here), or as acute rescue. It can be combined safely with acute treatments such as triptans, gepants, NSAIDs, and sumatriptan, and with other preventives, although adding two CGRP-targeted drugs simultaneously is not recommended. Patients should track headache days in a diary so response can be evaluated objectively at three months. Our neurologic team frequently coordinates this care.

How to Take It

Erenumab comes as a 70 mg or 140 mg prefilled autoinjector or prefilled syringe. The 140 mg dose is delivered as either one 140 mg injection or two 70 mg injections given consecutively. The medication is stored in the refrigerator between 36 and 46 degrees Fahrenheit in its original carton, protected from light. It must be allowed to come to room temperature for about 30 minutes before injection; do not warm it in the microwave, with hot water, or in direct sunlight. Once removed from the refrigerator, it can sit at room temperature (up to 77 degrees Fahrenheit) for up to seven days; if not used in that window, it must be discarded.

Injection sites include the upper outer thigh, abdomen at least two inches from the navel, or the back of the upper arm if a caregiver gives the injection. Rotate sites with each monthly dose to reduce skin irritation. After cleansing the area, the autoinjector is pressed firmly against the skin and held in place until both the yellow window appears and the second click is heard, which usually takes 15 seconds. If a dose is missed, give it as soon as possible and reset the monthly schedule from that day forward. The first week often brings mild injection-site redness, soreness, or muscle aches; constipation may also appear within the first one to two months and benefit from increased fluids, fiber, and a stool softener.

Monitoring and Follow-Up

Response to erenumab is evaluated primarily through a headache diary, ideally maintained for one month before starting and continuously thereafter. The standard practice is to reassess at three months. A meaningful response is typically defined as at least a 50 percent reduction in monthly migraine days, or a clinically important reduction in attack severity, duration, or disability scores such as MIDAS or HIT-6. If there is no response at three months on the 70 mg dose, escalation to 140 mg is reasonable; if no response at six months on the 140 mg dose, the medication is generally discontinued and an alternative class considered.

Blood pressure is the most important objective measurement to track. Post-marketing data have shown new or worsening hypertension in some patients, including cases requiring antihypertensive therapy or hospitalization, so blood pressure should be measured before each injection and at home periodically. A systolic rise of 10 mmHg or more or any reading above 140/90 mmHg warrants reevaluation. Patients with pre-existing hypertension need particularly close monitoring. There are no required laboratory monitoring tests because erenumab does not affect liver enzymes, kidney function, or blood counts. Constipation severity should be tracked: stool frequency less than three times per week, hard stools, or new abdominal pain represents a red flag. Severe constipation has occasionally led to hospitalization, ileus, or in rare cases bowel surgery.

Special Populations

Elderly patients have not been extensively studied; clinical trials enrolled few patients over 65, but no specific dose adjustment is required, and pharmacokinetic profile appears similar. Frail older adults should be monitored carefully for constipation given baseline risk. Renal and hepatic impairment do not require dose adjustment because monoclonal antibodies are eliminated by proteolysis rather than renal or hepatic clearance. Pregnancy data are limited; the medication has a very long half-life so the manufacturer recommends discontinuation prior to conception when possible, and migraine often improves spontaneously during pregnancy. The decision to continue erenumab in pregnancy should weigh the severity of disability, prior treatments tried, and patient preference, with shared decision-making.

Breastfeeding is generally considered low-risk because IgG antibodies are minimally absorbed from the infant gut, but data remain sparse. Pediatric safety and efficacy have not been established. Patients with significant cardiovascular disease should have baseline blood pressure assessed and discussed individually; case reports of Raynaud-like vasospastic events exist. Patients with constipation-predominant irritable bowel syndrome or chronic constipation may experience worsening symptoms.

When to Contact Your Doctor

Call the office for severe constipation lasting more than three days despite over-the-counter measures, new or worsening hypertension, severe abdominal pain, persistent injection-site reactions with spreading redness or warmth, or any signs of allergic reaction including rash, hives, swelling of the lips or face, wheezing, or difficulty swallowing. Anaphylaxis has been reported and warrants immediate emergency care. Worsening migraine frequency or severity, new neurologic symptoms such as visual changes that are different from typical aura, weakness, or speech difficulty should also be reported promptly. Patients should not stop a preventive course based on a single bad month; effects are evaluated over three months.

For evaluation of frequent migraines and consideration of CGRP-targeted prevention, contact us or schedule a visit with our St. Petersburg internal medicine team. Detailed dosing tables, drug interactions, and frequently asked questions are provided on this page below.