CGRP Inhibitors for Migraine and Headache Relief

CGRP inhibitors are a group of drugs used to manage and treat migraine disease and cluster headaches. CGRP stands for calcitonin gene-related peptide receptor.¹

How CGRP affects your body during a migraine

CGRP is a protein that is naturally found in our bodies. It acts as a messenger, helping nerve cells communicate with each other. For example, CGRP helps nerve cells send pain signals. During a migraine, nerves release chemicals, including CGRP. This leads to pain, inflammation, and narrowing (constriction) of blood vessels.²

Understanding the two types of CGRP treatment

There are two types of CGRP inhibitors: CGRP monoclonal antibodies (mAbs) and CGRP receptor antagonists (gepants).

• mAbs are used to prevent migraine attacks before they start.
• Gepants are used for both preventing migraine and treating migraines that are already underway (acute treatment).^1,3

Depending on the medication, these treatments may be given as a pill, an injection, a nose spray, or through a vein (intravenous or IV infusion).^1,2

How monoclonal antibodies (mAbs) prevent attacks

Monoclonal antibodies are proteins made in a lab. Scientists design mAbs to bind to specific targets. CGRP-targeting mAbs help prevent migraine but do not stop an attack once it has begun.^1-3

CGRP-targeting mAbs work by interfering with how nerves send CGRP pain signals. If you think of a lock and key, the CGRP protein is the key. When CGRP is released from a nerve cell, it binds to a specific receptor (the lock). This binding contributes to migraine pain. CGRP-targeting mAbs block the key from hitting the lock, either by binding to CGRP (the key) or to the CGRP receptor (the lock).^1,3

How gepants work for acute and preventive care

Gepants are small molecules that stop the CGRP protein from binding to its receptor. Gepants specifically bind the CGRP receptor "blocking the lock."

Similar to mAbs, this prevents CGRP from sending a pain signal. Unlike triptans—an older form of migraine medication—gepants do not cause blood vessels to constrict.^1,2

What CGRP drugs are approved for migraine?

Several CGRP inhibitors have been approved by the US Food and Drug Administration (FDA) to prevent or treat migraine.

There are four approved monoclonal antibodies:^1,2

• Aimovig® (erenumab-aooe) - an injection
• Ajovy® (fremanezumab-vfrm) - an injection
• Emgality® (galcanezumab-gnlm) - an injection
• Vyepti® (eptinezumab-jjmr) - an IV infusion

The are also four FDA-approved gepants:^1,2

• Nurtec® ODT (rimegepant) - a pill placed under the tongue
• Qulipta® (atogepant) - a pill
• Ubrelvy® (ubrogepant) - a pill
• Zavzpret™ (zavegepant) - a nasal spray

What are the possible side effects?

Side effects can vary depending on the specific treatment you are taking.

Common side effects of mAbs include:^1,2

• Constipation
• Mouth sores
• Hair loss
• A reaction at the injection site
• Rash or red or itchy skin
• Stuffy nose or scratchy throat
• Increased blood pressure

Common side effects of gepants include:^1,2

• Nausea or indigestion
• Stomach pain
• Sleepiness
• Fatigue
• Allergic reactions such as rashes
• Change the taste of food and drink

These are not all the possible side effects of CGRP inhibitors. Talk to your provider about what to expect when taking these drugs. You should also call your provider if you have any changes that concern you when taking CGRP inhibitors.

Considerations for special populations

Most CGRP inhibitors are approved for use in adults between 18 and 64. However, Ajovy is now available for the preventive treatment of episodic migraine in children ages 6 to 17. These drugs have not been widely tested in adults over age 65.²

At this time, there is not enough data to recommend use of these medications during pregnancy or breastfeeding. Active registries are currently collecting information that will help guide future recommendations.²

Important safety tips and drug interactions

• Nurtec ODT: May not be suitable for people with liver or kidney disease. It can react poorly with some other types of drugs used for infections, cancer, HIV, and high blood pressure.¹
• Ubrelvy: May react poorly with some drugs used for infections and pain. It is not recommended for people with end-stage kidney disease. You should not drink grapefruit juice when taking Ubrelvy.¹
• CBD (cannabidiol): Should be avoided when taking any gepant.²
• Aimovig: Not recommended for people with a latex allergy.¹

Before beginning any new medication, tell your provider about all of your health conditions. Share a list of any other drugs, vitamins, or supplements you take, including over-the-counter drugs