What Are CGRP Inhibitors?

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

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

There are 2 types of CGRP inhibitors: CGRP monoclonal antibodies (mAbs) and CGRP receptor antagonists (gepants). mAbs are used to prevent migraine attacks. Gepants are used for both preventing migraine and treating migraines that are already underway (acute treatment).^1,3

Depending on the drug, CGRP inhibitors may be given as a pill, as an injection, as a nose spray, or into a vein (intravenously, or IV).^1,2

How do mAbs work?

Monoclonal antibodies are proteins made in a lab. Scientists design mAbs to bind specific targets. CGRP-targeting mAbs help prevent migraine but do not stop a migraine 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 a key. When CGRP is released from a nerve cell it binds a specific receptor (the lock). The binding of CGRP to its receptor 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 do gepants work?

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

FDA-approved CGRP inhibitors

Several CGRP inhibitors have been approved by the US Food and Drug Administration (FDA) to prevent or treat migraine. There are 4 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 4 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 nose spray

What are the possible side effects?

Side effects can vary depending on the specific drug 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 doctor about what to expect when taking these drugs. You also should call your doctor if you have any changes that concern you when taking CGRP inhibitors.

Considerations for special populations

CGRP inhibitors are approved for use in adults between 18 and 64. Studies are underway to see whether these drugs are safe in children. They have not been tested in adults over age 65.²

Doctors do not know whether CGRP inhibitors are safe to take while pregnant or breastfeeding. Depending on which drug you take, you may need to stop the drug days or months before becoming pregnant.²

Other things to know

Nurtec ODT may not be suitable for people with liver or kidney disease. It can also react badly with some other types of drugs used for infections, cancer, HIV, and high blood pressure.¹

Ubrelvy may react badly 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 (cannabinol) should be avoided when taking any gepant.²

Aimovig is not recommended for people with a latex allergy.¹

Before beginning any treatment for migraine, tell your doctor about all of your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.