CGRP inhibitors

CGRP inhibitors are a newer class of medications developed specifically for the treatment of migraine disorders. They target the calcitonin gene-related peptide pathway, which plays a key role in migraine headaches. CGRP inhibitors have changed the treatment of migraine patients by offering targeted options for both prevention and acute treatment, especially for those who do not respond well to older therapies.

These migraine medications are now widely used in neurology and are supported by strong evidence from clinical trials, real-world studies, and guidance from organizations such as the American Headache Society. CGRP inhibitors are used in both episodic migraine and chronic migraine and are generally well tolerated when prescribed and monitored by a healthcare provider.

CGRP inhibitors are medications that block the activity of calcitonin gene-related peptide (CGRP). CGRP is a molecule released in the nervous system during migraine attacks. It contributes to headache pain, inflammation, and changes in blood vessels.

CGRP inhibitors work by blocking the effects of CGRP, a neuropeptide involved in causing migraines. CGRP is released during migraine attacks and causes dilation of blood vessels, increased pain signaling, and activation of pathways in the nervous system that lead to migraine symptoms.

Some CGRP inhibitors block the CGRP receptor directly, preventing CGRP from binding and triggering migraine pain. Others bind to the CGRP molecule itself, reducing its activity before it can act on receptors. By interrupting this pathway, CGRP inhibitors reduce migraine frequency, headache days, and the severity of migraine attacks.

Unlike triptans, CGRP inhibitors do not cause vasoconstriction and are not associated with the same cardiovascular limitations. This makes them an important treatment option for certain patients.

Anti-CGRP monoclonal antibodies (mAbs)

These medications are used primarily for migraine prevention and are given by injection or infusion.

• Erenumab (Aimovig).

• Fremanezumab (Ajovy).

• Galcanezumab (Emgality).

• Eptinezumab (Vyepti).

Erenumab targets the CGRP receptor, while the others bind directly to CGRP itself. Most are given as subcutaneous injections monthly or quarterly. Eptinezumab is given as an intravenous infusion.

Gepants (CGRP receptor antagonists)

Gepants are small-molecule CGRP receptor antagonists taken by mouth or nasal spray. They are used for acute treatment and, in some cases, migraine prevention.

• Ubrogepant (Ubrelvy).

• Rimegepant (Nurtec).

• Atogepant (Qulipta).

• Zavegepant (Zavzpret).

Rimegepant and atogepant are approved for preventive treatment, while ubrogepant and zavegepant are used for the acute treatment of migraine attacks.

CGRP inhibitors are used for the treatment and prevention of migraine and related headache disorders.

Migraine prevention in people with episodic migraine and chronic migraine. Preventive treatment helps reduce migraine frequency, migraine days, and overall headache burden. These medications are often considered when older preventive medications such as topiramate are ineffective or not tolerated.

Acute treatment of migraine to stop migraine attacks once they begin. They help reduce headache pain and other migraine symptoms such as nausea and sensitivity to light.

Cluster headaches and other uses: Galcanezumab is approved for the prevention of cluster headaches. CGRP inhibitors may also help reduce medication overuse headache by lowering reliance on acute pain medications.

CGRP inhibitors are generally well tolerated, but side effects can occur.

Common side effects include:

• Injection site reactions such as redness or pain.

• Constipation, especially with erenumab.

• Nausea or stomach upset with some gepants.

• Fatigue.

Less common side effects include changes in blood pressure, allergic reactions, or worsening constipation. Because CGRP plays a role in blood vessel function, long-term effects continue to be studied.

These are not all of the possible side effects of CGRP inhibitors. You should always seek medical advice from your healthcare provider for any questions or concerns about your medical condition or treatment. Read all patient information, medication guides, or drug information sheets that come with this medication. You can also report adverse effects to the Food and Drug Administration at www.fda.gov/medwatch or 1-800-FDA-1088.

Although these medications are generally well-tolerated and safe, there are certain warnings, precautions, and drug interactions you should be aware of.

Warnings

Before starting CGRP inhibitors, it is crucial to discuss any existing health conditions with your healthcare provider. You should be sure that your healthcare provider is aware of all your medical conditions, including:

• A history of severe constipation.

• Uncontrolled high blood pressure.

• Cardiovascular conditions or vascular disease.

• A history of allergic reactions to injectable medications.

Because CGRP inhibitors affect the nervous system and blood vessels, ongoing monitoring from a healthcare professional is recommended.

Contraindications

CGRP inhibitors should not be used in people with known hypersensitivity to the active drug or its components. Safety data are limited in pregnancy and breastfeeding.

Drug interactions

Gepants may interact with medications that affect liver enzymes. Always tell your healthcare provider about all prescription drugs, supplements, and over-the-counter products you are using.