What are the side effects of Calcitonin Gene-Related Peptide (CGRP) inhibitors?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

CGRP inhibitors are associated with side effects such as injection site reactions, constipation, muscle pain, and fatigue, with a potential for allergic reactions and long-term effects still being monitored 1.

Common Side Effects

  • Injection site reactions (pain, redness, itching) are common when CGRP inhibitors are administered subcutaneously.
  • Constipation, muscle pain, and fatigue are frequent side effects.
  • Upper respiratory symptoms like nasal congestion or sore throat can occur.

Less Common Side Effects

  • Allergic reactions ranging from mild rashes to serious anaphylaxis can occur, although rarely.
  • Specific medications in this class may have unique side effect profiles, such as erenumab being associated with hypertension and constipation more frequently than others.

Long-term Safety

  • Long-term safety data for CGRP inhibitors is still emerging, given their relatively recent introduction.
  • CGRP plays roles throughout the body beyond migraine pathways, explaining the diverse side effects.

Clinical Considerations

  • Most side effects are mild to moderate and tend to diminish over time.
  • Serious adverse events are rare, but patients should report persistent or severe side effects to their healthcare provider promptly.
  • Clinicians should consider these side effects when prescribing CGRP inhibitors for migraine prevention, weighing the benefits against the potential risks for each patient 1.

From the Research

Side Effects of CGRP Inhibitors

  • Constipation is a major adverse event associated with CGRP inhibitors, affecting more than 50% of patients treated with erenumab, fremanezumab, or galcanezumab 2
  • The constipation caused by CGRP inhibitors can be mechanistically deduced from the known pharmacological actions and pathophysiological implications of CGRP in the digestive tract 2
  • CGRP plays a role in maintaining peristaltic motor activity, ion and water secretion, and intestinal transit, and its inhibition can lead to constipation 2

Comparison of Side Effects Among CGRP Inhibitors

  • A study comparing erenumab, fremanezumab, and galcanezumab found that switching from one anti-CGRP monoclonal antibody to another may improve side effects in some patients 3
  • The most common side effects reported in patients treated with anti-CGRP monoclonal antibodies were injection site reaction/rash and constipation 4
  • A network meta-analysis found that different anti-CGRP monoclonal antibody regimens had varying efficacy and safety profiles, but did not specifically compare side effects among the different treatments 5

Side Effects in Specific Patient Populations

  • A study found that patients aged ≥65 years with daily or nondaily migraine had similar efficacy and tolerability profiles to patients <65 years when treated with anti-CGRP monoclonal antibodies 4
  • The most common side effects in patients ≥65 years were injection site reaction/rash and constipation, similar to those reported in younger patients 4

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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