Constipation as a Side Effect of Galcanezumab
Yes, constipation is a recognized side effect of galcanezumab, occurring more frequently than with placebo, though the overall incidence remains relatively low in clinical trials.
Incidence and Clinical Evidence
In integrated safety analyses of galcanezumab clinical trials, constipation was identified as one of the treatment-emergent adverse events (TEAEs) that occurred more frequently in galcanezumab-treated patients compared to placebo 1.
The mechanistic basis for this side effect is well-established: CGRP plays a physiological role in maintaining peristaltic motor activity and intestinal secretion, and blocking CGRP signaling through antibodies like galcanezumab interferes with these normal gastrointestinal functions 2.
Post-approval real-world surveys indicate that constipation may affect more than 50% of patients treated with anti-CGRP antibodies (including erenumab, fremanezumab, and galcanezumab), representing a higher rate than observed in pre-approval randomized controlled trials 2.
Mechanism of Action
CGRP in the gut is expressed by extrinsic primary afferent nerve fibers and intrinsic enteric nervous system neurons, where it functions as a major messenger of enteric sensory neurons that activate both ascending excitatory and descending inhibitory pathways enabling propulsive peristaltic motor activity 2.
CGRP also stimulates ion and water secretion into the intestinal lumen, and these combined motor-stimulating and prosecretory actions accelerate intestinal transit 2.
By blocking CGRP signaling, galcanezumab antagonizes these physiological functions, resulting in reduced peristaltic activity and decreased intestinal secretion, which manifests clinically as constipation 2.
Clinical Management Considerations
While constipation was noted in safety profiles, discontinuation rates due to adverse events in galcanezumab-treated patients remained low (1.8-3.0%), suggesting most cases are manageable 1.
Standard constipation management approaches should be employed, including increased fluid intake (≥1.5 L/day), dietary fiber from fruits, vegetables, and whole grains, and stimulant laxatives such as senna or bisacodyl if needed 3.
For persistent constipation not responding to first-line measures, additional laxatives such as polyethylene glycol, lactulose, or magnesium-based preparations can be considered 3.
Patients should be counseled about this potential side effect before initiating galcanezumab therapy and provided with proactive strategies to maintain regular bowel function 1.