Co-administering atogepant (a CGRP receptor antagonist for migraine prevention) with quinidine caused only a modest 25% increase in atogepant exposure that was not clinically significant, and no unexpected safety concerns emerged.
25% AUC IncreaseThe modest rise in atogepant exposure when co-administered with quinidine was deemed not clinically relevant, requiring no dose adjustment
What the researchers found
Co-administration of atogepant with quinidine gluconate resulted in no significant change in atogepant's peak plasma concentration. The overall systemic exposure (AUC) of atogepant increased by approximately 25%, but this increase was not considered clinically relevant.
Atogepant did not alter quinidine's mean plasma concentration at steady state. The incidence of treatment-emergent adverse events was highest when quinidine gluconate was given alone (42.4%), primarily driven by QT prolongation. Most adverse events were mild and resolved within 1-2 days. The modest exposure increase was attributed to quinidine's inhibition of CYP2D6 and P-gp, both minor contributors to atogepant clearance.
Why it matters
Migraine patients often take multiple medications, making drug interaction data essential for safe prescribing. This study provides reassurance that atogepant can be safely combined with drugs that inhibit P-gp and CYP2D6 pathways without needing dose adjustments — important practical information for clinicians managing patients on complex medication regimens.
How the study worked
This was a phase 1, open-label drug-drug interaction study in 33 healthy adult participants. Researchers measured atogepant blood levels when given alone and when co-administered with quinidine gluconate, comparing pharmacokinetic parameters including peak concentration (Cmax) and total exposure (AUC). Safety was assessed through monitoring of adverse events.
What this study cannot tell us
The study was conducted in healthy adults, not migraine patients who may have different metabolic profiles or be taking additional medications. The sample size of 33 participants is small. The open-label design means neither participants nor researchers were blinded. Only short-term co-administration was assessed, so long-term interaction effects remain unknown.
How to read the evidence
This is a phase 1 clinical trial — a controlled study in human participants, but conducted in healthy volunteers rather than the target patient population. Phase 1 studies provide foundational pharmacokinetic and safety data but sit below phase 2/3 trials in clinical evidence strength.
When this study was published
Published in 2024, this is a recent study reflecting the current regulatory and clinical development landscape for CGRP-targeted migraine therapies.
The bigger picture
CGRP receptor antagonists like atogepant represent a new class of peptide-targeted migraine therapies. As these drugs enter widespread clinical use, characterizing their drug interaction profiles is critical. This study adds to the growing body of evidence supporting atogepant's favorable pharmacokinetic profile, making it easier for clinicians to prescribe it confidently alongside other common medications.
Questions still open
- Would the drug interaction profile differ in migraine patients taking multiple preventive medications simultaneously?
- Are there other common migraine co-medications that could produce larger interaction effects with atogepant?
- Does the 25% AUC increase become clinically relevant in patients with impaired hepatic or renal function?
Common questions
What is atogepant and how does it relate to peptides?
Can I safely take atogepant with other medications?
Read the original research
Pharmacokinetics and Safety of Atogepant Co-administered with Quinidine Gluconate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.
Clinical pharmacology in drug development, 13(8), 930-937
Citation
Boinpally, Ramesh; Borbridge, Lisa; Wangsadipura, Veronica. (2024). Pharmacokinetics and Safety of Atogepant Co-administered with Quinidine Gluconate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.. Clinical pharmacology in drug development, 13(8), 930-937. https://doi.org/10.1002/cpdd.1407