Migraine Medication Zavegepant Safe and Well Tolerated in Lactating Women, Phase 1 Study Shows

A single-site, open-label, single-arm, phase 1 pharmacokinetic study (NCT06453356) found that zavegepant (Zavzpret; Pfizer) nasal spray was generally safe and well tolerated in healthy lactating women, with very low estimated infant exposure via breast milk following a single 10-mg dose. The study was designed to characterize the pharmacokinetics and analyze the safety of zavegepant in human breast milk and plasma, addressing a gap of evidence regarding medication exposure during lactation.

Recently published in HEADACHE, the small-scale, single-site study enrolled 12 healthy lactating women who received a single 10‑mg intranasal dose of zavegepant. Blood and breast milk samples were collected over 24 hours to assess the pharmacokinetic profile of the nasal spray, which was the study’s primary endpoint. Secondary outcomes included evaluating the safety of a single 10‑mg dose, characterizing plasma PK parameters, and estimating the milk-to-plasma drug concentration ratio in lactating women.

Led by Abhijeet Jakate, PhD, director of clinical pharmacology at Pfizer, the study reported low milk-to-plasma zavegepant ratios in lactating women. Overall, the geometric mean ratios (geometric % coefficient of variation) were 0.21 for the 24-hour area under the concentration–time curve (AUC₀–₂₄), 0.16 for the total AUC extrapolated to infinity, and 0.04 for maximum plasma concentration (Cmax).

The study also calculated the infant exposure relative to maternal dosing. Here, results revealed that the geometric mean body weight–normalized infant dose was 0.05 μg/kg/day, compared with 132.8 μg/kg/day for the mother, resulting in a relative infant dose of just 0.04%. All told, these findings suggested that infants would receive only a minimal amount of zavegepant through breast milk.

Only one treatment-emergent adverse event (TEAE; mild dizziness) was reported in a single participant (8%), but symptoms were mild and did not require interventional treatment. No other clinically meaningful abnormalities were observed in vital signs, laboratory tests, or local nasal assessments, indicating that the single 10‑mg dose was generally well tolerated.

“The study also adds to the scientific literature for lactation data involving the gepant class of anti-migraine medications,” noted study authors.¹ “Studies such as ours help quantify infant exposure via breast milk and may help to educate mothers and prescribers to optimize migraine therapy during lactation.”

Read more: Migraine Treatment Zavegepant Shows No Meaningful Impact on Oral Contraceptive Exposure

Zavegepant, first approved by the FDA in 2023, is a third-generation, non-oral, intranasal calcitonin gene-related peptide (CGRP) antagonist designed to offer a rapid-acting alternative to oral medications for acute migraine. The treatment has been previously studied for its real-world tolerability and consistency, including a study conducted at the Cleveland Clinic. In that study, patients using 10-mg intranasal zavegepant were examined for acute migraine reported meaningful pain relief, improved daily functioning, and high willingness to reuse the therapy through the validated migraine treatment optimization questionnaire-5 (MTOQ-5).²

Presented at the 2025 American Headache Society (AHS) Annual Meeting, lead author Eric Dunn, DO, a neurologist at Cleveland Clinic, and colleagues evaluated patient-reported outcomes of individuals using 10-mg intranasal zavegepant for acute migraine treatment. Overall, the drug exemplified encouraging results, including benefits on pain relief, functional improvement, and a high willingness to reuse.² Overall, the data offered an early glance at the effectiveness and tolerability of this third-generation (CGRP) receptor antagonist in clinical practice.

REFERENCES
1. Jakate A, Weng Y, Shkrodova A, et al. A phase 1 study of the breast milk and plasma pharmacokinetics of zavegepant 10 mg intranasal dose in healthy lactating women. Headache. 2026; 00: 1-8. doi:10.1111/head.70036
2. Dunn E, Mays M, Ong B, et al. Real-world outcomes of zavegepant use in a tertiary care setting using Migraine Treatment Optimization Questionnaire-5 (MTOQ-5). Presented at: Frontier (P-261), American Headache Society Annual Scientific Meeting; 2025; Cleveland Clinic, Cleveland, OH.