Are Calcitonin Gene-Related Peptide (CGRP) inhibitors safe for use in a breastfeeding woman with a history of migraines?

CGRP Inhibitors and Breastfeeding Safety

CGRP inhibitors should be avoided during breastfeeding due to insufficient safety data, and alternative migraine treatments with established safety profiles should be used instead. 1, 2

Why CGRP Inhibitors Are Not Recommended

The current evidence landscape for CGRP inhibitors during breastfeeding is severely limited:

• No human lactation data exists for any of the CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) or oral CGRP antagonists (gepants like rimegepant, atogepant, ubrogepant) 3, 4

• These medications are classified as third-line preventive agents even in the general population, reserved for patients who have failed multiple other preventive options 1

• The molecular structure of CGRP monoclonal antibodies (large proteins) theoretically suggests minimal breast milk transfer, but this has never been studied or confirmed in humans 3

• Guidelines explicitly state that special considerations including breastfeeding should guide medication choices, implicitly recommending against agents without safety data 4

Recommended Alternatives for Breastfeeding Women

For Acute Migraine Treatment:

First-line options with established safety:

• Paracetamol (acetaminophen) 1000 mg - preferred first-line agent with excellent safety profile and minimal breast milk transfer 2
• Ibuprofen - extensively studied for postpartum pain with no adverse infant effects reported 2, 5, 6
• Sumatriptan - most safety data among triptans; FDA recommends avoiding breastfeeding for 12 hours post-dose to minimize infant exposure, though many experts consider this overly cautious 2, 5, 6

Important limitations:

• Limit triptans to <10 days/month to prevent medication overuse headache 2
• Limit paracetamol/NSAIDs to <15 days/month for the same reason 2

Medications to absolutely avoid:

• Opioids and butalbital-containing compounds (dependency risk, rebound headaches, infant sedation/apnea) 2, 5
• Ergotamine derivatives and dihydroergotamine (contraindicated) 2, 7
• High-dose aspirin (Reye's syndrome association) 2, 5

For Preventive Treatment:

If preventive therapy is needed (≥2 disabling attacks per month despite optimized acute treatment):

First-line preventive agent:

• Propranolol 80-160 mg daily in long-acting formulations - has the best safety data with minimal breast milk transfer 2, 7, 6

Second-line option:

• Amitriptyline - if propranolol is contraindicated (asthma, cardiac failure, Raynaud disease, AV block, depression) 2, 7, 6

Contraindicated preventive agents:

• Topiramate, sodium valproate, atenolol, zonisamide, tizanidine 5, 6

Clinical Decision Algorithm

When a breastfeeding woman with migraine requests CGRP inhibitor therapy:

1. Assess acute treatment optimization first - ensure she's using appropriate acute medications (paracetamol, ibuprofen, or sumatriptan) at adequate doses early in the attack 2

2. Determine if preventive therapy is truly indicated:

   • ≥2 attacks per month causing disability for ≥3 days
   • Contraindication or failure of acute treatments
   • Use of acute medication >2 times per week 7

3. If prevention is needed, trial propranolol first at 80-160 mg daily before considering agents without safety data 2, 7

4. Assess efficacy after 2-3 months of propranolol at therapeutic dose before declaring treatment failure 1

5. Only if propranolol and amitriptyline both fail or are contraindicated should you have a risk-benefit discussion about CGRP inhibitors, acknowledging the complete absence of human lactation data 3, 4

Critical Pitfalls to Avoid

• Don't assume large molecular weight equals safety - while CGRP monoclonal antibodies theoretically have low breast milk transfer due to size, this assumption has never been validated in humans 3

• Don't confuse pregnancy data with lactation data - the limited pregnancy exposure data for CGRP inhibitors (showing no obvious harm in small case series) does not inform breastfeeding safety 3

• Don't overlook non-pharmacological approaches - hydration, regular meals, consistent sleep, trigger avoidance, and stress management should always accompany any medication strategy 2, 7

• Don't prescribe CGRP inhibitors as first-line prevention - these are third-line agents even in non-breastfeeding populations and should only be considered after failure of established preventive options 1

The evidence strongly supports using medications with established safety profiles during breastfeeding rather than agents with no human lactation data, regardless of theoretical considerations about drug transfer.