Ubrelvy and Spironolactone: No Clinically Significant Drug Interaction
There is no documented pharmacokinetic or pharmacodynamic interaction between ubrogepant (Ubrelvy) and spironolactone, and these medications can be safely co-administered with standard monitoring for spironolactone's known risks.
Key Interaction Assessment
No direct drug-drug interaction exists between ubrogepant and spironolactone based on their distinct mechanisms of action and metabolic pathways 1, 2.
Ubrogepant is a selective CGRP receptor antagonist metabolized primarily via CYP3A4, while spironolactone is an aldosterone antagonist with no significant CYP3A4 inhibition or induction properties 1, 3.
Neither medication affects the other's efficacy or safety profile when used concurrently 1, 2.
Standard Spironolactone Monitoring Applies
When prescribing spironolactone (regardless of concurrent ubrogepant use), implement the following monitoring protocol:
Check serum potassium and creatinine before initiation (potassium must be <5.0 mmol/L) 3, 4.
Recheck at 1 week, 4 weeks, then every 3-6 months during maintenance therapy 3, 4, 5.
If potassium rises to >5.5 mmol/L, reduce spironolactone dose to 12.5 mg daily or 25 mg on alternate days 3, 4.
If potassium reaches ≥6.0 mmol/L, discontinue spironolactone immediately 4.
Clinical Context for Combined Use
For Migraine + Hypertension/PCOS Patients
Spironolactone 25-100 mg daily is appropriate for resistant hypertension or PCOS-related hyperandrogenism 3, 5.
Ubrogepant 50-100 mg can be used as needed for acute migraine treatment (maximum 200 mg/24 hours) 1, 2.
The combination addresses both conditions without pharmacological interference 1, 2.
Critical Spironolactone Drug Interactions to Avoid
Do not combine spironolactone with potassium supplements, salt substitutes containing potassium, or other potassium-sparing diuretics (amiloride, triamterene) due to severe hyperkalemia risk 3, 4.
Avoid NSAIDs (ibuprofen, naproxen) with spironolactone, as they increase hyperkalemia and acute kidney injury risk 3, 4.
Do not use triple combination of ACE inhibitor + ARB + spironolactone due to excessive hyperkalemia risk without clinical benefit 3.
Exercise caution when spironolactone is combined with ACE inhibitors or ARBs alone—this is acceptable but requires vigilant potassium monitoring every 1-2 weeks initially 3, 5.
High-Risk Populations Requiring Extra Caution
Patients with the following characteristics need closer monitoring when on spironolactone (ubrogepant does not modify these risks):
- Age >65 years 4.
- Diabetes mellitus 3, 4.
- Renal insufficiency (eGFR <45-60 mL/min) 3.
- Dehydration or volume depletion 3, 4.
In these patients, do not exceed spironolactone 25 mg daily and monitor potassium/creatinine every 1-2 weeks for the first 3 months 3, 4.
Ubrogepant-Specific Considerations
Avoid ubrogepant in end-stage renal disease (not due to spironolactone interaction, but due to ubrogepant's own contraindication) 1.
Avoid ubrogepant in pregnancy 1.
Most common ubrogepant adverse effects are oropharyngeal pain, nasopharyngitis, and headache—none of which are potentiated by spironolactone 1, 2.
Common Pitfalls to Avoid
Do not discontinue spironolactone due to unfounded concerns about ubrogepant interaction—there is no evidence-based reason to do so 1, 2.
Do not neglect routine potassium monitoring simply because the patient is taking ubrogepant—spironolactone's hyperkalemia risk is independent of migraine medications 3, 4.
Do not add potassium supplementation while on spironolactone unless specifically indicated for documented hypokalemia on other diuretics 3, 4.