Can I take Ubrelvy (ubrogepant) on the same day as rizatriptan?

Can You Take Ubrelvy (Ubrogepant) on the Same Day as Rizatriptan?

Yes, you can safely take Ubrelvy (ubrogepant) on the same day as rizatriptan—these medications work through different mechanisms and can be used sequentially for migraine treatment without significant safety concerns. 1

Evidence for Same-Day Use

Pharmacokinetic Safety Data

• A Phase 1 study specifically evaluated coadministration of ubrogepant with sumatriptan (another triptan similar to rizatriptan) and found no treatment-emergent adverse events when both drugs were given together. 1
• Phase 3 trials (ACHIEVE I and II) demonstrated that participants who took ubrogepant followed by a triptan as rescue medication had similar rates of treatment-related adverse events compared to those taking ubrogepant alone (12.8% vs 14.9%). 1
• While there were slight alterations in ubrogepant pharmacokinetic parameters when coadministered with sumatriptan (24% reduction in maximum plasma concentration and delayed time to peak), these changes have minimal clinical relevance. 1

Mechanism-Based Rationale

• Rizatriptan is a serotonin 5-HT1B/1D receptor agonist that causes vasoconstriction of intracranial blood vessels. 2
• Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that works through an entirely different pathway. 1, 3
• Because these medications target different receptors and pathways, there is no mechanistic basis for dangerous drug-drug interactions. 1

Practical Clinical Approach

When to Use Sequential Dosing

• If rizatriptan provides inadequate pain relief after 2 hours, ubrogepant can be taken as a rescue medication. 2, 1
• Conversely, if ubrogepant is tried first and fails to provide sufficient relief, a triptan like rizatriptan can be added. 2
• The American College of Physicians recommends considering CGRP antagonists like ubrogepant for patients who do not tolerate or have inadequate response to triptans. 2

Timing Considerations

• Rizatriptan reaches maximum plasma concentration in approximately 1 hour with 45% bioavailability. 4
• Ubrogepant reaches maximum plasma concentration in approximately 1.5 hours. 1
• Allow at least 2 hours after taking rizatriptan before assessing response and considering ubrogepant as rescue therapy. 5, 3

Critical Safety Warnings

Medication Overuse Headache Risk

• Using acute migraine medications (including both triptans and CGRP antagonists) more than twice weekly can cause medication-overuse headache and transform episodic migraine into chronic daily headache. 6
• Triptans specifically should not be used more than 10 days per month. 2
• If you find yourself needing rescue medication frequently, preventive migraine therapy should be initiated rather than continuing to layer acute treatments. 2

Contraindications to Consider

• Rizatriptan is contraindicated with concurrent use of ergotamine derivatives, use within 24 hours of another triptan, hemiplegic or basilar migraine, coronary artery disease, MAOIs, impaired hepatic function, and pregnancy. 5
• Do not take a second triptan (different from rizatriptan) on the same day—only ubrogepant or other non-triptan rescue medications are appropriate. 5

Adverse Event Profile

Expected Side Effects

• Rizatriptan commonly causes chest pressure and heaviness, throat tightness, dizziness, drowsiness, and asthenia/fatigue (occurring in <10% of patients). 5, 4
• Ubrogepant's most common adverse events are nausea (2.1-4.1%), somnolence (0.4-4.1%), and dry mouth (0.4-4.1%). 3
• The combination does not appear to increase adverse event rates beyond what would be expected from either medication alone. 1

Cardiovascular Considerations

• A key advantage of ubrogepant is that it lacks the cardiovascular risks associated with triptans, making it particularly valuable for patients with cardiovascular disease who cannot use triptans. 7
• CGRP antagonists are free of cardiovascular adverse effects. 2

Comparative Efficacy Context

Performance Expectations

• Most triptans (including rizatriptan) demonstrate higher odds ratios for pain freedom at 2 hours compared to ubrogepant (OR range: 1.54-3.05). 7
• Rizatriptan 10 mg achieves pain freedom at 2 hours in approximately 40% of patients, compared to 21.2% for ubrogepant 100 mg. 4, 3
• This efficacy difference supports using rizatriptan as first-line treatment, with ubrogepant reserved for rescue when rizatriptan fails or is contraindicated. 2, 7

When Ubrogepant Should Be First-Line

• Consider using ubrogepant before rizatriptan in patients with cardiovascular disease, uncontrolled hypertension, or other contraindications to triptans. 2, 7
• Patients who have previously failed multiple triptans may benefit from trying ubrogepant as initial therapy. 2