What are the potential drug interactions and precautions when using Ubrelvy (Ubrogepant) for acute migraine treatment in an adult patient with a history of migraines and potential comorbid conditions, including cardiovascular disease?

Ubrelvy (Ubrogepant) Drug Interactions and Precautions

Ubrelvy is absolutely contraindicated with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole), requires dose reduction to 50 mg with moderate CYP3A4 inhibitors and BCRP/P-gp inhibitors, and should be avoided with strong CYP3A4 inducers—cardiovascular disease is NOT a contraindication, making ubrogepant an excellent option for patients with cardiovascular risk factors who cannot use triptans. 1

Critical Drug Interactions Requiring Dose Modification or Avoidance

Absolute Contraindications

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole) are absolutely contraindicated with ubrogepant—do not prescribe these combinations under any circumstances. 1

Moderate CYP3A4 Inhibitors (Reduce to 50 mg, Avoid Second Dose)

• Verapamil, cyclosporine, ciprofloxacin, fluconazole, fluvoxamine: Use only 50 mg initial dose and avoid taking a second dose within 24 hours. 1
• Patients taking these medications should not consume grapefruit or grapefruit juice, as this further inhibits CYP3A4 metabolism. 1

Weak CYP3A4 Inhibitors (Reduce to 50 mg for Both Doses)

• Use 50 mg for initial dose and 50 mg for second dose (if needed, at least 2 hours apart). 1

Strong CYP3A4 Inducers (Avoid Completely)

• Phenytoin, barbiturates, rifampin, St. John's Wort: Avoid concomitant use entirely, as these will reduce ubrogepant exposure to subtherapeutic levels. 1

Weak to Moderate CYP3A4 Inducers (Increase to 100 mg)

• Use 100 mg for both initial and second doses to compensate for increased metabolism. 1

BCRP and/or P-gp Inhibitors (Reduce to 50 mg)

• Quinidine, carvedilol, eltrombopag, curcumin: Use 50 mg for initial dose and 50 mg for second dose. 1

Cardiovascular Disease Considerations

Safety in Cardiovascular Disease

• Ubrogepant has NO vasoconstrictor activity and is safe in patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease—conditions that absolutely contraindicate triptans. 2, 3
• Post-hoc analysis of ACHIEVE I and II trials demonstrated that ubrogepant safety and efficacy did not differ across cardiovascular risk categories (no risk, low risk, moderate-high risk), with no evidence of increased cardiac adverse events in patients with ≥2 major cardiovascular risk factors. 3
• This makes ubrogepant an ideal first-line option for patients with cardiovascular comorbidities who require acute migraine treatment. 2, 3

Hypertension Warning

• New-onset hypertension or worsening of pre-existing hypertension has been reported with CGRP antagonists including ubrogepant in postmarketing surveillance, most frequently within 7 days of therapy initiation. 1
• Some cases required initiation of antihypertensive treatment or hospitalization. 1
• Monitor blood pressure in patients with pre-existing hypertension or cardiovascular risk factors, particularly during the first week of treatment. 1

Raynaud's Phenomenon Warning

• New-onset or worsening of pre-existing Raynaud's phenomenon may occur with ubrogepant. 1
• Use caution in patients with known peripheral vascular disease or circulation problems in fingers and toes. 1

Dosing Modifications for Hepatic and Renal Impairment

Severe Hepatic Impairment (Child-Pugh Class C)

• Reduce to 50 mg initial dose and 50 mg second dose (if needed). 1
• No dose adjustment needed for mild to moderate hepatic impairment. 1

Severe Renal Impairment (CrCl 15-29 mL/min)

• Reduce to 50 mg initial dose and 50 mg second dose (if needed). 1

End-Stage Renal Disease (CrCl <15 mL/min)

• Avoid use entirely—ubrogepant is not recommended in this population. 1

Hypersensitivity Reactions

• Serious hypersensitivity reactions including anaphylaxis, dyspnea, facial or throat edema, rash, urticaria, and pruritus have been reported with ubrogepant. 1
• Reactions can occur within minutes, hours, or days after administration—most occurred within hours and were not serious, but some led to discontinuation. 1
• If a serious or severe hypersensitivity reaction occurs, discontinue ubrogepant immediately and institute appropriate therapy. 1
• History of serious hypersensitivity to ubrogepant is an absolute contraindication to future use. 1

Pregnancy and Lactation

• Based on animal data, ubrogepant may cause fetal harm—discuss risks with patients of childbearing potential. 1
• A pregnancy registry exists for women taking ubrogepant (1-833-277-0206 or http://empresspregnancyregistry.com). 1
• Very small amounts of ubrogepant pass into breast milk—discuss risks and benefits with breastfeeding patients. 1

Frequency of Use and Medication Overuse Headache

• The safety of treating more than 8 migraines in a 30-day period has not been established with ubrogepant. 1
• Like all acute migraine medications, ubrogepant should be limited to no more than 2 days per week (approximately 8-10 days per month) to prevent medication overuse headache. 2, 4, 5
• If patients require acute treatment more frequently, initiate preventive therapy immediately rather than increasing frequency of acute medication use. 2, 4

Practical Clinical Algorithm for Ubrogepant Prescribing

1. Screen for absolute contraindications: Strong CYP3A4 inhibitors, history of serious hypersensitivity, end-stage renal disease. 1

2. Review all current medications for CYP3A4 interactions, BCRP/P-gp inhibitors, and adjust ubrogepant dose accordingly per Table 1 above. 1

3. Assess cardiovascular status: Unlike triptans, cardiovascular disease is NOT a contraindication—ubrogepant is preferred in this population. 2, 3

4. Check hepatic and renal function: Reduce to 50 mg if severe hepatic impairment (Child-Pugh C) or severe renal impairment (CrCl 15-29 mL/min). 1

5. Counsel on grapefruit avoidance if patient is taking moderate CYP3A4 inhibitors. 1

6. Monitor blood pressure in patients with hypertension or cardiovascular risk factors, particularly in first week. 1

7. Track frequency of use: Maintain headache diary to ensure not exceeding 8 migraines treated per 30 days and not using more than 2 days per week. 2, 4, 1

Common Pitfalls to Avoid

• Do not assume cardiovascular disease is a contraindication—this is a critical advantage of ubrogepant over triptans, and missing this opportunity deprives patients of effective treatment. 2, 3
• Do not overlook moderate CYP3A4 inhibitors (verapamil, fluconazole, ciprofloxacin)—these are commonly prescribed medications that require dose reduction and avoidance of second dose. 1
• Do not allow patients to exceed 8 treated migraines per month—this creates risk of medication overuse headache and exceeds studied safety parameters. 2, 4, 1
• Do not forget to counsel about delayed hypersensitivity reactions—these can occur days after administration, not just immediately. 1