Is Ubrelvy (lasmiditan) safe for an elderly woman with a history of tremors, currently taking primidone?

Ubrelvy Safety in Elderly Women Taking Primidone

Ubrelvy (ubrogepant, not lasmiditan) can be used cautiously in elderly women taking primidone for tremors, as there are no known direct drug-drug interactions between these medications, though both require careful monitoring for CNS side effects and the elderly patient should be assessed for cardiovascular risk factors before initiating migraine therapy. 1

Key Safety Considerations

No Direct Drug Interaction

• Ubrelvy (ubrogepant) is a CGRP antagonist-gepant that does not have documented interactions with primidone, which is metabolized to phenobarbital and acts primarily through GABAergic mechanisms 2, 3
• Primidone is a potent enzyme inducer affecting CYP3A4, but current evidence does not suggest this significantly impacts ubrogepant metabolism in a clinically meaningful way 2

Elderly-Specific Concerns with Ubrelvy

• The 2025 American College of Physicians guidelines note that CGRP antagonists-gepants like ubrelvy have limited comparative effectiveness data and significantly higher costs ($4,959-$5,994 annually for oral formulations) compared to first-line treatments 1
• Elderly patients are more susceptible to medication adverse effects and require careful evaluation of known and unknown comorbidities 4
• Ubrelvy may cause CNS side effects including somnolence and fatigue, which could be additive with primidone's known sedative effects 2, 3

Primidone Tolerability in the Elderly

• Primidone commonly causes early side effects including drowsiness and sedation, with up to one-third of patients failing to tolerate the medication 5
• The effective dose for essential tremor is typically low (250 mg/day is as effective as 750 mg/day with fewer side effects) 6
• Primidone is metabolized to phenobarbital, and therapeutic drug monitoring should include both compounds 2

Preferred Alternative Approaches

First-Line Acute Migraine Treatment in Elderly

• NSAIDs (ibuprofen 400 mg or naproxen 500-825 mg) combined with an antiemetic represent the safest and most cost-effective first-line acute treatment for migraine in elderly patients 1, 7, 4
• Triptans are generally NOT recommended in elderly patients due to high probability of cardiovascular disease or risk factors 4
• If triptans are used, regular blood pressure monitoring and cardiovascular risk assessment are imperative 4

Critical Safety Monitoring

• NSAIDs require careful monitoring in elderly patients, as they are implicated in 23.5% of adverse drug reaction hospitalizations in older adults 1
• Avoid NSAIDs when creatinine clearance is <30 mL/min 1
• Monitor for gastrointestinal toxicity, which increases with age and is dose-related and time-dependent 1
• Limit NSAID use to no more than twice weekly to prevent medication-overuse headache 7

Clinical Algorithm for This Patient

Step 1: Assess Cardiovascular and Renal Status

• Check blood pressure, cardiovascular risk factors, and renal function (creatinine clearance) before initiating any migraine therapy 1, 4
• Screen for orthostatic hypotension by measuring BP after 5 minutes sitting/lying, then 1 and/or 3 minutes after standing 1

Step 2: First-Line Acute Treatment

• Start with naproxen 500 mg at headache onset plus metoclopramide 10 mg for antiemetic effect if needed 1, 7
• If cardiovascular disease or renal impairment present, consider acetaminophen as safer alternative 1

Step 3: If First-Line Fails

• Consider ubrelvy only after NSAIDs and combination therapy (triptan + NSAID) have failed or are contraindicated 1
• Monitor closely for additive CNS effects (drowsiness, dizziness) given concurrent primidone use 5, 2

Step 4: Consider Preventive Therapy

• If acute treatment needed >2 days per month, initiate preventive therapy with beta-blockers (metoprolol, propranolol) or topiramate 7, 4
• Beta-blockers require monitoring for bradycardia and hypotension in elderly patients 1, 7

Critical Pitfalls to Avoid

• Never use opioids or butalbital for acute migraine treatment 1
• Avoid immediate-release calcium channel blockers due to increased risk of hypotension and falls in elderly 7
• Do not combine NSAIDs with anticoagulants (warfarin, DOACs) without careful bleeding risk assessment 1
• Avoid alpha-blockers for any indication in elderly due to postural hypotension risk 1
• Monitor for medication overuse headache (≥15 days/month with NSAIDs; ≥10 days/month with triptans) 1