Is it safe to combine Luvox (fluvoxamine) with Nurtec (rimegepant) in a patient with a history of migraines and mental health conditions?

Combining Luvox (Fluvoxamine) with Nurtec (Rimegepant)

It is safe to combine Luvox (fluvoxamine) with Nurtec (rimegepant) in patients with migraines and mental health conditions, as there is no clinically significant drug interaction between these medications and rimegepant has demonstrated favorable safety when used with SSRIs including fluvoxamine. 1

Evidence Supporting Safety of This Combination

Direct Evidence from Clinical Trials

• A large multicenter, long-term safety study (n=1800) specifically evaluated rimegepant in patients using SSRIs and other antidepressants for up to 52 weeks. 1
• Among participants using SSRIs (10.1% of the study population), adverse event rates were comparable to those not using SSRIs: 64.1% vs 60.0% for any adverse events, 3.3% vs 2.5% for serious adverse events, and 5.0% vs 2.4% for discontinuation due to adverse events. 1
• Participants with self-reported anxiety (23.2%) or depression (23.7%) showed similar safety profiles to those without these conditions when taking rimegepant. 1

Mechanism and Pharmacologic Considerations

• Rimegepant is a CGRP receptor antagonist that does not work through serotonergic mechanisms, unlike triptans which are 5-HT1B/1D agonists. 2
• Fluvoxamine is noted to have significant CYP450 interactions (CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6), but rimegepant's metabolism does not create clinically relevant interactions with SSRIs. 3
• Earlier concerns about serotonin syndrome with antimigraine drugs primarily involved triptans combined with SSRIs, not CGRP antagonists like rimegepant. 4

Clinical Context for This Combination

When This Combination is Appropriate

• Rimegepant is approved for both acute treatment of migraine attacks and preventive treatment of episodic migraine when taken every other day. 3, 2
• The 2024 VA/DoD guidelines suggest rimegepant for short-term (acute) treatment of migraine with a weak recommendation. 3
• For prevention, there is insufficient evidence to make a strong recommendation, though rimegepant has demonstrated efficacy in reducing monthly migraine days. 3, 2

Advantages of Rimegepant in Psychiatric Comorbidity

• Unlike triptans, rimegepant does not carry theoretical serotonin syndrome risk when combined with SSRIs. 1
• Rimegepant showed no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials, making it safer than some alternatives in patients with multiple medications. 2
• The orally disintegrating tablet formulation offers convenience and potentially faster response time. 2

Important Monitoring Considerations

What to Watch For

• While the combination is safe, monitor for general adverse effects of rimegepant, which most commonly include nausea (reported in clinical trials but generally well-tolerated). 2
• Continue monitoring for fluvoxamine's known side effects, including potential discontinuation syndrome if doses are missed (fluvoxamine has a shorter half-life). 3
• Be aware that fluvoxamine itself has been studied for migraine prophylaxis and showed favorable effects on headache attack frequency with only slight side effects. 5

Medication Overuse Considerations

• Ensure acute migraine medications (including rimegepant) are limited to avoid medication overuse headache: simple analgesics should be used fewer than 15 days per month, and migraine-specific medications fewer than 10 days per month. 6
• If using rimegepant for acute treatment more than twice weekly, consider adding or switching to preventive therapy. 6

Alternative and Complementary Strategies

First-Line Acute Treatments

• For acute migraine attacks, triptans (eletriptan, rizatriptan, sumatriptan) or sumatriptan-naproxen combination remain strongly recommended options. 3, 6
• NSAIDs (ibuprofen, naproxen) or aspirin-acetaminophen-caffeine combination are also strongly recommended for acute treatment. 3, 6
• A 1995 study demonstrated safety of sumatriptan with fluvoxamine in 14 patients across 103 migraine episodes, though theoretical serotonin syndrome concerns persist in guidelines. 4

Preventive Treatment Options

• For patients requiring migraine prevention while on fluvoxamine, consider CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) which have strong recommendations. 3, 6
• Topiramate, propranolol, or valproate are suggested for prevention, though fluvoxamine's CYP interactions should be considered. 3, 6
• Amitriptyline can address both migraine prevention and mood disorders, though fluvoxamine may already be optimally managing the psychiatric condition. 6, 7, 5

In summary, there is no contraindication to combining fluvoxamine with rimegepant, and clinical trial data specifically supports the safety of this combination. 1