Drug Interaction Between Sibelium (Flunarizine) and Naproxen
There are no documented clinically significant drug interactions between Sibelium (flunarizine) and naproxen, and they can be used together safely for migraine management.
Evidence Base
The available evidence does not identify any pharmacokinetic or pharmacodynamic interactions between flunarizine and naproxen:
No direct interaction studies exist between flunarizine and NSAIDs like naproxen in the medical literature 1, 2, 3, 4, 5
Different mechanisms of action make significant interactions unlikely: flunarizine is a calcium channel blocker that works on cerebral vasculature, while naproxen is an NSAID that inhibits prostaglandin synthesis 5
No metabolic pathway overlap: Flunarizine has a long half-life and distinct metabolism that does not involve the same pathways as naproxen 5
Clinical Considerations for Combined Use
When This Combination Makes Sense
Acute-on-chronic migraine management: Flunarizine serves as prophylaxis (10 mg daily at bedtime), while naproxen treats acute breakthrough attacks 6, 3
Complementary therapeutic roles: The American Academy of Family Physicians recommends NSAIDs like naproxen as first-line acute migraine treatment, which can be combined with prophylactic agents 6
Safety Monitoring
While the drugs don't interact directly, monitor for:
Flunarizine-specific adverse effects: Depression (8% incidence), weight gain, and daytime sedation—these are the drug's own side effects, not interaction-related 2, 3
Naproxen cardiovascular and GI risks: The American Heart Association notes NSAIDs carry cardiovascular risks (myocardial infarction, stroke, hypertension) and GI bleeding risk, particularly with chronic use 7, 8
Use lowest effective NSAID dose for shortest duration to minimize these inherent NSAID risks 8
Practical Prescribing
Flunarizine dosing: 10 mg once daily at bedtime to minimize sedation 3, 4
Naproxen for acute attacks: 500-550 mg at migraine onset, can repeat once if needed 6
Consider GI protection: If naproxen is used frequently (>3 times weekly), consider proton pump inhibitor co-prescription per American Gastroenterological Association recommendations 8
Common Pitfall to Avoid
Do not confuse the absence of interaction data with the presence of an interaction. The lack of reported interactions between flunarizine and naproxen across decades of clinical use in Europe (where flunarizine is widely prescribed) provides reassuring real-world evidence of safety 3, 5.