Preventive Migraine Medications with a Higher Likelihood of Being Safely Combined

Preventive Migraine Medications with a Higher Likelihood of Being Safely Combined

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Understanding Drug Compatibility

Understanding how different migraine medications work together is important for effective treatment. This guide will break down which preventive medications have a higher likelihood of being safely combined.

What are "Inclusions" in Medication Compatibility?

An "inclusion" represents how many times a medication can be safely combined with other medications. Think of it as a compatibility score - the higher the number, the more flexible the medication is in combination therapy.

Example:

  • A medication with 40 inclusions (like galcanezumab [Emgality]) can be safely combined with 40 different medication combinations
  • A medication with 4 inclusions (like amitriptyline) can only be safely combined with 4 different medication combinations

High Compatibility Medications (30+ Inclusions)

Medication Inclusions Why High Compatibility Notes
Eptinezumab (CGRP mAb) 40 Breaks down into simple components Acts outside blood-brain barrier
Fremanezumab (CGRP mAb) 40 Breaks down into simple components Acts outside blood-brain barrier
Erenumab (CGRP mAb) 40 Breaks down into simple components Acts outside blood-brain barrier
Galcanezumab (CGRP mAb) 40 Breaks down into simple components Acts outside blood-brain barrier
OnabotulinumtoxinA 37 Local injection effects Effects last about 3 months
Melatonin 33 Simple metabolism Caution with opioids
Candesartan 30 Minimal liver processing Mainly cleared unchanged

Medium Compatibility Medications (15-29 Inclusions)

Medication Inclusions Why Medium Compatibility Notes
Cyproheptadine 28 Forms glucuronide conjugate Antihistamine and antiserotonergic properties
Atenolol 24 95% kidney, 5% liver More compatible than other beta-blockers
Memantine 22 Multiple pathways NMDA receptor antagonist
Lisinopril 16 Kidney elimination ACE inhibitor
Metoprolol 16 Liver metabolism Beta-blocker
Nadolol 16 Mixed elimination Beta-blocker
Valproate 16 Liver metabolism Multiple mechanisms

Low Compatibility Medications (4-12 Inclusions)

Medication Inclusions Why Low Compatibility Notes
Nebivolol 12 Heavy liver metabolism Interactions with CYP450 inducers
Carbamazepine 8 Enzyme inducer Affects metabolism of many drugs
Propranolol 8 Extensive liver metabolism Multiple CYP450 interactions
Timolol 8 Liver metabolism Beta-blocker interactions
Topiramate 8 Complex metabolism Multiple mechanism interactions
Amitriptyline 4 Multiple metabolic pathways Anticholinergic effects
Clonidine 4 Alpha-2 agonist Interacts with antidepressants
Frovatriptan 4 CYP1A2 metabolism Interacts with CYP1A2 inhibitors
Guanfacine 4 CYP3A4 substrate Sensitive to enzyme inhibitors/inducers
Pindolol 4 Non-selective binding Multiple receptor interactions
Venlafaxine 4 CYP2D6 dependent Requires conversion to desvenlafaxine
Zonisamide 4 Multiple mechanisms Unique T-type calcium channel effects

Understanding Medication Compatibility

Medications demonstrate higher compatibility when they possess certain characteristics in how they're processed by the body. Those with simple metabolism pathways tend to interact less with other medications. This is especially true for drugs that undergo minimal liver processing or are broken down into basic components. Medications that work locally, such as injectable treatments like Botox, also have fewer interactions because their effects are more limited. 

Conversely, several factors can significantly reduce a medication's compatibility with other drugs. Medications that undergo complex liver metabolism have more interactions because they compete with other drugs for the same processing pathways. Those that either induce or inhibit enzyme activity can affect how other medications are metabolized. Furthermore, when multiple medications share the same metabolic pathways, they're more likely to interact with each other, potentially affecting their effectiveness or safety.

This understanding helps explain why newer medications like CGRP antagonists, which break down into simple components, and treatments with targeted mechanisms of action tend to have higher compatibility scores. It also explains why medications that heavily rely on liver processing or have multiple mechanisms of action typically have more limited combination options.


Source: https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1527897/full

Always consult with your healthcare provider about medication combinations, as individual factors may affect compatibility.

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