Choosing the safest acute therapy during chronic migraine prophylactic treatment: pharmacokinetic and pharmacodynamic considerations

ABSTRACT

Introduction: Drugs used in the treatment of migraine have been reported to be highly associated with the occurrence of clinically significant drug-drug interactions (DDIs). Multiple drug therapy regimens are used for migraine treatment, particularly for chronic migraine. In fact, additional pharmacological agents are usually administered during an acute migraine attack in patients chronically treated with the prophylactic therapy. The variety of drugs available for migraine prophylactic and acute treatment, and consequently their pharmacological interactions, might complicate the choice of a safe combination therapy.

Areas covered: This study discusses the prophylactic-acute DDIs from a pharmacokinetic and pharmacodynamic perspective, particularly interactions between antiepileptic drugs, tricyclic antidepressants, β-blockers, calcium channel blockers, triptans, nonsteroidal anti-inflammatory drugs and ergot derivatives. The available online tools have been used to evaluate the clinically significant DDIs.

Expert opinion: The interactions between different drugs might be accurately predicted by the huge and detailed knowledge about the molecular pathways involved in pharmacodynamics and pharmacokinetics. Pharmacogenomic research has shed further light onto the mechanisms involved in the inter-individual variation in drug response and DDIs. Based on this knowledge, this paper will provide suggestions to improve the appropriateness of the drug choice in the prescription of preventative and acute migraine medications.

KEYWORDS:

• Acute treatment
• chronic migraine
• CYP450
• drug-drug interactions
• prophylactic treatment

Article Highlights

• Drugs used in migraine treatment are highly associated with clinically significant DDIs.

• The DDIs might be predicted by using the free online tools evaluating the molecular pathways involved in pharmacodynamics, pharmacokinetics, and pharmacogenomics.

• During a beta-blockers migraine prophylactic treatment NSAIDs should be avoided as acute medication.

• Rizatriptan and other MAO-A-metabolized triptans should be used with precaution in patients treated with propranolol.

• The co-administration of amitriptyline and triptans or amitriptyline and ergot-derivatives is not recommended, whereas combination with acute drugs not affecting the CYP2D6 and CYP2C19 activity should be preferred.

• Antiepileptic drugs are safe and efficacious also in combination with acute migraine treatments; some concerns should arise only when they are co-administered with aspirin.

• The calcium channel blockers cinnarizine and flunarizie should not be administrated with drugs inhibiting the cytochrome P450 functionality, as metoclopramide, in patients with reduced activity of CYP2D6.

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Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.