A narrative review of the importance of pharmacokinetics and drug–drug interactions of preventive therapies in migraine management

Abstract

Objective To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug–drug interactions (DDIs) with the use of these therapies in migraine management. Background Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions. Methods A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta‐blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene‐related peptide pathway with medications that may be used for comorbid conditions. Results Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs. Conclusions DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine‐specific evidence‐based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.

Pharmacokinetic and pharmacodynamic considerations with psychiatric disorders and migraines

“…Topiramate has a minimal effect on the CYP450 system and low risk of interactions but may increase accumulation of ammonia and hyperammonemic encephalopathy when combined with valproate products. 19 Valproate products are known to inhibit glucuronidation, which increases exposure to lamotrigine and can increase risk of hypersensitivity reactions, including Stevens-Johnson syndrome. As antiseizure medications cause sedation and somnolence, it is also important to monitor for cumulative effects.…”

New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy

“…In contrast, gepants can interact with oral drugs that inhibit or induce the hepatic enzyme CYP3A4 (53). Among first-line migraine preventive drugs, topiramate is a weak inducer of CYP3A4 (55). In addition, verapamil and amlodipine can increase the plasma concentration of gepants (53,55).…”

“…Among first-line migraine preventive drugs, topiramate is a weak inducer of CYP3A4 (55). In addition, verapamil and amlodipine can increase the plasma concentration of gepants (53,55). Despite these theoretical concerns, the concomitant use of verapamil and topiramate was not prohibited during the rimegepant trial (12).…”

Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution

“…Beta-blockers can restrict blood flow to the brain by reducing blood vessel dilation, and they inhibit the nervous system’s electrical activity by making the nervous system less excitable. In addition, they can stabilize serotonin levels in the brain, fluctuations of which are associated with migraine [ 4 ]. Among the studied beta-blockers, propranolol (PRO) is considered the most effective in preventing migraine attacks and has been given the highest rating by the Canadian Headache Society (CHS), American Headache Society/American Association of Neurology (AAN/AHS), and the European Federation of Neurological Societies (EFNS) guidelines [ 5 ].…”