Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

Abstract

In the last few years, there have been significant advances in migraine management and prevention. Lasmiditan, ubrogepant, rimegepant and monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) are new drugs that were launched on the US pharmaceutical market; some of them also in Europe. This publication reviews the available worldwide references on the safety of these anti-migraine drugs with a focus on the possible drug–drug (DDI) or drug–food interactions. As is known, bioavailability of a drug and, hence, its pharmacological efficacy depend on its pharmacokinetics and pharmacodynamics, which may be altered by drug interactions. This paper discusses the interactions of gepants and lasmiditan with, i.a., serotonergic drugs, CYP3A4 inhibitors, and inducers or breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) inhibitors. In the case of monoclonal antibodies, the issue of pharmacodynamic interactions related to the modulation of the immune system functions was addressed. It also focuses on the effect of monoclonal antibodies on expression of class Fc gamma receptors (FcγR).

Headache in transgender and gender‐diverse patients: A narrative review

“…Cases of limb ischemia 62–64 and stroke 65 have been reported in patients on ART and dihydroergotamine. Almotriptan, eletriptan, rimegepant, and ubrogepant are all CYP 3A4 substrates and should also be avoided with ART 66,67 …”

“…Almotriptan, eletriptan, rimegepant, and ubrogepant are all CYP 3A4 substrates and should also be avoided with ART. 66,67 Coordinating care with between providers who prescribe GAHT or ART and/or pharmacists can help avoid unintended drug-drug interactions. Calcitonin gene-related peptide monoclonal antibodies and onabotulinumtoxinA are particularly attractive options for headache preventive therapy as these therapies avoid potential drug-drug interactions.…”

A Link Between Migraine and Prolactin: the Way Forward

“…This can be investigated when accumulating data are becoming available following administration of those new drugs. Considering pharmacokinetic parameters and differences between females and males, both in laboratory animals and humans, future basic and clinical studies may unfold some characteristics of sex-related responses [ 5 , 72 ].…”

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

“…To avoid increased risk of AEs or inadequate treatment of comorbid conditions when using polytherapy, DDIs should be considered when developing therapeutic regimens for the treatment of migraine 6 . A risk of DDIs within migraine treatment exists even in the absence of comorbid conditions because patients using migraine preventive treatment may also require acute migraine medication for breakthrough headaches 7 . Many DDIs are the result of coadministration of multiple drugs that undergo oxidative metabolism by the cytochrome P450 (CYP) enzymes, particularly the CYP3A4, CYP2D6, CYP1A2, and CYP2C isoenzymes 8 .…”

“… 6 A risk of DDIs within migraine treatment exists even in the absence of comorbid conditions because patients using migraine preventive treatment may also require acute migraine medication for breakthrough headaches. 7 Many DDIs are the result of coadministration of multiple drugs that undergo oxidative metabolism by the cytochrome P450 (CYP) enzymes, particularly the CYP3A4, CYP2D6, CYP1A2, and CYP2C isoenzymes. 8 Clinically significant drug interactions can be predicted by the type of isoenzyme involved in metabolism.…”