Drug interactions and risks associated with the use of triptans, ditans and monoclonal antibodies in migraine

Abstract

Purpose of review The aim of this study was to review current evidence concerning potential risks and interactions associated with concomitant use of drugs indicated for the abortive treatment of migraine, namely triptans and ditans, and more recently developed drugs used for the preventive treatment. The latter drug class encompasses monoclonal antibodies (mAbs), which target either calcitonin gene-related peptide (CGRP) or its receptor. Recent findings To date, no pharmacokinetic interactions between these drug classes have been reported. However, patients who suffer from triptan- (or ditan-) induced medication overuse headache or those who are nonresponders to triptans might respond less effectively to mAbs. Caution is warranted when coadministrating these drugs in migraine patients with comorbid cardiovascular disease or with an increased cardiovascular risk profile. Summary In this review, the main mechanisms of action of triptans, ditans and mAbs targeting CGRP or its receptor are summarized as well as the current evidence on their individual risks. Studies on risks and interactions in case of concomitant use of triptans, ditans and mAbs in migraine patients are relatively scarce. Therefore, these aspects have been considered from a theoretical and hypothetical point of view by taking both their overlapping target, CGRP, and contraindications into account.

Place of next generation acute migraine specific treatments among triptans, non-responders and contraindications to triptans and possible combination therapies

“…Triptans are agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors. Triptans mainly act on the 5-HT 1B and 5-HT 1D receptors, and additionally, some triptans bind the 5-HT 1F receptor with moderate to high affinity (7). Triptans constrict cranial arteries via the 5-HT 1B receptor subtype (7).…”

“…Triptans mainly act on the 5-HT 1B and 5-HT 1D receptors, and additionally, some triptans bind the 5-HT 1F receptor with moderate to high affinity (7). Triptans constrict cranial arteries via the 5-HT 1B receptor subtype (7). In addition, triptans may bind to central 5-HT 1B receptors (8).…”

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine

“…This stimulation of the postsynaptic potential ensures the continuation of cortical depression in migraine with aura and without aura [48]. Molecules such as olcegepant and telcagepant prevent binding of the initial CGRP, blocking the entire receptor activation process [49][50][51]. New oral drugs for migraine [52][53][54] include atogepant, 8imegepant, and 8imegepant [55,56], which have been recently reviewed [57].…”

Phase Ib, open‐label, fixed‐sequence, drug–drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine

“…CGRP‐targeted therapies have brought a new therapeutic option to patients with improved safety profiles that have not led to medication overuse headache 16,17 and extend treatment to patients with cardiovascular risk factors 18–21 . While CGRP‐targeted therapies approved for preventive treatment of migraine have demonstrated significant reductions in mean headache days and improved patient function and quality of life both during and in between attacks, 22 patients may still experience breakthrough migraine attacks that require acute treatment; thus, clinical drug–drug interaction (DDI) studies on the concomitant use of established and recently approved (acute and preventive) migraine treatment options are needed to inform physicians on the pharmacokinetic (PK) interactions and safety of these anti‐migraine therapy combinations 23 …”

“…[18][19][20][21] While CGRP-targeted therapies approved for preventive treatment of migraine have demonstrated significant reductions in mean headache days and improved patient function and quality of life both during and in between attacks, 22 patients may still experience breakthrough migraine attacks that require acute treatment; thus, clinical drug-drug interaction (DDI) studies on the concomitant use of established and recently approved (acute and preventive) migraine treatment options are needed to inform physicians on the pharmacokinetic (PK) interactions and safety of these anti-migraine therapy combinations. 23 Here we focus on the combination of atogepant, an oral CGRP receptor antagonist approved for the preventive treatment of episodic migraine, and ubrogepant, an oral CGRP receptor antagonist approved for the acute treatment of migraine. Following oral administration in humans, atogepant and ubrogepant are rapidly absorbed with time to maximum plasma drug concentrations (T max ) of ~1-2 h and ~ 1.5 h, respectively, and apparent terminal elimination half-life (t 1/2 ) of ~11 and 5-7 h, respectively, resulting in minimal to no accumulation with repeated daily dosing of either agent.…”