Metabolic and toxicological considerations regarding CGRP mAbs and CGRP antagonists to treat migraine in COVID-19 patients: a narrative review

ABSTRACT

Introduction

Migraine pharmacological therapies targeting calcitonin gene-related peptide (CGRP), including monoclonal antibodies and gepants, have shown clinical effect and optimal tolerability. Interactions between treatments of COVID-19 and CGRP-related drugs have not been reviewed.

Areas covered

An overview of CGRP, a description of the characteristics of each CGRP-related drug and its response predictors, COVID-19 and its treatment, the interactions between CGRP-related drugs and COVID-19 treatment, COVID-19 and vaccination-induced headache, and the neurological consequences of Covid-19.

Expert opinion

Clinicians should be careful about using gepants for COVID-19 patients, due to the potential drug interactions with drugs metabolized via CYP3A4 cytochrome. In particular, COVID-19 treatment (especially nirmatrelvir packaged with ritonavir, as Paxlovid) should be considered cautiously. It is advisable to stop or adjust the dose (10 mg atogepant when used for episodic migraine) of gepants when using Paxlovid (except for zavegepant). CGRP moncolconal antibodies (CGRP-mAbs) do not have drug – drug interactions, but a few days’ interval between a COVID-19 vaccination and the use of CGRP mAbs is recommended to allow the accurate identification of the possible adverse effects, such as injection site reaction. Covid-19- and vaccination-related headache are known to occur. Whether CGRP-related drugs would be of benefit in these circumstances is not yet known.

KEYWORDS:

• Post-acute COVID-19 syndrome
• headache disorders
• calcitonin gene-related peptide receptor antagonists
• SARS-CoV-2
• Covid-19

Article highlights

• CGRP related treatments have shown effect on migraine for both acute and preventive treatment.

• Rimegepant, atogepant and ubrogepant have drug-drug interaction and caution is necessary when using with nirmatrelvir packaged with ritonavir (Paxlovid), strong CYP3A4 inhibitor.

• CGRP mAbs do not have drug – drug interactions, but a few days’ interval between a COVID-19 vaccination and the use of CGRP mAbs is recommended to allow the identification of the cause of an injection site reaction.

• Covid-19- and vaccination-related headache and neurological symptoms are known to occur. Whether CGRP-related drugs would be of benefit in these circumstances is not yet known.

Declaration of interest

T Takizawa serves as a consultant/advisor and/or serves as advisory board for Eli Lilly, Otsuka, Amgen, Teijin and Pfizer. T Takizawa received honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Kowa, Kyowa Kirin, Eisai, UCB Japan, Takeda, and Santen Pharmaceutical. T Takizawa receives/received study funds from Eli Lilly, and Tsumura outside the submitted work. T Takizawa serves/served as site PI of clinical trials for Otsuka, Amgen, AbbVie, and Pfizer. N Imai serves as a consultant/advisor and/or serves as advisory board for Otsuka and Sawai. N Imai received honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Kyowa Kirin, and Sawai. N Imai serves/served as site PI of clinical trials for Eli Lilly, Otsuka, Amgen, Lundbeck, AbbVie, and Pfizer. J Nakahara received honoraria and research scholarships from Amgen and Daiichi Sankyo. D Garcia-Azorin serves as subject matter expert for the World Health Organization in COVID-19 and COVID-19 vaccine related topics. D Garcia-Azorin served as advisor for Lundbeck. D Garcia-Azorin received speaker honoraria from Eli Lilly, Teva, Lundbeck, Novartis, Chiesi, and Amgen. D Garcia-Azorin received study fund from the Castilla y Leon Regional Health Administration (SACYL), the Carlos III Institute, and Eli Lilly company outside of the submitted work. D Garcia-Azorin serves as site PI of clinical trials for Lundbeck and Pfizer. The authors have no other 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.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The publication of this review was supported by JSPS KAKENHI (grant number 22K15693 to TT).