A total of 39 million men, women, and children experience migraine headaches in the United States.1 Zavegepant (Zavzpret)-a nasal spray-is the newest approved treatment for adults with migraine headaches with or without aura. The spray should not be used to prevent migraine headaches.

Zavegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist. The release of CGRP around the brain leads to inflammation of the meninges and has been found to induce migraine headaches.1 Blocking the receptor for these peptides prevents their action.

Zavegepant's efficacy was determined in two randomized, double-blind, placebo-controlled trials. No patients enrolled in the studies were taking triptan migraine prevention medications or medications that work on the CGRP pathway. The first study included 623 people who received zavegepant and 646 who received placebo. Two hours after a single dose, a significantly greater percentage of people given zavegepant than placebo were free from headache pain and relieved of their most bothersome symptoms (pain free: 23.6% versus 14.9%; most bothersome symptoms free: 39.6% versus 31.1%). In the second study, 391 people received zavegepant and 401 received placebo. Two hours after a single dose, 22.5% and 41.9% of those receiving zavegepant were free from pain and their most bothersome symptoms, respectively, compared with 15.5% and 33.7% of those receiving placebo.

The most common adverse effects of zavegepant in clinical trials were taste disorders, nausea, nasal discomfort, and vomiting. Hypersensitivity reactions are possible. Patients with severe hepatic impairment should not receive zavegepant, as it has not been studied in this group, and neither should patients with a creatine clearance of less than 30 mL/min. The drug comes in a unit-dose nasal spray device. Patients should administer one 10-mg single spray in one nostril as needed. Patients should not prime the device, as the dose will be lost. No more than one dose per 24 hours or more than eight doses in a 30-day period should be administered, as safety for this number of doses has not been established.

Nurses and NPs should use a drug database to determine if the patient is currently receiving any organic anion transporting polypeptide 1B3 (OATP1B3) inhibitors or Na+/taurocholate cotransporting polypeptide (NTCP) inhibitors, which could potentially increase zavegepant levels. Examples of OATP1B3 inhibitors include simeprevir, rifampicin, and pioglitazone; NTCP inhibitors include rosiglitazone, zafirlukast, and cyclosporine. Alternatively, OATP1B3 or NTCP inducers could decrease zavegepant levels. Patients should avoid the use of intranasal decongestants, as they may decrease zavegepant absorption; however, if the drugs must be coadministered, patients should take the intranasal decongestant at least one hour after zavegepant. If hypersensitivity reactions occur, zavegepant should be discontinued.

For complete prescribing information for zavegepant nasal spray, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf.

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