Zavzpret From Pfizer

The FDA gas approved Zavegpant nasal spray (Zavzpret) from Pfizer Inc for the acute treatment of migraine with or without aura in adults.¹

Headache area on brain X-ray | Image credit: Iaremenko - stock.adobe.com

Affecting up to 40 million Americans, a migraine lasts from 4 to 72 hours and includes symptoms such as nausea, pulsating headache, sensitivity to light or sound, and/or vomiting.² The approval of zavegepant carries the limitation that the medication is not indicated for preventative migraine treatment.¹

PHARMACOLOGY AND PHARMACOKINETICS

Zavegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist. It reaches peak plasma concentrations approximately 30 minutes after a single 10-mg intranasal dose and displays an elimination halflife of 6.55 hours. It is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6.¹

DOSAGE AND ADMINISTRATION

The recommended dose of zavegepant is 10 mg as a single spray in 1 nostril as needed, with a maximum of 10 mg (1 spray) every 24 hours. The safety of more than 8 doses in a 30-day period has not been established. Zavegepant is supplied as a unit-dose nasal spray that delivers 10 mg in a single spray.¹

CLINICAL TRIALS

The efficacy of zavegepant for the acute treatment of migraine with or without aura in adults was evaluated in 2 double-blind, placebocontrolled, randomized trials. Study 1 (NCT04571060) and study 2 (NCT03872453) randomly assigned participants to treat a migraine of moderate to severe headache pain intensity with a single dose of 10-mg zavegepant or a placebo.² Rescue medications such as acetaminophen, antiemetic, and/or nonsteroidal anti-inflammatory drugs could be administered 2 hours after the initial treatment. Other classes of rescue medications, such as triptans, were not allowed within 48 hours of initial treatment.² Baseline preventative migraine medication was used by 13.4% of participants in study 1 and 13.6% of participants in study 2, with no participants using concomitant preventive medications that acted on the CGRP pathway.²

The coprimary end points for both studies were freedom from pain, which was defined as a reduction of moderate or severe headache pain to no headache pain, and freedom from most bothersome symptoms, which was defined as the absence of the self-identified most bothersome symptom at 2 hours after a single dose. Both studies found zavegepant to be statistically superior to placebo.²

Study 1 also assessed the secondary end points of pain relief at 2 hours post dose, return to normal function at 2 hours post dose, and sustained pain freedom from 2 to 48 hours post dose, and it found statistically significant differences between zavegepant and the placebo.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

The use of zavegepant is contraindicated in patients with a history of a hypersensitivity reaction to zavegepant or to any of the components of the medication.¹

Hypersensitivity reactions, including facial swelling and urticaria, have occurred in patients in clinical studies using zavegepant. If a hypersensitivity reaction occurs, zavegepant should be discontinued and appropriate therapy initiated. Zavegepant should not be used in patients with severe hepatic impairment or with a creatinine clearance of less than 30 mL/min. Adequate data are not available regarding the use of zavegepant during pregnancy or regarding the presence of zavegepant or its metabolites in human milk, the effects of zavegepant on the breastfed infant, or the effects of zavegepant on milk production. The safety and effectiveness of zavegepant in pediatric patients have not been established.¹

Zavegepant should not be used concomitantly with agents that inhibit OATP1B3 or NTCP transporters or with agents that induce OATP1B3 or NTCP transporters. The use of intranasal decongestants should be avoided during treatment with zavegepant. If this combination is unavoidable, then the intranasal decongestant should be administered at least 1 hour after zavegepant.¹

1 hour after zavegepant.¹ The most common adverse reactions are nasal discomfort, nausea, taste disorders, and vomiting.¹

About the Author

Monica Holmberg, PharmD, BCPS,is a pharmacist in Phoenix, Arizona, and a Pharmacy Times contributor.

References

1. Zavzpret. Prescribing information. Pfizer Inc; 2023. Accessed April 28, 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=19471
2. Pfizer’s Zavzpret (zavegepant) migraine nasal spray receives FDA approval. News release. Pfizer Inc. March 10, 2023. Accessed April 28, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizerszavzprettm-zavegepant-migraine-nasal-spray