Zavzpret From Pfizer

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

Affecting up to 40 million Americans, migraines last from 4 to 72 hours and include symptoms such as nausea, throbbing headache, sensitivity to light or sound, and/or vomiting.² Zavegepant’s approval carries the limitation that the drug is not indicated for the preventive treatment of migraine.¹

PHARMACOLOGY AND PHARMACOKINETICS

Zavegepant is a calcitonin gene linked receptor (CGRP) antagonist. It reaches peak plasma concentrations approximately 30 minutes after a single 10 mg intranasal dose and exhibits an elimination half-life of 6.55 hours. It is mainly 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 providing 10 mg in a single spray.¹

CLINICAL TRIALS

The efficacy of zavegepant for the treatment of acute migraine with or without aura in adults was evaluated in 2 randomized, double-blind, placebo-controlled trials. Study 1 (NCT04571060) and study 2 (NCT03872453) randomly assigned participants to treat moderate to severe migraine headache pain intensity with a single dose of 10 mg of zavegepant or a placebo.² Rescue drugs such as acetaminophen, antiemetics, and/or non-steroidal anti-inflammatory drugs can be given 2 hours after the initial treatment. Other classes of rescue drugs, such as triptans, are not permitted within 48 hours of initial treatment.² Baseline migraine preventive medication was used by 13.4% of participants in study 1 and 13.6% of participants in study 2, with no participants taking concomitant preventive medications acting on the CGRP pathway.²

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

Study 1 also assessed secondary endpoints 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 found statistically significant differences between zavegepant and placebo.^1,2

CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS

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

Hypersensitivity reactions, including facial swelling and urticaria, have occurred in patients in clinical studies using zavegepant. If a hypersensitivity reaction occurs, the 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 breast milk, the effect of zavegepant on a breastfed infant, or the effect of zavegepant on milk production. The safety and effectiveness of zavegepant in pediatric patients has not been established.¹

Zavegepant should not be used concomitantly with agents that inhibit the OATP1B3 or NTCP transporters or with agents that induce the OATP1B3 or NTCP transporters. Use of intranasal decongestants should be avoided during treatment with zavegepant. If this combination cannot be avoided, then an 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 disturbances, and vomiting.¹

About the Author

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

Reference

1. Zavzpret. Recipe information. Pfizer Inc; 2023. Accessed April 28, 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=19471
2. Pfizer Zavzpret migraine nasal spray (zavegepant) received 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