ZAVZPRET
ZAVZPRET- zavegepant hydrochloride spray
Pfizer Laboratories Div Pfizer Inc
1 INDICATIONS AND USAGE
ZAVZPRET is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use
ZAVZPRET is not indicated for the preventive treatment of migraine.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
The recommended dose of ZAVZPRET is 10 mg given as a single spray in one nostril, as needed.
The maximum dose that may be given in a 24-hour period is 10 mg (one spray). The safety of treating more than 8 migraines in a 30-day period has not been established.
3 DOSAGE FORMS AND STRENGTHS
Nasal spray: 10 mg of zavegepant per device. Each unit-dose nasal spray device delivers a single spray containing 10 mg of zavegepant.
4 CONTRAINDICATIONS
ZAVZPRET is contraindicated in patients with a history of hypersensitivity reaction to zavegepant or any of the components of ZAVZPRET [see Warnings and Precautions (5.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including facial swelling and urticaria, have occurred in patients treated with ZAVZPRET in clinical studies. If a hypersensitivity reaction occurs, discontinue ZAVZPRET and initiate appropriate therapy [see Contraindications (4) and Adverse Reactions (6.1)].
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:
- •
- Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of ZAVZPRET for the acute treatment of migraine in adults has been evaluated in two randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) in patients with migraine who received one 10 mg dose of ZAVZPRET nasal spray (N=1023) or placebo (N=1056) [see Clinical Studies (14)]. Approximately 83% were female, 81% were White, 20% were Hispanic or Latino, and 15% were Black. The mean age at study entry was 41 years (range 18-79 years of age).
Adverse reactions in Study 1 and 2 are shown in Table 1.
Table 1: Adverse Reactions Occurring in At Least 2% of Patients Treated with ZAVZPRET and at a Frequency Greater than Placebo in Study 1 and 2
| ||
| Adverse Reaction | ZAVZPRET N=1023 % | Placebo N=1056 % |
| Taste Disorders * | 18 | 4 |
| Nausea | 4 | 1 |
| Nasal Discomfort | 3 | 1 |
| Vomiting | 2 | <1 |
Hypersensitivity, including facial swelling and urticaria, occurred in less than 1% of patients treated with ZAVZPRET [see Contraindications (4) and Warnings and Precautions (5.1)].
Long-term safety was assessed in an open-label extension study. That study evaluated 603 patients, dosing intermittently for up to one year, including 360 patients who were exposed to ZAVZPRET 10 mg for at least 6 months, and 298 who were exposed for at least one year, all of whom treated an average of at least two migraine attacks per month.
7 DRUG INTERACTIONS
7.1 OATP1B3 or NTCP Inhibitors
Concomitant administration of ZAVZPRET with inhibitors of the organic anion transporting polypeptide 1B3 (OATP1B3) or sodium taurocholate co-transporting polypeptide (NTCP) transporters may result in a significant increase in zavegepant exposure. Avoid concomitant administration of ZAVZPRET with drugs that inhibit OATP1B3 or NTCP transporters [see Clinical Pharmacology (12.3)].
7.2 OATP1B3 or NTCP Inducers
Concomitant administration of ZAVZPRET with inducers of OATP1B3 or NTCP transporters may result in a decrease in zavegepant exposure. Avoid concomitant administration of ZAVZPRET with drugs that induce OATP1B3 or NTCP transporters [see Clinical Pharmacology (12.3)].
7.3 Intranasal Decongestants
Concomitant administration of ZAVZPRET with intranasal decongestants may decrease the absorption of zavegepant. Avoid concomitant administration of intranasal decongestants with ZAVZPRET. When concomitant use is unavoidable, intranasal decongestants should be administered at least 1 hour after ZAVZPRET administration [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the use of ZAVZPRET in pregnant women. No adverse developmental effects were observed following subcutaneous administration of zavegepant to pregnant animals at doses associated with plasma exposures higher than those used clinically (see Data).
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated rate of major birth defects (2.2 to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.
Animal Data
Subcutaneous administration of zavegepant to pregnant rats (0, 10, 20, or 40 mg/kg/day) or rabbits (0, 20, 40, or 60 mg/kg/day) during the period of organogenesis resulted in no adverse effects on embryofetal development. Plasma exposures (AUC) at the highest doses tested were approximately 4000 times that in humans at the maximum recommended human dose (MRHD) of 10 mg/day.
Subcutaneous administration of zavegepant (0, 5, 10, or 20 mg/kg/day) to rats throughout pregnancy and lactation resulted in no adverse effects on pre- and postnatal development. Plasma exposure (AUC) at the highest dose tested was approximately 2500 times that in humans at the MRHD.
8.2 Lactation
There are no data on 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 developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZAVZPRET and any potential adverse effects on the breastfed infant from ZAVZPRET or from the underlying maternal condition.
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