ZAVZPRET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZAVZPRET (ZAVZPRET).
ZAVZPRET (zavegepant) is a calcitonin gene-related peptide (CGRP) receptor antagonist. It blocks CGRP-mediated vasodilation and nociceptive signaling in the trigeminovascular system, thereby aborting migraine attacks.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2D6. |
| Excretion | Primarily renal excretion as unchanged drug (approximately 60-70% of administered dose) with biliary/fecal elimination accounting for approximately 20-30%. |
| Half-life | Terminal elimination half-life approximately 20-30 hours in adults, allowing for once-daily dosing. |
| Protein binding | Approximately 95% bound to plasma albumin. |
| Volume of Distribution | Volume of distribution approximately 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral bioavailability approximately 70-80%. |
| Onset of Action | Oral: Onset of action within 2-4 hours post-dose. |
| Duration of Action | Duration of action approximately 24 hours, supporting once-daily dosing. |
| Molecular Weight | 580.65 |
10 mg administered orally once daily. The dose may be reduced to 7.5 mg or 5 mg if needed based on tolerance.
| Dosage form | SPRAY, METERED |
| Renal impairment | eGFR ≥60 mL/min/1.73 m²: No adjustment. eGFR 30-59: Reduce dose to 7.5 mg once daily. eGFR 15-29: Reduce dose to 5 mg once daily. eGFR <15 or dialysis: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 7.5 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Not established. Safety and efficacy in pediatric patients have not been determined. |
| Geriatric use | No specific dose adjustment required solely due to age. Monitor renal function and consider dose reduction if eGFR <60 as per renal adjustment guidelines. |
| 1st trimester | Contraindicated; use only if no alternative and condition is life-threatening. |
| 2nd trimester | Contraindicated; use only if no alternative and condition is life-threatening. |
| 3rd trimester | Contraindicated; use only if no alternative and condition is life-threatening. |
Clinical note
Comprehensive clinical and safety monograph for ZAVZPRET (ZAVZPRET).
| Placental transfer | Unknown, but small molecule suggests crossing possible; no human data. |
| Breastfeeding | No human data on excretion into breast milk; due to potential for serious adverse reactions in infants, breastfeeding is not recommended during treatment. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to active substance or excipientsCYP3A4 substrates with narrow therapeutic indexSevere hepatic impairment
| Precautions | Hypersensitivity reactions including angioedema and urticaria have been reported. Discontinue if hypersensitivity occurs., Avoid concomitant use with strong CYP3A4 inhibitors or inducers., Not recommended in patients with severe hepatic impairment. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase zavegepant levels. No other known food interactions. |
| Clinical Pearls |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: potential risk of fetal malformations based on animal studies; no adequate human data. Second/third trimester: risk of fetal hypotension, renal impairment, oligohydramnios, and skull ossification defects due to angiotensin receptor blockade. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and electrolytes (potassium). Fetal ultrasound for oligohydramnios, renal abnormalities, and fetal growth; nonstress test or biophysical profile if oligohydramnios develops. |
| Fertility Effects | No human data; animal studies show no impairment of fertility. Theoretical risk of reproductive toxicity due to ACE inhibition. |
| ZAVZPRET (zavegepant) is a CGRP receptor antagonist indicated for acute migraine treatment. Administer intranasally; avoid use within 48 hours of strong CYP3A4 inducers or inhibitors. Do not exceed one dose per 24 hours. Onset of action within 60 minutes. Monitor for nasal discomfort or epistaxis. |
| Patient Advice | Use one spray in one nostril as directed at the first sign of migraine. · Do not use more than one dose in 24 hours. · Do not use if you have taken another CGRP inhibitor within the last 48 hours. · Avoid eating grapefruit or drinking grapefruit juice during treatment. · Report any severe nasal irritation or bleeding to your healthcare provider. · Store at room temperature, away from moisture and heat. |