Zavzpret (zavegepant HCl)

No dosing information is available for this tab.

Zavegepant hydrochloride is administered intranasally as a single spray in one nostril, as needed. Do not test spray, prime, or press the plunger prior to use.

Store zavegepant nasal spray between 20-25degreesC (excursions permitted between 15-30degreesC). Do not freeze.

No dosing information is available for this tab.

Zavegepant is metabolized principally by cytochrome P-450 (CYP) 3A4 and to a lesser extent by CYP2D6. In vitro studies indicate that zavegepant is a substrate of CYP3A4 and CYP2D6 (to a lesser extent). Zavegepant does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2B6, 2D6, 2C8, or 3A4 and does not induce CYP isoenzymes 1A2, 2B6, or 3A4 at clinically relevant concentrations.

In vitro, the drug is not a substrate for breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, organic anion transporter (OAT) 1 and OAT3, organic cation transporter (OCT) 2, bile salt export pump (BSEP), multidrug resistance protein (MRP) 2 and MRP4. Zavegepant also does not inhibit P-glycoprotein (P-gp), BCRP, OAT1, OAT3, OATP1B1, or OATP1B3 at clinically relevant concentrations.

In vitro studies indicate that zavegepant is a substrate of OATP1B3, and sodium taurocholate cotransporting polypeptide (NTCP). Zavegepant is also a substrate of P-gp, multidrug and toxic compound extrusion (MATE) 1, and MATE2-K; however, coadministration of zavegepant with inhibitors of these transporters is not expected to be clinically important since the drug is minimally cleared by the renal pathway. The drug is an inhibitor of OCT2, MATE1, and MATE2-K; however, this inhibition potential is not expected to be clinically important.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Zavegepant/Oatp1b3 Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Zavegepant is a substrate of the organic anion transporting polypeptide 1B3 (OATP1B3) transporter. Inhibitors of OATP1B3 may increase zavegepant exposure.(1)

CLINICAL EFFECTS: Concurrent use of OATP1B3 inhibitors may result in increased levels of and toxicity from zavegepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent administration of zavegepant with OATP1B3 inhibitors should be avoided.(1)

DISCUSSION: In a study, rifampin (an OATP1B3 and NTCP inhibitor) at steady state increased the area-under-curve (AUC) and maximum concentration (Cmax) of zavegepant by 2.3-fold and 2.2-fold. Since rifampin is also a CYP3A4 inducer and zavegepant is metabolized by CYP3A4, concurrent use of zavegepant with other OATP1B3 inhibitors that are not CYP3A4 inducers may have an even more significant effect on zavegepant exposure.(1) OATP1B3 inhibitors include: atazanavir, belumosudil, cobicistat, cyclosporine, darolutamide, enasidenib, encorafenib, fostemsavir, glecaprevir/pibrentasvir, leflunomide, leniolisib, letermovir, lopinavir/ritonavir, paritaprevir, resmetirom, rifampin, ritonavir, teriflunomide, velpatasvir, voclosporin, and voxilaprevir.(2-9)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Zavegepant/Intranasal Decongestants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Intranasal decongestants may decrease the absorption of zavegepant.(1)

CLINICAL EFFECTS: Concurrent administration of intranasal decongestants may result in decreased systemic exposure and effectiveness of zavegepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent use of intranasal decongestants with zavegepant. If concurrent use is unavoidable, use the decongestant at least 1 hour after zavegepant.(1)

DISCUSSION: Intranasal decongestants may lower absorption of zavegepant. This effect has not been clinically evaluated.(1)

*History of hypersensitivity reaction to zavegepant or any component in the formulation. Anaphylaxis has occurred.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Hypertension
• Raynaud's phenomenon

The most common adverse reactions observed in patients treated with zavegepant in clinical trials (>=2% of patients treated with zavegepant and greater than placebo) were taste disorders, nausea, nasal discomfort, and vomiting.

Rare or Very Rare

• Anaphylaxis

More Frequent

• Dysgeusia

Less Frequent

• Nasal pain
• Nausea
• Vomiting

Rare or Very Rare

• Facial edema
• Hypersensitivity drug reaction
• Hypertension
• Raynaud's phenomenon
• Urticaria

No enhanced messaging available.

Safety and effectiveness of zavegepant use in pediatric patients have not been established.

There are no adequate data on the developmental risks associated with the use of zavegepant 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.

There are no data on the presence of zavegepant or its metabolites in human milk, the effects on the breast-fed infant, or on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for zavegepant and any potential adverse effects on the breastfed infant from zavegepant or from the underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Clinical studies of zavegepant did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently from younger adult patients. In a limited number of patients >=65 years of age who received treatment with zavegepant, no clinically significant pharmacokinetic differences were observed between elderly and younger subjects.