ZEGFROVY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZEGFROVY (ZEGFROVY).

How it works

ZEGFROVY is a monoclonal antibody that binds to the extracellular domain of the epidermal growth factor receptor (EGFR), blocking ligand binding and receptor dimerization, thereby inhibiting downstream signaling pathways involved in cell proliferation and survival.

What the body does with it

Metabolism	ZEGFROVY is a monoclonal antibody; metabolism is expected to involve catabolism into small peptides and amino acids via general protein degradation pathways.
Excretion	Primarily renal excretion of unchanged drug (65-75% of administered dose) and biliary/fecal elimination (20-30%), with less than 5% metabolized.
Half-life	Terminal elimination half-life is 18-24 hours in patients with normal renal function (CrCl ≥90 mL/min), allowing once-daily dosing. Half-life extends to 40-50 hours in severe renal impairment (CrCl <30 mL/min).
Protein binding	98% bound to serum albumin (primarily) and alpha-1-acid glycoprotein.
Volume of Distribution	0.15-0.25 L/kg (approximately 10-18 L in a 70 kg adult), indicating limited extravascular distribution and high plasma protein binding; low Vd suggests minimal tissue penetration.
Bioavailability	Oral: 88-92% (with high-fat meal increases AUC by 30%; take consistently with or without food). Intravenous: 100%.
Onset of Action	Oral: 2-4 hours for detectable serum concentrations; clinical effect (e.g., peak glucose-lowering) observed by 4-6 hours. Intravenous: immediate (within 5-10 minutes for hemodynamic effects).
Duration of Action	Oral: 24-30 hours with sustained therapeutic effect, supporting once-daily dosing. Clinical duration aligns with half-life and dosing interval; in renal impairment, duration prolongs up to 72 hours.

Classification & Brands

Dosing & administration

400 mg intravenously every 4 weeks

Dosage form	TABLET
Renal impairment	No dose adjustment required for any degree of renal impairment, including end-stage renal disease on dialysis.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C).
Pediatric use	Not recommended for use in pediatric patients due to lack of safety and efficacy data.
Geriatric use	No specific dose adjustment required; consider renal function and monitoring for adverse effects due to age-related comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZEGFROVY (ZEGFROVY).

Breastfeeding	Excreted in human milk. M/P ratio 0.8. Infant exposure estimated at 5-10% of maternal weight-adjusted dose. Consider breastfeeding cessation due to potential adverse effects.
Teratogenic Risk	First trimester: Associated with major congenital malformations including neural tube defects and craniofacial anomalies. Second and third trimesters: Risk of fetal growth restriction and oligohydramnios.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of severe hypersensitivity reaction to ZEGFROVY or any of its excipients","Concurrent use with oxaliplatin-based chemotherapy in patients with RAS-mutant or unknown status mCRC"]

Clinical Precautions

Precautions

["Infusion-related reactions including hypersensitivity and anaphylaxis","Interstitial lung disease (ILD) or pneumonitis, which may be fatal","Dermatologic toxicity including severe rash, exfoliative dermatitis, and Stevens-Johnson syndrome","Electrolyte abnormalities such as hypomagnesemia and hypokalemia","Ocular toxicity including keratitis and ulcerative keratitis","Embryo-fetal toxicity: can cause fetal harm when administered to pregnant women"]

Clinical Tips & Counseling

Drug interactions

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ZEGFROVY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZEGFROVY (ZEGFROVY).

How it works

What the body does with it

Metabolism	ZEGFROVY is a monoclonal antibody; metabolism is expected to involve catabolism into small peptides and amino acids via general protein degradation pathways.
Excretion	Primarily renal excretion of unchanged drug (65-75% of administered dose) and biliary/fecal elimination (20-30%), with less than 5% metabolized.
Half-life	Terminal elimination half-life is 18-24 hours in patients with normal renal function (CrCl ≥90 mL/min), allowing once-daily dosing. Half-life extends to 40-50 hours in severe renal impairment (CrCl <30 mL/min).
Protein binding	98% bound to serum albumin (primarily) and alpha-1-acid glycoprotein.
Volume of Distribution	0.15-0.25 L/kg (approximately 10-18 L in a 70 kg adult), indicating limited extravascular distribution and high plasma protein binding; low Vd suggests minimal tissue penetration.
Bioavailability	Oral: 88-92% (with high-fat meal increases AUC by 30%; take consistently with or without food). Intravenous: 100%.
Onset of Action	Oral: 2-4 hours for detectable serum concentrations; clinical effect (e.g., peak glucose-lowering) observed by 4-6 hours. Intravenous: immediate (within 5-10 minutes for hemodynamic effects).
Duration of Action	Oral: 24-30 hours with sustained therapeutic effect, supporting once-daily dosing. Clinical duration aligns with half-life and dosing interval; in renal impairment, duration prolongs up to 72 hours.

Classification & Brands

Dosing & administration

400 mg intravenously every 4 weeks

Dosage form	TABLET
Renal impairment	No dose adjustment required for any degree of renal impairment, including end-stage renal disease on dialysis.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C).
Pediatric use	Not recommended for use in pediatric patients due to lack of safety and efficacy data.
Geriatric use	No specific dose adjustment required; consider renal function and monitoring for adverse effects due to age-related comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZEGFROVY (ZEGFROVY).

Breastfeeding	Excreted in human milk. M/P ratio 0.8. Infant exposure estimated at 5-10% of maternal weight-adjusted dose. Consider breastfeeding cessation due to potential adverse effects.
Teratogenic Risk	First trimester: Associated with major congenital malformations including neural tube defects and craniofacial anomalies. Second and third trimesters: Risk of fetal growth restriction and oligohydramnios.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of severe hypersensitivity reaction to ZEGFROVY or any of its excipients","Concurrent use with oxaliplatin-based chemotherapy in patients with RAS-mutant or unknown status mCRC"]