HERCEPTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HERCEPTIN (HERCEPTIN).

How it works

Trastuzumab is a humanized monoclonal antibody that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2). It inhibits HER2-mediated signaling, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) and inhibition of tumor cell proliferation.

What the body does with it

Metabolism	Metabolism of trastuzumab is not typical; it is a monoclonal antibody that is catabolized into peptides and amino acids via general protein degradation pathways, primarily in the reticuloendothelial system.
Excretion	Trastuzumab is eliminated primarily via the reticuloendothelial system and catabolism; renal excretion is minimal (<20% of an administered dose is excreted in urine, likely as small peptides). Biliary/fecal excretion is not a major route; metabolic degradation yields amino acids.
Half-life	The terminal elimination half-life is approximately 28–38 days (mean 28.5 days). This long half-life allows for every-3-week dosing (loading dose 8 mg/kg, then 6 mg/kg q3w).
Protein binding	Trastuzumab is approximately 95% bound to plasma proteins (primarily immunoglobulins and albumin).
Volume of Distribution	The volume of distribution is approximately 44 mL/kg (0.044 L/kg), indicating limited extravascular distribution and confinement mainly to the vascular space.
Bioavailability	Trastuzumab is administered intravenously; bioavailability is 100% by IV route. No subcutaneous formulation is currently approved (subcutaneous trastuzumab is available under trade name Herceptin Hylecta but is a separate product with recombinant hyaluronidase).
Onset of Action	Clinical response (tumor regression) may be observed within 2–4 weeks after starting therapy, though maximal effect requires multiple cycles. For cardiotoxicity monitoring, LVEF decline may occur within 4–8 weeks.
Duration of Action	Sustained suppression of HER2 signaling persists for several weeks post-infusion due to the long half-life. Therapeutic effect is maintained with continued dosing; after cessation, drug levels decline slowly over months.

Classification & Brands

Dosing & administration

Loading dose of 8 mg/kg IV over 90 minutes, followed by maintenance dose of 6 mg/kg IV over 30-90 minutes every 3 weeks. Alternatively, 4 mg/kg IV loading over 90 minutes, then 2 mg/kg IV over 30 minutes weekly.

Dosage form	VIAL
Renal impairment	No dose adjustment required for renal impairment. Herceptin is not significantly renally excreted.
Liver impairment	No specific dose adjustment recommended for hepatic impairment. Clinical trial data insufficient for Child-Pugh-based modifications.
Pediatric use	Safety and efficacy not established in pediatric patients. No standard dosing guidelines available.
Geriatric use	No specific dose adjustment required. Clinical trials included patients up to 89 years; no differences in safety or efficacy observed in elderly vs. younger adults.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for HERCEPTIN (HERCEPTIN).

Breastfeeding	It is unknown whether trastuzumab is excreted in human milk; however, because human IgG is present in breast milk and the potential for absorption and harm to the infant exists, breastfeeding is not recommended. M/P ratio is not known.
Teratogenic Risk	HERCEPTIN (trastuzumab) is associated with oligohydramnios, fetal renal failure, and pulmonary hypoplasia when administered during the second and third trimesters. First trimester exposure has not shown a clear teratogenic signal, but risks cannot be excluded.

Warnings & precautions

■ FDA Black Box Warning

Cardiomyopathy: Trastuzumab can cause left ventricular dysfunction, congestive heart failure, and cardiac failure. Risk is increased with concurrent anthracycline therapy. Assess cardiac function before and during treatment.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to trastuzumab or any component of the product"]

Clinical Precautions

Precautions

["Cardiac toxicity (monitor left ventricular ejection fraction)","Infusion reactions (fever, chills, dyspnea; may be severe)","Pulmonary toxicity (interstitial pneumonitis, acute respiratory distress syndrome)","Embryo-fetal toxicity (can cause fetal harm, advise effective contraception)"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

HERCEPTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HERCEPTIN (HERCEPTIN).

How it works

What the body does with it

Metabolism	Metabolism of trastuzumab is not typical; it is a monoclonal antibody that is catabolized into peptides and amino acids via general protein degradation pathways, primarily in the reticuloendothelial system.
Excretion	Trastuzumab is eliminated primarily via the reticuloendothelial system and catabolism; renal excretion is minimal (<20% of an administered dose is excreted in urine, likely as small peptides). Biliary/fecal excretion is not a major route; metabolic degradation yields amino acids.
Half-life	The terminal elimination half-life is approximately 28–38 days (mean 28.5 days). This long half-life allows for every-3-week dosing (loading dose 8 mg/kg, then 6 mg/kg q3w).
Protein binding	Trastuzumab is approximately 95% bound to plasma proteins (primarily immunoglobulins and albumin).
Volume of Distribution	The volume of distribution is approximately 44 mL/kg (0.044 L/kg), indicating limited extravascular distribution and confinement mainly to the vascular space.
Bioavailability	Trastuzumab is administered intravenously; bioavailability is 100% by IV route. No subcutaneous formulation is currently approved (subcutaneous trastuzumab is available under trade name Herceptin Hylecta but is a separate product with recombinant hyaluronidase).
Onset of Action	Clinical response (tumor regression) may be observed within 2–4 weeks after starting therapy, though maximal effect requires multiple cycles. For cardiotoxicity monitoring, LVEF decline may occur within 4–8 weeks.
Duration of Action	Sustained suppression of HER2 signaling persists for several weeks post-infusion due to the long half-life. Therapeutic effect is maintained with continued dosing; after cessation, drug levels decline slowly over months.

Classification & Brands

Dosing & administration

Dosage form	VIAL
Renal impairment	No dose adjustment required for renal impairment. Herceptin is not significantly renally excreted.
Liver impairment	No specific dose adjustment recommended for hepatic impairment. Clinical trial data insufficient for Child-Pugh-based modifications.
Pediatric use	Safety and efficacy not established in pediatric patients. No standard dosing guidelines available.
Geriatric use	No specific dose adjustment required. Clinical trials included patients up to 89 years; no differences in safety or efficacy observed in elderly vs. younger adults.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for HERCEPTIN (HERCEPTIN).

Breastfeeding	It is unknown whether trastuzumab is excreted in human milk; however, because human IgG is present in breast milk and the potential for absorption and harm to the infant exists, breastfeeding is not recommended. M/P ratio is not known.
Teratogenic Risk	HERCEPTIN (trastuzumab) is associated with oligohydramnios, fetal renal failure, and pulmonary hypoplasia when administered during the second and third trimesters. First trimester exposure has not shown a clear teratogenic signal, but risks cannot be excluded.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to trastuzumab or any component of the product"]

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…