ONTRUZANT
Clinical safety rating
cautionComprehensive clinical and safety monograph for ONTRUZANT (ONTRUZANT).
Comprehensive clinical and safety monograph for ONTRUZANT (ONTRUZANT).
Adjuvant treatment of HER2-overexpressing breast cancerTreatment of HER2-overexpressing metastatic breast cancerTreatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma
Oncruzant (trastuzumab) is a humanized monoclonal antibody that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), inhibiting HER2 signaling and antibody-dependent cellular cytotoxicity (ADCC).
| Metabolism | Monoclonal antibodies like trastuzumab are not metabolized by typical drug-metabolizing enzymes; they are catabolized into peptides and amino acids via general protein degradation pathways. |
| Excretion | Primarily hepatic metabolism; biliary excretion of metabolites. Renal elimination is minimal (<20% as unchanged drug). Fecal excretion accounts for >80% of administered dose. |
| Half-life | Terminal elimination half-life is approximately 18-21 days. This prolonged half-life supports a dosing interval of every 3 weeks and allows for sustained target concentrations. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily to albumin and immunoglobulins. |
| Volume of Distribution | Volume of distribution is approximately 3.0 L/kg, indicating extensive distribution into tissues beyond the vascular space, consistent with a monoclonal antibody that distributes into interstitial fluid and tissues. |
| Bioavailability | Only administered intravenously; bioavailability is 100% by IV route. No oral bioavailability data due to protein nature and degradation in GI tract. |
| Onset of Action | Onset of clinical effect is not immediate; measurable antitumor activity is observed after 2-4 weeks of therapy (first cycle). |
| Duration of Action | Duration of action is approximately 3 weeks, consistent with the dosing interval. Receptor blockade persists for at least 3-4 weeks after infusion, supporting every-3-week dosing. |
| Molecular Weight | 145531.5 |
Initial dose: 8 mg/kg IV over 90 minutes, followed by maintenance doses of 6 mg/kg IV every 3 weeks over 30-90 minutes.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment recommended for mild-to-moderate renal impairment; no data available for severe (CrCl <30 mL/min). |
| Liver impairment | No dose adjustment recommended for Child-Pugh A or B; use caution in Child-Pugh C due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor cardiac function closely in elderly due to higher risk of cardiotoxicity. |
| 1st trimester | ONTRUZANT (trastuzumab) should not be used during the first trimester unless the potential benefit justifies the potential risk to the fetus. IgG molecules cross the placenta only minimally in early pregnancy. |
| 2nd trimester | Use during the second trimester is associated with oligohydramnios and fetal renal impairment. Avoid unless benefit clearly outweighs risk. |
| 3rd trimester | Use during the third trimester can cause oligohydramnios, pulmonary hypoplasia, and neonatal renal dysfunction. Contraindicated unless essential. |
Clinical note
Comprehensive clinical and safety monograph for ONTRUZANT (ONTRUZANT).
| Placental transfer | Trastuzumab crosses the placenta, especially during the second and third trimesters, with fetal serum levels approximately 50% of maternal levels. |
| Breastfeeding | Trastuzumab is present in human milk at low levels, but data are limited. Because of the potential for adverse effects in the infant, breastfeeding is not recommended during therapy and for at least 7 months after the last dose. |
| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | Pregnancy Category D. Trastuzumab, the active ingredient, causes oligohydramnios, fetal renal failure, and fetal death when administered to pregnant women. Exposure during organogenesis (first trimester) is associated with major congenital anomalies including pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Second and third trimester exposure leads to oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal deformities, and neonatal death. |
| Fetal Monitoring | Monitor pregnant women exposed to ONTRUZANT for oligohydramnios by serial ultrasound (e.g., every 2-4 weeks). If oligohydramnios occurs, perform fetal monitoring (e.g., non-stress test, biophysical profile). Monitor maternal renal function and blood pressure. Postpartum, monitor infants for renal impairment, pulmonary hypoplasia, and growth retardation. |
| Fertility Effects | No specific human studies on fertility. In animal studies, trastuzumab did not affect male or female fertility. However, trastuzumab may cause menstrual irregularities due to its antiproliferative effect on HER2-expressing tissues in the reproductive tract. It is not known whether fertility is permanently impaired. |
■ FDA Black Box Warning
Cardiomyopathy: Trastuzumab can cause left ventricular cardiac dysfunction, including symptomatic heart failure. Risk is increased in patients receiving anthracyclines. Evaluate cardiac function before and during treatment.
| Serious Effects |
Hypersensitivity to trastuzumab or any excipients
| Precautions | Cardiomyopathy: Monitor cardiac function (LVEF) at baseline and every 3 months during treatment., Infusion reactions: Interrupt infusion for severe reactions; discontinue if life-threatening., Pulmonary toxicity: Monitor for dyspnea, pulmonary infiltrates, and acute respiratory distress syndrome., Embryo-fetal toxicity: May cause fetal harm; advise effective contraception during and after treatment. |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice if co-administered with drugs metabolized by CYP3A4 (ONTRUZANT is not hepatically metabolized). Maintain adequate hydration. |
| Clinical Pearls | ONTRUZANT is a biosimilar to trastuzumab; confirm HER2 status via IHC or FISH prior to initiation. Monitor for infusion-related reactions, especially with first dose; premedicate with antihistamines and corticosteroids. Assess left ventricular ejection fraction (LVEF) at baseline and every 3 months; hold if significant decline. Do not administer with anthracyclines; use only after anthracycline washout if prior exposure. |
| Patient Advice | ONTRUZANT is used to treat HER2-positive breast cancer and gastric cancer. · You will receive this medication as an intravenous infusion every 1 or 3 weeks. · Report any signs of heart problems such as shortness of breath, swelling, or cough. · Infusion reactions may occur; tell your nurse immediately if you have chills, fever, or breathing issues. · Avoid pregnancy while on this drug; use effective contraception during treatment and for 7 months after. · Do not receive live vaccines during treatment. |
Loading safety data…