OGIVRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OGIVRI (OGIVRI).
OGIVRI is a HER2/neu receptor antagonist. It binds to the extracellular domain of the HER2 receptor, inhibiting downstream signaling pathways and inducing antibody-dependent cellular cytotoxicity (ADCC).
| Metabolism | Trastuzumab is a monoclonal antibody; not metabolized by CYP450 enzymes; eliminated via intracellular catabolism. |
| Excretion | Primarily hepatic metabolism; renal excretion of unchanged drug accounts for <1% of administered dose. Biliary/fecal excretion not extensively studied; based on trastuzumab, negligible biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 5.8 days (range 1-32 days). This longer half-life supports every-3-week dosing regimens. |
| Protein binding | Highly bound, approximately 95% bound to plasma proteins (primarily albumin, immunoglobulins, and other serum proteins). |
| Volume of Distribution | Volume of distribution (Vd) is approximately 2.9 L/kg, indicating limited extravascular distribution consistent with a large monoclonal antibody that remains primarily in the vascular compartment. |
| Bioavailability | Administered intravenously; bioavailability is 100% (because it is an IV formulation). |
| Onset of Action | Not applicable; OGIVRI (trastuzumab-dkst) is a monoclonal antibody with a delayed onset. Clinical effects observed after several weeks of continuous therapy. |
| Duration of Action | Duration of action is dependent on receptor occupancy and tumor response; continuous dosing is required for sustained effect. Treatment typically given until disease progression or unacceptable toxicity. |
Intravenous infusion of 8 mg/kg on day 1, then 6 mg/kg on days 8 and 15 of each 21-day cycle, or 8 mg/kg on days 1 and 15 of each 28-day cycle for HER2-overexpressing metastatic gastric cancer.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for patients with mild to moderate renal impairment (CrCl 30-89 mL/min). No data available for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment recommended for patients with mild hepatic impairment (Child-Pugh A). No data available for moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. In clinical studies, patients ≥65 years had similar safety and efficacy compared to younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OGIVRI (OGIVRI).
| Breastfeeding | It is not known whether trastuzumab is excreted in human milk. However, human IgG is present in human milk and trastuzumab is a humanized IgG1 monoclonal antibody. Published data suggest that breast milk IgG does not enter the neonatal circulation in substantial amounts. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment and for 7 months after the last dose. M/P ratio: not determined. |
| Teratogenic Risk | FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. In trastuzumab (the active ingredient), oligohydramnios, renal failure, and fetal death have been reported post-marketing. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise women of reproductive potential to use effective contraception during treatment and for 7 months after the last dose. |
■ FDA Black Box Warning
Cardiomyopathy: Left ventricular dysfunction can occur with trastuzumab products, including OGIVRI. Discontinue for clinically significant decrease in left ventricular function.
| Serious Effects |
None known.
| Precautions | Cardiomyopathy, infusion-related reactions, pulmonary toxicity, exacerbation of chemotherapy-induced neutropenia, and embryo-fetal toxicity. |
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| Fetal Monitoring | Monitor left ventricular ejection fraction (LVEF) at baseline and every 3-4 months during treatment. If LVEF declines >10 points from baseline and to <50%, withhold trastuzumab and reassess within 3-4 weeks. If LVEF recovers to normal limits, resume; otherwise, consider permanent discontinuation. No specific fetal monitoring recommendations beyond routine obstetric care. For pregnant women, consider serial ultrasound to monitor amniotic fluid volume and fetal renal function. |
| Fertility Effects | Trastuzumab did not impair fertility in animal studies. However, oligomenorrhea and amenorrhea have been reported in women receiving trastuzumab. In premenopausal women, trastuzumab in combination with chemotherapy may increase the incidence of chemotherapy-induced amenorrhea. Advise women of reproductive potential to use effective contraception during and for 7 months after treatment. |