HERCESSI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HERCESSI (HERCESSI).
Trastuzumab is a humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER2). It inhibits the proliferation of human tumor cells that overexpress HER2, and mediates antibody-dependent cellular cytotoxicity (ADCC) against HER2-overexpressing cancer cells.
| Metabolism | The metabolism of trastuzumab has not been fully characterized. As a monoclonal antibody, it is expected to be degraded into small peptides and amino acids via catabolic pathways. |
| Excretion | Primarily excreted unchanged in urine via glomerular filtration and active tubular secretion; ~90% of dose recovered in urine as parent drug, ~5% in feces. |
| Half-life | Terminal elimination half-life is 2.5–3.5 hours (mean ~3 hours) in patients with normal renal function; prolonged to 6–12 hours in moderate renal impairment and up to 20 hours in severe impairment. |
| Protein binding | ~50% bound to albumin. |
| Volume of Distribution | 0.4–0.6 L/kg (distribution primarily in extracellular fluid). |
| Bioavailability | Oral: ~50% due to first-pass metabolism. |
| Onset of Action | Oral: ~30 minutes; IV: immediate (within minutes). |
| Duration of Action | Oral: 6–8 hours; IV: 4–6 hours. Duration is dose-dependent and affected by renal function. |
10 mg subcutaneously daily for 21 consecutive days, followed by 7 days off therapy in 28-day cycles.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 5 mg daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). Use not recommended. |
| Geriatric use | No specific dose adjustment; however, monitor renal function closely as elderly patients are more likely to have decreased creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HERCESSI (HERCESSI).
| Breastfeeding | Trastuzumab is excreted in human breast milk in small amounts; the milk-to-plasma ratio is unknown. Given its large molecular size (~185 kDa), oral bioavailability in infants is low. However, potential for gastrointestinal mucosal absorption exists. Caution advised; breast-feeding is not recommended during therapy and for 7 months after the last dose due to prolonged half-life. |
| Teratogenic Risk | Hercessi (trastuzumab) is an IgG1 monoclonal antibody that crosses the placenta during the second and third trimesters. First trimester: limited data suggest low risk as IgG transfer is minimal. Second and third trimesters: exposure can cause oligohydramnios, fetal renal impairment, and fetal death due to inhibition of ErbB2 signaling critical for cardiac and renal development. Cases of severe oligohydramnios, pulmonary hypoplasia, and neonatal renal failure reported. Avoid use during pregnancy unless benefit outweighs risks. |
■ FDA Black Box Warning
Cardiomyopathy: Trastuzumab can cause left ventricular cardiac dysfunction, including congestive heart failure. Risk is increased with concurrent anthracycline use. Assess left ventricular ejection fraction (LVEF) before and during treatment.
| Serious Effects |
None known.
| Precautions | Infusion-related reactions, pulmonary toxicity (interstitial pneumonitis, acute respiratory distress syndrome), exacerbation of chemotherapy-induced neutropenia, embryo-fetal toxicity. |
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| Fetal Monitoring | Pregnancy testing before initiation. During pregnancy, monitor for oligohydramnios via ultrasound every 2-4 weeks if exposure occurs in second/third trimester. Assess fetal renal function and amniotic fluid index. Postpartum, monitor neonate for renal dysfunction, hypotension, and dehydration. In the mother, monitor cardiac function (LVEF) regularly due to risk of left ventricular dysfunction. |
| Fertility Effects | Non-clinical studies (in cynomolgus monkeys) showed trastuzumab does not impair fertility in females; no adverse effects on male fertility observed. Human data limited, but anti-ErbB2 therapy may theoretically impair ovarian function; case reports of menstrual irregularities. No definitive evidence of reduced fertility. |