HERZUMA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HERZUMA (HERZUMA).
HER2/neu receptor antagonist; binds to extracellular domain of HER2, inhibiting downstream signaling pathways (PI3K/Akt and MAPK), and induces antibody-dependent cell-mediated cytotoxicity (ADCC).
| Metabolism | Not extensively metabolized; clearance involves proteolytic degradation; no major cytochrome P450 involvement. |
| Excretion | Primarily hepatic metabolism; limited renal excretion (<1% unchanged). Biliary/fecal excretion is not a major route. |
| Half-life | Elimination half-life is approximately 28-38 days (range 21-52 days). The long half-life supports dosing every 3 weeks. |
| Protein binding | Approximately 95% bound to albumin and other serum proteins. |
| Volume of Distribution | Approximately 15-20 L/kg (mean 17 L/kg), indicating extensive tissue distribution. |
| Bioavailability | IV administration only; bioavailability is 100% by IV route. |
| Onset of Action | Not applicable for oral route; IV infusion: clinical response may be observed within 2-4 weeks of initiating therapy. |
| Duration of Action | Prolonged due to long half-life; clinical effects persist for several weeks after infusion. Dosing interval is 3 weeks. |
4 mg/kg IV over 90 minutes, then 2 mg/kg IV over 30 minutes weekly, or 8 mg/kg IV over 90 minutes, then 6 mg/kg IV over 30-90 minutes every 3 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment. |
| Pediatric use | Not FDA-approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor cardiac function closely due to increased risk of cardiomyopathy in elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HERZUMA (HERZUMA).
| Breastfeeding | It is unknown if trastuzumab is excreted in human breast milk; however, human IgG is secreted into milk. The M/P ratio has not been determined. Due to potential for adverse effects in the nursing infant, advise women to discontinue breastfeeding during treatment and for 7 months after the last dose. |
| Teratogenic Risk | HERZUMA (trastuzumab) is associated with oligohydramnios, fetal renal failure, and death when administered during the second and third trimesters due to inhibition of fetal renal HER2/neu receptors. First trimester exposure carries unknown risk; however, placental transfer is minimal early in pregnancy. Use is contraindicated unless potential benefit outweighs risk. |
■ FDA Black Box Warning
Cardiomyopathy: Left ventricular dysfunction, heart failure; risk increased with prior anthracycline use or chest irradiation. Monitor left ventricular ejection fraction (LVEF) before and during treatment.
| Serious Effects |
["Known hypersensitivity to trastuzumab or any component"]
| Precautions | ["Infusion reactions (fatal): Monitor during infusion; reduce rate or discontinue for severe reactions.","Pulmonary toxicity: Interstitial pneumonitis, acute respiratory distress syndrome (ARDS); discontinue if severe.","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception.","Cardiac monitoring: Assess LVEF before and every 3 months during therapy; withhold if significant decline."] |
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| Fetal Monitoring | Monitor maternal renal function and amniotic fluid volume via ultrasound during and after therapy if exposed in second or third trimester. Assess fetal kidney function and growth. Monitor for signs of fetal hydrops and oligohydramnios. |
| Fertility Effects | Trastuzumab may impair fertility in females based on animal studies showing ovarian follicular depletion. Clinical data in humans suggest possible reversible menstrual cycle disruption; no long-term data on female or male fertility effects. |