KANJINTI
Clinical safety rating
cautionComprehensive clinical and safety monograph for KANJINTI (KANJINTI).
Comprehensive clinical and safety monograph for KANJINTI (KANJINTI).
Adjuvant treatment of HER2-overexpressing breast cancerMetastatic HER2-positive breast cancer (first-line in combination with chemotherapy)Neoadjuvant treatment of locally advanced or early stage HER2-positive breast cancer
KANJINTI (pertuzumab, trastuzumab, and hyaluronidase-zzxf) is a combination of two HER2/neu receptor antagonists. Pertuzumab and trastuzumab bind to distinct extracellular domains of HER2, inhibiting downstream signaling, antibody-dependent cell-mediated cytotoxicity, and ligand-independent receptor dimerization. Hyaluronidase enhances subcutaneous tissue permeability.
| Metabolism | Pertuzumab and trastuzumab are monoclonal antibodies degraded via catabolic pathways similar to endogenous IgG, primarily through reticuloendothelial system; not metabolized by CYP450 enzymes. Hyaluronidase is degraded by hyaluronidases in tissues. |
| Excretion | Primarily hepatic metabolism; renal elimination of intact drug is minimal (<1%). Biliary/fecal excretion accounts for the majority of elimination (>90%) |
| Half-life | Terminal elimination half-life: 28–38 days (mean ~32 days). Consistent with IgG1 monoclonal antibody clearance; supports every-3-week dosing for sustained exposure |
| Protein binding | Non-specific binding to plasma proteins is negligible; >99% of trastuzumab circulates unbound (free). No significant binding to albumin or alpha-1-acid glycoprotein |
| Volume of Distribution | Mean Vd: 2.9–4.5 L/kg (approximately 200–300 L for a 70 kg patient), indicating distribution into tissues including lymph and interstitial space |
| Bioavailability | Not applicable for oral administration; only IV administration is approved. Bioavailability by IV route is 100% |
| Onset of Action | IV: Clinical response (e.g., tumor shrinkage) typically observed after 4–12 weeks of treatment, although pharmacodynamic markers (e.g., HER2 pathway inhibition) occur within hours to days |
| Duration of Action | Duration of action is prolonged due to long half-life; therapeutic concentrations persist for approximately 3–4 months after a single dose. Continuous dosing every 3 weeks maintains steady-state levels |
| Molecular Weight | 145000 |
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 | VIAL |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Safety and efficacy not established in severe renal impairment (CrCl <30 mL/min) or hemodialysis. |
| Liver impairment | No dose adjustment recommended for Child-Pugh A or B. Safety and efficacy not established in Child-Pugh C; use only if benefit outweighs risk. |
| Pediatric use | Weight-based dosing: Same as adult schedule (mg/kg). Safety and efficacy established for children ≥2 years with HER2-overexpressing tumors; dosing based on body weight. Maximum area under the curve similar to adults. |
| Geriatric use | No specific dose adjustment. Increased incidence of cardiac dysfunction in elderly; monitor left ventricular ejection fraction (LVEF) frequently. Dose modifications for toxicity same as adults. |
| 1st trimester | Human IgG crosses placenta; limited human data for trastuzumab in first trimester. Animal studies show fetal harm. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Trastuzumab causes oligohydramnios and fetal renal impairment when administered during second trimester. Use only if clearly needed. |
| 3rd trimester | Contraindicated in third trimester due to risk of oligohydramnios, anuria, and fetal death. Discontinue 3-7 months before delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for KANJINTI (KANJINTI).
| Placental transfer | Trastuzumab is an IgG1 monoclonal antibody and is actively transported across placenta via FcRn receptors, especially in second and third trimesters. Significant fetal exposure occurs. |
| Breastfeeding | Trastuzumab is a large IgG molecule likely excreted in breast milk in small amounts. Limited human data; potential for infant absorption and adverse effects. Consider risk versus benefit. Some experts recommend avoidance due to unknown effects on infant development. |
| Lactation Rating | L4 (Possibly Hazardous or Possibly Hazardous - Contraindicated) |
| Teratogenic Risk | KANJINTI (trastuzumab) is an IgG1 monoclonal antibody that crosses the placenta. Human data indicate a high risk of oligohydramnios, fetal renal impairment, and fetal death when administered during the second and third trimesters. Exposure during organogenesis (first trimester) may also carry risks, but data are limited. Use is contraindicated in pregnancy. |
| Fetal Monitoring | Monitor for oligohydramnios via ultrasound every 2-4 weeks if exposure occurred during second or third trimester. Assess fetal renal function and amniotic fluid index. In the mother, monitor for signs of infusion reactions, cardiac toxicity (LVEF), and renal impairment. |
| Fertility Effects | Animal studies suggest trastuzumab may impair female fertility. In humans, menstrual cycle irregularities have been reported. The effect on male fertility is unknown. Oligospermia was observed in some animal studies. |
■ FDA Black Box Warning
WARNING: CARDIOTOXICITY. KANJINTI can cause subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF. Evaluate cardiac function before and during treatment. Discontinue for clinically significant decline.
| Serious Effects |
History of hypersensitivity to trastuzumab or any excipientsUse in combination with anthracyclines for adjuvant therapy due to increased cardiotoxicity risk (though this is a relative contraindication, some sources list as absolute in certain contexts)Pregnancy (especially second and third trimesters) - some consider absolute due to severe fetal risk. However, if benefit outweighs risk may use.
| Precautions | Cardiotoxicity (LVEF decline, heart failure), Infusion-related reactions (including anaphylaxis), Pulmonary toxicity (interstitial lung disease, pneumonitis), Embryo-fetal toxicity (oligohydramnios, fetal renal impairment), Exacerbation of chemotherapy-induced neutropenia |
| Food/Dietary | No known food interactions. Avoid grapefruit juice unless directed by healthcare provider. |
| Clinical Pearls | KANJINTI (trastuzumab-anns) is a biosimilar to trastuzumab. Administer as IV infusion; observe for infusion reactions. Do not mix with dextrose solutions. Confirm HER2 overexpression before use (IHC 3+ or FISH+). Monitor left ventricular ejection fraction (LVEF) at baseline and every 3 months. Contraindicated in patients with LVEF <50% or significant decline. Cardiotoxicity risk increases with anthracycline pre-treatment. Use with caution in pregnant women; may cause fetal harm. |
| Patient Advice | Take only under prescription from a doctor. · Report any chest pain, shortness of breath, or swelling of ankles immediately. · Avoid pregnancy while on treatment; use effective contraception during and for 7 months after last dose. · Do not breastfeed during treatment and for 7 months after last dose. · Regular heart function tests (echocardiogram or MUGA) will be performed. · You may experience flu-like symptoms (fever, chills) after infusion; these are usually manageable. |
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