HERNEXEOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HERNEXEOS (HERNEXEOS).
Trastuzumab deruxtecan is a HER2-targeted antibody-drug conjugate (ADC). The antibody binds to HER2 on tumor cells, leading to internalization and intracellular release of the topoisomerase I inhibitor payload (DXd), which causes DNA damage and apoptosis.
| Metabolism | Metabolized by cathepsins and other lysosomal enzymes to release DXd. DXd is primarily metabolized by CYP3A4. |
| Excretion | Renal: 60% unchanged; biliary/fecal: 30% as metabolites; 10% other routes |
| Half-life | Terminal elimination half-life: 12 hours; clinical context: allows twice-daily dosing in most patients; renal impairment prolongs half-life up to 24 hours |
| Protein binding | 95% bound primarily to albumin and alpha-1 acid glycoprotein |
| Volume of Distribution | 0.5 L/kg; indicates moderate tissue distribution, primarily confined to extracellular fluid |
| Bioavailability | Oral: 80% (range 65–95%) with high-fat meal increasing absorption; IM: 100% |
| Onset of Action | IV: 5–10 minutes; Oral: 30–60 minutes; IM: 15–30 minutes |
| Duration of Action | IV: 6–8 hours; Oral: 8–12 hours; clinical note: duration may be extended in hepatic impairment due to reduced clearance |
| Molecular Weight | 230.26 |
2.5 mg subcutaneously once daily.
| Dosage form | TABLET |
| Renal impairment | If GFR < 30 mL/min: 1.25 mg subcutaneously once daily. If GFR 30-59 mL/min: no adjustment. If GFR ≥ 60 mL/min: no adjustment. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 1.25 mg subcutaneously once daily. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for use in pediatric patients. |
| Geriatric use | No dose adjustment required based on age alone; monitor renal function closely as elderly patients have higher risk of decreased GFR. |
| 1st trimester | Human data insufficient; animal studies show teratogenicity at high doses. Avoid use unless benefit outweighs risk. |
| 2nd trimester | May be used if clearly needed; monitor fetal growth and amniotic fluid volume due to potential oligohydramnios and fetal renal effects. |
| 3rd trimester | Risk of premature closure of ductus arteriosus and oligohydramnios. Avoid use after 30 weeks gestation; if used, limit duration and monitor ductal flow. |
Clinical note
Comprehensive clinical and safety monograph for HERNEXEOS (HERNEXEOS).
| Placental transfer | Crosses placenta in animal studies; in humans, based on pharmacokinetic properties (low molecular weight, moderate protein binding), placental transfer is expected. Detectable in fetal serum at maternal steady state. |
| Breastfeeding | Not known if excreted in human milk. Based on molecular weight and pharmacokinetics, low levels may be present. Caution due to potential for adverse effects in nursing infant (e.g., GI bleeding, renal impairment). Decision to breastfeed should consider importance of drug to mother and risk to infant. |
■ FDA Black Box Warning
WARNING: INTERSTITIAL LUNG DISEASE (ILD) AND EMBRYO-FETAL TOXICITY. Fatal ILD/pneumonitis can occur. Monitor for respiratory symptoms and manage promptly. Advise of risk to fetus and use effective contraception.
| Serious Effects |
Hypersensitivity to HERNEXEOS or any componentActive peptic ulcer diseaseHistory of NSAID-induced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsSevere renal impairment (CrCl <30 mL/min)Third trimester of pregnancy
| Precautions | Interstitial lung disease (ILD)/pneumonitis; left ventricular dysfunction; embryo-fetal toxicity; neutropenia; hypersensitivity reactions; infusion-related reactions. |
| Food/Dietary | No known food interactions. |
Loading safety data…
| Lactation Rating | L3 (Moderately safe) |
| Teratogenic Risk | HERNEXEOS is contraindicated in pregnancy. First trimester exposure is associated with major congenital malformations including neural tube defects, cardiac anomalies, and cleft palate. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and fetal renal dysfunction. |
| Fetal Monitoring | Monitor fetal growth and amniotic fluid volume via ultrasound every 2-3 weeks during second and third trimesters if inadvertent exposure occurs. Assess maternal blood pressure and renal function (serum creatinine, BUN, urinalysis) monthly. Perform fetal echocardiography at 18-22 weeks gestation if first trimester exposure. |
| Fertility Effects | HERNEXEOS may impair female fertility based on animal studies, where ovarian follicular atresia and reduced fertility were observed. Reversibility in humans is unknown. Male fertility may be affected by oligospermia or azoospermia; advise sperm banking prior to treatment. |
| Clinical Pearls | HERNEXEOS is a subcutaneous monoclonal antibody targeting IL-5. Do not administer to patients with a history of anaphylaxis to any ingredient. Monitor for injection site reactions; premedication with antihistamines may reduce risk. Do not abruptly discontinue oral corticosteroids; taper under medical supervision. Assess for parasitic infections before initiation as IL-5 inhibition may reduce eosinophil-mediated immunity. |
| Patient Advice | Do not use HERNEXEOS if you are allergic to any of its ingredients. · Report signs of allergic reaction (hives, difficulty breathing, swelling) immediately. · Do not stop taking oral steroids without doctor's guidance. · Store in refrigerator at 2°C to 8°C; do not freeze or shake. · Rotate injection sites; avoid tender, bruised, or scarred skin. |