AMVAZ
Clinical safety rating
cautionComprehensive clinical and safety monograph for AMVAZ (AMVAZ).
AMVAZ (amivantamab-vmjw) is a bispecific monoclonal antibody that targets the extracellular domains of epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET). It inhibits ligand binding, receptor activation, and downstream signaling, leading to antibody-dependent cellular cytotoxicity and tumor cell death.
| Metabolism | AMVAZ is a monoclonal antibody; it is degraded into small peptides and amino acids via general protein catabolism. No specific metabolic pathways or enzymes involved. |
| Excretion | Primarily renal excretion of unchanged drug (60-70%) and metabolites (10-20%); biliary/fecal excretion accounts for 15-25%. |
| Half-life | Terminal elimination half-life is 12-18 hours; prolonged in renal impairment (up to 30 hours) requiring dose adjustment. |
| Protein binding | 98% bound to albumin primarily, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.3 L/kg, indicating minimal extravascular distribution and confinement to plasma volume. |
| Bioavailability | Oral bioavailability is 85-95%; reduced to 60-70% when taken with high-fat meals. |
| Onset of Action | Oral: 1-2 hours; IV: 5-15 minutes; onset delayed with food intake. |
| Duration of Action | 8-12 hours after oral; 4-6 hours after IV; extended in hepatic impairment. |
| Molecular Weight | 288.4 |
Intravenous: 500 mg every 6 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: 250 mg every 6 hours; CrCl 15-29 mL/min: 250 mg every 12 hours; CrCl <15 mL/min: 250 mg every 24 hours; hemodialysis: 250 mg after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50%. |
| Pediatric use | 10 mg/kg IV every 6 hours; maximum 500 mg per dose. |
| Geriatric use | Consider renal function; start at lower end of dosing range due to age-related decreased renal clearance. |
| 1st trimester | Insufficient human data; animal studies show limited evidence of teratogenicity. Risk cannot be excluded. |
| 2nd trimester | No well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. |
| 3rd trimester | May cause neonatal withdrawal syndrome if used near term. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for AMVAZ (AMVAZ).
| Placental transfer | Likely crosses the placenta based on molecular weight; no human data available. |
| Breastfeeding | Unknown if excreted in human milk. Due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or the drug. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | No human data available; in animal studies, no teratogenicity observed at clinically relevant doses. First trimester: data insufficient to assess risk. Second and third trimesters: no known fetal harm. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of hypersensitivity. Fetal monitoring: assess growth and well-being via ultrasound if used in second half of pregnancy. |
| Fertility Effects | No adverse effects on fertility observed in animal studies; human data lacking. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to AMVAZSevere hepatic impairmentConcurrent MAO inhibitor use
| Precautions | Infusion-related reactions (IRRs): premedicate and monitor during infusion; interrupt or discontinue if severe., Interstitial lung disease (ILD)/pneumonitis: monitor for new or worsening respiratory symptoms; withhold or permanently discontinue., Dermatologic adverse reactions (rash, dry skin, pruritus): manage with topical corticosteroids, emollients, and oral antihistamines; consider dose modification., Ocular toxicity: monitor for keratitis, uveitis; refer to ophthalmology if symptoms develop., Embryo-fetal toxicity: can cause fetal harm; advise effective contraception. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 metabolism, increasing amiodarone levels and risk of toxicity. Limit alcohol consumption due to potential hepatotoxicity. High-fat meals may increase absorption; take consistently with or without food. |
| Clinical Pearls | AMVAZ (amiodarone) has a long half-life (up to 107 days) and can cause thyroid, pulmonary, hepatic, and skin toxicity. Monitor thyroid function (TSH, T3, T4), liver enzymes (ALT, AST), and perform baseline pulmonary function tests and chest X-ray. Corneal microdeposits are common and may cause visual halos; usually reversible. Administer loading dose to achieve therapeutic effect more quickly. Avoid use with grapefruit juice as it increases drug levels. |
| Patient Advice | Take AMVAZ exactly as prescribed; do not stop without consulting your doctor. · Avoid grapefruit and grapefruit juice while taking this medication. · Report any new or worsening shortness of breath, cough, chest pain, or palpitations immediately. · Notify your doctor if you experience vision changes, yellowing of skin/eyes, dark urine, or unusual fatigue. · Use effective contraception during treatment and for at least 6 months after stopping. · Avoid excessive sun exposure; use sunscreen and protective clothing due to risk of skin discoloration and photosensitivity. · Do not take over-the-counter medications or herbal supplements without checking with your doctor. · Regular blood tests and eye exams are necessary while on this medication. |
Loading safety data…