Rybrevant Faspro

• Dry Skin and Pruritus: Excessive skin dryness and intense itching.
• Nausea and Constipation: Digestive upsets are common but usually manageable with supportive care.
• Hypoalbuminemia: A decrease in the level of albumin in the blood, which can contribute to swelling.
• Increased Alanine Aminotransferase (ALT): A sign of potential liver stress.
• Electrolyte Imbalances: Specifically low levels of magnesium, potassium, or sodium.

• Ocular Toxicity: Severe inflammation of the eye (keratitis) or changes in vision.
• Severe Dermatologic Toxicity: Toxic epidermal necrolysis or Stevens-Johnson syndrome (extremely rare).
• Severe Venous Thromboembolism: Deep vein thrombosis or pulmonary embolism.

> Warning: Stop taking Amivantamab and call your doctor immediately if you experience any of these.

• Interstitial Lung Disease (ILD) / Pneumonitis: This is a serious inflammation of the lungs. Symptoms include new or worsening shortness of breath, cough, or fever. It can be life-threatening.
• Severe Infusion Reactions: If you experience difficulty breathing, swelling of the face or throat, or a rapid drop in blood pressure during or after your infusion.
• Vision Changes: Eye pain, severe redness, or sudden blurring of vision. This may indicate keratitis (inflammation of the cornea).
• Severe Skin Reactions: Blistering or peeling skin, which could indicate a severe dermatological emergency.

With prolonged use, the most significant long-term concerns involve the skin and nails. Chronic paronychia can lead to nail loss or secondary fungal infections. Chronic dry skin can lead to fissures (cracks in the skin) that are painful and prone to infection. Patients may also experience long-term fatigue or persistent mild edema. Because amivantamab is a relatively new drug, long-term data spanning several decades is still being collected.

As of the most recent FDA updates in 2024, there are no Black Box Warnings for amivantamab. However, the drug carries significant warnings for Infusion-Related Reactions, Interstitial Lung Disease, and Embryo-Fetal Toxicity. The absence of a black box warning does not imply the drug is without risk; rather, it means the risks are currently managed through standard warnings and precautions in the prescribing information.

Report any unusual symptoms to your healthcare provider. Many side effects of amivantamab can be managed with dose interruptions, dose reductions, or supportive medications (like topical steroids for rash) if caught early.

Patients undergoing treatment with amivantamab require regular monitoring to ensure safety:

• Liver Function Tests (LFTs): Blood tests to check ALT, AST, and bilirubin should be performed periodically, as the drug can cause liver enzyme elevations.
• Electrolytes: Monitoring for low magnesium, potassium, and calcium is necessary, as EGFR inhibitors are known to cause 'wasting' of these minerals through the kidneys.
• Physical Exams: Regular assessment of the skin and nails to catch paronychia or severe rash early.
• Respiratory Assessment: Continuous monitoring for cough or shortness of breath at every clinical visit.

Amivantamab is unlikely to affect the ability to drive or operate machinery directly. However, some patients may experience fatigue or dizziness following an infusion. It is recommended that patients see how the drug affects them before attempting to drive, especially after the first few doses.

There is no direct contraindication between amivantamab and alcohol. However, alcohol can dehydrate the skin and body, potentially worsening the skin dryness and fatigue associated with the drug. Patients should discuss their alcohol consumption with their oncologist.

Amivantamab does not cause a physical withdrawal syndrome and does not typically require a tapering schedule. However, stopping the drug can lead to a 'flare' or rapid progression of the cancer. Treatment should only be discontinued under the direction of an oncologist, usually due to disease progression or severe toxicity.

> Important: Discuss all your medical conditions, especially lung or skin problems, with your healthcare provider before starting Amivantamab.

• Corticosteroids: While used as pre-medication, long-term high-dose steroids can mask the early signs of infection or interstitial lung disease, requiring clinicians to be more vigilant.
• Anticoagulants: Patients on warfarin or DOACs (like apixaban) should be monitored closely, as cancer and its treatments can alter the risk of both bleeding and clotting (venous thromboembolism is a known risk with amivantamab).

• Grapefruit and Starfruit: Unlike many oral cancer pills, amivantamab is not processed by the CYP3A4 enzyme in the gut or liver. Therefore, grapefruit juice does not significantly affect the levels of amivantamab in the blood.
• General Nutrition: No specific food restrictions exist, but maintaining high protein intake is often recommended to manage the hypoalbuminemia (low protein in the blood) that can occur during treatment.

• St. John’s Wort: This herbal supplement is a potent inducer of many metabolic pathways. While it may not affect amivantamab levels directly, it can interfere with many other medications used in cancer care. Its use is generally discouraged.
• Antioxidant Supplements: Some oncologists advise against high-dose antioxidant supplements (like Vitamin E or C) during active treatment, as they could theoretically interfere with the oxidative stress mechanisms used by some cancer therapies to kill tumor cells.

• Serum Albumin: Amivantamab can cause a decrease in measured serum albumin. This is not an interference with the test itself, but a physiological effect of the drug.
• Imaging: Amivantamab can cause changes on CT scans (pneumonitis) that may be difficult to distinguish from cancer progression or infection. Radiologists should be informed that the patient is receiving an EGFR/MET bispecific antibody.

For each major interaction, the management strategy involves:

• Mechanism: Usually pharmacodynamic (additive toxicities) rather than pharmacokinetic (changing drug levels).
• Clinical Consequence: Increased risk of skin, lung, or liver toxicity.
• Management Strategy: Frequent lab monitoring, dose delays, or use of supportive medications.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter skin creams.

There is a theoretical risk of cross-sensitivity with other monoclonal antibodies, particularly those that are also IgG1-based or target the EGFR pathway (like cetuximab or panitumumab). If a patient has had a severe reaction to another EGFR-targeting antibody, amivantamab should be administered with extreme caution and enhanced pre-medication.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous reactions to antibody treatments, before prescribing Amivantamab.

Amivantamab is not approved for use in children. The safety and efficacy in patients under 18 years of age have not been established. Clinical trials are currently restricted to adult populations as the specific mutations targeted by amivantamab (EGFR exon 20 insertions) are virtually non-existent in pediatric malignancies.

In clinical trials, approximately 40% of patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. However, elderly patients may be more susceptible to certain side effects like dehydration from diarrhea or complications from skin infections. Close monitoring of fluid status and skin integrity is essential in this population.

• Mild to Moderate (CrCl 30-89 mL/min): No dose adjustment is required. The drug's clearance is not significantly affected by these levels of renal dysfunction.
• Severe (CrCl < 30 mL/min): Amivantamab has not been studied in this population. It should be used with caution, and patients should be monitored closely for any signs of increased toxicity.

• Mild: No dose adjustment is required for patients with mild hepatic impairment.
• Moderate to Severe: There is no data available for these populations. Because monoclonal antibodies are not primarily cleared by the liver, significant changes in pharmacokinetics are not expected, but the risk of hepatotoxicity may be higher.

> Important: Special populations require individualized medical assessment. Always inform your doctor if you are planning a pregnancy or have underlying organ dysfunction.

The pharmacodynamics of amivantamab are characterized by a dose-dependent saturation of the EGFR and MET receptors. In clinical studies, the weight-based dosing (1050 mg or 1400 mg) was shown to maintain serum concentrations above the levels required for target saturation throughout the dosing interval. There is no evidence of tolerance development; the drug remains active as long as the receptors are expressed and the signaling pathways are relevant to tumor survival.

| Parameter | Value |

|---|---|

| Bioavailability | 100% (Intravenous) |

| Protein Binding | Not applicable (Monoclonal Antibody) |

| Half-life | 11 - 15 days |

| Tmax | End of infusion |

| Metabolism | Proteolysis (not CYP-mediated) |

| Excretion | Reticuloendothelial system |

Amivantamab is a large, complex protein with a molecular weight of approximately 148 kDa. It is produced using recombinant DNA technology in a mammalian cell line (Chinese Hamster Ovary cells). The molecular formula is typical of a human IgG1 antibody, consisting of two heavy chains and two light chains. It is highly soluble in aqueous buffers used for infusion but sensitive to heat and mechanical agitation (shaking).

Amivantamab is classified as an Endoglycosidase [EPC] in some regulatory frameworks, but therapeutically it is a bispecific monoclonal antibody. It belongs to the broader class of antineoplastic agents and targeted therapies. It is unique in its ability to target two distinct drivers of oncogenesis simultaneously, distinguishing it from monospecific antibodies like cetuximab.