Rybrevant Special Precautions

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infusion-related reactions: Infusion-related reactions commonly occurred in patients treated with amivantamab (see Adverse Reactions).
Prior to initial infusion (Week 1), antihistamines, antipyretics, and glucocorticoids should be administered to reduce the risk of IRRs. For subsequent doses, antihistamines and antipyretics should be administered. The initial infusion should be administered in split doses on Week 1, Day 1 and 2.
Patients should be treated in a setting with appropriate medical support to treat IRRs. Infusions should be interrupted at the first sign of IRRs of any severity and post-infusion medicinal products should be administered as clinically indicated. Upon resolution of symptoms, the infusion should be resumed at 50% of the previous rate. For recurrent Grade 3 or Grade 4 IRRs, Rybrevant should be permanently discontinued (see Dosage & Administration).
Interstitial lung disease: Interstitial lung disease (ILD) or ILD-like adverse reactions (e.g., pneumonitis) have been reported in patients treated with amivantamab, including fatal events (see Adverse Reactions). Patients should be monitored for symptoms indicative of ILD/pneumonitis (e.g., dyspnoea, cough, fever). If symptoms develop, treatment with Rybrevant should be interrupted pending investigation of these symptoms. Suspected ILD or ILD-like adverse reactions should be evaluated and appropriate treatment should be initiated as necessary. Rybrevant should be permanently discontinued in patients with confirmed ILD or ILD-like adverse reactions (see Dosage & Administration).
Venous thromboembolic (VTE) events with concomitant use with lazertinib: In patients receiving Rybrevant in combination with lazertinib, VTE events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), including fatal events, were reported (see Adverse Reactions). Consistent with clinical guidelines, patients should receive prophylactic dosing of either a direct acting oral anticoagulant (DOAC) or a low-molecular weight heparin (LMWH). Use of Vitamin K antagonists is not recommended.
Signs and symptoms of VTE events should be monitored. Patients with VTE events should be treated with anticoagulation as clinically indicated. For VTE events associated with clinical instability treatment should be withheld until the patient is clinically stable. Thereafter, both drugs can be resumed at the same dose.
In the event of recurrence despite appropriate anticoagulation, Rybrevant should be discontinued. Treatment can continue with lazertinib at the same dose (see Dosage & Administration).
Skin and nail reactions: Rash (including dermatitis acneiform), pruritus and dry skin occurred in patients treated with amivantamab (see Adverse Reactions). Patients should be instructed to limit sun exposure during and for 2 months after Rybrevant therapy. Protective clothing and use of broad-spectrum UVA/UVB sunscreen are advisable. Alcohol-free emollient cream is recommended for dry areas. A prophylactic approach to rash prevention should be considered. This includes prophylactic therapy with an oral antibiotic (e.g., doxycycline or minocycline, 100 mg twice daily) starting on Day 1 for the first 12 weeks of treatment and after completion of oral antibiotic therapy, topical antibiotic lotion to the scalp (e.g., clindamycin 1%) for the next 9 months of treatment. Non-comedogenic skin moisturiser on the face and whole body (except scalp) and chlorhexidine solution to wash hands and feet should be considered beginning on Day 1 and continued for the first 12 months of treatment.
Prescriptions for topical and/or oral antibiotics and topical corticosteroids are recommended to be available at the time of initial dosing to minimise any delay in reactive management should rash develop despite prophylactic treatment. If skin reactions develop, topical corticosteroids and topical and/or oral antibiotics should be administered. For Grade 3 or poorly-tolerated Grade 2 events, systemic antibiotics and oral steroids should also be administered. Patients presenting with severe rash that has an atypical appearance or distribution or lack improvement within 2 weeks should be referred promptly to a dermatologist. Rybrevant should be dose reduced, interrupted, or permanently discontinued based on severity (see Dosage & Administration).
Toxic epidermal necrolysis (TEN) has been reported. Treatment with this medicinal product should be discontinued if TEN is confirmed.
Eye disorders: Eye disorders, including keratitis, occurred in patients treated with amivantamab (see Adverse Reactions). Patients presenting with worsening eye symptoms should promptly be referred to an ophthalmologist and should discontinue use of contact lenses until symptoms are evaluated. For dose modifications for Grade 3 or 4 eye disorders, see Dosage & Administration.
Sodium content: This medicinal product contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially "sodium-free". This medicinal product may be diluted in sodium chloride 9 mg/mL (0.9%) solution for infusion. This should be taken into consideration for patients on a controlled sodium diet (see Special precautions for disposal and other handling under Cautions for Usage).
Polysorbate content: This medicinal product contains 0.6 mg of polysorbate 80 in each mL, which is equivalent to 4.2 mg per 7 mL vial. Polysorbates may cause hypersensitivity reactions.
Effects on ability to drive and use machines: Rybrevant may have moderate influence on the ability to drive and use machines. See Adverse Reactions (e.g., dizziness, fatigue, visual impairment). If patients experience treatment-related symptoms, including vision-related adverse reactions, affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.