Rybrevant Special Precautions

The data described in Precautions reflects the safety profile of 380 patients with locally advanced or metastatic NSCLC who received 1050 mg (for patients <80 kg) or 1400 mg (for patients ≥80 kg) of RYBREVANT monotherapy in Study EDI1001.
Infusion-related reactions: Infusion-related reactions occurred in 67% of patients treated with RYBREVANT. Ninety-eight percent of IRRs were Grade 1-2. Ninety-nine percent of IRRs occurred at the first infusion with a median time to onset of 60 minutes. The most frequent signs and symptoms include chills, nausea, dyspnea, flushing, chest discomfort, and vomiting.
Prior to initial infusion (Week 1) of RYBREVANT, administer antihistamines, antipyretics, and glucocorticoids to reduce the risk of IRRs. For subsequent doses, administer antihistamines and antipyretics. Administer the initial infusion of RYBREVANT in split doses on Week 1, Days 1 and 2 (see Dosage & Administration).
Treat patients with RYBREVANT in a setting with appropriate medical support necessary to treat IRRs. Interrupt RYBREVANT infusion at the first sign of IRRs and institute post-infusion medication as clinically indicated. Upon resolution of symptoms, resume the infusion at 50% of the previous rate. For recurrent Grade 3 or 4 IRRs, permanently discontinue RYBREVANT (see Dosage & Administration).
Interstitial lung disease: Interstitial lung disease (ILD) or ILD-like adverse reactions (e.g. pneumonitis) occurred in 2.6% of patients treated with RYBREVANT. Patients with a medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD have not been studied.
Monitor patients for symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). If symptoms develop, interrupt treatment with RYBREVANT pending investigation of these symptoms. Evaluate suspected ILD and initiate appropriate treatment as necessary. Discontinue RYBREVANT in patients with confirmed ILD (see Dosage & Administration).
Skin and nail reactions: Rash (including dermatitis acneiform), pruritus and dry skin occurred in patients treated with RYBREVANT. Most cases were Grade 1 or 2, with Grade 3 events occurring in 3% of patients. Rash leading to RYBREVANT discontinuation occurred in 0.3% of patients. Rash usually developed within the first 4 weeks of therapy, with a median time to onset of 14 days. Nail toxicity occurred in patients treated with RYBREVANT. Most events were Grade 1 or 2, with Grade 3 nail toxicity occurring in 1.8% of patients.
Toxic epidermal necrolysis (TEN) has been reported. Permanently discontinue RYBREVANT if TEN is confirmed.
Instruct patients to limit sun exposure during and for 2 months after RYBREVANT therapy. Protective clothing and use of sunscreen is advisable. Alcohol-free emollient cream is recommended for dry areas with the use of RYBREVANT. If skin or nail reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 or poorly-tolerated Grade 2 events, add systemic antibiotics and oral steroids and consider dermatologic consultation. Withhold, dose reduce, or permanently discontinue RYBREVANT based on severity (see Dosage & Administration).
Eye disorders: Eye disorders, including keratitis (0.5%), occurred in patients treated with RYBREVANT. Other reported adverse reactions included dry eye, blurred vision, eye pruritus, visual impairment, aberrant eyelash growth, ocular hyperemia, conjunctival hyperemia, blepharitis and uveitis. All events were Grade 1-2. Refer patients presenting with worsening eye symptoms promptly to an ophthalmologist and advise discontinuation of contact lenses until symptoms are evaluated.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. If patients experience treatment-related symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.