rybrevant faspro

Important safety information

Hypersensitivity and Administration-Related Reactions (ARR) : Premedicate with antihistamines, antipyretics, and glucocorticoids. Monitor patients for any signs and symptoms of ARRs. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO based on severity. ( 2.8 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening symptoms indicative of ILD/pneumonitis. Immediately withhold RYBREVANT FASPRO in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. ( 2.8 , 5.2 ) Venous Thromboembolic (VTE) Events with Concomitant Use with Lazertinib: Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as medically appropriate. Withhold RYBREVANT FASPRO and lazertinib based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO and lazertinib at the same dose at the discretion of the healthcare provider. Permanently discontinue RYBREVANT FASPRO and continue lazertinib for recurrent VTE despite therapeutic anticoagulation. ( 2.8 , 5.3 ) Dermatologic Adverse Reactions : Can cause severe rash including toxic epidermal necrolysis (TEN) and dermatitis acneiform. At treatment initiation, prophylactic and concomitant medications are recommended. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO based on severity. ( 2.5 , 2.8 , 5.4 ) Ocular Toxicity : Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO based on severity. ( 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Hypersensitivity and Administration-Related Reactions RYBREVANT FASPRO can cause hypersensitivity and administration-related reactions (ARR); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours. Local injection site reactions are described separately in Section 6.1. RYBREVANT FASPRO (Subcutaneous Amivantamab) with Lazertinib In PALOMA-3 [see Adverse Reactions (6.1) ] , in the 206 patients who received RYBREVANT FASPRO in combination with lazertinib, all Grade ARR occurred in 13%, including 0.5% Grade 3. Of the patients who experienced ARR, 89% occurred with the initial dose (Week 1, Day 1). Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT FASPRO as recommended [see Dosage and Administration (2.4) ] . Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO injection, if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO based on severity [see Dosage and Administration (2.8) ] . 5.2 Interstitial Lung Disease/Pneumonitis RYBREVANT FASPRO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. RYBREVANT FASPRO (Subcutaneous Amivantamab) with Lazertinib In PALOMA-3 [see Adverse Reactions (6.1) ] , in 206 patients who received RYBREVANT FASPRO in combination with lazertinib, ILD/pneumonitis occurred in 6%, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9%. In total, 5% of patients permanently discontinued RYBREVANT FASPRO and lazertinib due to ILD/pneumonitis. Intravenous Amivantamab with Lazertinib In MARIPOSA [see Adverse Reactions (6.1) ] , in 421 patients who received intravenous amivantamab in combination with lazertinib, ILD/pneumonitis occurred in 3.1%, including Grade 3 in 1% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued intravenous amivantamab and lazertinib due to ILD/pneumonitis. Intravenous Amivantamab with Carboplatin and Pemetrexed Based on the pooled safety population [see Adverse Reactions (6.1) ] , in 281 patients who received intravenous amivantamab in combination with carboplatin and pemetrexed, ILD/pneumonitis occurred in 2.1%, including 1.8% Grade 3 ILD/pneumonitis. Of these, 2.1% of patients permanently discontinued intravenous amivantamab due to ILD/pneumonitis. Intravenous Amivantamab as a Single Agent In CHRYSALIS [see Adverse Reactions (6.1) ] , in 302 patients who received intravenous amivantamab as a single agent, ILD/pneumonitis occurred in 3.3%, including 0.7% Grade 3. Three patients (1%) permanently discontinued intravenous amivantamab due to ILD/pneumonitis. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT FASPRO in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed [see Dosage and Administration (2.8) ] . 5.3 Venous Thromboembolic (VTE) Events with Concomitant Use with Lazertinib RYBREVANT FASPRO in combination with lazertinib can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of therapy [see Adverse Reactions (6.1) ] . RYBREVANT FASPRO (Subcutaneous Amivantamab) with Lazertinib In PALOMA-3 [see Adverse Reactions (6.1) ] , in the 206 patients who received RYBREVANT FASPRO in combination with lazertinib, all Grade VTE occurred in 11% and 1.5% were Grade 3. Of the 206 patients treated with RYBREVANT FASPRO in combination with lazertinib, 80% received prophylactic anticoagulation at study entry. In the 164 patients treated with RYBREVANT FASPRO in combination with lazertinib who received prophylactic anticoagulation, all Grade VTE occurred in 7%. In the 42 patients treated with RYBREVANT FASPRO in combination with lazertinib who did not receive prophylactic anticoagulation, all Grade VTE occurred in 17%. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390). Intravenous Amivantamab with Lazertinib In MARIPOSA [see Adverse Reactions (6.1) ] , in 421 patients who received intravenous amivantamab in combination with lazertinib, VTEs occurred in 36%, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of intravenous amivantamab, 1% of patients had VTE leading to dose reductions of intravenous amivantamab, and 3.1% of patients had VTE leading to permanent discontinuation of intravenous amivantamab. The median time to onset of VTEs was 84 days (range: 6 to 777). Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT FASPRO and lazertinib based on severity [see Dosage and Administration (2.8) ] . Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO and lazertinib at the same dose level at the discretion of the healthcare provider [see Dosage and Administration (2.8) ] . In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT FASPRO. Treatment can continue with lazertinib at the same dose level at the discretion of the healthcare provider [see Dosage and Administration (2.8) ] . Refer to the lazertinib prescribing information for recommended lazertinib dosage modification. 5.4 Dermatologic Adverse Reactions RYBREVANT FASPRO can cause severe rash including toxic epidermal necrolysis…