Rybrevant Special Precautions

Infusion-Related Reactions: RYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension and vomiting. The median time to IRR onset is approximately 1 hour.
RYBREVANT with Carboplatin and Pemetrexed: Based on the pooled safety population [see Clinical Trials Experience under Adverse Reactions], IRR occurred in 50% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modifications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT due to IRR.
RYBREVANT as a Single Agent: In CHRYSALIS, [see Clinical Trials Experience under Adverse Reactions], IRR occurred in 66% of patients treated with RYBREVANT as a single agent. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62%, and 1.3% of patients permanently discontinued RYBREVANT due to IRR.
Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended [see Recommended Premedications under Dosage & Administration]. Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions [see Administration under Dosage & Administration].
Monitor patients for signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Interstitial Lung Disease/Pneumonitis: RYBREVANT can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
RYBREVANT with Carboplatin and Pemetrexed: Based on the pooled safety population [see Clinical Trials Experience under Adverse Reactions], ILD/pneumonitis occurred in 2.1% treated with RYBREVANT in combination with carboplatin and pemetrexed with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT due to ILD/pneumonitis.
RYBREVANT as a Single Agent: In CHRYSALIS, [see Clinical Trials Experience under Adverse Reactions], ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT as a single agent, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT due to ILD/pneumonitis.
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Dermatologic Adverse Reactions: RYBREVANT can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.
RYBREVANT with Carboplatin and Pemetrexed: Based on the pooled safety population [see Clinical Trials Experience under Adverse Reactions], rash occurred in 82% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT and 3.1% discontinued pemetrexed.
RYBREVANT as a Single Agent: In CHRYSALIS, [see Clinical Trials Experience under Adverse Reactions], rash occurred in 74% of patients treated with RYBREVANT as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients [see Clinical Trials Experience under Adverse Reactions].
Toxic epidermal necrolysis (TEN) occurred in one patient (0.3%) treated with RYBREVANT as a single agent.
Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin.
When initiating treatment with RYBREVANT, administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic adverse reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Ocular Toxicity: RYBREVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.
RYBREVANT with Carboplatin and Pemetrexed: Based on the pooled safety population [see Clinical Trials Experience under Adverse Reactions], ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed. All events were Grade 1 or 2.
RYBREVANT as a Single Agent: In CHRYSALIS, [see Clinical Trials Experience under Adverse Reactions], keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2.
Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Administration of other EGFR inhibitor molecules to pregnant animals has resulted in an increased incidence of impairment of embryo-fetal development, embryo lethality, and abortion. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT. [See Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation.]
Use in Children: The safety and efficacy of RYBREVANT have not been established in pediatric patients.
Use in the Elderly: Of the 130 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the MARIPOSA-2 study, 40% were ≥65 years of age and 10% were ≥75 years of age.
Of the 151 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the PAPILLON study, 37% were ≥65 years of age and 8% were ≥75 years of age.
Of the 302 patients with locally advanced or metastatic NSCLC treated with RYBREVANT as a single agent in the CHRYSALIS study, 39% were ≥65 years of age and 11% were ≥75 years of age.
No clinically important differences in safety or efficacy were observed between patients who were ≥65 years of age and younger patients.