ojemda

Important safety information

Hemorrhage: Major hemorrhagic events can occur during treatment with OJEMDA. Withhold, resume at reduced dose, or permanently discontinue based on severity. ( 5.1 ) Skin Toxicity Including Photosensitivity : Advise patients to monitor for new or worsening skin reactions. Advise patients to limit direct ultraviolet exposure and use precautionary measures such as sunscreen, sunglasses and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose or permanently discontinue based on severity. ( 5.2 ) Hepatotoxicity: OJEMDA can cause hepatotoxicity. Monitor liver function tests prior to administration and during treatment. Withhold, reduce the dose or permanently discontinue based on severity. ( 5.3 ) Effect on Growth : Reductions in growth velocity have been reported. Routinely monitor growth in pediatric patients. ( 5.4 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise of the potential risk to a fetus and to use effective nonhormonal contraception. ( 5.5 , 8.1 , 8.3 ) NF1 Associated Tumors : Increased tumor growth may occur with OJEMDA. (5.6, 13.2) 5.1 Hemorrhage Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with OJEMDA. In the pooled safety population [see Adverse Reactions (6.1) ], hemorrhagic events occurred in 37% of patients, including epistaxis in 26% and intratumoral hemorrhage in 9%. Serious events of bleeding occurred in 5% of patients including Grade 5 tumor hemorrhage in 1 patient (0.6%). OJEMDA was permanently discontinued for hemorrhage in 2% of patients. Advise patients and caregivers of the risk of hemorrhage during treatment with OJEMDA. Monitor for signs and symptoms of hemorrhage and evaluate as clinically indicated . Withhold and resume at reduced dose upon improvement, or permanently discontinue based on severity [see Dosage and Administration (2.5) ]. 5.2 Skin Toxicity Including Photosensitivity OJEMDA can cause rash, including maculopapular rash and photosensitivity. In the pooled safety population [see Adverse Reactions (6.1) ], rash occurred in 67% of patients treated with OJEMDA, including Grade 3 rash in 12%. Rash resulted in dose interruption in 15% of patients and dose reduction in 7% of patients. OJEMDA was permanently discontinued due to rash in 1% of patients (n=2). In the pooled safety population, dermatitis acneiform occurred in 26% of patients treated with OJEMDA, including Grade 3 dermatitis acneiform in 0.6% of patients (n=1). Dose reduction was required in 2% of patients (n=3) due to dermatitis acneiform. Monitor for new or worsening skin reactions. Consider dermatologic consultation and initiate supportive care as clinically indicated. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction [see Dosage and Administration (2.5) ]. Photosensitivity In the pooled safety population [see Adverse Reactions (6.1) ], photosensitivity occurred in 12% of patients treated with OJEMDA, including Grade 3 events in 0.6% of patients (n=1). Advise patients to use precautionary measures against ultraviolet exposure such as use of sunscreen, sunglasses, and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction [see Dosage and Administration (2.5) ]. 5.3 Hepatotoxicity OJEMDA can cause hepatotoxicity. In the pooled safety population [see Adverse Reactions (6.1) ] , increased alanine aminotransferase (ALT) occurred in 42% and increased aspartate aminotransferase (AST) occurred in 74%, including Grade 3 ALT in 4% and increased AST in 2% of patients treated with OJEMDA. The median time to onset of increased ALT or AST was 14 days (range: 3 to 280 days). Increased ALT or AST leading to dose interruption occurred in 5% of patients and dose reductions were required in 1.2% of patients. Increased bilirubin occurred in 23% of patients, including Grade 3 increased bilirubin in 0.6% of patients (n=1) treated with OJEMDA. Hyperbilirubinemia leading to dose discontinuation occurred in a single adult patient with an advanced non-CNS solid tumor. Monitor liver function tests, including ALT, AST and bilirubin, before initiation of OJEMDA, one month after initiation and then every three months thereafter and as clinically indicated. Withhold and resume at the same or reduced dose upon improvement, or permanently discontinue OJEMDA based on the severity [see Dosage and Administration (2.5) ]. 5.4 Effect on Growth OJEMDA can cause reductions in growth velocity. In FIREFLY-1 [see Adverse Reactions (6.1) ] , treatment-emergent adverse effects on growth were reported in 46% of 133 patients 18 years of age or younger; 35% were Grade 3 or higher. Reduction in growth velocity resulted in dose interruption in 5% of patients, dose reduction in 2.3% of patients, and permanent discontinuation in 3% of patients. The median change from baseline in height percentile was -14 (z-score change -0.6) for evaluable patients on study for 12 months (N=107) and -20 (z-score change -0.9) for evaluable patients on study for 18 months (N=95). Growth velocity improved after interruption of treatment with OJEMDA. Among 81 evaluable patients, the median annualized growth velocity ranged from 0.86 to 1.8 cm/year during the 2-year treatment period. Of those, 17 patients had height measurements recorded at least 90 days off-treatment and had a 4.2 cm/year median annualized growth velocity. Routinely monitor patient growth during treatment with OJEMDA [see Adverse Reactions (6) , Use in Specific Populations (8.4) ]. 5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, OJEMDA may cause fetal harm when administered to a pregnant woman. Tovorafenib was embryo lethal in rats at doses approximately 0.8-fold the human exposure at the recommended dose based on area under the curve (AUC). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 28 days after the last dose, since OJEMDA can render some hormonal contraceptives ineffective [see Drug Interactions (7.2) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with OJEMDA and for 2 weeks after the last dose [see Use in Specific Populations (8.1 , 8.3) ]. 5.6 NF1 Associated Tumors Based on nonclinical data in NF1 models without BRAF alterations, tovorafenib may promote tumor growth in patients with NF1 tumors [see Nonclinical Toxicology (13.2) ]. Confirm evidence of a BRAF alteration prior to initiation of treatment with OJEMDA .