LYSODREN (MITOTANE) TABLET [ESTEVE PHARMACEUTICALS, S.A.] The recommended dosage reduction for adverse reactions is to decrease the usual daily dose by 500 – 1000 mg. Table 1 describes the dosage modifications for specific adverse reactions. Table 1: Recommended Dosage Modifications for LYSODREN for Adverse Reactions Adverse Reaction Severity * Dosage Modification * Severity defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Adrenal Crisis and Adrenal Insufficiency [see Warnings and Precautions (5.1) ] All Grades Withhold LYSODREN during shock, trauma, infection or adrenal insufficiency until recovery to Grade ≤1 or baseline. Resume LYSODREN at a reduced dose or permanently discontinue based on severity. Central Nervous System (CNS) Toxicity [see Warnings and Precautions (5.2) ] Grade 2 Measure mitotane plasma level and modify the dosage according to the following recommendations: Mitotane plasma level less than 14 mg/L: reduce the daily dose by 1000 mg. Mitotane plasma level in the therapeutic window (14 to 20 mg/L): reduce the daily dose by 1500 mg. Mitotane plasma level above 20 mg/L: withhold LYSODREN until recovery to grade ≤1 or baseline. Seven to ten (7-10) days after sympto erapeutic window (14 to 20 mg/L): reduce the daily dose by 1500 mg. Mitotane plasma level above 20 mg/L: withhold LYSODREN until recovery to grade ≤1 or baseline. Seven to ten (7-10) days after symptoms resolve, resume LYSODREN at reduced dose. Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to grade ≤ 1 or baseline. Seven to ten (7-10) days after symptoms resolve, resume LYSODREN at a reduced dose or permanently discontinue based on severity. Gastrointestinal (GI) toxicity Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Mitotane plasma level less than 14 mg/L: reduce the daily dose by 1000 mg. Mitotane plasma level in the therapeutic window (14 to 20 mg/L): reduce the daily dose by 1500 mg. Mitotane plasma level above 20 mg/L: withhold LYSODREN until recovery to grade ≤1 or baseline. After symptoms resolve, resume LYSODREN at a reduced dose or permanently discontinue based on severity. Hepatotoxicity [see Warnings and Precautions (5.4) ] Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following ced dose or permanently discontinue based on severity. Hepatotoxicity [see Warnings and Precautions (5.4) ] Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to Grade ≤1 or baseline. Resume at a reduced dose or permanently discontinue based on severity. Hematologic Toxicity [see Warnings and Precautions (5.5) ] Grade 2 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to Grade ≤1 or baseline. Resume at the same dose. Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to Grade ≤1 or baseline. Resume at a reduced dose or permanently discontinue based on severity. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 2 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to Grade ≤1 or baseline. Resume at the same dose. Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN u SODREN until recovery to Grade ≤1 or baseline. Resume at the same dose. Grade 3 or 4 Measure mitotane plasma level and modify the dosage according to the following recommendations: Withhold LYSODREN until recovery to Grade ≤1 or baseline. Resume at a reduced dose or permanently discontinue based on severity.