INQOVI

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. INQOVI is a combination of decitabine, a nucleoside metabolic inhibitor, and cedazuridine, a cytidine deaminase inhibitor, indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION The recommended dosage of INQOVI is 1 tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on Days 1 through 5 of each 28-day cycle. ( 2.2 ) Take INQOVI on an empty stomach. ( 2.2 ) 2.1 Important Administration Information Do NOT substitute INQOVI for an intravenous decitabine product within a cycle. Consider administering antiemetics prior to each dose to minimize nausea and vomiting [see Adverse Reactions (6.1) ] . 2.2 Recommended Dosage The recommended dosage of INQOVI is 1 tablet (containing 35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of each 28-day cycle for a minimum of 4 cycles until disease progression or unacceptable toxicity. A complete or partial response may take longer than 4 cycles. Instruct patients of the following: Take INQOVI at the same time each day. Swallow tablets whole. Do not cut, crush, or chew tablets. Do not consume food 2 hours before and 2 hours after each dose. Take one tablet a day for 5 days in each cycle. If the patient misses a dose within 12 hours of the time it is usually taken, instruct patients to take the missed dose as soon as possible and then to resume the normal daily dosing schedule. Extend the dosing period by one day for every missed dose to complete 5 daily doses for each cycle. Do not take an additional dose if vomiting occurs after INQOVI administration but continue with the next schedule dose. INQOVI is a hazardous drug. Follow applicable special handling and disposal procedures. 1 2.3 Monitoring and Dosage Modifications for Adverse Reactions Hematologic Adverse Reactions Obtain complete blood cell counts prior to initiating INQOVI and before each cycle. Delay the next cycle if absolute neutrophil count (ANC) is less than 1,000/μL and platelets are less than 50,000/μL in the absence of active disease. Monitor complete blood cell counts until ANC is 1,000/μL or greater and platelets are 50,000/μL or greater [see Warnings and Precautions (5.1) ] . If hematologic recovery occurs (ANC at least 1,000/μL and platelets at least 50,000/μL) within 2 weeks of achieving remission, continue INQOVI at the same dose. If hematologic recovery does not occur (ANC at least 1,000/μL and platelets at least 50,000/μL) within 2 weeks of achieving remission, Delay INQOVI for up to 2 additional weeks AND Resume at a reduced dose by administering INQOVI on Days 1 through 4. Consider further dose reductions in the order listed in Table 1 if myelosuppression persists after a dose reduction. Maintain or increase dose in subsequent cycles as clinically indicated. Table 1: Recommended INQOVI Dose Reductions for Myelosuppression Dose Reduction Dosage First 1 tablet orally once daily on Days 1 through 4 Second 1 tablet orally once daily on Days 1 through 3 Third 1 tablet orally once daily on Days 1, 3 and 5 Manage persistent severe neutropenia and febrile neutropenia with supportive treatment [see Warnings and Precautions (5.1) ] . Non-Hematologic Adverse Reactions Delay the next cycle for the following non-hematologic adverse reactions and resume at the same or reduced dose upon resolution: Serum creatinine 2 mg/dL or greater Serum bilirubin 2 times upper limit of normal (ULN) or greater Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 times ULN or greater Active or uncontrolled infection Warnings and cautions 5 WARNINGS AND PRECAUTIONS Myelosuppression : Fatal and serious myelosuppression and infectious complications can occur. Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor for response and toxicity. Delay the next cycle and resume at the same or reduced dose as recommended. ( 2.3 , 5.1 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effect