b'INQOVI (decitabine and cedazuridine) tablets, for oral use.decitabine or azacitidine and there was no limit for body weight or surface Prescription Only.area. Among the patients who received INQOVI, 61% of patients were Initial U.S. Approval: 2020exposed for 6 months or longer and 24% were exposed to INQOVI for Brief Summary of Prescribing Informationgreater than 1 year. For complete Prescribing Information, consult official package insert.Serious adverse reactions occurred in 68% of patients who received 1 INDICATIONS AND USAGEINQOVI. Serious adverse reactions in 5% of patients included febrile INQOVI is indicated for treatment of adult patients with myelodysplasticneutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse syndromes (MDS), including previously treated and untreated, de novoreactions occurred in 6% of patients. These included sepsis (1%), septic and secondary MDS with the following French-American-British subtypesshock (1%), pneumonia (1%), respiratory failure (1%), and one case each (refractory anemia, refractory anemia with ringed sideroblasts, refractoryof cerebral hemorrhage and sudden death. anemia with excess blasts, and chronic myelomonocytic leukemia [CMML])Permanent discontinuation due to an adverse reaction occurred in 5%and intermediate-1, intermediate-2, and high-risk International Prognosticof patients who received INQOVI. The most frequent adverse reactions Scoring System groups.resulting in permanent discontinuation were febrile neutropenia (1%) and 4 CONTRAINDICATIONSpneumonia (1%). None.Dose interruptions due to an adverse reaction occurred in 41% of patients 5 WARNINGS AND PRECAUTIONSwho received INQOVI. Adverse reactions requiring dosage interruptions in 5.1 Myelosuppression 5% of patients who received INQOVI included neutropenia (18%), febrile Fatal and serious myelosuppression can occur with INQOVI. Based onneutropenia (8%), thrombocytopenia (6%), and anemia (5%). laboratory values, new or worsening thrombocytopenia occurred in 82% Dose reductions due to an adverse reaction occurred in 19% of patients who of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred received INQOVI. Adverse reactions requiring dosage reductions in 2%in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurredof patients who received INQOVI included neutropenia (12%), anemia (3%), in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropeniaand thrombocytopenia (3%). occurred in 33% of patients, with Grade 3 or 4 occurring in 32%.The most common adverse reactions ( 20%) were fatigue, constipation, Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrilehemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, neutropenia) is the most frequent cause of INQOVI dose reduction orrash, dizziness, febrile neutropenia, edema, headache, cough, decreased interruption, occurring in 36% of patients. Permanent discontinuation dueappetite, upper respiratory tract infection, pneumonia, and transaminase to myelosuppression (febrile neutropenia) occurred in 1% of patients.increased. The most common Grade 3 or 4 laboratory abnormalitiesMyelosuppression and worsening neutropenia may occur more frequently( 50%) were leukocytes decreased, platelet count decreased, neutrophil in the first or second treatment cycles and may not necessarily indicatecount decreased, and hemoglobin decreased. progression of underlying MDS.Table 2 summarizes the adverse reactions in the pooled safety population. Fatal and serious infectious complications can occur with INQOVI. PneumoniaTable 2: Adverse Reactions ( 10%) in Patients Who Received INQOVI occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsisin Pooled Safety Populationoccurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septicIntravenous shock in 1% [see Adverse Reactions (6.1) in the full Prescribing Information] INQOVI DecitabineINQOVI. Obtain complete blood cell counts prior to initiation of INQOVI, prior toCycle 1Cycle 1All Cycles each cycle, and as clinically indicated to monitor response and toxicity.N=107 N=106 N=208Administer growth factors and anti-infective therapies for treatment orAllGradesAllGradesAllGradesprophylaxis as appropriate. Delay the next cycle and resume at the same orGrades3-4 Grades3-4Grades3-4reduced dose as recommended [see Dosage and Administration (2.3) inAdverse Reactions (%) (%) (%) (%) (%) (%)the full Prescribing Information].General disorders and administration site conditions5.2 Embryo-Fetal ToxicityFatigue1 29 2 25 0 55 5Based on findings from human data, animal studies, and its mechanism Hemorrhage 24 2 17 0 43 3of action, INQOVI can cause fetal harm when administered to a pregnant2woman. In nonclinical studies with decitabine in mice and rats, decitabineEdema3 10 0 11 0 30 0.5was teratogenic, fetotoxic, and embryotoxic at doses less than thePyrexia 7 0 7 0 19 1recommended human dose.Gastrointestinal disordersAdvise pregnant women of the potential risk to a fetus. Advise females ofConstipation 20 0 23 0 44 0reproductive potential to use effective contraception during treatment with4INQOVI and for 6 months after the last dose. Advise males with femaleMucositis5 18 1 24 2 41 4partners of reproductive potential to use effective contraception duringNausea 25 0 16 0 40 0.5treatment with INQOVI and for 3 months after the last dose [see Use inDiarrhea 16 0 11 0 37 1Specific Populations (8.1, 8.3) in the full Prescribing Information] 6. Transaminase 6 ADVERSE REACTIONSincreased7 12 1 3 0 21 3The following clinically significant adverse reactions are described elsewhere in the labeling:Abdominal pain8 9 0 7 0 19 1\x7f Myelosuppression [see Warnings and Precautions (5.1) in the fullVomiting 5 0 5 0 15 0Prescribing Information] Musculoskeletal and connective tissue disorders 6.1 Clinical Trials ExperienceMyalgia9 9 2 16 1 42 3Because clinical trials are conducted under widely variable conditions,Arthralgia10 9 1 13 1 40 3adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflectRespiratory, thoracic, and mediastinal disordersthe rates observed in practice.Dyspnea11 17 3 9 3 38 6Myelodysplastic Syndrome and Chronic Myelomonocytic LeukemiaCough12 7 0 8 0 28 0The safety of INQOVI was evaluated in a pooled safety population thatBlood & lymphatic system disordersincludes patients enrolled in Study ASTX727-01-B and Study ASTX727-02Febrile neutropenia 10 10 13 13 33 32[see Clinical Studies (14) in the full Prescribing Information]. Patients were randomized to receive INQOVI (35 mg decitabine and Skin and subcutaneous tissue disorders100 mg cedazuridine) orally once daily on Days 1 through 5 in Cycle 1 Rash13 12 1 11 1 33 0.5and decitabine 20 mg/m2 intravenously on Days 1 through 5 in Cycle 2, (continued)or the reverse sequence, and then INQOVI (35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of each 28-day cyclein Cycles 3 and beyond. Patients were allowed to have one prior cycle of'