b'24INQOVI (decitabine and cedazuridine) tablets, for oral use.reactions occurred in 6% of patients. These included sepsis (1%), septic Prescription Only.shock (1%), pneumonia (1%), respiratory failure (1%), and one case each Initial U.S. Approval: 2020of cerebral hemorrhage and sudden death. Brief Summary of Prescribing InformationPermanent discontinuation due to an adverse reaction occurred in 5%For complete Prescribing Information, consult official package insert.of patients who received INQOVI. The most frequent adverse reactions 1 INDICATIONS AND USAGEresulting in permanent discontinuation were febrile neutropenia (1%) and INQOVI is indicated for treatment of adult patients with myelodysplasticpneumonia (1%). syndromes (MDS), including previously treated and untreated, de novoDose interruptions due to an adverse reaction occurred in 41% of patients and secondary MDS with the following French-American-British subtypeswho received INQOVI. Adverse reactions requiring dosage interruptions in (refractory anemia, refractory anemia with ringed sideroblasts, refractory5% of patients who received INQOVI included neutropenia (18%), febrile anemia with excess blasts, and chronic myelomonocytic leukemia [CMML])neutropenia (8%), thrombocytopenia (6%), and anemia (5%). and intermediate-1, intermediate-2, and high-risk International PrognosticDose reductions due to an adverse reaction occurred in 19% of patients who Scoring System groups.received INQOVI. Adverse reactions requiring dosage reductions in2%4 CONTRAINDICATIONSof patients who received INQOVI included neutropenia (12%), anemia (3%), None.and thrombocytopenia (3%). 5 WARNINGS AND PRECAUTIONSThe most common adverse reactions ( 20%) were fatigue, constipation, 5.1 Myelosuppressionhemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, Fatal and serious myelosuppression can occur with INQOVI. Based onrash, dizziness, febrile neutropenia, edema, headache, cough, decreased laboratory values, new or worsening thrombocytopenia occurred in 82% appetite, upper respiratory tract infection, pneumonia, and transaminase of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred increased. The most common Grade 3 or 4 laboratory abnormalitiesin 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred( 50%) were leukocytes decreased, platelet count decreased, neutrophil in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropeniacount decreased, and hemoglobin decreased. occurred in 33% of patients, with Grade 3 or 4 occurring in 32%.Table 2 summarizes the adverse reactions in the pooled safety population. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction orTable 2: Adverse Reactions ( 10%) in Patients Who Received INQOVI interruption, occurring in 36% of patients. Permanent discontinuation duein Pooled Safety Populationto myelosuppression (febrile neutropenia) occurred in 1% of patients.Intravenous Myelosuppression and worsening neutropenia may occur more frequentlyINQOVI DecitabineINQOVIin the first or second treatment cycles and may not necessarily indicateCycle 1Cycle 1All Cycles progression of underlying MDS.N=107 N=106 N=208Fatal and serious infectious complications can occur with INQOVI. PneumoniaAllGradesAllGradesAllGradesoccurred in 21% of patients, with Grade 3 or 4 occurring in 15%. SepsisGrades3-4 Grades3-4Grades3-4occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. FatalAdverse Reactions (%) (%) (%) (%) (%) (%)pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1% [see Adverse Reactions (6.1) in the full Prescribing Information].General disorders and administration site conditionsObtain complete blood cell counts prior to initiation of INQOVI, prior toFatigue1 29 2 25 0 55 5each cycle, and as clinically indicated to monitor response and toxicity.Hemorrhage2 24 2 17 0 43 3Administer growth factors and anti-infective therapies for treatment orEdema 10 0 11 0 30 0.5prophylaxis as appropriate. Delay the next cycle and resume at the same or3reduced dose as recommended [see Dosage and Administration (2.3) inPyrexia 7 0 7 0 19 1the full Prescribing Information].Gastrointestinal disorders5.2 Embryo-Fetal ToxicityConstipation4 20 0 23 0 44 0Based on findings from human data, animal studies, and its mechanism Mucositis5 18 1 24 2 41 4of action, INQOVI can cause fetal harm when administered to a pregnant woman. In nonclinical studies with decitabine in mice and rats, decitabineNausea 25 0 16 0 40 0.5was teratogenic, fetotoxic, and embryotoxic at doses less than theDiarrhea6 16 0 11 0 37 1recommended human dose.Transaminase Advise pregnant women of the potential risk to a fetus. Advise females ofincreased7 12 1 3 0 21 3reproductive potential to use effective contraception during treatment withAbdominal pain8 9 0 7 0 19 1INQOVI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception duringVomiting 5 0 5 0 15 0treatment with INQOVI and for 3 months after the last dose [see Use inMusculoskeletal and connective tissue disordersSpecific Populations (8.1, 8.3) in the full Prescribing Information].Myalgia9 9 2 16 1 42 36 ADVERSE REACTIONSArthralgia10 9 1 13 1 40 3The following clinically significant adverse reactions are describedRespiratory, thoracic, and mediastinal disorderselsewhere in the labeling:Myelosuppression [see Warnings and Precautions (5.1) in the fullDyspnea11 17 3 9 3 38 6Prescribing Information]Cough12 7 0 8 0 28 06.1 Clinical Trials ExperienceBlood & lymphatic system disordersBecause clinical trials are conducted under widely variable conditions,Febrile neutropenia 10 10 13 13 33 32adverse event rates observed in clinical trials of a drug cannot be directlySkin and subcutaneous tissue disorderscompared with rates of clinical trials of another drug and may not reflect the rates observed in practice.Rash13 12 1 11 1 33 0.5Myelodysplastic Syndrome and Chronic Myelomonocytic LeukemiaNervous system disordersThe safety of INQOVI was evaluated in a pooled safety population thatDizziness14161110332includes patients enrolled in Study ASTX727-01-B and Study ASTX727-02Headache15220130300[see Clinical Studies (14) in the full Prescribing Information].Neuropathy 408013016Patients were randomized to receive INQOVI (35 mg decitabine and Metabolism and nutritional disorders100 mg cedazuridine) orally once daily on Days 1 through 5 in Cycle 1and decitabine 20 mg/m2 intravenously on Days 1 through 5 in Cycle 2, Decreased appetite10160242or the reverse sequence, and then INQOVI (35 mg decitabine and 100 mgInfections and cedazuridine) orally once daily on Days 1 through 5 of each 28-day cycle infestationsin Cycles 3 and beyond. Patients were allowed to have one prior cycle ofUpper respiratory decitabine or azacitidine and there was no limit for body weight or surfacetract infection176030231area. Among the patients who received INQOVI, 61% of patients were exposed for 6 months or longer and 24% were exposed to INQOVI forPneumonia1877752115greater than 1 year.Sepsis1966211411Serious adverse reactions occurred in 68% of patients who receivedCellulitis204132125INQOVI. Serious adverse reactions in5% of patients included febrile(continued)neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse'