Cedazuridine and Decitabine

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. In combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Decitabine is a nucleoside metabolic inhibitor that is believed to exert its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in cancer cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.

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. Take INQOVI on an empty stomach.

None. None.

Myelosuppression: Severe myelosuppression, including fatal adverse reactions 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. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression In MDS or CMML, the most common adverse reactions (incidence ≥ 20%) are fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.

Drugs Metabolized by Cytidine Deaminase: Avoid coadministration with INQOVI. Effects of INQOVI on Other Drugs Drugs Metabolized by Cytidine Deaminase Cedazuridine is an inhibitor of the cytidine deaminase (CDA) enzyme. Coadministration of INQOVI with drugs that are metabolized by CDA may result in increased systemic exposure with potential for increased toxicity of these drugs. Avoid coadministration of INQOVI with drugs that are metabolized by CDA.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F).