Overview
11 DESCRIPTION Decitabine Decitabine is a nucleoside metabolic inhibitor. Decitabine is a white to off-white solid with the molecular formula of C 8 H 12 N 4 O 4 and a molecular weight of 228.21 daltons. Its international union of pure and applied chemistry (IUPAC) chemical name is 4-amino-1-[(2 R ,4 S ,5 R )-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2(1 H )-one and it has the...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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.
Indications
- 1 INDICATIONS AND USAGE 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.
Common Doses
- 35 mg
- 100 mg
- 2 mg
Dosage
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) ]. Take INQOVI on an empty stomach at least 2 hours before or 2 hours after eating.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] 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.
Interactions
- 7 DRUG INTERACTIONS Drugs Metabolized by Cytidine Deaminase : Avoid coadministration with INQOVI. ( 7 ) 7.1 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 [see Clinical Pharmacology (12.3) ] . Avoid coadministration of INQOVI with drugs that are metabolized by CDA.