Decitabine/cedazuridine

Decitabine/cedazuridine is a combination drug used in the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). It is a combination of two active ingredients: decitabine, a cytidine analogue and DNA methyltransferase inhibitor, and cedazuridine, a cytidine deaminase inhibitor.

Mechanism of Action

The combination of decitabine and cedazuridine works synergistically to inhibit DNA methylation, a process that is often dysregulated in cancer. Decitabine is incorporated into the DNA where it traps and inhibits DNA methyltransferases, leading to hypomethylation and reactivation of silenced genes. Cedazuridine inhibits the degradation of decitabine in the gut and liver, thereby increasing its bioavailability.

Pharmacokinetics

Following oral administration, cedazuridine inhibits the action of cytidine deaminase in the gut and liver, allowing more decitabine to reach the systemic circulation. The combination drug is rapidly absorbed, with peak plasma concentrations reached within 1-2 hours. It is primarily excreted in the urine.

Clinical Use

Decitabine/cedazuridine is indicated for the treatment of adults with MDS, including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes, and CMML. It is also used in patients with acute myeloid leukemia who are not candidates for standard induction chemotherapy.

Side Effects

Common side effects include fatigue, constipation, hemorrhage, muscle pain, nausea, pneumonia, and decreased appetite. Serious side effects may include myelosuppression, infections, and liver problems.

See Also

• Myelodysplastic syndrome
• Chronic myelomonocytic leukemia
• DNA methylation
• Cytidine analogue
• DNA methyltransferase inhibitor
• Cytidine deaminase inhibitor