In July 2020, the U.S. Food and Drug Administration approved decitabine and cedazuridine (Inqovi®) tablets for the treatment of adults with myelodysplastic syndromes (MDS).
Oral formulation of the antimetabolite decitabine combined with an inhibitor of the enzyme that degrades decitabine in the gastrointestinal tract
Mechanism of Action
Decitabine is a nucleoside metabolic inhibitor that inhibits the methylation of DNA that causes cellular differentiation and leads to cell death. Decitabine is available as an injectable product as a single agent. The oral combination product includes a cedazuridine, a substance that blocks the enzyme cytidine deaminase that breaks down decitabine in the gastrointestinal tract. The combination of this cedazuridine increases the exposure of decitabine when administered orally without substantial degradation in the gut and liver.
Treatment of adult patients with previously treated and untreated MDS
One tablet (decitabine 35 mg and cedazuridine 100 mg) orally daily for five days each 28 days
Give by mouth on an empty stomach for five days on days 1–5 of a 28-day regimen at the same time each day. Tablets should be taken whole, not cut or crushed. Do not eat food for two hours before or after each dose.
Severe (grades 3 and 4) myelosuppression has been reported. Adverse reactions in more than 20% of patients include fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and increased transaminase levels.
- Antiemetics may be required prior to each dose to minimize treatment-related nausea or vomiting.
- If the patient misses a dose within 12 hours of its usual time, take the dose as soon as possible and then resume the normal daily dosing time.
- Extend the dosing period by one day for every missed dose to complete five daily doses for each cycle.
- Dose modifications or delays are recommended for hematologic toxicity, increased serum creatinine, increased bilirubin and hepatic transaminates, and infection.
- Assess for drug-drug interactions prior to therapy, particularly for drugs that are metabolized by cytidine deaminase. Cedazuridine inhibits cytidine deaminase and may inhibit the metabolism of some agents, increasing their concentrations and effects.
- Because of the risk of embryo-fetal toxicity, all patients should use effective birth control to avoid pregnancy or getting a partner pregnant during therapy and for three (men) and six (women) months after the last dose.
- Maintain the drug in its original package. Tablets are supplied in blister cards in a child-resistant carton.
- Store the medication at room temperature, out of the reach of children and pets.
- Use hazardous drug precautions when handling the drug.
- Do not exceed the five-day regimen for each cycle.
- Avoid pregnancy or getting a partner pregnant during therapy and for three (men) and six (women) months after treatment has completed. Do not breastfeed while taking this medication.
- Keep the medication in its original package and handle medication as hazardous drug.
No change in effectiveness has been found between patients older than 65 years and younger patients.
Use hazardous drug precautions.