decitabine/cedazuridine

General

Pronunciation:
de-sye-ta-been/sed-az-ure-i-deen

Trade Name(s)

Inqovi

Ther. Class.

antineoplastics

Pharm. Class.

antimetabolites

cytidine deaminase inhibitors

Indications

Treatment of various myelodysplastic syndromes (MDS).

Action

Decitabine– inhibits DNA methyltransferase, causing apoptosis; has more effect on rapidly replicating cells. Cedazuridine– acts as a cytidine deaminase inhibitor, preventing the degradation of decitabine in the GI tract and liver; leads to an increase in systemic exposure of decitabine.

Therapeutic Effect(s):

Decreased progression of disease and improved rate of conversion from bring transfusion dependent to independent of red blood cell and platelet transfusions.

Pharmacokinetics

Absorption: Cedazuridine increases the oral bioavailability of decitabine.

Distribution: Widely distributed to extravascular tissues.

Metabolism and Excretion: Decitabine– degraded by cytidine deaminase and undergoes physicochemical degradation; Cedazuridine– undergoes physicochemical degradation; 27% excreted unchanged in feces, 21% excreted unchanged in urine.

Half-life: Decitabine– 1.5 hr; Cedazuridine– 6.7 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr (decitabine); 3 hr (cedazuridine)	unknown

Contraindication/Precautions

Contraindicated in:

OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Moderate renal impairment (↑ risk for adverse reactions)
Severe renal impairment or end-stage renal disease (safety not established).
Rep: Women of reproductive potential and men with female partners of reproductive potential
Pedi: Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: arrhythmias, edema, hypotension

Derm: rash

Endo: hyperglycemia, hypoglycemia

F and E: hypocalcemia, hyponatremia

GI: abdominal pain, constipation, diarrhea, hypoalbuminemia, ↑ liver enzymes, mucositis, nausea, vomiting

GU: renal impairment, ↓ fertility (males)

Hemat: ANEMIA, BLEEDING, NEUTROPENIA, THROMBOCYTOPENIA

Metabolic: ↓ appetite, ↓ weight

MS: arthralgia, myalgia

Neuro: peripheral neuropathy, dizziness, falls, headache, insomnia

Resp: cough, dyspnea

Misc: INFECTION, fatigue, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

Do not substitute IV decitabine for decitabine/cedazuridine.

PO (Adults): One tablet (decitabine 35 mg/cedazuridine 100 mg) once daily on Days 1–5 of each 28–day cycle; continue for a minimum of four cycles until disease progression or unacceptable toxicity.

Availability

Tablets: decitabine 35 mg/cedazuridine 100 mg

Assessment

Monitor for signs and symptoms of infection (fever, chills, sore throat) during therapy. If active or uncontrolled infection occurs, delay next cycle and resume at same or reduced dose when resolved.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

Obtain CBC prior to each cycle and as clinically indicated. Administer growth factors and anti-infectives for treatment or prophylaxis. If ANC <1,000/mm³ and platelets <50,000/mm³ in the absence of active disease, delay next cycle. Monitor CBC until recovery (ANC ≥1,000/mm³ and platelets ≥50,000/mm³ ). If recovery occurs within 2 wks of achieving remission, continue at same dose. If recovery does not occur within 2 wks, delay cycle for up to 2 additional wks and resume at reduced dose on Days 1–4. May require further dose reductions.

If serum creatinine ≥2 mg/dL OR serum bilirubin≥2 × ULN OR AST or ALT ≥2 × ULN, delay next cycle and resume at same or reduced dose when resolved.

Implementation

Dose reduction recommendations: 1st reduction: 1 tablet PO once daily on Days 1–4. 2nd reduction: 1 tablet PO once daily on Days 1–3. 3rd reduction: 1 tablet PO once daily on Days 1, 3, and 5.
PO Administer once daily at the same time each day on an empty stomach. Do not consume food 2 hrs before and 2 hrs after each dose. DNC: Swallow tablets whole; do not cut, crush, or chew.

Patient/Family Teaching

Instruct patient to take medication as directed once daily for 5 days in each cycle. Take missed doses as soon as possible within 12 hrs of the time it is usually taken, and then to resume normal daily dosing schedule. Extend the dosing period by one day for every missed dose to complete 5 daily doses for each cycle. Do not take an additional dose if vomiting occurs after administration but continue with next scheduled dose. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional promptly is signs and symptoms of low blood cell counts (fever, chills, body aches, bruising more easily than usual) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
Rep: May cause fetal harm. Advise females or reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during and for at least 2 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. May impair fertility in males.

Evaluation/Desired Outcomes