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Decitabine and cedazuridine: Drug information

Decitabine and cedazuridine: Drug information
(For additional information see "Decitabine and cedazuridine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Inqovi
Brand Names: Canada
  • Inqovi
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, DNA Methylation Inhibitor;
  • Cytidine Deaminase Inhibitor
Dosing: Adult

Note: Do not substitute decitabine/cedazuridine oral tablets for IV decitabine within a treatment cycle. Administer anti-infective prophylaxis as clinically appropriate. Consider the use of antiemetics prior to each decitabine/cedazuridine dose. Begin next cycle only if ANC ≥1,000/mm3 and platelets ≥50,000/mm3 (in the absence of active disease).

Myelodysplastic syndromes

Myelodysplastic syndromes: Oral: Decitabine 35 mg/cedazuridine 100 mg once daily on days 1 to 5 of each 28-day treatment cycle for a minimum of 4 cycles, until disease progression or unacceptable toxicity. May take longer than 4 cycles for a complete or partial response (Ref).

Missed dose: If a dose is missed within 12 hours of the time it is usually administered, administer the missed dose as soon as possible and then resume the normal daily dosing schedule. Extend the dosing period by 1 day for every missed dose to complete 5 daily doses for each cycle. If a dose is vomited, do not administer an additional dose (continue with the next scheduled dose).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function may be estimated using the Cockcroft-Gault equation.

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl ≥30 to 59 mL/minute: No dosage adjustment necessary; monitor for increased incidence of adverse reactions.

CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

CrCl <15 mL/minute (end-stage kidney disease): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Acute kidney toxicity during treatment: Serum creatinine ≥2 mg/dL: Delay the next cycle and resume at the same or at a reduced dose (eg, administer fewer days per cycle) upon resolution.

Dosing: Hepatic Impairment: Adult

Initial dose titration in patients with preexisting hepatic impairment :

Mild impairment (total bilirubin >1 to 1.5 times ULN or AST > ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, mild impairment had no effect on decitabine or cedazuridine pharmacokinetics.

Moderate (total bilirubin >1.5 to 3 times ULN and any AST) to severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Acute hepatotoxicity during treatment:

Serum bilirubin ≥2 times ULN: Delay the next cycle and resume at the same or at a reduced dose (eg, administer fewer days per cycle) upon resolution.

AST or ALT ≥2 times ULN: Delay the next cycle and resume at the same or at a reduced dose (eg, administer fewer days per cycle) upon resolution.

Dosing: Adjustment for Toxicity: Adult
Decitabine/Cedazuridine Recommended Dosage Reduction Levels for Hematologic Toxicity

Usual (initial) dose

Decitabine 35 mg/cedazuridine 100 mg once daily on days 1 through 5 of a 28-day treatment cycle

Dose Reduction Level

Decitabine/Cedazuridine Dose Reduction Schedule

First

Decitabine 35 mg/cedazuridine 100 mg once daily on days 1 through 4

Second

Decitabine 35 mg/cedazuridine 100 mg once daily on days 1 through 3

Third

Decitabine 35 mg/cedazuridine 100 mg once daily on days 1, 3, and 5

Decitabine/Cedazuridine Recommended Dosage Modifications for Adverse Reactions

Adverse reaction

Severity

Decitabine/cedazuridine dosage modification

a In the absence of active disease.

b Hematologic recovery: ANC ≥1,000/mm3 and platelets ≥50,000/mm3.

Hematologic toxicity

Neutropeniaa

ANC <1,000/mm3 (grade 3)

Withhold decitabine/cedazuridine and monitor CBC as clinically indicated.

Administer supportive care (growth factors and anti-infectives) for persistent severe neutropenia or febrile neutropenia as clinically indicated.

Resume next cycle when ANC ≥1,000/mm3 and platelets ≥50,000/mm3.

Hematologic recoveryb within 2 weeks of achieving remission: Continue decitabine/cedazuridine at same dose.

Hematologic recoveryb does not occur within 2 weeks of achieving remission: Withhold decitabine/cedazuridine for up to 2 additional weeks; resume at reduced dose (administration on days 1 to 4). Consider further dose reduction if bone marrow suppression continues. Reduced dose may be continued or increased in subsequent cycles as clinically indicated.

Thrombocytopeniaa

Platelets <50,000/mm3 (grade 3)

Withhold decitabine/cedazuridine and monitor CBC as clinically indicated.

Resume next cycle when ANC ≥1,000/mm3 and platelets ≥50,000/mm3.

Hematologic recoveryb within 2 weeks of achieving remission: Continue decitabine/cedazuridine at same dose.

Hematologic recoveryb does not occur within 2 weeks of achieving remission: Withhold decitabine/cedazuridine for up to 2 additional weeks; resume at reduced dose (administration on days 1 to 4). Consider further dose reduction if bone marrow suppression continues. Reduced dose may be maintained or increased in subsequent cycles as clinically indicated.

Nonhematologic toxicity

Infection

Any active or uncontrolled

Withhold decitabine/cedazuridine; administer anti-infective treatment and prophylaxis as clinically indicated.

Upon resolution, resume at same dose or reduced dose (eg, administer fewer days per cycle).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see decitabine.

>10%:

Dermatologic: Skin rash (12%)

Endocrine & metabolic: Decreased serum albumin (22%), decreased serum calcium (16%), decreased serum glucose (14%), increased serum glucose (19%)

Gastrointestinal: Constipation (20%), diarrhea (16%), nausea (25%), stomatitis (18%; grades 3/4: 1%)

Hematologic & oncologic: Anemia (71%; grades 3/4: 55%), febrile neutropenia (10% to 33%; grades 3/4: 10% to 32%), hemorrhage (24%; grades 3/4: 2%), leukopenia (79%; grades 3/4: 65%), neutropenia (73%; grades 3/4: 71%), thrombocytopenia (82%; grades 3/4: 76%)

Hepatic: Increased serum alanine aminotransferase (13%), increased serum alkaline phosphatase (22%), increased serum transaminase (12%)

Infection: Sepsis (6% to 14%)

Nervous system: Dizziness (16%), fatigue (29%), headache (22%)

Respiratory: Dyspnea (17%), pneumonia (7% to 21%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (3%), edema (10%), hypotension (4%)

Dermatologic: Cellulitis (4%), Sweet’s syndrome (1%)

Endocrine & metabolic: Decreased serum sodium (9%), weight loss (5%)

Gastrointestinal: Abdominal pain (9%), decreased appetite (10%), vomiting (5%)

Hepatic: Increased serum aspartate aminotransferase (6%)

Nervous system: Falling (4%), insomnia (6%), neuropathy (4%)

Neuromuscular & skeletal: Arthralgia (9%), myalgia (9%)

Renal: Increased serum creatinine (7%), renal insufficiency (9%)

Respiratory: Cough (7%), upper respiratory tract infection (6%)

Miscellaneous: Fever (7%)

<1%: Hematologic & oncologic: Tumor lysis syndrome

Postmarketing:

Cardiovascular: Cardiomyopathy

Hematologic & oncologic: Differentiation syndrome

Respiratory: Interstitial pulmonary disease

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to decitabine, cedazuridine, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Fatal and serious myelosuppression can occur with decitabine/cedazuridine. New or worsening thrombocytopenia (including grades 3 or 4) occurred commonly. Neutropenia and anemia (including grades 3 or 4) were also common. Neutropenic fever occurred in one-third of patients; grades 3 or 4 neutropenic fever events were reported. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying myelodysplastic syndromes. Hematologic toxicity (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of decitabine/cedazuridine treatment interruption and/or dose reduction.

• Infection: Serious and sometimes fatal complications due to infection have occurred with decitabine/cedazuridine. Pneumonia and sepsis have been observed, including grade 3 or 4 events; rare fatalities due to pneumonia, sepsis, and septic shock were also reported.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Inqovi: 35-100 MG

Generic Equivalent Available: US

No

Pricing: US

Tablets (Inqovi Oral)

35-100 mg (per each): $1,982.82

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Inqovi: 35-100 MG

Prescribing and Access Restrictions

Decitabine/cedazuridine is available through specialty distributors, specialty pharmacies, and various specialty institutions/accounts. Examples from the manufacturer may be found at https://www.inqovi.com/Content/pdf/pharmacy-guide.pdf.

Administration: Adult

Oral: Administer at approximately the same time of day. Swallow tablet whole; do not cut, crush, or chew. Administer on an empty stomach; do not consume food 2 hours before and 2 hours after dose. Consider the use of antiemetics prior to each decitabine/cedazuridine dose.

Hazardous Drugs Handling Considerations

Decitabine is a hazardous agent (NIOSH 2016 [group 1]); decitabine/cedazuridine is a cytotoxic drug (per product labeling).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Myelodysplastic syndromes: Treatment of 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 adults.

Medication Safety Issues
High alert medication

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Cytidine Deaminase Substrates: Cedazuridine may increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant.

Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of decitabine/cedazuridine. Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last decitabine/cedazuridine dose.

Pregnancy Considerations

Based on the mechanism of action, data from animal reproduction studies, as well as limited human data, in utero exposure to decitabine/cedazuridine may cause fetal harm.

Breastfeeding Considerations

It is not known if decitabine or cedazuridine are present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 2 weeks after the last decitabine/cedazuridine dose.

Monitoring Parameters

Monitor CBC (at baseline, prior to each cycle, and as clinically indicated); monitor serum creatinine, CrCl, AST, ALT, total bilirubin. Evaluate pregnancy status prior to use (in patients who could become pregnant). Monitor for signs/symptoms of infection. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Decitabine is a hypomethylating agent. After phosphorylation, decitabine is incorporated into DNA and inhibits DNA methyltransferase causing hypomethylation and subsequent cell death (within the S-phase of the cell cycle). Hypomethylation in cancer cells may restore normal function to genes that are necessary for control of cellular differentiation and proliferation.

Cedazuridine is a cytidine deaminase (CDA) inhibitor. CDA is an enzyme that catalyzes the degradation of cytidine, including the cytidine analog decitabine; high CDA levels in the GI tract and liver degrade decitabine and limit its oral bioavailability. The combination of cedazuridine with decitabine increases systemic decitabine exposure.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V/Fss (apparent): Decitabine: 417 L; Cedazuridine: 296 L.

Metabolism: Decitabine: Primarily via cytidine deaminase, also via physiochemical degradation; Cedazuridine: Conversion to epimer via physiochemical degradation.

Bioavailability: Decitabine: Cedazuridine increases oral decitabine exposure; Cedazuridine: 20%.

Half-life elimination: Decitabine: 1.5 hours; Cedazuridine: 6.7 hours.

Time to peak: Decitabine: 1 hour (range: 0.3 to 3 hours); Cedazuridine: 3 hours (range: 1.5 to 6.1 hours).

Excretion: Cedazuridine: Feces (51%; 27% as unchanged drug); Urine (46%; 21% as unchanged drug).

Clearance (apparent): Decitabine: 197 L/hour; Cedazuridine: 30.3 L/hour.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AU) Australia: Inqovi;
  • (PR) Puerto Rico: Inqovi
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020;136(6):674-683. doi:10.1182/blood.2019004143 [PubMed 32285126]
  3. Garcia-Manero G, McCloskey J, Griffiths EA, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over phase 3 study (ASCERTAIN study) of an oral hypomethylating agent ASTX727 (cedazuridine/decitabine) compared to IV decitabine. Blood. 2019;134(suppl 1):846. doi:10.1182/blood-2019-122980
  4. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  5. Inqovi (decitabine and cedazuridine) [prescribing information]. Princeton, NJ: Taiho Oncology Inc; July 2020.
  6. Inqovi (decitabine and cedazuridine) [prescribing information]. Princeton, NJ: Taiho Oncology Inc; March 2022.
  7. Inqovi (decitabine and cedazuridine) [product monograph]. Oakville, Ontario, Canada: Taiho Pharma Canada Inc; March 2022.
  8. Refer to manufacturer's labeling.
  9. Savona MR, McCloskey JK, Griffiths EA, et al. Efficacy of oral decitabine/cedazuridine (ASTX727) in the CMML subgroup from the ASCERTAIN phase 3 study. Blood. 2021;138(suppl 1):3682. doi:10.1182/blood-2021-154179
  10. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed July 17, 2020.
Topic 128935 Version 56.0

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