cedazuridine + decitabine: clinical use

Prescribing considerations

• Initiation and supervision require experience with anticancer therapy.
• Consider antiemetic prophylaxis where nausea or vomiting is anticipated.
• Review infection risk, baseline organ function, cardiac history, reproductive plans and concomitant medicines.
• Use caution with hepatic impairment, severe renal impairment, unstable cardiac disease or previous severe heart failure.
• Use cytotoxic handling and disposal procedures; tablets must remain intact.
• The tablet contains lactose and is unsuitable for certain rare hereditary disorders of carbohydrate metabolism.

Contraindications and cautions

• Hypersensitivity to either active ingredient or an excipient.
• Breastfeeding.

Monitoring

• Full blood count before treatment and regularly thereafter, with prompt assessment of fever, bleeding or other signs of myelosuppression.
• Liver and renal function before and during treatment.
• Clinical response and toxicity.
• Signs of infection, interstitial lung disease, differentiation syndrome and heart failure.

Clinical pharmacology

Decitabine is a pyrimidine analogue that inhibits DNA methyltransferase after intracellular activation and incorporation into DNA. Cedazuridine inhibits cytidine deaminase-mediated first-pass degradation, producing decitabine exposure comparable to intravenous decitabine in crossover pharmacokinetic studies.

Formulation and product differences

• Fixed-combination oral film-coated tablet containing both active ingredients.
• Cedazuridine enables oral decitabine exposure by limiting breakdown in the gut and liver.
• Food reduces decitabine exposure, so fasting administration is required.
• The intact coating limits handling exposure; tablets must not be crushed, divided or chewed.

Tablet

Route: Oral

Strengths: 35 mg + 100 mg