Decitabine

L01B - Antimetabolites ATC L01BC08 Small molecule approved 2006 Oral Parenteral Natural product Orphan

JFDA label: Decicip

Mechanism of Action

Inhibitor of DNA (cytosine-5)-methyltransferase 3A — DNA (cytosine-5)-methyltransferase 3A inhibitor; Inhibitor of DNA (cytosine-5)-methyltransferase 1 — DNA (cytosine-5)-methyltransferase 1 inhibitor; Inhibitor of DNA — DNA inhibitor

Target	Action	Gene / class
DNA efficacy	INHIBITOR
DNA (cytosine-5)-methyltransferase 1 efficacy	INHIBITOR	DNMT1
DNA (cytosine-5)-methyltransferase 3A efficacy	INHIBITOR	DNMT3A

Indications

Approved

Myelodysplastic syndromes

Off-label

Acute myeloid leukemia

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer’s labeling Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (11)

Very Common edema · heart murmur · hypotension · Peripheral edema

Common cardiac failure · chest discomfort · chest pain · chest wall pain · facial edema · hypertension · Tachycardia

Nervous system disorders (15)

Very Common anxiety · chills · confusion · dizziness · Fatigue · headache · hypoesthesia · insomnia · lethargy · pain · rigors

Common Depression · falling · malaise · mouth pain

Hepatobiliary disorders (5)

Very Common Hyperbilirubinemia · increased serum alkaline phosphatase

Common Ascites · decreased serum bilirubin · increased serum AST

Renal and urinary disorders (3)

Common dysuria · Polyuria · Urinary tract infection

Blood and lymphatic system disorders (12)

Very Common anemia · bruise · febrile neutropenia · leukopenia · lymphadenopathy · Neutropenia · oral mucosal petechiae · petechia · thrombocytopenia

Common Hematoma · pancytopenia · thrombocythemia

Immune system disorders (1)

Common Transfusion reaction

Metabolism and nutrition disorders (14)

Very Common Hyperglycemia · hyperkalemia · hypoalbuminemia · hypokalemia · hypomagnesemia · hyponatremia

Common decreased serum bicarbonate · dehydration · Hyperuricemia · hypochloremia · hypoproteinemia · increased lactate dehydrogenase · increased serum bicarbonate · weight loss

Gastrointestinal disorders (21)

Very Common abdominal pain · anorexia · constipation · decreased appetite · diarrhea · dyspepsia · Nausea · stomatitis · vomiting

Common abdominal distention · dysphagia · gastroesophageal reflux disease · gingival hemorrhage · glossalgia · hemorrhoids · loose stools · Mucosal inflammation · oral candidiasis · oral mucosa ulcer · tongue ulcer · toothache

Skin and subcutaneous tissue disorders (10)

Very Common cellulitis · erythema · Pallor · pruritus · skin rash

Common Alopecia · catheter site erythema · night sweats · urticaria · xeroderma

Musculoskeletal and connective tissue disorders (8)

Very Common Arthralgia · back pain · limb pain · weakness

Common muscle spasm · musculoskeletal pain · Myalgia · ostealgia

Eye disorders (1)

Common Blurred vision

Ear and labyrinth disorders (1)

Common Otalgia

Infections and infestations (4)

Common bacteremia · Candidiasis · staphylococcal infection · tooth abscess

General disorders and administration site conditions (6)

Very Common Fever · lesion · Localized tenderness

Common Catheter infection · catheter pain · swelling at injection site

Respiratory, thoracic and mediastinal disorders (16)

Very Common Cough · dyspnea · epistaxis · pharyngitis · pneumonia · rales

Common abnormal breath sounds · Hypoxia · pharyngolaryngeal pain · pleural effusion · post nasal drip · pulmonary edema · pulmonary signs and symptoms · sinus congestion · sinusitis · upper respiratory tract infection

Dosing

Source: Lexicomp

Myelodysplastic syndromes (MDS): IV: 15 mg/m2 over 3 hours every 8 hours (45 mg/m2/day) for 3 days (135 mg/m2/cycle) every 6 weeks; treatment is recommended for at least 4 cycles and may continue until the patient no longer benefits. Adjustment for prolonged hematologic toxicity (ANC 3 and platelets 3): >6 weeks but 2 every 8 hours (33 mg/m2/day) for 3 days (99 mg/m2/cycle) >8 weeks but 2 every 8 hours (33 mg/m2/day) for 3 days (99 mg/m2/cycle); maintain or increase dose with subsequent cycles if clinically indicated or 20 mg/m2 over 1 hour daily for 5 days every 28 days (delay subsequent treatment cycles until hematologic recovery [ANC ≥1,000/mm3 and platelets ≥50,000/mm3]); treatment is recommended for at least 4 cycles and may continue until the patient no longer benefits. Acute myeloid leukemia (AML) (off-label use): Adults ≥60 years: IV: 20 mg/m2 over 1 hour daily for 5 days every 28 days until relapse, disease progression, or unacceptable toxicity (Cashen 2010; Kantarjian 2012)

Refer to adult dosing.

Preexisting impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution. Renal toxicity during treatment: Serum creatinine ≥2 mg/dL: Temporarily hold treatment until resolution.

Preexisting impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution. Hepatotoxicity during treatment: ALT and/or bilirubin ≥2 times ULN: Temporarily hold treatment until resolution.

Warnings & Precautions

Source: Lexicomp

Bone marrow suppression

Neutropenia and thrombocytopenia commonly occur; anemia and neutropenic fever have also been reported. Myelosuppression and worsening neutropenia are more common in first two treatment cycles and may not correlate with progression of underlying MDS. Hematologic toxicity may require dosage adjustment (after the first cycle), growth factor support, and/or antimicrobial agents. Monitor for infection. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

FDA category D

Adverse events were observed in animal reproduction studies. Based on the mechanism of action, decitabine may cause fetal harm if administered during pregnancy. Women of childbearing potential should be advised to use effective contraception to avoid pregnancy during treatment and for 1 month after treatment. In addition, males should be advised to avoid fathering a child while on decitabine therapy and for 2 months after treatment.

Lactation

Because of the potential for serious adverse reactions in the nursing infant, a decision should be made to discontinue breast-feeding or the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	CBC with differential and platelets (with each cycle and more frequently if needed); liver enzymes (prior to treatment initiation and periodically); serum creatinine (prior to treatment initiation and periodically)

Chemistry & Properties

Formula	C8H12N4O4
Molecular weight	228.21 g/mol
IUPAC name	4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one
CAS	2353-33-5
PubChem CID	451668
InChIKey	`XAUDJQYHKZQPEU-KVQBGUIXSA-N`
logP	-2.14 (XLogP -1.2)
Polar surface area	123.49 Å²
H-bond acceptors / donors	8 / 3
Drug-likeness (QED)	0.53
Lipinski violations	0

SMILES

Nc1ncn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	35.0%
Half-life	1.78 h
Volume of distribution	5.573 L/kg
Protein binding	-0.5%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Certolizumab pegol	major
Cladribine	major
Clozapine	major
Deferiprone	major
Etanercept	major
Fingolimod	major
Golimumab	major
Infliximab	major
Leflunomide	major
Measles virus vaccine live attenuated	major
Mumps virus strain B level jeryl lynn live antigen	major
Natalizumab	major
Ozanimod	major
Rotavirus vaccine	major
Rubella virus vaccine	major
Samarium (153Sm) lexidronam	major
Siponimod	major
Smallpox (Vaccinia) Vaccine, Live	major
Talimogene laherparepvec	major
Teriflunomide	major
Thalidomide	major
Tofacitinib	major
Typhoid vaccine (live)	major
Upadacitinib	major
Varicella Zoster Vaccine (Recombinant)	major
Yellow Fever Vaccine	major
Aldesleukin	moderate
Alefacept	moderate
Alemtuzumab	moderate
Anakinra	moderate
Anthrax vaccine	moderate
Azathioprine	moderate
Bendamustine	moderate
Bifidobacterium longum infantis	moderate
Bleomycin	moderate
Busulfan	moderate
Canakinumab	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Decicip	Vial 50 mg	1 vial	ORIENT DRUG STORE CO	—