Decitabine (Dacogen) is a nucleic acid synthesis inhibitor. It is used in the treatment of myelodysplastic syndrome and acute myeloid leukemia.

Decitabine Uses:

• Myelodysplastic syndromes:

  • Used in the treatment of myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System (IPSS) groups.

• Off Label Use of Decitabine in Adults:

  • Acute myeloid leukemia

Decitabine (Dacogen) Dose in Adults

Decitabine (Dacogen) Dose in the treatment of Acute myeloid leukemia (AML) (off-label):

• Adults ≥60 years:

  • IV: 20 mg per m² over one hour every day for 5 days every 28 days until relapse, disease progression, or unacceptable toxicity.

Decitabine (Dacogen) Dose in the treatment of Myelodysplastic syndromes (MDS): IV:

• 3-day regimen:

  • 15 mg per m² over 3 hours every 8 hours (45 mg per m² per day) for 3 days (135 mg per m² per cycle);
  • Repeat every 6 weeks upon hematologic recovery (ANC ≥1,000/mm³ and platelets ≥50,000/mm³);
  • Treatment is recommended for a minimum of 4 cycles (complete or partial response may take longer than 4 cycles).

Or

• 5-day regimen:

  • 20 mg/m² over one hour once a day for 5 days;
  • Repeat every 4 weeks upon hematologic recovery (ANC ≥1,000/mm³ and platelets ≥50,000/mm³);
  • The treatment is recommended for a minimum of 4 cycles (complete or partial response may take longer than 4 cycles).

Use in Children:

Not indicated.

Decitabine (Dacogen) Pregnancy Risk Category:

• Decitabine can cause harm to fetal health based on its mechanism of action and information gleaned from animal reproduction studies.
• Effective contraception should be used by males who have female partners with reproductive potential during treatment and for three months after the last dose of decitabine.
• There is not much information available on the pregnancy effects of decitabine.
• Before starting therapy, assess your pregnancy.
• Effective contraception should be used by females with reproductive potential during treatment and for six months after the last dose of decitabine.

Use of decitabine during breastfeeding

• It is unknown if decitabine can be found in breast milk.
• The manufacturer advises against breastfeeding during therapy as well as for at least one week following the last dose of decitabine.

Decitabine (Dacogen) Dose in Kidney Disease:

• Preexisting impairment:

  • Manufacturer's labeling doesn't provide any dosage adjustments(has not been studied); monitor more frequently for excessive toxicity.

• Renal toxicity during treatment:

  • Serum creatinine ≥2 mg/dL:
    • Temporarily withhold decitabine; do not resume until after resolution.

Decitabine (Dacogen) Dose in Liver disease:

• Preexisting impairment:

  • Manufacturer's labeling doesn't provide any dosage adjustments (has not been studied);
  • Monitor more frequently for excessive toxicity.

• Hepatotoxicity during treatment:

  • ALT and/or bilirubin ≥2 times ULN:
    • Temporarily withhold decitabine;
    • Do not resume until after resolution.

Common Side Effects of Decitabine (Dacogen):

• Cardiovascular:

  • Peripheral Edema
  • Edema
  • Heart Murmur
  • Hypotension

• Central Nervous System:

  • Fatigue
  • Headache
  • Insomnia
  • Rigors
  • Dizziness
  • Chills
  • Pain
  • Confusion
  • Lethargy
  • Hypoesthesia
  • Anxiety

• Dermatologic:

  • Pallor
  • Skin Rash
  • Erythema
  • Cellulitis
  • Pruritus

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hypoalbuminemia
  • Hypomagnesemia
  • Hypokalemia
  • Hyponatremia
  • Hyperkalemia

• Gastrointestinal:

  • Nausea
  • Constipation
  • Diarrhea
  • Vomiting
  • Anorexia
  • Decreased Appetite
  • Abdominal Pain
  • Stomatitis
  • Dyspepsia

• Hematologic & Oncologic:

  • Neutropenia
  • Thrombocytopenia
  • Anemia
  • Petechia
  • Febrile Neutropenia
  • Leukopenia
  • Bruise
  • Oral Mucosal Petechiae
  • Lymphadenopathy

• Hepatic:

  • Hyperbilirubinemia
  • Increased Serum Alkaline Phosphatase

• Local:

  • Localized Tenderness

• Neuromuscular & Skeletal:

  • Arthralgia
  • Limb Pain
  • Back Pain
  • Weakness

• Respiratory:

  • Cough
  • Dyspnea
  • Pneumonia
  • Pharyngitis
  • Rales
  • Epistaxis

• Miscellaneous:

  • Fever
  • Lesion

Less Common Side Effects Of Decitabine (Dacogen):

• Cardiovascular:

  • Tachycardia
  • Chest Wall Pain
  • Chest Pain
  • Chest Discomfort
  • Facial Edema
  • Hypertension
  • Cardiac Failure

• Central Nervous System:

  • Depression
  • Falling
  • Malaise
  • Mouth Pain

• Dermatologic:

  • Alopecia
  • Xeroderma
  • Urticaria
  • Catheter Site Erythema
  • Night Sweats

• Endocrine & Metabolic:

  • Hyperuricemia
  • Weight Loss
  • Increased Lactate Dehydrogenase
  • Dehydration
  • Hypochloremia
  • Increased Serum Bicarbonate
  • Decreased Serum Bicarbonate
  • Hypoproteinemia

• Gastrointestinal:

  • Mucosal Inflammation
  • Gingival Hemorrhage
  • Hemorrhoids
  • Loose Stools
  • Tongue Ulcer
  • Oral Candidiasis
  • Toothache
  • Dysphagia
  • Abdominal Distention
  • Gastroesophageal Reflux Disease
  • Glossalgia
  • Oral Mucosa Ulcer

• Genitourinary:

  • Urinary Tract Infection
  • Dysuria

• Hematologic & Oncologic:

  • Hematoma
  • Pancytopenia
  • Thrombocythemia

• Hepatic:

  • Ascites
  • Increased Serum AST
  • Decreased Serum Bilirubin

• Hypersensitivity:

  • Transfusion Reaction

• Infection:

  • Candidiasis
  • Bacteremia
  • Staphylococcal Infection
  • Tooth Abscess

• Local:

  • Catheter Infection
  • Catheter Pain
  • Swelling At Injection Site

• Neuromuscular & Skeletal:

  • Myalgia
  • Muscle Spasm
  • Ostealgia
  • Musculoskeletal Pain

• Ophthalmic:

  • Blurred Vision

• Otic:

  • Otalgia

• Renal:

  • Polyuria

• Respiratory:

  • Hypoxia
  • Upper Respiratory Tract Infection
  • Abnormal Breath Sounds
  • Pharyngolaryngeal Pain
  • Pulmonary Edema
  • Sinusitis
  • Pleural Effusion
  • Post Nasal Drip
  • Pulmonary Signs And Symptoms
  • Sinus Congestion

Contraindications to Decitabine (Dacogen):

The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Suppression of bone marrow

  • Myelosuppression, also known as thrombocytopenia and neutropenia, is a common side effect of decitabine.
  • It can include Grades 3 and 4, thrombocytopenia and neutropenia. These conditions may prove to be fatal or serious.
  • Worsening neutropenia and myelosuppression are more common during the first two treatment cycles. They may not be associated with progression of the underlying MDS.
  • Monitoring blood counts (including platelets), at baseline and during each cycle is a good idea to assess response and to check for toxicity.
  • Treatment for hemologic toxicity can include dose reduction, delay, discontinuation, growth factors support and/or antimicrobial agent use.
  • Keep an eye out for infections.

Decitabine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Monitor CBC with differential and platelets (prior to treatment and with each cycle; more frequently if needed);
• Liver enzymes (prior to treatment initiation and periodically);
• Serum creatinine (prior to treatment initiation and periodically);
• Pregnancy test prior to treatment in females of reproductive potential.

How to administer Decitabine (Dacogen)?

• Infuse intravenously for between 1 and 3 hours, depending on the dosing regimen. Infusions by IV are administered for myelodysplastic conditions over 3 hours (15 mg/m dose) and over 1 hour (20 mg/m dose). Infusions of IV fluid over one hour are recommended for the treatment and prevention of acute myeloidleukemia.
• According to the manufacturer, antiemetics should be used for premedication.

Mechanism of action of Decitabine (Dacogen):

• Decitabine is hypomethylating agent. 
• Decitabine, after phosphorylation is completed, is incorporated into DNA.
• It inhibits DNA methyltransferase and causes hypomethylation and death (within S-phase).

Metabolism:

• Possibly via deamination by cytidine deaminase

Half-life elimination:

• ~0.5 to 0.6 hours

International Brand Names of Decitabine:

• Dacogen
• Xalibo
• Decbine

Decitabine Brand Names in Pakistan:

There is no brand available in Pakistan.