Decitabine parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions containing decitabine.
Drugs List
Therapeutic Indications
Uses
Leukaemia - acute myeloid
Treatment of adult patients with newly diagnosed de novo or secondary acute myeloid leukaemia (AML), who are not candidates for standard induction chemotherapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
20 mg/metre squared body surface area intravenously daily for 5 consecutive days (one treatment cycle). The total daily dose must not exceed 20 mg/metre squared and the total dose per treatment cycle must not exceed 100 mg/metre squared.
The cycle should be repeated every 4 weeks depending on the patient's clinical response.
Patients should be treated for a minimum of 4 cycles and continued for as long as the patient continues to benefit. If after 4 cycles, the patient's haematological values (e.g. platelet counts or absolute neutrophil count), have not returned to pre-treatment levels or if disease progression occurs (peripheral blast counts are increasing or bone marrow blast counts are worsening), the patient may be considered to be a non responder and alternative therapies should be considered.
Additional Dosage Information
Dose reductions are not recommended, adverse reactions should be managed by interrupting treatment.
Treatment should be suspended in the following cases:
Febrile neutropenia (temperature greater than or equal to 38.5 degrees celsius and neutrophil count less than 1 x 10 to the power 9/L).
Acute viral, bacterial or fungal infection (requiring intravenous anti-infectives or extensive supportive care).
Haemorrhage (gastrointestinal, genito-urinary or pulmonary with platelet count less than 25 x 10 to the power 9/L or any central nervous system haemorrhage)
Once symptoms have improved or have been stabilised by supportive measures, treatment with decitabine may be resumed.
Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required.
Administration
For intravenous infusion over 1 hour.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Females of childbearing potential
Hepatic impairment
Renal impairment - creatinine clearance below 30 ml/minute
Severe congestive cardiac failure
Unstable cardiac disorder
Administration of live vaccines is not recommended
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider use of anti-infective prophylaxis during neutropenic phase
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Prophylactic G-CSF should be considered
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor liver function tests at baseline and before each dose
Monitor renal function at baseline and prior to each dose
Perform full blood count before each treatment cycle
Monitor for signs and symptoms of interstitial lung disease
Monitor full blood count regularly
Monitor patients for signs and symptoms of cardiac failure
Monitor platelet count prior to each dose
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report symptoms of infection immediately
Consider high dose IV steroids if differentiation syndrome is suspected
Risk of developing opportunistic infections
Consider interrupting treatment if differentiation syndrome occurs
Consider interrupting treatment if haemorrhage occurs
Interrupt treatment if febrile neutropenia occurs
Interrupt treatment if severe infection develops
Female: Contraception required during and for 6 months after treatment
Male: Contraception required during and for 3 months after treatment
In patients receiving decitabine, there have been reports of interstitial lung disease (including pulmonary fibrosis, pulmonary infiltrates and organising pneumonia) without signs of infectious aetiology. Consequently, in the event of a patient developing acute onset or unexplained worsening of pulmonary symptoms, a careful assessment of the patient should be performed to exclude interstitial lung disease. If interstitial lung disease is diagnosed, appropriate treatment should be initiated.
Differentiation syndrome (also known as retinoic acid syndrome)
Differentiation syndrome has been reported in some patients treated with this agent. Differentiation syndrome may be fatal. If patients present with signs and symptoms suggestive of differentiation syndrome, treatment with high dose intravenous corticosteroids and haemodynamic monitoring should be considered. Interruption of the suspected causative agent should be considered until the symptoms resolve. Once symptoms have resolved, if treatment with the suspected causative agent is resumed, caution is advised.
Pregnancy and Lactation
Pregnancy
Decitabine is contraindicated during pregnancy.
The manufacturer recommends that decitabine should not be used during pregnancy. At the time of writing there is no data on the use of decitabine in human pregnancy. Studies in animals have shown teratogenic effects.
Lactation
Decitabine is contraindicated during breastfeeding.
The manufacturer recommends that decitabine is contraindicated during breastfeeding. It is unknown if decitabine will be excreted in breast milk. However, due to the molecular weight and the lack of plasma protein binding it is likely but, the very short terminal half-life will limit the amount excreted. A risk to neonates cannot be excluded.
Side Effects
Abnormal liver function
Acute febrile dermatosis (Sweet's syndrome)
Anaemia
Anaphylactic reaction
Anaphylactic shock
Anaphylactoid reaction
Caecitis
Cardiomyopathy
CNS haemorrhage
Diarrhoea
Differentiation syndrome
Enterocolitis
Epistaxis
Febrile neutropenia
Gastro-intestinal haemorrhage
Haemorrhage
Headache
Hyperbilirubinaemia
Hyperglycaemia
Hypersensitivity reactions
Infections
Interstitial lung disease
Leucopenia
Nausea
Neutropenia
Neutropenic colitis
Pancytopenia
Pneumonia
Pyrexia
Sepsis
Septic shock
Sinusitis
Stomatitis
Thrombocytopenia
Urinary tract infections
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 11 October 2019.
Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 25 August 2015.
Summary of Product Characteristics: Dacogen 50mg powder for concentrate for solution for infusion. Janssen-Cilag Ltd. Revised February 2022.
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