Azacitidine powder for suspension for injection
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Powder for suspension for injection containing azacitidine.
Drugs List
Therapeutic Indications
Uses
Acute myeloid leukaemia (AML) - not eligible for stem cell transplant
Chronic myelomonocytic syndrome (CMML)-ineligible for stem cell transplant
High-risk myelodysplastic syndrome(MDS)-ineligible for stem cell transplant
Treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:
Intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS)
Chronic myelomonocytic leukaemia (CMML) with 10 to 29% marrow blasts without myeloproliferative disorder
Acute myeloid leukaemia (AML) with 20 to 30% blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification
Acute myeloid leukaemia (AML) with greater than 30% marrow blasts, according to the WHO classification.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
The recommended starting dose for the first treatment cycle is 75mg/square metre body surface area, daily for 7 days, followed by a rest period of 21 days (28-day treatment cycle).
A minimum of 6 cycles is recommended and treatment should be continued as long as the patient continued to benefit or until disease progression or unacceptable toxicity.
Patients with Renal Impairment
No dose adjustments required in patients with renal impairment.
If unexplained reduction in serum bicarbonate to less than 20 mmol/L, reduce dose by 50% in next cycle.
If elevations in serum creatinine or blood urea nitrogen greater than or equal to 2 fold above baseline and upper limit of normal (ULN), suspend treatment until levels return to normal or baseline and reduce dose by 50% in next cycle.
Additional Dosage Information
Dose adjustment due to haematological toxicity:
Patients without reduced baseline blood counts prior to first treatment
Platelet count less than or equal to 50 x 10 to the power 9/L and/or absolute neutrophil count (ANC) less than or equal to 1 x 10 to the power 9/L: Suspend treatment until levels recover to higher than these.
Recovery within 14 days: Resume treatment at normal dose.
Recovery longer than 14 days:
Platelet count less than or equal to 50 x 10 to the power 9/L and/or ANC less than or equal to 1 x 10 to the power 9/L: Reduce dose by 50%.
Platelet count greater than 50 x 10 to the power 9/L and/or ANC greater than 1 x 10 to the power 9/L: Dose as normal (100% of the dose).
Patients with reduced baseline blood counts prior to first treatment
Platelet count, ANC or white blood cell count (WBC), less than a 50% decrease compared to baseline or greater than a 50% decrease but an improvement in cell line differentiation: Dose as normal.
Platelet count, ANC or WBC, greater than a 50% decrease compared to baseline with no improvement in cell line differentiation: Suspend treatment until levels have recovered and dose as follows:
Recovery within 14 days: Resume treatment at normal dose.
Recovery longer than 14 days: Determine bone marrow cellularity.
Bone marrow cellularity greater than 50%: Resume treatment at normal dose.
Bone marrow cellularity less than or equal to 50%, suspend treatment and reduce dose as follows:
Bone marrow cellularity between 15% and 50%, recovery within 21 days: Resume treatment at normal dose.
Bone marrow cellularity less than 15%, recovery within 21 days: Resume treatment at normal dose.
Bone marrow cellularity between 15% and 50%, recovery longer than 21 days: Reduce dose by 50%.
Bone marrow cellularity less than 15%, recovery longer than 21 days: Reduce dose to 33%.
Note:
Haematological toxicity is defined as the lowest count reached in a given cycle (nadir) if platelets less than or equal to 50 x 10 to the power 9/L and/or ANC less than or equal to 1 x 10 to the power 9/L.
Recovery is defined as an increase of cell line(s) where haematological toxicity was observed of at least half of the difference of nadir and baseline count plus nadir count (i.e. blood count at recovery greater than or equal to nadir count plus (0.5x (baseline count-nadir count)).
Administration
For subcutaneous injection.
To be administered as a subcutaneous injection into the upper arm, thigh or abdomen. Injection sites should be rotated. New injections should be given at least 2.5cm away from previous sites and areas which are tender, bruised, red or hardened should be avoided.
Doses of more than 100mg (4ml) should be equally divided into 2 syringes and injected into 2 separate sites.
Contraindications
Children under 18 years
Advanced liver cancer
Breastfeeding
Pregnancy
Precautions and Warnings
Females of childbearing potential
Dehydration
Hepatic impairment
Pulmonary disease
Renal impairment
Severe congestive cardiac failure
Unstable cardiac disorder
Consider anti-infective prophylaxis in immunocompromised patients
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
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
Monitor liver function tests at baseline and before each dose
Monitor renal function at baseline and prior to each dose
Monitor serum creatinine prior to and during treatment
Perform full blood count before each treatment cycle
Consider dose reduction if BUN and serum creatinine rise during treatment
Monitor closely patient with pre-existing renal impairment
Monitor for bleeding during treatment
Monitor for constipation; give laxatives as required
Monitor patients for signs of tumour lysis syndrome
Monitor serum sodium bicarbonate
Advise patient to report oliguria and anuria
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider the use of anti-emetics before and during therapy
Consider treatment interruption & dose reduction in haematological toxicity
Discontinue if necrotising fasciitis occurs
Discontinue permanently if severe hypersensitivity reactions occur
Male & female: Contraception required during & for 3 months after treatment
Patients with extensive tumour burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, especially in patients with baseline serum albumin less than 30g/L.
Patients with a known history of cardiovascular or pulmonary disease are at an increased risk of cardiac events, caution is advised in these patients. Cardiopulmonary assessment before and during treatment should be considered.
Pregnancy and Lactation
Pregnancy
Azacitidine is contraindicated during pregnancy.
The manufacturer recommends azacitidine should not be used during pregnancy, especially during the first trimester. There is no data on the use of azacitidine in human pregnancy. Studies in mice have shown reproductive toxicity.
Lactation
Azacitidine is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding is contraindicated during azacitidine therapy. It is unknown whether azacitidine and its metabolites are excreted in human breast milk, however, due to the molecular weight it is expected that it will, a risk to neonates cannot be excluded.
Side Effects
Abdominal pain
Acute febrile dermatosis (Sweet's syndrome)
Alopecia
Anaemia
Anorexia
Anxiety
Arthralgia
Bruising at injection site
Cellulitis
Chest pain
Confusion
Conjunctival haemorrhage
Constipation
Decreased appetite
Diarrhoea
Discolouration (injection site)
Diverticulitis
Dizziness
Dyspepsia
Dyspnoea
Ecchymosis
Epistaxis
Erythema
Erythema at injection site
Fatigue
Febrile neutropenia
Gastro-intestinal haemorrhage
Gingival bleeding
Haematoma
Haematoma (injection site)
Haematuria
Haemorrhage (injection site)
Haemorrhoidal bleeding
Headache
Hepatic coma
Hepatic failure
Herpes simplex
Hypersensitivity reactions
Hypertension
Hypokalaemia
Hypotension
Induration (injection site)
Inflammation (injection site)
Injection site reactions
Insomnia
Interstitial lung disease
Intracranial bleeding
Itching (injection site)
Lethargy
Leukopenia
Local pain (injection site)
Maculopapular rash
Malaise
Musculoskeletal pain
Myalgia
Myelosuppression
Nasopharyngitis
Nausea
Necrosis (injection site)
Necrotising fasciitis
Neutropenia
Neutropenic sepsis
Nodules (injection site)
Ocular haemorrhage
Pancytopenia
Pericarditis
Petechiae
Pharyngitis
Pharyngolaryngeal pain
Pleural effusion
Pneumonia
Pruritus
Purpura
Pyoderma gangrenosum
Pyrexia
Rash
Rash at injection site
Renal failure
Renal tubular acidosis
Rhinitis
Serum creatinine increased
Sinusitis
Skin infection
Somnolence
Stomatitis
Syncope
Thrombocytopenia
Tumour lysis syndrome
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vomiting
Weight loss
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: July 2021
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.
Summary of Product Characteristics: Azacitidine betapharm 25mg/ml powder for suspension for injection. Dr Reddy's Laboratories (UK) Ltd. Revised March 2020.
Summary of Product Characteristics: Vidaza 25mg/ml powder for suspension for injection. Celgene Ltd. Revised November 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 June 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.