Drugs List

Therapeutic Indications

Uses

Leukaemia - acute myeloid

Newly diagnosed, therapy-related acute myeloid leukaemia (t-AML), or AML with myelodysplasia-related changes (AML-MRC).

Administration

For intravenous infusion only, over a period of 90 minutes.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

History of mediastinal radiotherapy
Within 7 months of discontinuing trastuzumab
Cardiac disorder
Dehydration
Renal impairment - creatinine clearance 15-29ml/minute
Severe hepatic impairment
Wilson's disease

Administration of live vaccines is not recommended
Consider anti-infective prophylaxis in immunocompromised patients
Advise ability to drive/operate machinery may be affected by side effects
Cardiotoxic -Avoid anthracyclines for up to 7 months after last trastuzumab
Consider premedication with hypouricaemic agent
Maintain adequate hydration of patient prior / during treatment
Treatment to be initiated and supervised by a specialist
Different preparations of intravenous daunorubicin are not interchangeable
Consult local policy on the safe use of anti-cancer drugs
Never rechallenge treatment after a severe hypersensitivity reaction
Staff: Not to be handled by pregnant staff
Assess baseline cardiac function prior to treatment
Consider echocardiogram before treatment
Monitor renal and hepatic function before and during treatment
Perform ECG before treatment
Perform full blood count before treatment
Monitor haematological parameters regularly throughout treatment
Monitor patients as drug is cumulative
Monitor patients for signs of tumour lysis syndrome
Monitor uric acid levels
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Discontinue if any deterioration in cardiac status occurs
Risk of cardiomyopathy increases with high cumulative dosage
Discontinue if cardiomyopathy occurs
Discontinue if patients show signs of acute copper toxicity
Discontinue permanently if severe hypersensitivity reactions occur
Interrupt treatment if mild hypersensitivity reactions occur
May affect the gastro-intestinal absorption of other drugs
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment

Daunorubicin with cytarabine encapsulated in liposomes is not equivalent or interchangeable with other cytarabine or daunorubicin containing products, due to substantial differences in pharmacokinetic properties. The medicinal product name and correct dosage and dosing schedule should be verified prior to administration.

Absolute neutrophil count and platelet count may have an increased time to recovery, and may require additional monitoring.

High cumulative doses of daunorubicin may increase the incidence of adverse cardiac events. Total daunorubicin exposure must be considered, with particular consideration to patients who have received radiation therapy to the mediastinum, as the threshold for potential adverse cardiac events may be lower in these patients.

Pregnancy and Lactation

Pregnancy

Daunorubicin and cytarabine encapsulated in liposomes is contraindicated in pregnancy.

At the time of writing there is limited data available on the use of daunorubicin and cytarabine encapsulated in liposomes in pregnant women.

The manufacturer states that, based on animal studies and the drug's mechanism of action, daunorubicin and cytarabine encapsulated in liposomes should not be used in pregnant women unless the potential benefit clearly outweighs the potential risk.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Daunorubicin and cytarabine encapsulated in liposomes is contraindicated during breastfeeding.

It is unknown if daunorubicin and cytarabine encapsulated in liposomes is excreted in human breast milk. However due to the potential for serious adverse reactions in the nursing infant it should not be given to women who are breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal insufficiency
Alopecia
Anaemia
Anxiety
Arrhythmias
Cardiotoxicity
Chest pain
Chills
Colitis
Constipation
Cough
Decreased appetite
Delirium
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Epistaxis
Fatigue
Febrile neutropenia
Haemorrhage
Headache
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Infections
Mucositis
Musculoskeletal pain
Nausea
Neutropenia
Night sweats
Oedema
Palmar-Plantar Erythrodysaesthesia syndrome
Pleural effusion
Pruritus
Pyrexia
Rash
Sleep disorders
Thrombocytopenia
Tumour lysis syndrome
Visual impairment (irreversible)
Vomiting

Presentation

Parenteral formulations of daunorubicin with cytarabine.

Drugs List

Therapeutic Indications

Uses

Leukaemia - acute myeloid

Newly diagnosed, therapy-related acute myeloid leukaemia (t-AML), or AML with myelodysplasia-related changes (AML-MRC).

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

For intravenous infusion only, over a period of 90 minutes.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

History of mediastinal radiotherapy
Within 7 months of discontinuing trastuzumab
Cardiac disorder
Dehydration
Renal impairment - creatinine clearance 15-29ml/minute
Severe hepatic impairment
Wilson's disease

Administration of live vaccines is not recommended
Consider anti-infective prophylaxis in immunocompromised patients
Advise ability to drive/operate machinery may be affected by side effects
Cardiotoxic -Avoid anthracyclines for up to 7 months after last trastuzumab
Consider premedication with hypouricaemic agent
Maintain adequate hydration of patient prior / during treatment
Treatment to be initiated and supervised by a specialist
Different preparations of intravenous daunorubicin are not interchangeable
Consult local policy on the safe use of anti-cancer drugs
Never rechallenge treatment after a severe hypersensitivity reaction
Staff: Not to be handled by pregnant staff
Assess baseline cardiac function prior to treatment
Consider echocardiogram before treatment
Monitor renal and hepatic function before and during treatment
Perform ECG before treatment
Perform full blood count before treatment
Monitor haematological parameters regularly throughout treatment
Monitor patients as drug is cumulative
Monitor patients for signs of tumour lysis syndrome
Monitor uric acid levels
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Discontinue if any deterioration in cardiac status occurs
Risk of cardiomyopathy increases with high cumulative dosage
Discontinue if cardiomyopathy occurs
Discontinue if patients show signs of acute copper toxicity
Discontinue permanently if severe hypersensitivity reactions occur
Interrupt treatment if mild hypersensitivity reactions occur
May affect the gastro-intestinal absorption of other drugs
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment

Daunorubicin with cytarabine encapsulated in liposomes is not equivalent or interchangeable with other cytarabine or daunorubicin containing products, due to substantial differences in pharmacokinetic properties. The medicinal product name and correct dosage and dosing schedule should be verified prior to administration.

Absolute neutrophil count and platelet count may have an increased time to recovery, and may require additional monitoring.

High cumulative doses of daunorubicin may increase the incidence of adverse cardiac events. Total daunorubicin exposure must be considered, with particular consideration to patients who have received radiation therapy to the mediastinum, as the threshold for potential adverse cardiac events may be lower in these patients.

Pregnancy and Lactation

Pregnancy

Daunorubicin and cytarabine encapsulated in liposomes is contraindicated in pregnancy.

At the time of writing there is limited data available on the use of daunorubicin and cytarabine encapsulated in liposomes in pregnant women.

The manufacturer states that, based on animal studies and the drug's mechanism of action, daunorubicin and cytarabine encapsulated in liposomes should not be used in pregnant women unless the potential benefit clearly outweighs the potential risk.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Daunorubicin and cytarabine encapsulated in liposomes is contraindicated during breastfeeding.

It is unknown if daunorubicin and cytarabine encapsulated in liposomes is excreted in human breast milk. However due to the potential for serious adverse reactions in the nursing infant it should not be given to women who are breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal insufficiency
Alopecia
Anaemia
Anxiety
Arrhythmias
Cardiotoxicity
Chest pain
Chills
Colitis
Constipation
Cough
Decreased appetite
Delirium
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Epistaxis
Fatigue
Febrile neutropenia
Haemorrhage
Headache
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Infections
Mucositis
Musculoskeletal pain
Nausea
Neutropenia
Night sweats
Oedema
Palmar-Plantar Erythrodysaesthesia syndrome
Pleural effusion
Pruritus
Pyrexia
Rash
Sleep disorders
Thrombocytopenia
Tumour lysis syndrome
Visual impairment (irreversible)
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: September 2018.

Reference Sources

Summary of Product Characteristics: Vyxeos 44mg/100mg powder for concentrate for solution for infusion. Jazz pharmaceuticals UK. Revised August 2018.