Drugs List

Therapeutic Indications

Uses

Inducing remissions of acute myelogenous and lymphocytic leukaemias

Inducing remissions of acute myelogenous and lymphocytic leukaemias

Administration

For intravenous use only via drip tubing.
Once reconstituted and further diluted, the solution should be injected over a 20 minute period into the side arm of a rapidly flowing intravenous infusion of 0.9% sodium chloride.

Contraindications

Recent exposure or co-existing varicella or herpes zoster
Uncontrolled systemic infection
Breastfeeding
Buccal ulceration
Cardiac disorder
Myelosuppression
Pregnancy

Precautions and Warnings

Elderly
History of mediastinal radiotherapy
Predisposition to hyperuricaemia
Within 7 months of discontinuing trastuzumab
Bone marrow infiltrated with malignant cells
Dehydration
Hepatic impairment - serum bilirubin above 20 micromol / L
Renal impairment - serum creatinine greater than 105 micromol / L

Administration of live vaccines is not recommended
Consider dose modification with a history of cardiotoxic medication
May potentiate myelosuppression if history of radiotherapy or chemotherapy
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
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Treat and control infections prior to commencing therapy
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
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Assess baseline cardiac function prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before each treatment cycle
Monitor cardiac function regularly, drug is cardiotoxic.
Monitor patients for signs of tumour lysis syndrome
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Discontinue at the first signs of cardiac failure
Lifetime cumulative dose in children 2 - 18yrs is limited to 300mg/m sq
Lifetime cumulative dose in children under 2yrs is limited to 10mg/kg
Lifetime cumulative dose in patients over 18yrs is limited to 600mg/m sq
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment

Treat and eliminate infections prior to commencing therapy and apply aseptic precautions during cytotoxic therapy. Anti-infective therapy should be initiated in presence of suspected or confirmed infection and during a phase of aplasia and should be continued for some time after bone marrow has regenerated.

Monitor cardiac function regularly, drug is cardiotoxic and the risk of congestive heart failure increases significantly when the total cumulative dosage exceeds 600 mg/square metre in adults, 300 mg/square metre in children over 2 years or 10 mg/kg in children under 2 years.
Consider dose modification in patients with a history of cardiotoxic medication.

Daunorubicin may potentiate myelosuppression in patients with a history of radiotherapy or chemotherapy. Where radiation therapy has previously been administered to the mediastinum, the cumulative dose should be restricted to 400 mg/square metre in adults.

Pregnancy and Lactation

Pregnancy

Daunorubicin is contraindicated in pregnancy.

Daunorubicin crosses the placenta and animal studies have shown it to be mutagenic, carcinogenic and teratogenic. There is also the possibility that treatment during pregnancy may produce delayed effects in the offspring.
However, the manufacturer concludes as leukaemias can be fatal, if a woman requires treatment with this agent and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

The effect of concurrent therapies must also be considered.

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 is contraindicated in breastfeeding.

It is not known whether this agent or its metabolites are excreted in human breast milk. However due to the potential for serious toxicity in the nursing infant it is recommended that breastfeeding is discontinued during treatment.

The effect of concurrent therapies must also be considered.

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
Alopecia
Amenorrhoea
Anaemia
Anaphylactoid reaction
Anaphylaxis
Arrhythmias
Ascites
Aspartate aminotransferase increased
Azoospermia
Bone marrow aplasia
Bone marrow depression
Cardiomyopathy
Cardiotoxicity
Chills
Congestive cardiac failure
Contact dermatitis
Cyanosis
Dehydration
Diarrhoea
Dyspnoea
ECG changes
Erythema
Fever
Flushing
Haemorrhage
Heart block
Hepatomegaly
Hyperpigmentation
Hyperuricaemia
Hypoxia
Increase in alkaline phosphatase
Increased susceptibility to infection
Leucopenia
Mucositis
Myocardial ischaemia
Myocarditis
Nausea
Nephrotic syndrome
Neutropenia
Oedema
Opportunistic infections
Pain
Pericarditis
Phlebitis
Pleural effusion
Premature ventricular contractions
Pruritus
Rash
Red urine
Renal impairment
Secondary leukaemia
Serum bilirubin increased
Shock
Stomatitis
Tachycardia
Thrombocytopenia
Thrombophlebitis
Tissue necrosis and ulceration with extravasation
Tumour lysis syndrome
Urticaria
Vomiting

Presentation

Injections of daunorubicin hydrochloride

Drugs List

Therapeutic Indications

Uses

Inducing remissions of acute myelogenous and lymphocytic leukaemias

Inducing remissions of acute myelogenous and lymphocytic leukaemias

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For intravenous use only via drip tubing.
Once reconstituted and further diluted, the solution should be injected over a 20 minute period into the side arm of a rapidly flowing intravenous infusion of 0.9% sodium chloride.

Contraindications

Recent exposure or co-existing varicella or herpes zoster
Uncontrolled systemic infection
Breastfeeding
Buccal ulceration
Cardiac disorder
Myelosuppression
Pregnancy

Precautions and Warnings

Elderly
History of mediastinal radiotherapy
Predisposition to hyperuricaemia
Within 7 months of discontinuing trastuzumab
Bone marrow infiltrated with malignant cells
Dehydration
Hepatic impairment - serum bilirubin above 20 micromol / L
Renal impairment - serum creatinine greater than 105 micromol / L

Administration of live vaccines is not recommended
Consider dose modification with a history of cardiotoxic medication
May potentiate myelosuppression if history of radiotherapy or chemotherapy
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
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Treat and control infections prior to commencing therapy
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
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Assess baseline cardiac function prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before each treatment cycle
Monitor cardiac function regularly, drug is cardiotoxic.
Monitor patients for signs of tumour lysis syndrome
Antibody response to non-live vaccines may be diminished
Consider the use of anti-emetics before and during therapy
Discontinue at the first signs of cardiac failure
Lifetime cumulative dose in children 2 - 18yrs is limited to 300mg/m sq
Lifetime cumulative dose in children under 2yrs is limited to 10mg/kg
Lifetime cumulative dose in patients over 18yrs is limited to 600mg/m sq
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment

Treat and eliminate infections prior to commencing therapy and apply aseptic precautions during cytotoxic therapy. Anti-infective therapy should be initiated in presence of suspected or confirmed infection and during a phase of aplasia and should be continued for some time after bone marrow has regenerated.

Monitor cardiac function regularly, drug is cardiotoxic and the risk of congestive heart failure increases significantly when the total cumulative dosage exceeds 600 mg/square metre in adults, 300 mg/square metre in children over 2 years or 10 mg/kg in children under 2 years.
Consider dose modification in patients with a history of cardiotoxic medication.

Daunorubicin may potentiate myelosuppression in patients with a history of radiotherapy or chemotherapy. Where radiation therapy has previously been administered to the mediastinum, the cumulative dose should be restricted to 400 mg/square metre in adults.

Pregnancy and Lactation

Pregnancy

Daunorubicin is contraindicated in pregnancy.

Daunorubicin crosses the placenta and animal studies have shown it to be mutagenic, carcinogenic and teratogenic. There is also the possibility that treatment during pregnancy may produce delayed effects in the offspring.
However, the manufacturer concludes as leukaemias can be fatal, if a woman requires treatment with this agent and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

The effect of concurrent therapies must also be considered.

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 is contraindicated in breastfeeding.

It is not known whether this agent or its metabolites are excreted in human breast milk. However due to the potential for serious toxicity in the nursing infant it is recommended that breastfeeding is discontinued during treatment.

The effect of concurrent therapies must also be considered.

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
Alopecia
Amenorrhoea
Anaemia
Anaphylactoid reaction
Anaphylaxis
Arrhythmias
Ascites
Aspartate aminotransferase increased
Azoospermia
Bone marrow aplasia
Bone marrow depression
Cardiomyopathy
Cardiotoxicity
Chills
Congestive cardiac failure
Contact dermatitis
Cyanosis
Dehydration
Diarrhoea
Dyspnoea
ECG changes
Erythema
Fever
Flushing
Haemorrhage
Heart block
Hepatomegaly
Hyperpigmentation
Hyperuricaemia
Hypoxia
Increase in alkaline phosphatase
Increased susceptibility to infection
Leucopenia
Mucositis
Myocardial ischaemia
Myocarditis
Nausea
Nephrotic syndrome
Neutropenia
Oedema
Opportunistic infections
Pain
Pericarditis
Phlebitis
Pleural effusion
Premature ventricular contractions
Pruritus
Rash
Red urine
Renal impairment
Secondary leukaemia
Serum bilirubin increased
Shock
Stomatitis
Tachycardia
Thrombocytopenia
Thrombophlebitis
Tissue necrosis and ulceration with extravasation
Tumour lysis syndrome
Urticaria
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: June 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) 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 7 June 2016.

Summary of Product Characteristics: Daunorubicin. Winthrop Pharmaceuticals UK Ltd. Revised November 2013.