Drugs List

Therapeutic Indications

Uses

Adult acute non-lymphocytic leukaemia
Carcinoma - prostate (adjunct to other treatment)
Hepatocellular carcinoma
Leukaemia - chronic myeloid
Lymphoma - non-Hodgkin's
Metastatic breast cancer
Treatment of Multiple Sclerosis

Administration

For administration by intravenous infusion only.

Mitoxantrone should be administered as an intravenous infusion via the tubing of fast running infusion.

Some manufacturers advise administration as an intravenous infusion.

Contraindications

Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Allergic disposition
Children under 18 years
History of mediastinal radiotherapy
History of thoracic radiotherapy
History of treatment with anthracyclines
Risk factors for cardiovascular disorder
Septicaemia
Within 7 months of discontinuing trastuzumab
Cardiac disorder
Dehydration
Hepatic impairment
History of asthma
Myelosuppression
Renal impairment

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 3 months after treatment
Monitor cardiac function when a history of exposure to cardiotoxic agents
Advise ability to drive/operate machinery may be affected by side effects
Cardiotoxic -Avoid anthracyclines for up to 7 months after last trastuzumab
Give pre-treatment counselling and consideration of oocyte cryopreservation
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Some brands contain metabisulfite, may cause bronchospasm/allergies
Consult local policy on the safe use of anti-cancer drugs
Dilute and use as an infusion
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor haematological parameters before and during treatment
Monitor cardiac function during prolonged treatment
Monitor cardiac function in patients with cardiac disease
Monitor cardiac function when a history of chest radiotherapy
Monitor patients for signs of tumour lysis syndrome
Monitor serum biochemistry regularly
Advise patient that blue discolouration of skin, nails & sclera may occur
Advise patient to expect blue-green discolouration of the urine
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Not licensed for use in children under 18 years
Lifetime cumulative dose should be limited to 160mg/metre squared
Male & female: Contraception required during & for 6 months after treatment

Functional cardiac changes, including potentially fatal congestive heart failure and decreases in left ventricular ejection fraction have been reported during therapy or months to years after therapy stopped. In the majority of cases, patients had previously received treatment with anthracyclines, had mediastinal/thoracic radiotherapy or had pre-existing heart disease. It is recommended that such patients are treated with mitoxantrone at full cytotoxic doses but added caution is required and careful regular cardiac examinations are recommended from the start of treatment. Some manufacturers advise all cancer patients should have an echocardiogram or multi-gated acquisition to evaluate left-ventricular function before the initial dose of mitoxantrone.

Multiple sclerosis patients should have an echocardiogram or multi-gated acquisition to evaluate left-ventricular function before the initial dose of mitoxantrone. This should be repeated prior to each dose of mitoxantrone and every year for 5 years after cessation of therapy. It is recommended that patients with multiple sclerosis should not receive a lifetime cumulative dose greater than 72mg per metre squared. Mitoxantrone should not be used if left-ventricular ejection fraction is less than 50 percent or if a clinically significant reduction in left-ventricular ejection fraction.

Ensuring a negative pregnancy test prior to each dose is recommended by some manufacturers.

Some manufacturers advise women treated with mitoxantrone have an increased risk of transient or persistent amenorrhoea. Preservation of gametes should be discussed prior to commencing treatment.

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Mitoxantrone has a cytocidal effect on both proliferating and non-proliferating human cells.

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 14-17 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

Contraindicated in nursing mothers.

Mitoxantrone is excreted in breast milk and significant concentrations (18 nanogram/ml) have been detected 28 days after the last administration. There is the potential for serious adverse reactions in infants.

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 leukaemia
Alopecia
Amenorrhoea
Anaemia
Anaphylaxis
Anorexia
Anxiety
Arrhythmias
Asthenia
Blue discoloration of skin and nails
Blue discoloration of the sclera (reversible)
Blue-green discoloration of urine
Bone marrow failure
Burning pain at injection site
Cardiomyopathy
Cardiotoxicity
Cardiovascular effects
Confusion
Congestive cardiac failure
Conjunctivitis
Constipation
Contusion
Diarrhoea
Discolouration (injection site)
Dyspnoea
ECG changes
Erythema at injection site
Fatigue
Fever
Gastrointestinal bleeding
Granulocytopenia
Haemorrhage
Headache
Hepatic impairment
Hepatotoxicity
Hypersensitivity reactions
Hyperuricaemia
Hypotension
Increase in blood urea nitrogen
Increases in hepatic enzymes
Infections
Leucopenia
Mucositis
Myelodysplastic syndrome
Myelosuppression
Myocardial infarction
Nail dystrophy
Nausea
Necrosis (injection site)
Nephrotoxicity
Neutropenia
Oedema
Onycholysis
Pancreatitis
Paraesthesia
Phlebitis (injection site)
Pneumonia
Rash
Reduced left ventricular output
Septicaemia
Serum creatinine increased
Sinus bradycardia
Somnolence
Stomatitis
Swelling (injection site)
Taste disturbances
Thrombocytopenia
Tiredness
Tumour lysis syndrome
Upper respiratory tract infection
Urinary tract infections
Vomiting
Weakness
Weight changes
White blood cell count decreased

Presentation

Concentrate for solution for infusion containing mitoxantrone.

Drugs List

Therapeutic Indications

Uses

Adult acute non-lymphocytic leukaemia
Carcinoma - prostate (adjunct to other treatment)
Hepatocellular carcinoma
Leukaemia - chronic myeloid
Lymphoma - non-Hodgkin's
Metastatic breast cancer
Treatment of Multiple Sclerosis

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 networks protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

For administration by intravenous infusion only.

Mitoxantrone should be administered as an intravenous infusion via the tubing of fast running infusion.

Some manufacturers advise administration as an intravenous infusion.

Contraindications

Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Allergic disposition
Children under 18 years
History of mediastinal radiotherapy
History of thoracic radiotherapy
History of treatment with anthracyclines
Risk factors for cardiovascular disorder
Septicaemia
Within 7 months of discontinuing trastuzumab
Cardiac disorder
Dehydration
Hepatic impairment
History of asthma
Myelosuppression
Renal impairment

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 3 months after treatment
Monitor cardiac function when a history of exposure to cardiotoxic agents
Advise ability to drive/operate machinery may be affected by side effects
Cardiotoxic -Avoid anthracyclines for up to 7 months after last trastuzumab
Give pre-treatment counselling and consideration of oocyte cryopreservation
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Some brands contain metabisulfite, may cause bronchospasm/allergies
Consult local policy on the safe use of anti-cancer drugs
Dilute and use as an infusion
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor haematological parameters before and during treatment
Monitor cardiac function during prolonged treatment
Monitor cardiac function in patients with cardiac disease
Monitor cardiac function when a history of chest radiotherapy
Monitor patients for signs of tumour lysis syndrome
Monitor serum biochemistry regularly
Advise patient that blue discolouration of skin, nails & sclera may occur
Advise patient to expect blue-green discolouration of the urine
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Not licensed for use in children under 18 years
Lifetime cumulative dose should be limited to 160mg/metre squared
Male & female: Contraception required during & for 6 months after treatment

Functional cardiac changes, including potentially fatal congestive heart failure and decreases in left ventricular ejection fraction have been reported during therapy or months to years after therapy stopped. In the majority of cases, patients had previously received treatment with anthracyclines, had mediastinal/thoracic radiotherapy or had pre-existing heart disease. It is recommended that such patients are treated with mitoxantrone at full cytotoxic doses but added caution is required and careful regular cardiac examinations are recommended from the start of treatment. Some manufacturers advise all cancer patients should have an echocardiogram or multi-gated acquisition to evaluate left-ventricular function before the initial dose of mitoxantrone.

Multiple sclerosis patients should have an echocardiogram or multi-gated acquisition to evaluate left-ventricular function before the initial dose of mitoxantrone. This should be repeated prior to each dose of mitoxantrone and every year for 5 years after cessation of therapy. It is recommended that patients with multiple sclerosis should not receive a lifetime cumulative dose greater than 72mg per metre squared. Mitoxantrone should not be used if left-ventricular ejection fraction is less than 50 percent or if a clinically significant reduction in left-ventricular ejection fraction.

Ensuring a negative pregnancy test prior to each dose is recommended by some manufacturers.

Some manufacturers advise women treated with mitoxantrone have an increased risk of transient or persistent amenorrhoea. Preservation of gametes should be discussed prior to commencing treatment.

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Mitoxantrone has a cytocidal effect on both proliferating and non-proliferating human cells.

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 14-17 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

Contraindicated in nursing mothers.

Mitoxantrone is excreted in breast milk and significant concentrations (18 nanogram/ml) have been detected 28 days after the last administration. There is the potential for serious adverse reactions in infants.

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 leukaemia
Alopecia
Amenorrhoea
Anaemia
Anaphylaxis
Anorexia
Anxiety
Arrhythmias
Asthenia
Blue discoloration of skin and nails
Blue discoloration of the sclera (reversible)
Blue-green discoloration of urine
Bone marrow failure
Burning pain at injection site
Cardiomyopathy
Cardiotoxicity
Cardiovascular effects
Confusion
Congestive cardiac failure
Conjunctivitis
Constipation
Contusion
Diarrhoea
Discolouration (injection site)
Dyspnoea
ECG changes
Erythema at injection site
Fatigue
Fever
Gastrointestinal bleeding
Granulocytopenia
Haemorrhage
Headache
Hepatic impairment
Hepatotoxicity
Hypersensitivity reactions
Hyperuricaemia
Hypotension
Increase in blood urea nitrogen
Increases in hepatic enzymes
Infections
Leucopenia
Mucositis
Myelodysplastic syndrome
Myelosuppression
Myocardial infarction
Nail dystrophy
Nausea
Necrosis (injection site)
Nephrotoxicity
Neutropenia
Oedema
Onycholysis
Pancreatitis
Paraesthesia
Phlebitis (injection site)
Pneumonia
Rash
Reduced left ventricular output
Septicaemia
Serum creatinine increased
Sinus bradycardia
Somnolence
Stomatitis
Swelling (injection site)
Taste disturbances
Thrombocytopenia
Tiredness
Tumour lysis syndrome
Upper respiratory tract infection
Urinary tract infections
Vomiting
Weakness
Weight changes
White blood cell count decreased

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: March 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Mitoxantrone 2mg/ml Sterile Concentrate. Hospira UK Ltd. Revised February 2016.

Summary of Product Characteristics: Mitoxantrone 2mg/ml concentrate for solution for infusion. Accord Heathcare Limited. Revised November 2016.

Summary of Product Characteristics: Onkotrone Injection 2mg/ml concentrate for solution for infusion. Baxter Healthcare Ltd. Revised September 2010.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 March 2018