Drugs List

Therapeutic Indications

Uses

Advanced adult soft tissue sarcomas ( except mesothelioma, Kaposi sarcoma)
Advanced Hodgkin's disease - as adjunctive chemotherapy
Metastatic malignant melanoma

Treatment of metastatic malignant melanoma.

Used in combination with other cytotoxic agents to treat:
Advanced Hodgkin's disease
Advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma)

Administration

For administration by intravenous injection or infusion.

Intravenous Injection
Doses up to 200 mg/square metre may be given as a slow intravenous injection over 1 to 2 minutes.
After reconstitution with water for injection, without further dilution, dacarbazine preparations are hypo-osmolar and should be given by slow intravenous injection, rather than rapid bolus injection.

Intravenous Infusion
Larger doses ranging from 200 to 850 mg/square metre should be administered as a 15 to 30 minute intravenous infusion.
The patency of the vein should be tested prior to infusion with a 5 to 10 ml flush of sodium chloride infusion solution or glucose 5% infusion. After the infusion of dacarbazine, the same flush solution should be used to flush any remaining drug from the tubing.

Contraindications

Breastfeeding
Leucopenia
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment
Thrombocytopenia

Precautions and Warnings

Children under 18 years
Elderly
Mild hepatic impairment
Mild renal impairment
Myelosuppression

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Protect from light during infusion
Staff: Not to be handled by pregnant staff
Bone marrow suppression is cumulative
Monitor eosinophil levels
Monitor full blood count regularly
Monitor hepatic function regularly
Monitor liver size
Monitor renal function regularly
Consider the use of anti-emetics before and during therapy
If veno-occlusive disorder occurs, discontinue and do not restart therapy
Consider discontinuation if severe haematological events occur
Discontinue if hepatic function deteriorates
Discontinue if hypersensitivity reactions occur
Discontinue if renal function deteriorates
Advise patient to avoid alcohol during treatment
Male & female: Contraception required during & for 6 months after treatment

Cases of veno-occlusive disease have been reported, therefore frequent monitoring of liver size, function and blood counts (eosinophils) are required. If symptoms of veno-occlusive disease occurs, treatment should be discontinued and treatment with high dose corticosteroids with or without fibrinolytic agents have been shown to be successful. Symptoms of veno-occlusive disease include; fever, eosinophilia, abdominal pain, enlarged liver, jaundice and shock.

Pregnancy and Lactation

Pregnancy

Dacarbazine is contraindicated during pregnancy.

Animal studies have shown mutagenic, teratogenic and carcinogenic effects.

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

Dacarbazine is contraindicated in breastfeeding.

At the time of writing there is limited data on the use of dacarbazine during breastfeeding. It not known whether it is excreted into human breast milk, a risk to the infant cannot be excluded.

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
Agranulocytosis
Allergic reaction
Alopecia
Anaemia
Anaphylactic reaction
Anorexia
Blood dyscrasias
Bone marrow depression
Confusion
Convulsions
Diarrhoea
Elevation of liver enzymes
Eosinophilia
Erythema
Exanthematous rash
Facial flushing
Facial paraesthesia
Fever
Haematological toxicity
Headache
Hepatic impairment
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatomegaly
Hepatotoxicity
Hyperpigmentation of skin
Impaired vision
Increase in alkaline phosphatase
Influenza-like syndrome
Irritation (injection site)
Jaundice
Lethargy
Leucopenia
Nausea
Pancytopenia
Rash
Renal impairment
Shock
Skin photosensitivity
Thrombocytopenia
Urticaria
Visual disturbances
Vomiting

Presentation

Infusions of dacarbazine (as dacarbazine citrate)

Drugs List

Therapeutic Indications

Uses

Advanced adult soft tissue sarcomas ( except mesothelioma, Kaposi sarcoma)
Advanced Hodgkin's disease - as adjunctive chemotherapy
Metastatic malignant melanoma

Treatment of metastatic malignant melanoma.

Used in combination with other cytotoxic agents to treat:
Advanced Hodgkin's disease
Advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma)

Dosage

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

Duration of therapy should be determined considering the type and stage of the underlying disease, the combination therapy administered and the individual response to dacarbazine. Adverse effects should also be taken into consideration.

Adults

Elderly

Children

Patients with Renal Impairment

Administration

For administration by intravenous injection or infusion.

Intravenous Injection
Doses up to 200 mg/square metre may be given as a slow intravenous injection over 1 to 2 minutes.
After reconstitution with water for injection, without further dilution, dacarbazine preparations are hypo-osmolar and should be given by slow intravenous injection, rather than rapid bolus injection.

Intravenous Infusion
Larger doses ranging from 200 to 850 mg/square metre should be administered as a 15 to 30 minute intravenous infusion.
The patency of the vein should be tested prior to infusion with a 5 to 10 ml flush of sodium chloride infusion solution or glucose 5% infusion. After the infusion of dacarbazine, the same flush solution should be used to flush any remaining drug from the tubing.

Contraindications

Breastfeeding
Leucopenia
Pregnancy
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment
Thrombocytopenia

Precautions and Warnings

Children under 18 years
Elderly
Mild hepatic impairment
Mild renal impairment
Myelosuppression

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Protect from light during infusion
Staff: Not to be handled by pregnant staff
Bone marrow suppression is cumulative
Monitor eosinophil levels
Monitor full blood count regularly
Monitor hepatic function regularly
Monitor liver size
Monitor renal function regularly
Consider the use of anti-emetics before and during therapy
If veno-occlusive disorder occurs, discontinue and do not restart therapy
Consider discontinuation if severe haematological events occur
Discontinue if hepatic function deteriorates
Discontinue if hypersensitivity reactions occur
Discontinue if renal function deteriorates
Advise patient to avoid alcohol during treatment
Male & female: Contraception required during & for 6 months after treatment

Cases of veno-occlusive disease have been reported, therefore frequent monitoring of liver size, function and blood counts (eosinophils) are required. If symptoms of veno-occlusive disease occurs, treatment should be discontinued and treatment with high dose corticosteroids with or without fibrinolytic agents have been shown to be successful. Symptoms of veno-occlusive disease include; fever, eosinophilia, abdominal pain, enlarged liver, jaundice and shock.

Pregnancy and Lactation

Pregnancy

Dacarbazine is contraindicated during pregnancy.

Animal studies have shown mutagenic, teratogenic and carcinogenic effects.

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

Dacarbazine is contraindicated in breastfeeding.

At the time of writing there is limited data on the use of dacarbazine during breastfeeding. It not known whether it is excreted into human breast milk, a risk to the infant cannot be excluded.

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
Agranulocytosis
Allergic reaction
Alopecia
Anaemia
Anaphylactic reaction
Anorexia
Blood dyscrasias
Bone marrow depression
Confusion
Convulsions
Diarrhoea
Elevation of liver enzymes
Eosinophilia
Erythema
Exanthematous rash
Facial flushing
Facial paraesthesia
Fever
Haematological toxicity
Headache
Hepatic impairment
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatomegaly
Hepatotoxicity
Hyperpigmentation of skin
Impaired vision
Increase in alkaline phosphatase
Influenza-like syndrome
Irritation (injection site)
Jaundice
Lethargy
Leucopenia
Nausea
Pancytopenia
Rash
Renal impairment
Shock
Skin photosensitivity
Thrombocytopenia
Urticaria
Visual disturbances
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: November 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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 5 November 2014.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 5 November 2014.

Summary of Product Characteristics: Dacarbazine tablets. Medac GmbH. Revised May 2014.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.