Drugs List

Therapeutic Indications

Uses

By regional arterial perfusion-localised malignant melanoma (extremities)
By regional arterial perfusion-localised soft tissue sarcoma (extremities)
Myeloma - multiple
Neuroblastoma in childhood
Treatment of carcinoma of the ovary

Administration

For intravenous use and regional arterial perfusion only.

If a high dose of melphalan injection is administered with or without autologous bone marrow transplantation, administration via a central venous line is recommended.

For regional arterial perfusion, the literature should be consulted for detailed methodology.

Contraindications

Breastfeeding
Pregnancy
Severe myelosuppression

Precautions and Warnings

Recent radiotherapy
Porphyria
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with renal impairment
Consider use of anti-infective prophylaxis during neutropenic phase
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration during therapy
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Doses above 140mg per metre squared require haematopoietic stem cell rescue
If extravasation occurs follow local policy & seek expert help immediately
Monitor blood counts regularly
Monitor closely patient with pre-existing renal impairment
Monitor patients for signs of tumour lysis syndrome
Dose reduction may be required in myelosuppression &/or bone marrow aplasia
Potentially leukaemogenic
Potentially mutagenic
Interrupt therapy if leukocyte and platelet counts fall significantly
Male & female: May cause infertility
Male & female: Ensure adequate contraception during treatment

Alkylating agents are not recommended for use in patients with porphyria. However N.A.P.O.S - The Drug Database for Acute Porphyria, classify melphalan as probably not porphyrinogenic.

Patients with renal impairment should be closely observed as they may also have uraemic marrow suppression. Dosage reduction may be necessary for such patients. A clinically significant rise in blood urea may occur in patients with pre-existing renal impairment.

Pregnancy and Lactation

Pregnancy

Melphalan is contraindicated during pregnancy.

Melphalan is mutagenic and structurally similar to known teratogenic compounds. It is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug. The potential hazard to the foetus must be balanced against the expected benefit to the mother.

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

Contraindicated in breastfeeding.

Due to the low molecular weight of melphalan, excretion into the breast milk is likely. Therefore there is the potential for severe toxicity in the nursing infant.

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

Abnormal liver function tests
Allergic reaction
Alopecia
Amenorrhoea
Anaemia
Anaphylactic shock
Blood urea increased
Bone marrow depression
Cardiac arrest
Compartment syndrome
Creatine phosphokinase increased
Diarrhoea
Haemolytic anaemia
Hepatitis
Interstitial pneumonitis
Jaundice
Leucopenia
Leukaemia
Maculopapular rash
Muscle fibrosis
Muscle necrosis
Muscular atrophy
Myalgia
Nausea
Oedema
Pruritus
Pulmonary fibrosis
Rash
Rhabdomyolysis
Sensation of warmth
Sterility (male, permanent)
Stomatitis
Thrombocytopenia
Tingling sensation
Urticaria
Veno-occlusive disease
Vomiting

Presentation

Melphalan injection

Drugs List

Therapeutic Indications

Uses

By regional arterial perfusion-localised malignant melanoma (extremities)
By regional arterial perfusion-localised soft tissue sarcoma (extremities)
Myeloma - multiple
Neuroblastoma in childhood
Treatment of carcinoma of the ovary

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.

Melphalan should not be administered without haematopoietic stem cell rescue at doses above 140 mg/ metre squared of body surface area.

Patients with Renal Impairment

Administration

For intravenous use and regional arterial perfusion only.

If a high dose of melphalan injection is administered with or without autologous bone marrow transplantation, administration via a central venous line is recommended.

For regional arterial perfusion, the literature should be consulted for detailed methodology.

Contraindications

Breastfeeding
Pregnancy
Severe myelosuppression

Precautions and Warnings

Recent radiotherapy
Porphyria
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with renal impairment
Consider use of anti-infective prophylaxis during neutropenic phase
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration during therapy
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Doses above 140mg per metre squared require haematopoietic stem cell rescue
If extravasation occurs follow local policy & seek expert help immediately
Monitor blood counts regularly
Monitor closely patient with pre-existing renal impairment
Monitor patients for signs of tumour lysis syndrome
Dose reduction may be required in myelosuppression &/or bone marrow aplasia
Potentially leukaemogenic
Potentially mutagenic
Interrupt therapy if leukocyte and platelet counts fall significantly
Male & female: May cause infertility
Male & female: Ensure adequate contraception during treatment

Alkylating agents are not recommended for use in patients with porphyria. However N.A.P.O.S - The Drug Database for Acute Porphyria, classify melphalan as probably not porphyrinogenic.

Patients with renal impairment should be closely observed as they may also have uraemic marrow suppression. Dosage reduction may be necessary for such patients. A clinically significant rise in blood urea may occur in patients with pre-existing renal impairment.

Pregnancy and Lactation

Pregnancy

Melphalan is contraindicated during pregnancy.

Melphalan is mutagenic and structurally similar to known teratogenic compounds. It is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug. The potential hazard to the foetus must be balanced against the expected benefit to the mother.

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

Contraindicated in breastfeeding.

Due to the low molecular weight of melphalan, excretion into the breast milk is likely. Therefore there is the potential for severe toxicity in the nursing infant.

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

Abnormal liver function tests
Allergic reaction
Alopecia
Amenorrhoea
Anaemia
Anaphylactic shock
Blood urea increased
Bone marrow depression
Cardiac arrest
Compartment syndrome
Creatine phosphokinase increased
Diarrhoea
Haemolytic anaemia
Hepatitis
Interstitial pneumonitis
Jaundice
Leucopenia
Leukaemia
Maculopapular rash
Muscle fibrosis
Muscle necrosis
Muscular atrophy
Myalgia
Nausea
Oedema
Pruritus
Pulmonary fibrosis
Rash
Rhabdomyolysis
Sensation of warmth
Sterility (male, permanent)
Stomatitis
Thrombocytopenia
Tingling sensation
Urticaria
Veno-occlusive disease
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: July 2013

Reference Sources

British National Formulary, 65th Edition (2013) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, 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.

Summary of Product Characteristics: Melphalan 50mg injection/infusion. Aspen Pharma Trading. Revised November 2012

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

N.A.P.O.S - The Drug Database for Acute Porphyria
https://www.drugs-porphyria.com/languages/UnitedKingdom/index.php?l=gbr
Last Reviewed 8th July 2010
Last Accessed 16th July 2013