Drugs List

Therapeutic Indications

Uses

Breast cancer
Conditioning prior to allogeneic haematopoietic stem cell transplant
Leukaemia - acute lymphoblastic
Leukaemia - acute myeloid
Malignant lymphoma
Myeloma - multiple
Neuroblastoma in childhood
Treatment of carcinoma of the ovary

Alone or in combination in the treatment of:
Multiple myeloma
Malignant lymphoma (Hodgkin and non-Hodgkin lymphoma)
Acute lymphoblastic and myeloblastic leukaemia
Childhood neuroblastoma
Ovarian cancer
Mammary adenocarcinoma

In combination as a reduced intensity conditioning (RIC) treatment prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in malignant haematological diseases in adults.

In combination as a conditioning regimen prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in haematological diseases in the paediatric patients as:
Myeloablative conditioning (MAC) treatment in case of malignant haematological diseases.
RIC treatment in case of non-malignant haematological diseases.

Administration

For intravenous use 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.

Contraindications

Breastfeeding
Child >12 years - if used as conditioning therapy prior to alloHSCT for AML
Pregnancy

Precautions and Warnings

Children under 2 years
Elderly
History of progenitor cell transplantation
Predisposition to thromboembolic disease
Recent radiotherapy
Restricted sodium intake
Active liver disease
Children under 2 years -if used as conditioning treatment prior to alloHSCT
Epileptic disorder
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with renal impairment
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration during therapy
Premedication with anti-infective recommended during treatment
Treatment to be prescribed under the supervision of a specialist
Contains alcohol
Contains propylene glycol
Consult local policy on the safe use of anti-cancer drugs
Doses above 140mg per metre squared require haematopoietic stem cell rescue
If accidental contact with eyes or mucous membranes - rinse with cool water
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor blood counts regularly
Monitor closely patient with pre-existing renal impairment
Monitor hepatic function in patients with hepatic impairment
Monitor patients for development of second primary malignancies
Monitor renal function
Consider hepatic veno-occlusive disease if hepatic impairment occurs
Increased risk of venous thromboembolism
Potentially leukaemogenic
Potentially mutagenic
Risk of myelodysplastic syndrome and secondary malignancies
Interrupt therapy if leukocyte and platelet counts fall significantly
Suspend treatment if thromboembolic events occur
Male & female: May cause infertility
Male & female: Contraception required during & for 6 months after treatment

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.

The manufacturer states that the use of melphalan should be avoided during pregnancy, particularly during the first trimester. 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.

Lactation

Melphalan is contraindicated during breastfeeding.

The manufacturer recommends that melphalan is contraindicated during 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.

Side Effects

Abdominal distension
Abnormal liver function tests
Acute kidney injury
Acute myeloid leukaemia
Acute respiratory distress syndrome
Allergic reaction
Alopecia
Amenorrhoea
Anaemia
Anaphylactic shock
Azoospermia
Bone marrow depression
Cardiac arrest
Cardiac failure
Cardiomyopathy
Creatine phosphokinase increased
Deep vein thrombosis (DVT)
Diarrhoea
Feeling hot
Gastro-intestinal haemorrhage
Graft versus host disease
Haemolytic anaemia
Haemophagocytic lymphohistiocytosis
Haemorrhage
Haemorrhagic cystitis
Hepatotoxicity
Infections
Interstitial lung disease
Intracranial bleeding
Jaundice
Maculopapular rash
Mucosal inflammation
Multiorgan failure
Myelodysplastic syndrome
Myelosuppression
Nausea
Neutropenia
Oedema
Paraesthesia
Pneumonitis
Pruritus
Pulmonary fibrosis
Pulmonary haemorrhage
Pulmonary hypertension
Pyrexia
Rash
Renal failure
Respiratory failure
Second primary malignancies
Septic shock
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Thromboembolism
Thrombotic microangiopathy
Toxic epidermal necrolysis
Urticaria
Veno-occlusive disease
Vomiting

Presentation

Parenteral formulations of melphalan.

Drugs List

Therapeutic Indications

Uses

Breast cancer
Conditioning prior to allogeneic haematopoietic stem cell transplant
Leukaemia - acute lymphoblastic
Leukaemia - acute myeloid
Malignant lymphoma
Myeloma - multiple
Neuroblastoma in childhood
Treatment of carcinoma of the ovary

Alone or in combination in the treatment of:
Multiple myeloma
Malignant lymphoma (Hodgkin and non-Hodgkin lymphoma)
Acute lymphoblastic and myeloblastic leukaemia
Childhood neuroblastoma
Ovarian cancer
Mammary adenocarcinoma

In combination as a reduced intensity conditioning (RIC) treatment prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in malignant haematological diseases in adults.

In combination as a conditioning regimen prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in haematological diseases in the paediatric patients as:
Myeloablative conditioning (MAC) treatment in case of malignant haematological diseases.
RIC treatment in case of non-malignant haematological diseases.

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 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.

Contraindications

Breastfeeding
Child >12 years - if used as conditioning therapy prior to alloHSCT for AML
Pregnancy

Precautions and Warnings

Children under 2 years
Elderly
History of progenitor cell transplantation
Predisposition to thromboembolic disease
Recent radiotherapy
Restricted sodium intake
Active liver disease
Children under 2 years -if used as conditioning treatment prior to alloHSCT
Epileptic disorder
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with renal impairment
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration during therapy
Premedication with anti-infective recommended during treatment
Treatment to be prescribed under the supervision of a specialist
Contains alcohol
Contains propylene glycol
Consult local policy on the safe use of anti-cancer drugs
Doses above 140mg per metre squared require haematopoietic stem cell rescue
If accidental contact with eyes or mucous membranes - rinse with cool water
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor blood counts regularly
Monitor closely patient with pre-existing renal impairment
Monitor hepatic function in patients with hepatic impairment
Monitor patients for development of second primary malignancies
Monitor renal function
Consider hepatic veno-occlusive disease if hepatic impairment occurs
Increased risk of venous thromboembolism
Potentially leukaemogenic
Potentially mutagenic
Risk of myelodysplastic syndrome and secondary malignancies
Interrupt therapy if leukocyte and platelet counts fall significantly
Suspend treatment if thromboembolic events occur
Male & female: May cause infertility
Male & female: Contraception required during & for 6 months after treatment

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.

The manufacturer states that the use of melphalan should be avoided during pregnancy, particularly during the first trimester. 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.

Lactation

Melphalan is contraindicated during breastfeeding.

The manufacturer recommends that melphalan is contraindicated during 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.

Side Effects

Abdominal distension
Abnormal liver function tests
Acute kidney injury
Acute myeloid leukaemia
Acute respiratory distress syndrome
Allergic reaction
Alopecia
Amenorrhoea
Anaemia
Anaphylactic shock
Azoospermia
Bone marrow depression
Cardiac arrest
Cardiac failure
Cardiomyopathy
Creatine phosphokinase increased
Deep vein thrombosis (DVT)
Diarrhoea
Feeling hot
Gastro-intestinal haemorrhage
Graft versus host disease
Haemolytic anaemia
Haemophagocytic lymphohistiocytosis
Haemorrhage
Haemorrhagic cystitis
Hepatotoxicity
Infections
Interstitial lung disease
Intracranial bleeding
Jaundice
Maculopapular rash
Mucosal inflammation
Multiorgan failure
Myelodysplastic syndrome
Myelosuppression
Nausea
Neutropenia
Oedema
Paraesthesia
Pneumonitis
Pruritus
Pulmonary fibrosis
Pulmonary haemorrhage
Pulmonary hypertension
Pyrexia
Rash
Renal failure
Respiratory failure
Second primary malignancies
Septic shock
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Thromboembolism
Thrombotic microangiopathy
Toxic epidermal necrolysis
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: February 2022

Reference Sources

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: Phelinun 200mg powder and solvent for concentrate for solution for infusion. Adienne S.r.l. S.U. Revised January 2021.

The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.