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MELPHALAN is a brand name for Melphalan. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Melphalan Injection, at conventional intravenous dose, is indicated in the treatment of multiple myeloma and ovarian cancer. Melphalan Injection, at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the treatment of multiple myeloma and childhood neuroblastoma. In the…
Verbatim from this product's MHRA label. Tap a section to expand.
Parenteral administration:
Melphalan Injection is for intravenous use only. Melphalan Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m2. When further diluted in an infusion solution, Melphalan has reduced stability and the rate of degradation increases rapidly with rise in temperature.
If Melphalan is infused at a room temperature of approximately 25°C, the total time from preparation of the injection solution to the completion of infusion should not exceed 1 hour.
Multiple myeloma:
Melphalan Injection is administered on an intermittent basis alone, or in combination with other cytotoxic drugs. Administration of prednisone has also been included in a number of regimens. g. once every 4 weeks), provided there has been recovery of the peripheral blood count during this period.
0 mg/kg body weight), but haematopoietic stem cell rescue becomes essential following doses in excess of 140 mg/m2 body surface area. Hydration and forced diuresis are also recommended.
Ovarian adenocarcinoma:
When used intravenously as a single agent, a dose of 1 mg/kg body weight (approximately 40 mg/m2 body surface area) given at intervals of 4 weeks has often been used. 4 mg/kg body weight (12 to 16 mg/m2 body surface area) have been used at intervals of 4 to 6 weeks.
Advanced neuroblastoma:
Doses of between 100 and 240 mg/m2 body surface area (sometimes divided equally over 3 consecutive days) together with haematopoietic stem cell rescue, have been used either alone or in combination with radiotherapy and/or other cytotoxic drugs.
Special populations Use in Children Melphalan, at conventional dosage, is only rarely indicated in children and dosage guidelines cannot be stated. High dose Melphalan Injection, in association with haematopoietic stem cell rescue, has been used in childhood neuroblastoma and dosage guidelines based on body surface area, as for adults, may be used.
Use in the elderly Although Melphalan is frequently used at conventional dosage in the elderly, there is no specific information available relating to its administration to this patient subgroup. Experience in the use of high dose Melphalan in elderly patients is limited.
For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the indication and dose received and also when given in combination with other therapeutic agents.
The following convention has been utilised for the classification of frequency:- Very common ≥1/10, common ≥1/100 and <1/10, uncommon ≥1/1000 and <1/100, rare ≥1/10,000 and <1/1000, very rare <1/10,000. Blood and Lymphatic System Disorders Very bone marrow depression leading to leucopenia, common: thrombocytopenia and anaemia Rare: haemolytic anaemia Immune System Disorders Rare: allergic reactions (see Skin and Subcutaneous Tissue Disorders) Allergic reactions to melphalan such as urticaria, oedema, skin rashes and anaphylactic shock have been reported uncommonly following initial or subsequent dosing, particularly after intravenous administration.
Cardiac arrest has also been reported rarely in association with such events. Respiratory, Thoracic and Mediastinal Disorders Rare: interstitial pneumonitis and pulmonary fibrosis (including fatal reports) Gastrointestinal Disorders Very common: nausea, vomiting and diarrhoea; stomatitis at high dose Rare: stomatitis at conventional dose The incidence of diarrhoea, vomiting and stomatitis becomes the dose-limiting toxicity in patients given high intravenous doses of melphalan in association with autologous bone marrow transplantation.
Cyclophosphamide pretreatment appears to reduce the severity of gastro-intestinal damage induced by high-dose melphalan and the literature should be consulted for details. Hepatobiliary Disorders Rare: hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice; veno- occlusive disease following high dose treatment Skin and Subcutaneous Tissue Disorders Very common: alopecia at high dose Common: alopecia at conventional dose Rare: maculopapular rashes and pruritus (see Immune System Disorders) Musculoskeletal and Connective Tissue Disorders Injection, following isolated limb perfusion: Very common: muscle atrophy, muscle fibrosis, myalgia, blood creatine phosphokinase increased.
Melphalan is a cytotoxic drug, which falls into the general class of alkylating agents. It should be prescribed only by physicians experienced in the management of malignant disease with such agents. As with all high dose chemotherapy, precautions should be taken to prevent tumour lysis syndrome.
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended. Since Melphalan is myelosuppressive, frequent blood counts are essential during therapy and the dosage should be delayed or adjusted if necessary.
Melphalan Injection solution can cause local tissue damage, should extravasation occur and consequently, it should not be administered by direct injection into a peripheral vein. It is recommended that Melphalan Injection solution is administered by injecting slowly into a fast-running intravenous infusion via a swabbed injection port, or via a central venous line.
In view of the hazards involved and the level of supportive care required, the administration of high dose Melphalan Injection should be confined to specialist centres, with the appropriate facilities and only be conducted by experienced clinicians.
In patients receiving high dose Melphalan Injection, consideration should be given to the prophylactic administration of anti-infective agents and the administration of blood products as required. Consideration should be given to ensure adequate performance status and organ function before using high dose Melphalan Injection.
Melphalan Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m2. As with all cytotoxic chemotherapy, adequate contraceptive precautions should be practiced when either partner is receiving Melphalan.
Safe handling of Melphalan The handling of Melphalan formulations should follow guidelines for the handling of cytotoxic drugs according to the Royal Pharmaceutical Society of Great Britain Working Party on the handling of cytotoxic drugs.
Melphalan should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan. - Severe myelosuppression (leukocytes <2000 / mm3, thrombocytes <50,000 / mm3).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Consideration should therefore be given to ensure adequate performance status and organ function, before using high dose Melphalan Injection in elderly patients. Dosage in renal impairment Melphalan clearance, though variable, may be decreased in renal impairment.
Currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction when administering Melphalan Tablets to patients with renal impairment, but it may be prudent to use a reduced dosage initially until tolerance is established.
When Melphalan Injection is used at conventional intravenous dosage (16-40 mg/m2 body surface area), it is recommended that the initial dose should be reduced by 50% and subsequent dosage determined according to the degree of haematological suppression.
For high intravenous doses of Melphalan Injection (100 to 240 mg/m2 body surface area), the need for dose reduction depends upon the degree of renal impairment, whether haematopoietic stem cells are re-infused, and the therapeutic need.
Melphalan Injection should not be given without haematopoietic stem cell rescue at doses above 140 mg/m2. As a guide, for high dose Melphalan treatment without haematopoietic stem cell rescue in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min) a dose reduction of 50% is usual.
High dose Melphalan (above 140 mg/m2) without haematopoietic stem cell rescue should not be used in patients with more severe renal impairment. High dose Melphalan with haematopoietic stem cell rescue has been used successfully even in dialysis dependent patients with end-stage renal failure.
The relevant literature should be consulted for details. Thromboembolic events Melphalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone is associated with an increased risk of venous thromboembolism (predominantly deep vein thrombosis and pulmonary embolism).
Thromboprophylaxis should be administered for at least the first 5 months of treatment especially in patients with additional thrombotic risk factors. 8) If the patient experiences any thromboembolic events, treatment must be discontinued and standard anticoagulation therapy started.
Once the patient has been stabilised on the anticoagulation treatment and any complications of the thromboembolic event have been managed, melphalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone may be restarted at the original dose dependent upon a benefit-risk assessment.
The patient should continue anticoagulation therapy during the course of melphalan treatment. Method of administration For intravenous administration, it is recommended that Melphalan Injection is injected slowly into a fast-running infusion solution via a swabbed injection port.
If direct injection into a fast-running infusion is not appropriate, Melphalan Injection solution may be administered diluted in an infusion bag. 9%) solution for injection is used. Should any visible turbidity or crystallisation appear in the diluted solutions, the […]
Common: compartment syndrome Not known: muscle necrosis, rhabdomyolysis Renal and Urinary Disorders Common: temporary significant elevation of the blood urea has been seen in the early stages of melphalan therapy in myeloma patients with renal damage General Disorders and Administration Site Conditions Very common: subjective and transient sensation of warmth and/or tingling Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Monitoring Since Melphalan is a potent myelosuppressive agent, it is essential that careful attention should be paid, both during and after treatment, to the monitoring of blood counts, to avoid the possibility of excessive myelosuppression and the risk of irreversible bone marrow aplasia.
Blood counts may continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in leukocyte or platelet counts, treatment should be temporarily interrupted. Melphalan should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.
Renal Impairment Melphalan clearance may be reduced in patients with renal impairment who may also have uraemic marrow suppression. Dose reduction may therefore be necessary (see Posology and Method of Administration). See Undesirable Effects for elevation of blood urea.
Mutagenicity Melphalan is mutagenic in animals and chromosome aberrations have been observed in patients being treated with the drug. Carcinogenicity Melphalan, in common with other alkylating agents, has been reported to be leukaemogenic.
There have been reports of acute leukaemia occurring after melphalan treatment for diseases such as amyloid, malignant melanoma, multiple myeloma, macroglobulinaemia, cold agglutinin syndrome and ovarian cancer. A comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents, including melphalan, significantly increased the incidence of acute leukaemia.
The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of melphalan. Effects on Fertility Melphalan causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients.
There is evidence from some animal studies that Melphalan can have an adverse effect on spermatogenesis. Therefore, it is possible that Melphalan may cause temporary or permanent sterility in male patients. 75% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Solvent vial contains 2250 mg of Sulfobutyl-ether-β-cyclodextrin. 3 mg) of propylene glycol which may cause alcohol-like symptoms. In case of hypersensitivity to this substance the administration is contraindicated. Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce serious adverse effects in neonates.
Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce adverse effects in children less than 5 years old. While propylene glycol has not been shown to cause reproductive or developmental toxicity in animals or humans, it may reach the foetus and was found in milk.
As a consequence, administration of propylene glycol to pregnant patients should be considered on a case by case basis. Medical monitoring is required in patients with impaired renal or hepatic functions because various adverse events attributed to propylene glycol have been reported such as renal dysfunction (acute tubular necrosis), acute renal failure and liver dysfunction.