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Phelinun is a brand name for Melphalan. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: High-dose of PHELINUN used alone or in combination with other cytotoxic medicinal products and/or total body irradiation is indicated in the treatment of: - multiple myeloma, - malignant lymphoma (Hodgkin, non-Hodgkin lymphoma), - acute lymphoblastic and myeloblastic leukemia, - childhood neuroblastoma, 3 - ovarian…
Verbatim from this product's EMA label. Tap a section to expand.
PHELINUN administration must be supervised by a physician experienced in the use of chemotherapeutic medicinal products and in conditioning treatment prior to haematopoietic stem cell transplantation. 0 mg/kg body weight). The dose can be divided equally over 2 or 3 consecutive days.
Autologous hematopoietic stem cell transplantation is required following doses above 140 mg/m2 body surface area. Malignant haematological diseases before allogeneic haematopoietic stem cell transplantation The recommended dose is 140 mg/m2 as a single daily infusion or 70 mg/m2 once daily for two consecutive days.
0 mg/kg body weight). The dose can be divided equally over 2 or 3 consecutive days. Autologous hematopoietic stem cell transplantation is required following doses above of 140 mg/m2 body surface area. Childhood neuroblastoma The recommended dose to consolidate a response obtained with a conventional treatment is one single dose between 100 mg/m2 and 240 mg/m2 body surface area (sometimes divided equally over 3 consecutive days) together with autologous haematopoietic stem cell transplantation.
The infusion is used either alone or in combination with radiotherapy and/or other cytotoxic medicinal products. Haematological diseases before allogeneic haematopoietic stem cell transplantation The recommended dose is as follows: - malignant haematological diseases: 140 mg/m2 as a single daily infusion; - non-malignant haematological diseases: 140 mg/m2 as a single daily infusion or 70 mg/m2 once daily for two consecutive days.
Thromboembolic complications 4 Thrombosis prophylaxis needs to be administered during at least the first 5 months of the treatment, in particular to patients who are more at risk of thrombosis. 8). Special populations Elderly There is no dose recommendation for the administration of PHELINUN to elderly.
However, frequently conventional doses of melphalan are applied in the elderly. Experience in the use of high dose melphalan in elderly patients is limited. Consideration should therefore be given to ensure adequate performance status and organ function, before using high dose melphalan in elderly patients.
4). The clearance of melphalan, although variable, may be reduced with impaired renal function. High-dose melphalan with haematopoietic stem cell rescue has been used successfully even in dialysis dependent patients with end-stage renal failure.
Summary of the safety profile The most frequently reported adverse reactions were haematologic and gastrointestinal toxicities, and immune system disorders, these being considered as expected consequences of myelosuppression. Infections, acute and chronic Graft versus Host Disease (GvHD) were reported as the major causes of morbidity and mortality in the allo HSCT setting.
Bone marrow failure, stomatitis, mucosal inflammation, gastrointestinal haemorrhage, diarrhea, nausea, vomiting, amenorrhoea, ovarian disorders and premature menopause were also commonly reported. Tabulated list of adverse reactions 10 The adverse drug reactions (ADRs) described in this section were identified from information included in other melphalan containing products, the screening of the published literature and the European database EudraVigilance concerning the use of melphalan as part of combination regimens for allo-HSCT setting.
With the exception of Stevens-Johnson syndrome and Toxic epidermal necrolysis identified for only one patient, ADRs reported for at least two patients have been captured in the table below. Frequencies are described as very common (1/10), common (1/100 to <1/10), uncommon (1/1 000 to <1/100), rare (1/10 000 to <1/1,000), very rare (<1/10 000), and not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. MedDRA System Organ Class Frequency Adverse Drug Reactions Infections and infestations Common Infection Uncommon Septic shock Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uncommon Secondary primary malignancy, Secondary acute myeloid leukaemia Myelodysplastic syndrome Blood and lymphatic system disorders Very Common Myelosuppression leading to Neutropenia, Thrombocytopenia Anaemia Uncommon Thrombotic microangiopathy Rare Haemolytic anaemia Immune system disorders Very common Acute graft versus host disease, Chronic graft versus host disease Rare Hypersensitivity (urticaria, oedema, skin rashes, and anaphylactic shock) Not known Haemophagocytic lymphohistiocytosis Nervous system disorders Uncommon Haemorrhage intracranial Cardiac disorders Rare Cardiac arrest Not known Cardiac failure, Cardiomyopathy, Pericardial effusion Vascular disorders Not known Haemorrhage, Deep venous thrombosis and Lung embolism Respiratory, thoracic and mediastinal disorders Uncommon Interstitial lung disease, Pulmonary fibrosis, Idiopathic pneumonia syndrome, Pulmonary haemorrhage, Respiratory failure, Acute respiratory distress syndrome, Pneumonitis Not known Pulmonary hypertension Gastrointestinal disorders Common Diarrhoea, 11 MedDRA System Organ Class Frequency Adverse Drug Reactions Nausea, Vomiting, Stomatitis, Gastrointestinal haemorrhage Hepatobiliary disorders Uncommon Hepatotoxicity, Venoocclusive liver disease Rare Liver function test abnormal, Jaundice Skin and subcutaneous tissue disorders Very common Alopecia after high dose Common Alopecia after conventional dose Uncommon Rash maculo-papular, alopecia Rare Pruritus Not known Stevens-Johnson syndrome, Toxic epidermal necrolysis Renal and urinary disorders Uncommon Acute kidney injury, Renal failure Not known Cystitis haemorrhagic, Nephrotic syndrome Reproductive system and breast disorders Common Amenorrhoea, Ovarian failure, Ovarian disorder, Premature menopause, Azoospermia General disorders and administration site conditions Common Mucosal inflammation, Multiple organ dysfunction syndrome, Pyrexia Uncommon Feeling hot, Paraesthesia Investigations Not known Blood creatinine increased Description of selected adverse reactions Infections and GvHD although not directly related to melphalan, were the major causes of morbidity and mortality, especially in the setting of allogeneic transplantation.
Melphalan can cause local tissue damage. 2). Hepatic veno-occlusive disease is a major complication that can occur during treatment with melphalan. Monitoring Since melphalan is a potent myelosuppressive agent, it is essential that careful attention is paid to the monitoring of blood counts to avoid the possibility of excessive myelosuppression and the risk of irreversible bone marrow aplasia or irreversible bone marrow failure.
Cytopenia may continue to fall after treatment is stopped. So, at the first sign of an abnormally, large fall in leukocyte or severe thrombocytopenia, treatment should be temporarily interrupted. PHELINUN should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.
It is recommended to ensure patients’ adequate hydration and forced diuresis and the prophylactic administration of anti-infective agents (bacterial fungal, viral). The administration of blood products should be considered if required.
It is recommended to monitor the general and renal status of patients receiving high-doses of PHELINUN. The incidence of diarrhoea, vomiting and stomatitis becomes the dose-limiting toxicity in patients given high intravenous doses of PHELINUN in association with autologous bone marrow 6 transplantation.
Cyclophosphamide pre-treatment appears to reduce the severity of gastrointestinal damage induced by high-dose PHELINUN and the literature should be consulted for details. Mutagenicity Melphalan is mutagenic in animals and chromosome aberrations have been observed in patients being treated with the medicinal product.
Carcinogenicity Acute myeloide leukemia (AML) and myelodysplastic syndromes. Melphalan has been reported to be leukaemogenic (acute leukemia and myelodysplastic syndromes). 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.
1. 6).
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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.
For high intravenous doses of melphalan (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 be given with haematopoietic stem cell rescue at doses above 140 mg/m2.
Hepatic impairment No dose adjustment is required for patients with mild hepatic impairment and that there are insufficient data in patients with moderate or severe heptic impairment. 4). 8). 8). 8). PHELINUN is for intravenous use only.
Risk of extravasation could be observed when PHELINUN is administered via peripheral intravenous route. In case of extravasation, the administration should be interrupted immediately and a central venous line route should be used. If high-dose is administered with or without transplantation, the administration as dilution via a central venous line is recommended to avoid extravasation.
It is recommended that PHELINUN as concentrate (5 mg/ml) is injected slowly into the port of a fast- running infusion solution. 9%) 5 solution for injection in a “slow-running” solution in a infusion bag. The total time from preparation of the solution to the completion of infusion should not exceed 1 hour and 30 minutes.
When further diluted in an infusion solution, PHELINUN has reduced stability and the rate of degradation increases rapidly with rise in temperature. It is recommended to let the infusion run at a temperature below 25°C. Precaution to be taken before handling or administering the medicinal product The preparation of injectable cytotoxic solutions […]
Infections and infestations All patients in the target population are at risk of infections due to their immunodeficient status. Myelosuppression and immunosuppressive effects induced by melphalan may facilitate the development of infections which may have fatal outcome in the most severe manifestations.
Adoption of prohylactic measures such as the administration of anti-infective agents can be useful. Graft versus host disease GvHD is a very common complication in the allogeneic HSCT setting. Up to ≈ 60% patients develop acute and/or chronic GvHD.
The severity of GvHD may vary from mild to fatal in the most severe manifestations of the disease. The occurrence of GvHD can be prevented by using immunosuppressive therapy after haematopoietic stem cell transplantation as prophylaxis.
Paediatric population 12 Respiratory, thoracic and mediastinal disorders On the basis of the identified safety reports in the literature, the paediatric population appears more susceptible to develop respiratory complications than adults.
In particular, fatal respiratory complications were reported as higher for infants below 2 years than for children and adolescents. Gastrointestinal disorders On the basis of the identified safety reports in the literature, the paediatric population appears more susceptible to develop gastrointestinal complications.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of melphalan, in particular when used in combination with thalidomide or lenalidomide and prednisone, as it has been determined that these combinations increase the leukaemogenic risk.
Before, during and after treatment the doctor needs to examine the patients with the usual checks to detect cancer early and start treatment if necessary. Solid tumors The use of alkylating agents has been linked to the development of a second primary malignancy (SPM).
In particular when melphalan is used in combination with lenalidomide and prednisone, and to a lesser extent in combination with thalidomide and prednisone, it has been linked to an increased chance of solid SPM for elderly patients with newly diagnosed multiple myeloma.
Thromboembolic complications The use of melphalan in combination with lenalidomide and prednisone or thalidomide or dexamethasone has been associated with an increased risk of thromboembolic complications. 8). Should thromboembolic complications occur for the patient, treatment needs to be stopped and the standard anticoagulant therapy needs to be started.
As soon as the patient is stabilised by the anticoagulant therapy and the complications of the thromboembolic incident are under control, melphalan can be used in combination with lenalidomide and prednisone, or thalidomide and prednisone or dexamethasone can be resumed in the original dose contingent on the assessment of the risks and benefits.
The patient needs to continue the anticoagulant therapy during the melphalan treatment. Renal impairment Since patients with renal impairment may have marked bone marrow suppression, these patients should be closely monitored. Melphalan clearance may be reduced in patients with renal impairment who may also have uraemic marrow suppression.
8). 1). 7 The safety and efficacy of melphalan as part of the conditioning regimen prior to allo-HSCT in children below the age of 2 years with ALL has not been established. 1). 42% w/v). The amount in 10 ml of this medicine is equivalent to 10 ml beer or 4 ml wine.
42 % w/v). The amount in 40 ml of this medicine is equivalent to 40 ml beer or 17 ml wine. For comparison, for an adult drinking a glass of wine or 500 ml of beer, the blood alcohol concentration (BAC) is likely to be about 50 mg/100 ml.
Co-administration with medicinal products containing propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects, in particular in young children with low or immature metabolic capacity. Adults A dose of 200 mg/m2 of this medicine administered to adult weighing 70 kg […]