- NAME OF THE MEDICINAL PRODUCT
Melphalan Powder for Injection BP 50mg Taj Pharma
- QUALITATIVE AND QUANTITATIVE COMPOSITION
Melphalan Hydrochloride BP equivalent to 50 mg melphalan per vial.
- PHARMACEUTICAL FORM
Freeze-dried powder for injection.
- CLINICAL PARTICULARS
4.1 Therapeutic indications
Melphalan Injection, at conventional intravenous dosage, 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.
Melphalan Injection, administered by regional arterial perfusion, is indicated in the treatment of localised malignant melanoma of the extremities and localised soft tissue sarcoma of the extremities.
In the above indications, Melphalan may be used alone or in combination with other cytotoxic drugs.
4.2 Posology and method of administration
Melphalan Injection is for intravenous use and regional arterial perfusion only. Melphalan Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m2.
For intravenous administration, it is recommended that Melphalan Injection solution 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.
Melphalan is not compatible with infusion solutions containing dextrose and it is recommended that?only?sodium chloride intravenous infusion 0.9% w/v is used.
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 1.5 hours.
Should any visible turbidity or crystallisation appear in the reconstituted or diluted solutions, the preparation must be discarded.
Care should be taken to avoid possible extravasation of Melphalan and in cases of poor peripheral venous access, consideration should be given to use of a central venous line.
If high dose 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.
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.
When used as a single agent, a typical intravenous Melphalan dosage schedule is 0.4 mg/kg body weight (16 mg/m2?body surface area) repeated at appropriate intervals (e.g. once every 4 weeks), provided there has been recovery of the peripheral blood count during this period.
High-dose regimens generally employ single intravenous doses of between 100 and 200 mg/m2?body surface area (approximately 2.5 to 5.0 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.
When combined with other cytotoxic drugs, intravenous doses of between 0.3 and 0.4 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.
Malignant melanoma:?Hyperthermic regional perfusion with Melphalan has been used as an adjuvant to surgery for early malignant melanoma and as palliative treatment for advanced but localised disease. The scientific literature should be consulted for details of perfusion technique and dosage used. A typical dose range for upper extremity perfusions is 0.6-1.0 mg/kg bodyweight and for lower extremity perfusions is 0.8-1.5 mg/kg body weight.
Soft tissue sarcoma:?Hyperthermic regional perfusion with Melphalan has been used in the management of all stages of localised soft tissue sarcoma, usually in combination with surgery. A typical dose range for upper extremity perfusions is 0.6-1.0 mg/kg body weight and for lower extremity perfusions is 1-1.4 mg/kg body weight.
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 sub-group.
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 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 (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 therapeutic need. Melphalan Injection should not be given without haematopoietic stem cell rescue at doses of 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.
Melphalan should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan.
4.4 Special warnings and precautions for use
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 practised 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.
Since Melphalan is a potent myelosuppressive agent, it is essential that careful attention should be paid 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.
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.
Melphalan is mutagenic in animals and chromosome aberrations have been observed in patients being treated with the drug.
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.
The label for the product will contain the following statements:
Keep out of the reach of children.
Store below 30? C
Do not refrigerate.
Protect from light
4.5 Interaction with other medicinal products and other forms of interaction
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Warnings and Precautions).
Nalidixic acid together with high-dose intravenous melphalan has caused deaths in children due to haemorrhagic entercolitis.
Impaired renal function has been described in bone marrow transplant patients who received high dose intravenous melphalan and who subsequently received ciclosporin to prevent graft-versus-host disease.
4.6 Pregnancy and lactation
The teratogenic potential of Melphalan has not been studied. In view of its mutagenic properties and structural similarity to known teratogenic compounds, it is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug.
The use of melphalan should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.
Mothers receiving Melphalan should not breastfeed.
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
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, <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 common:||bone marrow depression leading to leucopenia, thrombocytopenia and 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)|
|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.
|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.|
|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|
Gastro-intestinal effects, including nausea, vomiting and diarrhoea are the most likely signs of acute oral overdosage. The immediate effects of acute intravenous overdosage are nausea and vomiting. Damage to the gastro-intestinal mucosa may also ensue and diarrhoea, sometimes haemorrhagic, has been reported after overdosage. The principal toxic effect is bone marrow suppression, leading to leucopenia, thrombocytopenia and anaemia.
General supportive measures, together with appropriate blood and platelet transfusions, should be instituted if necessary and consideration given to hospitalisation, antibiotic cover, the use of haematological growth factors.
There is no specific antidote. The blood picture should be closely monitored for at least four weeks following overdosage until there is evidence of recovery.
- PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-2-chloroethyl groups enables alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking the two DNA strands and thereby preventing cell replication.
5.2 Pharmacokinetic properties
The absorption of oral melphalan is highly variable with respect to both the time to first appearance of the drug in plasma and peak plasma concentration.
In studies of the absolute bioavailability of melphalan the mean absolute bioavailability ranged from 56 to 85%.
Intravenous administration can be used to avoid variability in absorption associated with myeloablative treatment.
Melphalan is moderately bound to plasma proteins with reported percent binding ranging from 69% to 78%. There is evidence that the protein binding is linear in the range of plasma concentrations usually achieved in standard dose therapy, but that the binding may become concentration-dependent at the concentrations observed in high-dose therapy. Serum albumin is the major binding protein, accounting for about 55 to 60% the binding, and 20% is bound to ?1-acid glycoprotein. In addition, melphalan binding studies have revealed the existence of an irreversible component attributable to the alkylation reaction with plasma proteins.
Following administration of a two-minute infusion of doses ranging from 5 to 23 mg/m2?body surface area (approximately 0.1 to 0.6 mg/kg bodyweight) to 10 patients with ovarian cancer or multiple myeloma, the mean volumes of distribution at steady state and central compartment were 29.1 ? 13.6 litres and 12.2 ? 6.5 litres, respectively.
In 28 patients with various malignancies who were given doses of between 70 and 200 mg/m2?body surface area as a 2- to 20-min infusion, the mean volumes of distribution at steady state and central compartment were, respectively, 40.2 ? 18.3 litres and 18.2 ? 11.7 litres.
Melphalan displays limited penetration of the blood-brain barrier. Several investigators have sampled cerebrospinal fluid and found no measurable drug. Low concentrations (~10% of that in plasma) were observed in a single high-dose study in children.
In vivo?and?in vitro?data suggest that spontaneous degradation rather than enzymatic metabolism is the major determinant of the drug’s half-life in man.
In 13 patients given oral melphalan at 0.6 mg/kg bodyweight, the plasma mean terminal elimination half-life was 90 ? 57 min with 11% of the drug being recovered in the urine over 24 h.
In 8 patients given a single bolus dose of 0.5 to 0.6 mg/kg bodyweight, the composite initial and terminal half-lives were reported to be 7.7 ? 3.3 min and 108 ? 20.8 min, respectively. Following injection of melphalan, monohydroxymelphalan and dihydroxymelphalan were detected in the patients’ plasma, reaching peak levels at approximately 60 min and 105 min, respectively. A similar half-life of 126 ? 6 min was seen when melphalan was added to the patients’ serum?in vitro?(37?C), suggesting that spontaneous degradation rather than enzymic metabolism may be the major determinant of the drug’s half-life in man.
Following administration of a two-minute infusion of doses ranging from 5 to 23 mg/m2?body surface area (approximately 0.1 to 0.6 mg/kg bodyweight) to 10 patients with ovarian cancer or multiple myeloma, the pooled initial and terminal half-lives were, respectively, 8.1 ? 6.6 min and 76.9 ? 40.7 min. A mean clearance of 342.7 ? 96.8 ml/min was recorded.
In 15 children and 11 adults given high-dose i.v. melphalan (140 mg/m2?body surface area) with forced diuresis, the mean initial and terminal half-lives were found to be 6.5 ? 3.6 min and 41.4 ? 16.5 min, respectively. Mean initial and terminal half-lives of 8.8 ? 6.6 min and 73.1 ? 45.9 min, respectively, were recorded in 28 patients with various malignancies who were given doses of between 70 and 200 mg/m2?body surface area as a 2- to 20-min infusion. The mean clearance was 564.6 ? 159.1 ml/min.
Following hyperthermic (39?C) perfusion of the lower limb with 1.75 mg/kg bodyweight, mean initial and terminal half-lives of 3.6 ? 1.5 min and 46.5 ? 17.2 min, respectively, were recorded in 11 patients with advanced malignant melanoma. A mean clearance of 55.0 ? 9.4 ml/min was recorded.
Special Patient Populations
- Renal impairment
Melphalan clearance may be decreased in renal impairment?(see Dosage and Administration – Renal impairment and Warnings and Precautions – Renal impairment).
No correlation has been shown between age and melphalan clearance or with melphalan terminal elimination half-life?(see Dosage and Administration).
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.
- PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Hydrochloric Acid, Povidone , Water for Injections BP.
6.3 Shelf life
6.4 Special precautions for storage
Store below 30? C
Protect from light
Do not refrigerate.
6.5 Nature and contents of container
Clear, neutral glass vial and bromobutyl rubber stopper with an aluminium collar.
Pack size: 50 mg
6.6 Special precautions for disposal and other handling
Preparation of Melphalan Injection Solution:
Melphalan Injection should be prepared?at room temperature?(approximately 25?C), by reconstituting the freeze-dried powder with the solvent-diluent provided.
It is important that both the freeze-dried powder and the solvent provided are at room temperature before starting reconstitution. Warming the diluent in the hand may aid reconstitution. 10 ml of this vehicle should be added quickly, as a single quantity into the vial containing the freeze dried powder, and immediately shaken vigorously (for approximately 1 minute) until a clear solution, without visible particles, is obtained. Each vial must be reconstituted individually in this manner. The resulting solution contains the equivalent of 5 mg per ml anhydrous melphalan and has a pH of approximately 6.5.
Melphalan Injection solution has limited stability and should be prepared immediately before use. Any solution unused after one hour should be discarded according to standard guidelines for handling and disposal of cytotoxic drugs.
The reconstituted solution should not be refrigerated as this will cause precipitation.
7.Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).
Melphalan Powder for Injection BP 50mg Taj Pharma
Package Leaflet: Information for the User
Read all of this leaflet carefully before you start using this medicine
- Keep this leaflet. You may need to read it again.
- If you have any further questions about your illness or your medicine, ask your doctor or nurse.
- If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.
In this leaflet:
1?What Melphalan is and what it is used for
2?Before you have Melphalan
3?How to have Melphalan
4?Possible side effects
5?How to store Melphalan
1 WHAT MELPHALAN IS AND WHAT IT IS USED FOR
Melphalan injection contains a medicine called melphalan. This belongs to a group of medicines called cytotoxics (also called chemotherapy). Melphalan is used to treat cancer. It works by reducing the number of abnormal cells your body makes.
Melphalan is used for:
- Multiple myeloma– a type of cancer that develops from cells in the bone marrow called plasma cells. Plasma cells help to fight infection and disease by producing antibodies
- Advanced?cancer of the ovaries
- Childhood neuroblastoma– cancer of the nervous system
- Malignant melanoma– skin cancer
- Soft tissue sarcoma– cancer of the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body
Ask your doctor if you would like more explanation about these diseases.
2 BEFORE YOU HAVE MELPHALAN
Do not have Melphalan if:
- You are allergic (hypersensitive) to melphalan or any of the other ingredients of Melphalan injection (See section 6: Further information)
Do not have Melphalan if the above applies to you. If you are not sure, talk to your doctor or nurse before having Melphalan.
Take special care with Melphalan
Before you use Melphalan, tell your doctor or nurse if:
- you have had radiotherapy or chemotherapy, now or recently
- you have a kidney problem.
If you are not sure if any of the above apply to you, talk to your doctor or nurse before having Melphalan.
Taking other medicines
Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This includes herbal medicines.
In particular, tell your doctor or nurse if you are taking any of the following:
- other cytotoxic drugs (chemotherapy)
- nalidixic acid (an antibiotic used to treat urinary tract infections)
- ciclosporin (used to prevent rejection of organs or tissues following a transplant or to treat certain skin conditions like psoriasis and eczema or to treat rheumatoid arthritis).
Having vaccines while you are taking Melphalan
If you are going to have a vaccination speak to your doctor or nurse before you have it. This is because some vaccines (like polio, measles, mumps and rubella) may give you an infection if you have them whilst you are being treated with Melphalan.
Pregnancy and breast-feeding
Do not have Melphalan if you are planning to have a baby. This applies to both men and women. Melphalan may harm your sperm or eggs. Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner are having this injection. Ask your doctor for advice.
If you are already pregnant, it is important to talk to your doctor before having Melphalan.
Do not breast-feed while having Melphalan. Ask your doctor or midwife for advice.
3 HOW TO HAVE MELPHALAN
Melphalan should only be prescribed for you by a specialist doctor who is experienced in treating blood problems or cancer.
Melphalan injection can be given:
- as an infusion into your vein
- as a perfusion to a particular part of your body through an artery.
Your doctor will decide how much Melphalan you will have. The amount of Melphalan depends on:
- your body weight or body surface area (a specific measurement taking into account your weight and your size)
- other drugs you are having
- your disease
- your age
- whether or not you have kidney problems.
When you are given Melphalan, your doctor will take regular blood tests. This is to check the number of cells in your blood. Your doctor may sometimes change your dose as a result of these tests.
If you have more Melphalan than you need
Your doctor will give you Melphalan so it is unlikely that you will receive too much. If you think you have been given too much or have missed a dose, tell your doctor or nurse.
4 POSSIBLE SIDE EFFECTS
Like all medicines, Melphalan can cause side effects, although not everybody gets them.
If you get any of the following, talk to your specialist doctor or go to hospital straight away:
- allergic reaction, the signs may include:
- a rash, lumps or hives on the skin
- swollen face, eyelids or lips
- sudden wheeziness and tightness of the chest
- collapse (due to cardiac arrest)
- any signs of fever or infection (sore throat, sore mouth or urinary problems)
- any?unexpectedbruising or bleeding or feeling extremely tired, dizzy or breathless, as this could mean that too few blood cells of a particular type are being produced
- if you?suddenlyfeel unwell (even with a normal temperature)
- if your muscles are achy, stiff or weak?andyour urine is darker than usual or brown or red in colour ? when you have Melphalan directly into your arm or leg.
Talk to your doctor if you have any of the following side effects which may also happen with this medicine:
Very common (affects more than 1 in 10 people)
- a drop in the number of blood cells and platelets
- feeling sick (nausea), being sick (vomiting) and diarrhoea
- mouth ulcers – with high doses of Melphalan
- hair loss – with high doses of Melphalan
- a tingling or warm feeling where Melphalan was injected
- problems with your muscles like wasting and aching – when you have Melphalan directly into your arm or leg
Common (affects less than 1 in 10 people)
- hair loss – with usual doses of Melphalan
- high levels of a chemical called urea in your blood – in people with kidney problems who are being treated for myeloma
- a muscle problem which can cause pain, tightness, tingling, burning or numbness – called compartment syndrome. This can happen when you have Melphalan directly into your arm or leg
Rare (affects less than 1 in 1,000 people)
- an illness where you have a low number of red blood cells as they are being destroyed prematurely – this can make you feel very tired, breathless and dizzy and can give you headaches or make your skin or eyes yellow
- lung problems which may make you cough or wheeze and make it difficult to breathe
- liver problems which may show up in your blood tests or cause jaundice (yellowing of the whites of eyes and skin)
- mouth ulcers – with normal doses of Melphalan
- skin rashes or itching skin
The following side effects also happen with Melphalan:
- leukaemia – cancer of the blood
- in women: your periods stopping
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
5 HOW TO STORE MELPHALAN
- Keep out of the reach and sight of children.
- Do not use Melphalan after the expiry date, which is stated on the pack after ?Exp?.
- Do not store Melphalan Injection above 30?C. Do not refrigerate. Keep the vial in the outer carton, to protect from light.
- Your Melphalan Injection will be prepared for use by a healthcare professional. Once prepared it should be used immediately and must not be stored or refrigerated.
6 FURTHER INFORMATION
What Melphalan contains
The active ingredient is melphalan. Each Melphalan injection contains 50 mg of melphalan.
The other ingredients are: povidone K12 and hydrochloric acid. Melphalan is dissolved in a diluent before being injected. The diluent contains water, sodium citrate, propylene glycol and ethanol.
What Melphalan looks like and contents of the pack
Each pack contains one Melphalan Injection vial and one Melphalan Injection Diluent vial.
7.Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).