Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about ALKERAN injection. It does not contain all of the available information.

It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of giving you ALKERAN injection against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor.

Keep this leaflet while being treated. You may need to read it again.

What ALKERAN injection is used for

ALKERAN injection contains melphalan as the active ingredient. It belongs to a group of medicines called cytotoxics.

ALKERAN injection is used to treat multiple myeloma, a cancer of the blood.

It is thought to work by stopping cancer cells from growing and multiplying.

This medicine may be used in combination with other medicines to treat cancer.

Ask your doctor if you have any questions about why ALKERAN injection has been prescribed for you.

Your doctor may have prescribed it for another purpose.

This medicine is available only with a doctor's prescription.

There is no evidence that it is addictive.

Before you are given it

When you must not be given it

You must not be given ALKERAN injection if you have an allergy to:

• melphalan
• any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue or any other parts of the body; rash, itching or hives on the skin.

You must not be given ALKERAN injection if you have an infection or a high temperature.

Your doctor may decide to delay your treatment until the infection has gone. A mild illness, such as a cold, is not usually a reason to delay treatment.

You must not be given this medicine if you are trying to become pregnant or to father a child.

ALKERAN injection may harm eggs and sperm. Reliable contraceptive methods must be taken to avoid pregnancy whilst you or your partner is being treated with this medicine and for at least 12 weeks after either partner stops being given it.

You must not be given ALKERAN injection if you are pregnant or breast feeding unless you and your doctor have discussed the risks and benefits involved.

You must not be given this medicine after the expiry date has passed or if the packaging is torn or shows signs of tampering.

Use in Children

The safety and effectiveness in children has not been established.

If you are not sure if you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you are allergic to any other medicines or any foods, preservatives of dyes.

Tell your doctor if you have or have had any of the following conditions:

• you have recently received or are receiving radiotherapy or chemotherapy
• you have recently been vaccinated or are planning to be vaccinated
• kidney disease
• blood disorders
• you have received ALKERAN treatment previously.

If you have not told your doctor about any of the above, tell them before you are given ALKERAN injection.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your supermarket, pharmacy or health food shop.

Some medicines may be affected by ALKERAN injection or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines. These include:

• nalidixic acid
• cyclosporin
• cisplatin
• carmustine
• other cytotoxic drugs
• vaccinations with 'live' organism vaccines.

Your doctor has more information on medicines to be careful with or avoid while being given this medicine.

How it is given

How much is given

Your doctor will decide what dose and for how long you will be given ALKERAN injection.

Your doctor may order regular blood tests while you are being given ALKERAN injection in order to monitor your blood cell count and to change your dosage if necessary.

How it is given

ALKERAN injection will be given to you under the supervision of a doctor.

It is a sterile powder which is dissolved and then further diluted before intravenous infusion or 'drip' into a vein.

If you take too much (overdose)

As ALKERAN injection is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience any side effects after being given ALKERAN injection, tell your doctor immediately.

Symptoms of overdose may include severe nausea and vomiting, convulsions and stomach pain.

While you are receiving it

Things you must do

It is important that you visit your doctor regularly, so your doctor can check your progress and make sure your medicine is working.

Tell any other doctor, dentist or pharmacist that you are being given ALKERAN injection, especially if you are about to be started on any new medicines or radiotherapy.

Do not have any vaccinations without your doctor's approval.

ALKERAN may lower your body's resistance and there is a chance you might get the infection the vaccination is meant to prevent.

Tell your doctor if you become pregnant, are trying to become pregnant or trying to father a child.

If you are about to undergo surgery or an operation, tell your doctor or surgeon that you are being given ALKERAN injection.

This medicine can lower the number of white blood cells and platelets in your blood. This means that you have an increased chance of getting an infection or bleeding.

The following precautions should be taken to reduce your risk of infection or bleeding:

• avoid people who have infections

Check with your doctor immediately if you think you may be getting an infection, or if you get a fever, chills, cough, hoarse throat, lower back or side pain or find it painful or difficult to urinate.

• be careful when using a toothbrush, tooth pick or dental floss

Check with your doctor before having dental work.
Your doctor, dentist, nurse or pharmacist may recommend other ways to clean your teeth and gums.

• be careful not to cut yourself when using sharp objects such as a razor or nail cutters
• avoid contact sports or other situations where you may bruise or get injured.

Things to be careful of

Be careful driving or operating machinery until you know how ALKERAN injection affects you.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are being given ALKERAN injection.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

The following side-effects have been reported with ALKERAN injection:

• production of bone marrow cells may be reduced.

Your doctor will frequently test your blood count, but you should tell him at once if you notice any signs of fever, infection, unexpected bruising, bleeding or signs of blood in your urine.

• hair loss
• in some women, periods may stop
• in some men, sperm production may be reduced or stop.

Tell your doctor if you notice any of the following and they worry you:

• nausea and vomiting
• diarrhoea
• mild skin rash or itching
• tingling sensation
• persistent cough or breathlessness
• pain or swelling at the injection site.

Tell your doctor immediately if you notice any of the following:

• wheezing, swelling of the lips or mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting
• frequent infections such as fever, sore throat or mouth ulcers
• bruising or bleeding more easily than normal, nose bleeds
• unusual tiredness, looking pale, feeling weaker, dizzy or more tired than usual
• jaundice, a yellowing of the whites of the eyes or skin
• problems with your eyesight
• unusually fast heart beat.

Tell your doctor if you notice anything else that is making you feel unwell, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of side effects.

You may not experience any of them.

After using it

Things to be aware of

Because of the way this medicine works there is a chance it might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer, such as leukaemia.

Discuss these possible effects with your doctor.

Storage

Keep ALKERAN injection in a cool, dry place where it stays below 30°C, protected from light.

Keep this medicine where children cannot reach it, such as in a locked cupboard.

Return any unused or expired medicine to your pharmacist.

Product description

What it looks like

ALKERAN injection is supplied in a carton containing:

• one clear glass vial containing sterile, white or off white powder for injection
• one 10 mL clear glass vial containing a sterile, clear, colourless solution of diluent.

The diluent is used to dissolve the powder.

Ingredients

Each vial of sterile powder for injection contains 50 mg melphalan and povidone.

Each vial of sterile diluent contains sodium citrate, propylene glycol, ethanol and water for injections.

Sponsor

Aspen Pharmacare Australia Pty Limited
34-36 Chandos Street
St Leonards NSW 2065 Australia

Australian registration number:
AUST R 79834

This leaflet was prepared in August 2010.

Published by MIMS November 2010

1 Name of Medicine

Melphalan.

2 Qualitative and Quantitative Composition

Alkeran Injection is a composite pack containing 2 components, a single use vial containing melphalan hydrochloride equivalent to 50 mg melphalan and a vial of sterile diluent.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Component 1: powder for injection. A clear, glass vial containing white or off-white powder, practically free of visible particles when dissolved.
Component 2: sterile diluent. A clear, glass vial containing a clear colourless solution, practically free of visible particles.
Alkeran Injection is reconstituted using the sterile diluent provided.

4 Clinical Particulars

4.9 Overdose

Symptoms and signs. Overdoses resulting in death have been reported. Overdoses, including doses up to 290 mg/m², have produced the following symptoms: severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis and cholinomimetic effects. Damage to the gastrointestinal lining may also ensue. Severe mucositis, stomatitis, colitis, diarrhoea and haemorrhage of the gastrointestinal tract occur at high doses (> 100 mg/m²). Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia caused by an associated inappropriate secretion of antidiuretic hormone (ADH) syndrome has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely.
Treatment. The principal toxic effect is bone marrow suppression, leading to leucopenia, thrombocytopenia and anaemia. Haematologic parameters should be closely followed for at least 4 weeks following overdosage until there is evidence of recovery. An uncontrolled study suggests that administration of autologous bone marrow or haemopoietic growth factors (i.e. filgrastim) may shorten the period of pancytopenia. General supportive measures together with appropriate blood and platelet transfusions and antibiotics should be instituted as deemed necessary by the physician. This drug is not removed from plasma to any significant degree by haemodialysis or haemoperfusion. A paediatric patient survived a 254 mg/m² overdose treated with standard supportive care.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. Secondary malignancies, including acute nonlymphocytic leukaemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including melphalan). Some patients also received other chemotherapeutic agents or radiation therapy. Precise quantitation of the risk of myeloproliferative syndrome or carcinoma is not possible. 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 amyloidosis, malignant melanoma, multiple myeloma, macroglobulinaemia, cold agglutinin syndrome and ovarian cancer. Published reports of leukaemia in patients who have received melphalan (and other alkylating agents) suggest that the risk of leukaemogenesis increases with chronicity of treatment and with cumulative dose.
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 potential benefits from Alkeran Injection therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.
Before the start of the treatment, the leukaemogenic risk (AML and MDS) must be balanced against the potential therapeutic benefit, especially if the use of melphalan in combination with thalidomide or lenalidomide and prednisone is considered, as it has been shown that these combinations increase the leukaemogenic risk. Before, and during and after treatment doctors must therefore examine the patient at all times by usual measurements to ensure the early detection of cancer and initiate treatment if necessary.
Although adequate and well controlled carcinogenicity studies have not been conducted in animals, there is clear evidence from animal studies that melphalan is carcinogenic. Intraperitoneal (IP) administration of melphalan in rats (5.4 or 10.8 mg/m²) and mice (2.25 or 4.5 mg/m²) three times per week for 6 months followed by a 12 months postdose observation produced peritoneal sarcoma in rats, and lung tumours and lymphosarcomas (males) in mice. Lung tumours were also increased in two other studies in mice (total dose: 144 mg/m² dermal given as 10 injections over a period of 10 weeks; 3.2-51 mg/m² IP given as 12 injections over a period of 4 weeks) while in one of these studies (dermal), skin papillomas were increased, although nonsignificantly.
Chromosome aberrations have been observed in patients being treated with melphalan. Melphalan has been shown to cause chromatid and chromosome damage in human lymphocytes at a single dose of 20 mg IV (~10.6 mg/m², comparable to a therapeutic dose of 16 mg/m²) and in rat bone marrow cells at a single intramuscular dose of 6 mg/m². Melphalan also showed mutagenic effects on germ cells in male mice at 17.1-21.9 mg/m².

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

It is known chemically as 4-[bis (2-chloroethyl) amino]- L-phenylalanine. The molecular formula is C₁₃H₁₈Cl₂N₂O₂ and the molecular weight is 305.20. Melphalan is the active L-isomer of the compound and was first synthesised in 1953. Melphalan is practically insoluble in water and has a pKa₁ of ~ 2.5.
Melphalan also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSMELPHA.gif CAS number. CAS No: 148-82-3.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription only medicine).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/ALKINJST.gif