Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about METASTRON. It does not contain all the available information, nor does it take the place of talking to your doctor or treatment provider.

All medicines have risks and benefits. Your doctor has weighed the risks of you being treated with METASTRON against the expected benefits.

If you have any concerns about being given this medicine, ask your doctor or nuclear medicine technologist giving you METASTRON.

Keep this leaflet. You may need to read it again.

What METASTRON is used for

METASTRON contains strontium Sr-89, which sends out radioactive radiation for some time also known as a radionuclide or radioisotope. Radionuclide agents may be used in low doses to help diagnose certain conditions. When given in higher doses, some radionuclides can be used as treatments for certain conditions, as is the case with METASTRON.

The purpose of METASTRON is to relieve bone pain that is caused by prostate cancer. METASTRON is a bone-seeking substance which delivers most of the radiation to the painful bone lesions and spares other organs. Therefore it will not relieve tumour pain outside the bone and it is not a cure for cancer .

It may take about 10 to 20 days after a dose of METASTRON before you feel any relief of pain. Sometimes the pain flares up for a few days after you have received METASTRON. You will then be given pain killers.

Before you are given METASTRON

When you must not be given it

You must not be given METASTRON if you have:

• Severe problems with your bone marrow which cause the blood to contain very low levels of some types of white blood cells (which help fight infection) or platelets (which control blood clotting).

METASTRON is also not suitable as a major treatment where there is pressure on your spinal cord from a tumour or bony fragment of spine.

Before you are given it

Your doctor must know about all of the following before you are given METASTRON. Tell your doctor if you:

1. have allergies to:

• any other medicines
• any other substances, such as foods, substances to maintain food quality or freshness (preservatives) or colourants (dyes).
• any of the ingredients of METASTRON listed at the end of this leaflet.

2. have, or have had any medical conditions, especially:

• severe kidney disease or
• any problems controlling your bladder
• problems with your blood (eg blood cell counts) caused by disease or a previous medical treatment

3. plan to have surgery
4. have had any previous chemotherapy or radiotherapy, particularly in the last 12 weeks or,
5. previously have received METASTRON or another type of bone-seeking radiopharmaceutical or medicines called cytotoxic agents which are used to treat cancer.

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

Taking other medicines

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

Some medicines may interfere with the absorption of METASTRON or should not given at the same time as METASTRON. These include:

• calcium containing medicines taken in the last two (2) weeks
• cytotoxic agents used within the last twelve (12) weeks to treat cancer.

Your doctor or treatment provider has more information on medicines to be careful with or to avoid when you are given METASTRON.

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

How METASTRON is given

Your doctor may have special instructions for you to follow to get ready for your treatment. If you have any questions, ask your doctor.

METASTRON is given as an injection into a vein. METASTRON must only be given by a doctor or nuclear medicine technologist who is licensed to use an unsealed source.

Your doctor will decide what dose of METASTRON you will receive, depending on your condition and other factors, such as your weight and results of blood tests.

METASTRON is usually given as a single dose. A repeat dose may be required sometimes in three (3) months, but usually in more than six (6) months, depending on how you recover.

After being given METASTRON

Things you must do

If you are about to start taking any new medicine, tell your doctor (and pharmacist as appropriate) that you have been given METASTRON.

Things to be careful of

METASTRON is eliminated from the body in the urine and faeces (stools). Therefore, for 2 weeks after treatment you will need to take special care to prevent contamination of clothing, bed linen and the environment. Follow these steps:

• use a normal toilet instead of a urinal
• flush the toilet twice after using
• wipe any spilled urine with a tissue and flush away
• wash your hands after using or cleaning the toilet
• wash your clothes and bed linen immediately if they become soiled with urine, stools or blood. Wash them separately from other clothes
• wash away any blood if you cut or injure yourself

Things that may help your condition

METASTRON can temporarily lower the number of white blood cells in your blood, and this can increase your chances of getting an infection.

It can also lower the number of platelets in your blood, which are necessary for proper blood clotting. If you are told that your blood counts become abnormally low, there are certain precautions you can take to reduce the risk of infection or bleeding:

• avoid people with infections
• be careful when using a toothbrush, toothpick or dental floss
• wash your hands before and after you touch your eyes or the inside of your nose
• be careful not to cut yourself when using a razor or other sharp objects
• avoid contact sports or other situations where injury or bruising could occur.

Side effects

Some people experience a temporary increase in pain some time in the first few days after being given METASTRON. This is usually mild and can be managed by pain killers.

Your doctor will do blood tests regularly because the most common side effect after METASTRON therapy is a fall in the number of white blood cells and/or platelets. In some cases, especially where patients have received chemotherapy or radiotherapy, the fall may be severe and may require a blood transfusion. Tell your doctor immediately if you notice any of the following:

• any type of infection eg. sore throat, cough or chest infection (as this may be a sign of pneumonia)
• fever
• skin rash or sores on the body
• hot flush
• bruising
• bleeding from nose or gums,
• visual disturbances or headache, nausea and/or vomiting
• blood in the urine or bowel movements

These may be serious side effects of METASTRON. You may need urgent medical attention.

Occasionally other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell. Do not be alarmed by this list of side effects. You may not experience any of them.

Overdose

The dose of METASTRON you will receive will be calculated by a qualified nuclear medicine doctor and given to you in a highly specialised setting by either the doctor or nuclear medicine technologist. Therefore the possibility of overdose is minimal.

Storage

METASTRON will be stored by the hospital or clinic.

The hospital or clinic will make sure that METASTRON is not be used if the expiry date (EXP) printed on the pack has passed.

Further information

This is not all the information that is available on METASTRON. If you have any more questions or are not sure about anything, ask your doctor, or treatment provider.

Product description

Ingredients

Each 4mL vial contains strontium chloride ⁸⁹Sr (43.6-90.4 mg) in sterile water for injections

Australian Registration Number:
AUST R 42958

Sponsor

METASTRON is made in England and supplied in Australia by:

GE Healthcare Australia Pty Ltd
32 Phillip St
Parramatta NSW 2150

This leaflet was prepared in October 2014.

Metastron is a trademark of GE Healthcare

GE and the GE Monogram are trademarks of General Electric Company.

Published by MIMS May 2016

Name of the medicine

Strontium (⁸⁹Sr) chloride.

Description

A sterile aqueous solution of Strontium [⁸⁹Sr] chloride for intravenous injection. Each vial contains 43.6-90.4 mg of strontium chloride (10.9-22.6 mg per millilitre).
The radioactive concentration is 37 MBq/mL (total 150 MBq/vial). The specific activity is 2.96 to 6.17 MBq/mgSr. The pH of the solution is 4 to 7.5. The injection is sterilised by autoclaving and it contains no bactericide. The reference date, lot number, volume, radioactive concentration and total radioactive content for each batch are stated on the container labels. The activities quoted are to the activity reference date stated on the label.

Pharmacology

The behaviour of strontium in healthy man has been studied under the auspices of the International Committee for Radiation Protection (IRCP).
Strontium imitates calcium in vivo, and therefore localises in bone mineral, especially at sites of increased bone deposition. Strontium is not thought to concentrate in lytic bone lesions. In normal subjects 82% of an administered dose is initially distributed in the soft tissues and is removed with a half-life of about 2 days. However, approximately 15% is retained in the soft tissues for a much longer period.
The strontium initially lost from soft tissue is partly excreted and partly taken up by the skeleton, which reaches a maximum content of 25% of the administered strontium.
The behaviour of intravenous strontium in patients with bone metastases has been studied using strontium-85, a radioactive tracer with a gamma emission convenient for measurement. This study showed that sclerotic metastatic bone lesions accumulated strontium more than did normal bone. It was also observed that the biological half-life of strontium in the lesions was long compared to the 50.5 day physical half-life of strontium-89, whilst normal trabecular bone turned over strontium with its usual initial half-life of about 14 days. This behaviour favours the delivery of larger radiation doses to the lesions for a given dose to the bone marrow. Whole body retention at three months varied from 11% to 88% depending on the degree of skeletal involvement.
In normal subjects approximately 75% of the administered activity is excreted via the kidneys and the gut in a ratio of about 4:1 urine:faeces. The majority of the excreted activity is excreted during the first 2 days.
Strontium renal plasma clearance varies widely in patients with bone metastases from prostate cancer depending largely upon the extent of metastatic lesions; it is significantly below levels in normal subjects. Based on studies in elderly patients (55-80 years) up to 90% of an administered dose may be retained for prolonged periods in patients with extensive bone metastases.
Excretion in urine is at its highest on the day of injection and on the following day. Excretion after one week postinjection normally accounts for less than 10% of the total activity excreted. Urinary excretion is reduced in the presence of impaired renal function; inevitably resulting in accumulation of Metastron and a higher body radiation dose.

Indications

Metastron is indicated as an alternative to external beam radiotherapy for the palliation of pain from bone metastases secondary to prostatic carcinoma at the stage of hormone therapy failure.
See Precautions concerning expected time to pain relief, repeat doses and use of radiotherapy or cytotoxic therapy.

Contraindications

Use of the product in patients with evidence of seriously compromised bone marrow, particularly low neutrophil and platelet counts, is contraindicated unless the potential benefit of the treatment is considered to outweigh the risk (see also Precautions and Adverse Effects).
Metastron should not be used as a primary treatment for cord compression secondary to spinal metastases where prompt treatment may be necessary.

Precautions

It is recommended that the presence of bone metastases is confirmed, for example with a technetium-99m labelled MDP bone image, prior to therapy.
Calcium therapy should be discontinued at least 2 weeks before Metastron administration.
The haematology of patients should be measured prior to treatment with particular attention to platelets. Haematology should also be monitored regularly for at least 8 weeks following treatment. Care should be exercised in the pretreatment assessment of the haematological status of patients who, for the same cause, have previously received extensive bone radiation and/or another injectable bone seeking isotope.
The potential for cumulative marrow suppression, as a result of previous treatments, e.g. deep X-ray or chemotherapy, should be borne in mind when using Metastron.
Some degree of haematological toxicity, occasionally severe, is to be expected following administration of Metastron. Typically, platelets will be depressed by about 30% (95% confidence limits 10-55%) compared to preadministration levels. The nadir of platelet depression in most patients is about four to six weeks following the administration of Metastron. Thereafter, recovery, often partial only, occurs slowly, during six months post-treatment, unless the patient's disease process or additional therapy intervenes. Leucocyte counts are also depressed to varying degrees; the fall in leucocyte count carries the potential risk of serious secondary infection. Patients with bone marrow involvement are more likely to suffer from severe suppression of platelets/ leucocyte counts. In considering repeat administration of Metastron, the patient's haematological response to their initial dose, their current platelet and leucocyte levels and any other evidence of marrow depletion should be carefully considered.
Because Metastron is excreted primarily by the kidneys, in patients with significant renal dysfunction the possible risks of administering Metastron should be weighed against the possible benefits.
Strontium is excreted principally via the kidneys with some biliary excretion. The patient and carers should be advised that for a few days following Metastron administration the urine and faeces will be radioactive, the toilet should be flushed twice, and any spilled urine wiped away with a tissue which is then flushed away. It is important that staff clearing such spilled activity take appropriate precautions to reduce the radiation hazard to themselves, e.g. by careful hand washing afterwards. Soiled clothing should be washed immediately and separately from other clothing.
Special precautions, such as urinary catheterisation, should be taken following administration of Metastron to patients who are significantly incontinent to minimise risks of radioactive contamination of clothing, bed linen and the patient environment. Because a large proportion of the administered Metastron may be excreted during the first two days particular care is required in disposing of the excreta during the first 48 to 72 hours.
The expected time of onset of pain relief is approximately 10 to 20 days following Metastron administration. This should be taken into account in patient management. It is not recommended that Metastron is administered to patients with very short life expectancies.
Caution should be exercised in interpreting the effects of Metastron because of the known placebo effect of drugs in patients with pain (in up to 30-50% cases) due to bone metastases from prostate cancer. Pain relief soon after injection of Metastron is likely to be a placebo effect; nonplacebo effect appears in 10-20 days after treatment. Freedom from pain is achieved in 10-20% of patients.
A small number of patients have reported a transient increase in pain at 36 to 72 hours postinjection. This was usually mild and generally controllable by analgesics.
A calcium-like flushing sensation has been observed in patients following a rapid (less than 30 second injection) administration.
Controlled clinical studies of a second dose have not been conducted. Repeat administrations should not normally be performed within 6 months of the previous Metastron injection. However, if a patient relapses in three to six months and the platelet count shows reasonable recovery from the previous dose, a repeat dose may be given not less than three months after the previous dose. Data to support recommendations for further repeat doses are lacking. Further administrations are not indicated in patients who have not responded to a previous administration of Metastron.
Use of local beam therapy for pain relief prior to or after therapy with Metastron may be appropriate but there are no adequate data from clinical studies to support this use. Close monitoring for haematological toxicity is essential.
A cytotoxic agent may be administered to a patient who has previously received Metastron provided that their haematological parameters are stable and within the normal range. An interval of 12 weeks is recommended between administration of the two therapies.
Prostate carcinoma which has failed hormone therapy may be resistant to cytotoxic chemotherapy.
Radiopharmaceuticals should be used only by physicians who are qualified by training and experienced in the use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorised to licence the use of radionuclide.
As in the use of any radionuclide material, care should be taken to minimise radiation exposure to the patient consistent with proper management and to ensure minimum radiation exposure to occupational workers as well as patients.
The advice of the person responsible for radiological protection should be sought before postmortem or cremation if significant quantities of strontium are likely to be present in a patient following death. These procedures do not normally present any significant radiological risk.
This is a radioactive product intended for pharmaceutical use. Because of the small mass of chemical substances present there is negligible risk to persons handling or administering the product, other than that from the radioactive nature of the product.

Adverse Effects

Blood and lymphatic system disorders.

Vascular disorders.

General disorders, administration site conditions.

Dosage and Administration

Metastron is supplied in single dose vials ready for intravenous injection and should be used without dilution.
The recommended dose is 100 to 150 MBq per administration. Alternatively, in particularly heavy or light framed patients, a dose of 1.5 to 2.0 MBq/kg ‘fat free’ bodyweight may be used. A dose of 2.0 MBq/kg or a maximum of 150 MBq should not be exceeded.
Although the higher dose (150 MBq) has not been shown clearly to be more efficacious, it has been used without evidence of increased toxicity and may be used in order to avoid the possibility of underdosing in some patients. However, when using the higher dose, the potential for increased bone marrow suppression should be borne in mind.
Repeat doses: see Precautions.
Only one vial of Metastron should be used to obtain an individual dose. Any residue should be disposed of via an authorised route. Once the radioactivity has fallen below the recommended dose (and while the product is still within its shelf life) it should be used only for patients requiring less than the recommended dose.

Radioactivity.

Nuclear data.

Radiation dosimetry.

Presentation

Solution for injection, 43.6 to 90.4 mg (10.9 to 22.6 mg/mL), (150 MBq, sterile, aqueous solution), 4 mL:1's (single use vial).
The activity reference date is stated on the label. The product is available from stock weekly, with an activity reference date of 1200 hrs GMT, on the Friday following dispatch.

Storage

Store at room temperature (below 25°C).
The product should not be used later than 4 weeks after the activity reference date stated on the container label.

Poison Schedule

Unscheduled.