Water For Injections
Ciba
AREDIA® DRY POWDER 15, 30 and 90 mg
(pamidronate disodium)
Patient Information Leaflet
What you need to know about Aredia Dry Powder
Your doctor has decided that you need this medicine to help treat your condition.
Please read this leaflet carefully before you start to take your medicine. It contains important information. Keep the leaflet in a safe place because you may want to read it again.
If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.
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.
This medicine will usually be referred to just as Aredia in this leaflet.
In this leaflet:
1. What Aredia is and what it’s used for
2. Things to consider before you start to take Aredia
3. How to take Aredia
4. Possible side effects
5. How to store Aredia
6. Further information
1. What Aredia is and what it’s used for
The Aredia pack includes vials containing the Aredia powder, and ampoules containing Water for Injections. These are used to make up the injection solution.
The active ingredient in Aredia is called pamidronate disodium. This is one of a group of medicines called bisphosphonates which can help to regulate the amount of calcium in the blood.
High blood calcium levels (hypercalcaemia) occur in a number of conditions, including some types of cancer. Often, hypercalcaemia is caused by the release of calcium from bones. Aredia sticks to bones and helps to reduce the release of calcium into the blood. If untreated, hypercalcaemia can cause symptoms such as nausea, tiredness and confusion.
Aredia is used to treat high blood calcium levels caused by some cancers. In some patients with cancer, it is also used to treat bone disease and to help relieve bone pain. Aredia is also used to treat Paget’s disease.
2. Things to consider before you take Aredia
Some people MUST NOT take Aredia. Talk to your doctor if:
• you think you may be allergic to Aredia or any other bisphosphonate, or to the other ingredients of Aredia powder (these are listed at the end of the leaflet).
Aredia is not suitable for treating children.
You should also ask yourself these questions before taking Aredia:
• Do you suffer from any kidney disease?
• Do you suffer from any heart problems?
• Do you have any I iver problems?
• Have you ever had thyroid problems?
• Are you likelyto suffer from calciumor Vitamin D deficiency?
• Have you had any problems with your teeth or jaw?
• Are you suffering from a feverish illness e.g. flu or something similar?
• Are you pregnant or breastfeeding?
If the answer to any of these q uesti ons is YES, tell your doctor or nurse because Aredia might not be the right medicine for you.
Are you taking other medicines?
Some medicines can interfere with your treatment. Tell the doctor or nurse if you are taki ng any of the fol lowi ng:
• Other medicines for high calcium levels such as calcitonin
• Other bisphosphonates
• Other medicines that may affect the kidneys (Your doctor or nurse will know which drugs these are.)
• Thalidomide (used to treat some cancers).
Always tell your doctor about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.
Other special warnings
• Visiting the dentist:
• Because treatment with Aredia may affect your jaw bone, you must make ZSS6U2
su re that your dentist knows that you are having Aredia before you have any dental treatment or surgery.
• Go to the dentist before you start your treatment.
• The dentist should avoid invasive dental procedures during treatment with Aredia.
• Make sure you are careful with your dental hygiene and go to the dentist regularly throughout your Aredia treatment.
• You must make sure that you do not become dehydrated whileyou are being treated with Aredia. Talk to your doctor to make sure you are aware how much you must drink.
• Whilst you are being treated with Aredia, you r doctor wi 11 want to check you r progress by carrying out a number of tests e.g. blood tests and kidney function tests. Remind your doctor you are taking Aredia before he/she does any tests. Aredia may affect the results.
• Pregnancy and breastfeeding:
• If you are pregnant, your doctor should not prescribe Aredia to you except in cases of life-threatening hypercalcaemia.
• Breastfeedingduringtherapy with Aredia is not recommended.
Will there be any problems with driving or using machinery?
If you feel sleepy or dizzy after being treated with Aredia, do not drive or use machinery until these effects wear off.
Table 1
|
Initial serum calcium |
Recommended total | |
|
(mmol/L) |
(mg %) |
dose (mg) |
|
up to 3.0 |
up to 12.0 |
15-30 |
|
3.0-3.5 |
12.0 -14.0 |
30-60 |
|
3.5-4.0 |
14.0 -16.0 |
60-90 |
|
>4.0 |
>16.0 |
90 |
3. How to take Aredia
Your doctor will have decided on the right dose depending on your condition.
A doctor or nurse will prepare the injection by dissolving Aredia powder in the water provided and then diluting this solution with a special infusion fluid. The made-up solution must be stored in a refrigerator and used with 24 hours.
Aredia is given by very slow injection into a vein (intravenous infusion). The infusion will take from one to several hours depending on the dose. Your doctor will decide how many infusions you need and how often they will be given.
Dosage guidelines are as follows:
For hypercalcaemia
15-90 mg given as a single or several infusions.
For bone diseases and bone pain
90 mg every 4 weeks. In some patients the dose may be given every 3 weeks at the same time as chemotherapy.
For Paget’s disease
180 to 210 mg given as either 30 mg once a week for 6 weeks, or 60 mg every other week for 6 weeks.
Your doctor may also give you a test dose of 30 mg to see how you respond to the treatment.
Your doctor may also have prescribed treatment with Calcium and Vitamin D at the same time as Aredia.
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For the Medical and Pharmaceutical Professions
Administering Aredia
Instructions for use and handling
Powder in vials should be first dissolved in sterile water for injection, i.e. 15 mg in 5 mL. The sterile water for injection is available in ampoules which are supplied together with vials. The pH of the reconstituted solution is 6.0-7.0. The reconstituted solution should be further diluted with a calcium-free infusion solution (0.9% w/v sodium chloride or 5% w/v glucose solution) before administration. It is i mportant that the powder be completely dissolved before the reconstituted solution is withdrawn for dilution.
Incompatibilities
Studies with glass bottles, as well as infusion bags made from polyvinylchloride and polyethylene (prefilled with 0.9% w/v sodium chloride solution or 5% w/v glucose solution) showed no incompatibility with Aredia.
To avoid potential incompatibilities, Aredia reconstituted solution is to be diluted with 0.9% w/v sodium chloride solution or 5% w/v glucose solution. Aredia reconstituted solution must not be mixed with calcium-containing solution such as Ringer’s solution.
Special precautions for storage
Protect vials from heat (store below 30°C). The reconstituted solution is chemically and physically stable for 24 hours at room temperature. However, from a microbiological point of view, it is preferable to use the product immediately after aseptic reconstitution and dilution.
If not used immediately, the duration and conditions of storage prior to use are the care provider’s responsibility. The total time between reconstitution, dilution and storage in a refrigerator at 2 to 8°C and end of administration must not exceed 24 hours.
Therapeutic indications
Treatment of conditions associated with increased osteoclast activity:
• Tumour-induced hypercalcaemia
• Osteolytic lesions and bone pain in patients with bone metastases associated with breast cancer or multiple myeloma
• Paget's disease of bone.
Posology and method of administration
Aredia must never be given as a bolus injection (see SmPC Section 4.4). The reconstituted solution of Aredia from powder in vials should be diluted in a calcium-free infusion solution (0.9 % w/v sodium chloride solution or 5% w/v glucose solution) and infused slowly.
The infusion rate should not exceed 60 mg/ hour (1 mg/min), and the concentration of Aredia in the infusion solution should not exceed 90 mg/250 ml. A dose of 90 mg should normally be administered as a 2-hour infusion in 250 mL infusion solution. However, in patients with established or suspected renal impairment (e.g. those with tumour-induced hypercalcaemia or multiple myeloma) it is recommended that the infusion rate does not exceed 90 mg in 500 mL over 4 hours (see also SmPC Section 4.2).
In order to minimise local reactions at the infusion site, the cannula should be inserted carefully into a relatively large vein.
Tumour-induced hypercalcaemia
Patients must be adequately rehydrated, using 0.9% w/v sodium chloride solution, prior to and during administration of Aredia.
The total dose of Aredia to be used fora treatment course depends on the patient's initial serum calcium levels. The following guidelines are derived from clinical data on uncorrected calcium values. However, doses within the ranges given are also applicable for calcium values corrected for serum protein or albumin in rehydrated patients.
The total dose of Aredia may be administered either in a single infusion or in multiple infusions over 2 to 4 consecutive days. The maximum dose per treatment course is 90 mg for both initial and repeated courses.
A significant decrease in serum calcium is generally observed 24 to 48 hours after administration of Aredia, and normalisation is usually achieved within 3 to 7 days. If normocalcaemia is not achieved within this
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time, a further dose may be given. The duration of the response may vary from patient to patient, and treatment can be repeated whenever hypercalcaemia recurs. Clinical experience to date suggests that Aredia may become less effective as the number of treatments increases.
Predominantly lytic bone metastases and multiple myeloma
The recommended dose of Aredia for the treatment of predominantly lytic bone metastases and multiple myeloma is 90 mg administered as a single infusion every 4 weeks.
In patients with bone metastases who receive chemotherapy at 3-weekly intervals, Aredia 90 mg may also be given on a 3-weekly schedule.
Paget's disease of Bone
The recommended treatment course consists of a total dose of 180 to 210mg administered in unit doses of either 30 mg once a week for 6 consecutive weeks, or 60 mg every other week over 6 weeks. Experience to date suggests that any mild and transient unwanted effects (see SmPC Section 4.8) tend to occur after the first dose. For this reason if unit doses of 60 mg are used it is recommended that treatment be started with an initial dose of 30 mg followed by 60 mg every other week (i.e. total dose 210 mg). Each dose of 30 or 60 mg should be diluted in 125 or 250 ml 0.9% w/v sodium chloride solution respectively, and the infusion rate should not exceed 60 mg/hour (1 mg/min). This regimen or increased dose levels according to disease severity, up to a maximum total dose of 360 mg (in divided doses of 60 mg) can be repeated every 6 months until remission of disease is achieved, and if relapse occurs.
Renal Impairment
Aredia should not be administered to patients with severe renal impairment (creatinine clearance < 30 mL/min) unless in cases of life-threatening tumour-induced hypercalcaemia where the benefit outweighs the potential risk. Because there is only limited clinical experience in patients with severe renal impairment no dose recommendations for this patient population can be made (see SmPC Section 4.4 and 5.2).
As with other i.v. bisphosphonates, renal monitoring is recommended, for instance, measurement of serum creatinine prior to each dose of Aredia. In patients receiving Aredia for bone metastases or multiple myeloma who show evidence of deterioration in renal function, Aredia treatment should be withheld until renal function returns to within 10% of the baseline value. This recommendation is based on a clinical study, in which renal deterioration was defined as follows:
• For patients with normal baseline creatinine, increase of 0.5 mg/dL.
• For patients with abnormal baseline creatinine, increase of 1.0 mg/dL.
A pharmacokinetic study conducted in patients with cancer and normal or impaired renal function indicates that the dose adjustment is not necessary in mild (creatinine clearance 61-90 mL/min) to moderate renal impairment (creatinine clearance 30-60 mL/min). In such patients, the infusion rate should not exceed 90 mg/4h (approximately 20-22 mg/h).
Hepatic impairment
Although patients with hepatic impairment exhibited higher mean AUC and Cmax values compared to patients with normal hepatic function, this is not perceived as being clinically relevant. As pamidronate is still rapidly cleared from the plasma almost entirely into the bone and as it is administered on a monthly basis for chronic treatment, drug accumulation is not expected. Therefore no dose adjustment is necessary in patients with mild to moderate abnormal hepatic function (see SmPC Section 5.2). Clinical data in patients with severe hepatic impairment is not available (see SmPC Section 4.4). Pamidronate should be administered to this patient population with caution.
Children
There is no clinical experience with Aredia in children. Therefore until further experience is gained, Aredia is only recommended for use in adult patients.
What if you have had too much Aredia? (Overdose)
If you think you have either been given or have taken too much Aredia tell your doctor or nurse straight away. If you think you have either been given it or have taken it too often, also tell your doctor or nurse straight away.
What if you miss a dose of Aredia?
If you miss one of your appointments, please let your doctor or nurse know immediately.
4. Possible side effects
Aredia is suitable for most people, but, like all medicines, it can sometimes cause side effects. The side effects are usually mild and disappear as treatment continues. It is sometimes not clear whether the symptoms are related to your illness or to your treatment.
A very common effect is a mild fever with flu like symptoms such as sore throat, shivering, high temperature or hot flushes, which occur at the start of treatment and last for 24-48 hours.
Some patients notice an increase in bone pain soon after starting treatment. This usually improves after a few days. If it does not, tell your doctor.
Unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may occur. Contact your doctor if you experience pain, weakness or discomfort in your thigh, hip or groin as this may be an early indication of a possible fracture of the thigh bone.
Some side effects can be serious
Tell the doctor straight away if you notice:
• Bronchospasm with wheezing or coughing and difficulty in breathing, or swelling of your face, lips or hands.
• If you feel faint (you might have low blood pressure), have a rash, or experience itching or facial swelling.
These might be the result of an allergic
reaction which is very rare (likely to affect
fewer than 1 in 10,000 patients).
The side effects listed below have also
been reported.
Up to 1 in 10 people have experienced:
• Pain, redness or swelling at the infusion site
• Skin rash or unexplained bruising/ increased bleeding
• Joint or muscle pain
• Nausea, vomiting, loss of appetite, stomach pain, gastritis, constipation or diarrhoea
• Headache, sleeplessness, tiredness
• Conjunctivitis
• Tingling in hands and feet and muscle spasms (symptoms of low level of calcium)
• High blood pressure
• Low level of white blood cells (leucopenia) or red blood cells (anaemia)
• Changes in blood test results (including low potassium, low phosphate, low magnesium and raised serum creatinine levels or, very rarely, raised potassium or sodium levels)
• Irregular heart rhythm.
Up to 1 in 100 people have experienced:
• Generalised pain
• Muscle cramps
• Dizziness, lethargy, feeling agitated, seizures
• Problems with vision, painful red eyes
• Low blood pressure
• Itching, indigestion
• Deterioration of kidney function (e.g. unexpected change in the amount of urine produced and/or its appearance), abnormal liver function tests or increases in serum urea
• Problems with teeth, jaw, or bones.
Up to 1 in 1,000 people have experienced:
A change in kidney function known as glomerulosclerosis, some of the symptoms of this condition may be, fluid retention, nausea and fatigue. Tell your doctor if you suspect that you might have these symptoms
Up to 1 in 10,000 people have experienced:
• Cardiac or respiratory effects which may include a difficulty in breathing and fluid retention
• Changes in kidney function, including worsening of an existing kidney problem e.g. blood in urine
• A flare-up of cold sores or shingles
• Confusion or visual hallucinations (seeing things that are not there)
• Painful and/or swollen eye.
If any of the symptoms described above become troublesome, or if you notice anything else not mentioned here, please go and see your doctor.
Patients taking Aredia have also reported experiencing the following:
• Shortness of breath, respiratory failure
• Severe and occasionally incapacitating bone, joint and/or muscle pain
• Renal disorders.
5. How to store Aredia
The vials of Aredia powder before they are made up into the injection should be stored below 30°C. The made-up solution must be stored in a refrigerator and used with 24 hours.
Any unused solution should be thrown away. Keep out of the reach and sight of children. Do not use Aredia after the expiry date which is printed on the outside of the pack.
If your doctor tells you to stop taking Aredia and you have been keeping some at home, please take any unused vials back to your pharmacist to be destroyed. Do not throw them away with your normal household water or waste. This will help to protect the environment.
6. Further information
Aredia is available in clear glass vials containing either 15, 30, or 90 mg of pamidronate disodium powder. The vials also contain the inactive ingredients mannitol and phosphoric acid.
Aredia packs contain 1, 2 or 4 vials of powder. Each pack also contains 1 ampoule of water (5 ml ampoules for 15 and 30 mg vials and 10 ml ampoules for 90 mg vials) for every Aredia vial.
Not all of the pack sizes are marketed.
The product licence holder is Novartis Pharmaceuticals UK Limited, trading as Ciba Laboratories, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, England.
The manufacturer responsible for the release on to the market is Novartis Pharmaceuticals UK Limited, Wimblehurst Road, Horsham, West Sussex RH12 5AB, England or Novartis Pharmaceuticals UK Limited, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, United Kingdom.
This leaflet was revised in 07/2013.
If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.
AREDIA is a registered Trade Mark Copyright Novartis Pharmaceuticals UK Limited
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