Pamidronate Disodium 9mg/Ml Concentrate For Solution For Infusion
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Pamidronate Disodium 3 mg/ml Concentrate for Solution for Infusion Pamidronate Disodium 6 mg/ml Concentrate for Solution for Infusion Pamidronate Disodium 9 mg/ml Concentrate for Solution for Infusion
Read all of this leaflet carefully before you start to take this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• 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.
In this leaflet:
1. What Pamidronate Disodium is and what it is used for
2. Before you use Pamidronate Disodium
3. How to use Pamidronate Disodium
4. Possible side effects
5. Howto store Pamidronate Disodium
6. Further information
Pamidronate Disodium belongs to a group of medicines called bisphosphonates, which work by reducing the amount of calcium in the blood.
Pamidronate Disodium is used to help reduce the amount of calcium in the blood. High blood calcium levels (hypercalcaemia) occur in a number of conditions, including some types of cancer associated with bone pain.
Often, hypercalcaemia is caused by the release of calcium from bones.
You should tell your doctor if you are taking the following:
• Other medicines for high calcium levels, such as calcitonin
• Other medicines which may affect the kidneys (your doctor or nurse will know which drugs these are)
• Thalidomide, used to treat some cancers.
Pregnancy and breast-feeding Pregnancy
If you are pregnant or think you may be pregnant you must not use Pamidronate Disodium. Your doctor will only advise you to take this medicine during pregnancy if your life is at risk from high blood calcium levels (hypercalcaemia).
Pamidronate Disodium is also used in Paget's disease, a disease which results in a change in bone structure (deformities). Pamidronate Disodium is absorbed into bones and helps to reduce the release of calcium into the blood.
Breast-feeding
You must not breast-feed your baby if you are being treated with Pamidronate Disodium.
Ask your doctor for advice before taking any medicine.
In some patients with cancer, Pamidronate Disodium is also used to treat bone disease and to help relieve bone pain.
Driving and using machines
Pamidronate Disodium may, in rare cases, cause drowsiness and/or dizziness. If affected you should not drive or operate dangerous machinery.
Do not use Pamidronate Disodium
• if you are allergic (hypersensitive) to pamidronate disodium or to any of the other ingredients of this medicine (listed in section 6 ‘Further information')
• if you are pregnant or breast-feeding.
Take special care with Pamidronate Disodium
• If you have a history of kidney disease
• If you have a history of heart disease
• If you have undergone thyroid surgery
• If you have a fever e.g. flu or something similar
• If you have severe liver problems
• If you are at risk of having calcium or vitamin D deficiency
• If you have problems with your teeth or jaw.
If any of the above apply to you, tell your doctor before starting treatment with Pamidronate Disodium.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Certain other medicines may influence the effect of Pamidronate Disodium, or their effect may be influenced by Pamidronate Disodium.
• You should not take other bisphosphonates, whilst being treated with Pamidronate Disodium.
Pamidronate Disodium should only be given under the supervision of a physician. Your doctor will decide on a suitable dose depending on your condition.
Pamidronate Disodium is diluted and then given by slow injection into a vein (intravenous infusion).
The infusion will last 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: Hypercalcaemia:
15 - 90 mg given as a single or several infusions.
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.
Paget’s disease:
30 mg once a week for 6 weeks, or 60 mg every other week over 6 weeks.
When doses of 60 mg are given your doctor may give you a test dose of 30 mg to see how you respond to the treatment.
Children:
This medicine is not recommended for children and should only be used in adult patients.
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The following information is intended for medical or healthcare professionals only: SZ00000LT000
Instructions for use
Do not use if particles are present.
Any portion of the contents remaining after use should be discarded.
The concentrate must be further diluted with a calcium-free infusion solution before administration.
The reconstituted solution is to be diluted with 0.9% w/v sodium chloride solution or 5% w/v glucose solution. The reconstituted solution must not be mixed with calcium-containing solution such as Ringer's solution.
Incompatibilities
Pamidronate disodium will form complexes with divalent cations and should not be added to calcium-containing intravenous solutions.
Special precautions for storage
Storage after dilution:
Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Posology and method of administration
Pamidronate disodium must never be given as a bolus injection (See SmPC Section 4.4). The concentrate must be diluted before use (see below) and must be infused slowly.
The infusion rate should never exceed 60 mg/hour (1 mg/min), and the concentration of pamidronate disodium in the infusion solution should not exceed 60 mg/250 ml. 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 20 mg/hour (see also "Patients with renal impairment”). In order to minimise local reactions at the infusion site, the cannula should be inserted carefully into a relatively large vein.
Until further experience is gained, pamidronate disodium is only recommended for use in adult patients. Tumour-induced hypercalcaemia
It is recommended that patients be rehydrated with 0.9% w/v sodium chloride solution before or during treatment.
The total dose of pamidronate disodium to be used for a 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.
|
Initial serum calcium |
Recommended total | |
|
(mmol/l) |
(mg %) |
dose (mg) |
|
up to 3.0 |
up to 12.0 |
15-30 |
|
LO co o co |
12.0 - 14.0 |
30-60 |
|
o LO co |
14.0 - 16.0 |
60-90 |
|
>4.0 |
> 16.0 |
90 |
The total dose of pamidronate disodium may be administered either in a single infusion or in multiple infusions over 2-4 consecutive days. The maximum dose per treatment course is 90 mg for both initial and repeated courses. Continued on the next page >>
Like all medicines, Pamidronate Disodium can cause side effects.
Side effects can be serious
Tell your doctor straight away if you notice the following, as they may be signs of an allergic reaction:
• Difficulty in breathing or wheezing and dizziness
• Swelling of the face and throat.
Tell your doctor straight away if you notice the following:
• Fluid retention, feeling sick or tiredness as these may be symptoms of a change in kidney function known as glomerulosclerosis
• Pain, swelling, or gum infections, loosening of teeth, numbness or a feeling of heaviness in the jaw, as these may be signs of a bone problem known as osteonecrosis.
The frequency of having osteonecrosis is not known but reported cases have predominantly been in cancer patients and have affected the jaw.
The side effects listed below have also been reported.
Common (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).
Uncommon (Up to 1 in 100 people have experienced):
• 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 or jaw.
Rare (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.
Very Rare (Up to 1 in 10,000 people have experienced):
• Cardiac effects which may include a difficulty in breathing and fluid retention
• 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).
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Prepared product should be used immediately. If this is not possible it can be stored for up to 24 hours at 2-8°C before use.
If your doctor tells you to stop taking Pamidronate Disodium 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.
What Pamidronate Disodium contains
The active substance is: pamidronate disodium 15 mg, 30 mg, 60 mg or 90 mg.
Each ml of concentrate for solution for infusion contains either 3 mg, 6 mg or 9 mg pamidronate disodium.
1 vial of 5 ml of sterile concentrate contains 15 mg of pamidronate disodium.
1 vial of 10 ml of sterile concentrate contains either 30 mg, 60 mg or 90 mg of pamidronate disodium.
The other ingredients are:
mannitol, sodium hydroxide, phosphoric acid,
water for injection.
What Pamidronate Disodium looks like and contents of the pack
Pamidronate Disodium is a clear and colourless solution and comes in clear, colourless glass vials.
Pamidronate Disodium 3 mg, 6 mg and 9 mg comes in packs of 1, 2, 4, 5, 6, and 10 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Sandoz Ltd.,
Frimley Business Park,
Frimley, Camberley, Surrey, GU16 7SR, UK.
Manufacturer
Lek Pharmaceuticals d.d.,
Verovskova 57,
1526 Ljubljana,
Slovenia.
or
Salutas Pharma GmbH,
Otto-von-Guericke-Allee 1,
D-39179 Barleben,
Germany.
This leaflet was last approved in 07/2011 (to be
amended after approval).
Keep Pamidronate Disodium out of the reach and sight of children.
Do not use Pamidronate Disodium after the expiry date on the carton.
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A significant decrease in serum calcium is generally observed 24-48 hours after administration of pamidronate disodium, and normalisation is usually achieved within 3 to 7 days. If normocalcaemia is not achieved within this 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 pamidronate disodium may become less effective as the number of treatment increases.
Osteolytic lesions and bone pain in bone metastases associated with breast cancer
The recommended dose is 90 mg every 4 weeks. This dose may also be administered at 3 weekly
intervals to coincide with chemotherapy if desired.
Osteolytic lesions and bone pain in multiple myeloma The recommended dose is 90 mg every 4 weeks.
Paget's disease of bone
The recommended treatment course consists of a total dose of 180 mg 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 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 additional dose of 30 mg one week in advance (i.e. total dose 210 mg). This regimen or increased dose levels according to disease severity, up to a maximum total dose of 360 mg (omitting the initial 30 mg dose) can be repeated every 6 months until remission of disease is achieved, and if relapse occurs.
Patients with renal impairment
Pamidronate disodium 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 pamidronate disodium. In patients receiving pamidronate disodium for bone metastases or multiple myeloma who show evidence of deterioration in renal function, pamidronate disodium 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).
Patients with 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 being clinically relevant. As pamidronate is still rapidly cleared from the plasma almost entirely into the bone and as 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 of pamidronate disodium in children. Therefore until further experience is gained, pamidronate disodium is only recommended for use in adult patients.
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