Zoledronic Acid 4mg/100ml Solution For Infusion
Package leaflet: Information for the user
Zoledronic Acid 4 mg/100 ml solution for infusion
Zoledronic acid
Read all of this leaflet carefully before you
are given this medicine because it contains
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What Zoledronic Acid is and what it is used for
2. What you need to know before you are given Zoledronic Acid
3. How Zoledronic Acid is used
4. Possible side effects
5. How to store Zoledronic Acid
6. Contents of the pack and other information
The active substance in Zoledronic Acid is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by attaching itself to the bone and slowing down the rate of bone change. It is used:
• To prevent bone complications, eg.
fractures, in adult patients with bone metastases (spread of cancer from primary site to the bone).
• To reduce the amount of calcium in the blood in adult patients where it is too high due to the presence of a tumour. Tumours can accelerate normal bone change in such a way that the release of calcium from bone is increased. This condition is known as tumour-induced hypercalcaemia (TIH).
Follow carefully all instructions given to you by your doctor.
Your doctor will carry out blood tests before you start treatment with Zoledronic Acid and will check your response to treatment at regular intervals.
You should not be given Zoledronic Acid:
- if you are breast-feeding.
- if you are allergic (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic Acid belongs), or any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor before you are given Zoledronic Acid:
- if you have or have had a kidney problem.
- if you have or have had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth. Your doctor may recommend a dental examination before you start treatment with Zoledronic acid.
- if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zoledronic Acid and inform your doctor about your dental treatment.
While being treated with Zoledronic Acid, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups.
Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of a condition called osteonecrosis of the jaw.
Patients who are undergoing chemotherapy and/or radiotherapy, who are taking steroids, who are undergoing dental surgery, who do not receive routine dental care, who have gum disease, who are smokers, or who were previously treated with a bisphosphonate (used to treat or prevent bone disorders) may have a higher risk of developing osteonecrosis of the jaw.
Reduced levels of calcium in the blood (hypocalcaemia), sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with zoledronic acid. Irregular heart beat (cardiac arrhythmia), seizures, spasm and twitching (tetany) have been reported as secondary to severe hypocalcaemia. In some instances the hypocalcaemia may be life-threatening. If any of these apply to you, tell your doctor straight away. If you have pre-existing hypocalcaemia, it must be corrected before initiating the first dose of Zoledronic Acid. You will be given adequate calcium and vitamin D supplements.
Patients aged 65 years and over
Zoledronic Acid can be given to people aged 65 years and over. There is no evidence to suggest that any extra precautions are needed.
Children and adolescents
Zoledronic Acid is not recommended for use in adolescents and children below the age of 18 years.
Other medicines and Zoledronic Acid
Tell your doctor if you are taking, have recently taken or might take any other medicines. It is especially important that you tell your doctor if you are also taking:
- Aminoglycosides (medicines used to treat severe infections), calcitonin (a type of medicine used to treat post-menopausal osteoporosis and hypercalcaemia), loop diuretics (a type of medicine to treat high blood pressure or oedema) or other calciumlowering medicines, since the combination of these with bisphosphonates may cause the calcium level in the blood to become too low.
- Thalidomide (a medicine used to treat a certain type of blood cancer involving the bone) or any other medicines which may harm your kidneys.
- Other medicines that also contain zoledronic acid, or any other bisphosphonate, since the combined effects of these medicines taken together with Zoledronic Acid are unknown.
- Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zoledronic Acid has been associated with reports of osteonecrosis of the jaw (ONJ).
Pregnancy and breast-feeding
You should not be given Zoledronic Acid if you are pregnant. Tell your doctor if you are or think that you may be pregnant or are planning to become pregnant.
You must not be given Zoledronic Acid if you are breast-feeding.
Ask your doctor for advice before taking any medicine while you are pregnant or breast-feeding.
Driving and using machines
There have been very rare cases of drowsiness and sleepiness with the use of zoledronic acid. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Zoledronic Acid contains sodium citrate
This medicinal product contains less than 1 mmol sodium (23 mg) per dose (100ml), i.e. essentially 'sodium-free'.
- Zoledronic Acid must only be given by healthcare professionals trained in administering bisphosphonates intravenously, i.e. through a vein.
- Your doctor will recommend that you drink enough water before each treatment to help prevent dehydration.
- Carefully follow all the other instructions given to you by your doctor, pharmacist or nurse.
How much Zoledronic Acid is given
- The usual single dose given is 4 mg.
If you have a kidney problem, your doctor will give you a lower dose depending on the severity of your kidney problem.
How often Zoledronic Acid is given
- If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zoledronic Acid every three to four weeks.
- If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic Acid.
Patients whose blood calcium levels are not too high will also be prescribed calcium and vitamin D supplements to be taken each day.
How Zoledronic Acid is given
- Zoledronic acid is given as a drip (infusion) into a vein which should take at least 15 minutes and should be administered as a single intravenous solution in a separate infusion line.
If you are given more Zoledronic Acid than you should be
If you have received doses higher than those recommended, you must be carefully monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphorus and magnesium) and/or changes in kidney function, including severe kidney impairment. If your level of calcium falls too low, you may have to be given supplemental calcium by infusion.
^ Beacon
PHARMACEUTICALS
The following information is intended for healthcare professionals only:
How to prepare and administer Zoledronic Acid
- Zoledronic Acid contains 4 mg of zoledronic acid in 100 ml of infusion solution for immediate use in patients with normal renal function.
- For single use only. Any unused solution should be discarded. Only clear solution free from particles and discolouration should be used. Aseptic techniques must be followed during the preparation of the infusion.
- From a microbiological point of view, the diluted solution for infusion 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°C - 8°C. The refrigerated solution should be equilibrated to room temperature prior to administration.
- The solution containing zoledronic acid must not be further diluted or mixed with other infusion solutions. It is given as a single 15-minute intravenous infusion in a separate infusion line. The hydration status of patients must be assessed prior to and following administration of Zoledronic Acid to ensure that they are adequately hydrated.
- Zoledronic Acid 4mg/100ml solution for infusion can be used immediately without further preparation for patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses should be prepared as instructed below.
To prepare reduced doses for patients with baseline CLcr < 60 ml/min, refer to Table 1 below.
Remove the volume of Zoledronic Acid solution indicated from the vial and replace with an equal volume
of sterile sodium chloride 9 mg/ml (0.9%) solution for injection, or 5% glucose solution for injection.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common ones are usually mild and will probably disappear after a short time.
Tell your doctor about any of the following side effects straight away:
Common (may affect up to 1 in 10 people):
- Severe kidney impairment (will normally be determined by your doctor with certain specific blood tests).
- Muscle cramps, dry skin or burning sensation (low blood calcium).
- Severe bone, joint and/or muscle pain, occasionally incapacitating.
Uncommon (may affect up to 1 in 100 people):
- Pain in the mouth, teeth and/or jaw, swelling or non-healing sores inside the mouth or jaw, numbness or a feeling of heaviness in the jaw, discharge, or loosening of a tooth. These could be signs of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience such symptoms while being treated with Zoledronic Acid or after stopping treatment.
- Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving zoledronic acid for postmenopausal osteoporosis. It is currently unclear whether zoledronic acid causes this irregular heart rhythm but you should report it to your doctor if you experience such symptoms after you have received zoledronic acid.
- Serious life-threatening allergic reaction with sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue, and throat, shortness of breath, wheezing or trouble breathing.
- Acute kidney failure - where little or no urine is passed. Other symptoms may include presence of blood or protein in the urine (detected during urine tests).
Rare (may affect up to 1 in 1,000 people):
- Serious allergic reaction causing swelling of the face, lips, tongue or throat which may cause difficulty in swallowing or breathing.
- As a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia).
- A kidney function disorder called Fanconi syndrome (will normally be determined by your doctor with certain urine tests).
Very rare (may affect up to 1 in 10,000 people):
- As a consequence of low calcium values: seizures, numbness and tetany (secondary to hypocalcaemia).
- Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.
Tell your doctor about any of the following side effects as soon as possible:
Very common (may affect more than 1 in 10 people):
- Low level of blood phosphate levels found during a blood test.
Common (may affect up to 1 in 10 people):
- Headache and a flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills and bone, joint and/or muscle ache. In most cases no specific treatment is required and the symptoms disappear after a short time (couple of hours or days).
- Gastrointestinal reactions such as nausea and vomiting as well as loss of appetite.
- Red and watery eyes (conjunctivitis).
- Reduction in red blood cells which can make the skin pale and cause weakness or breathlessness.
- Increases in blood urea and creatinine levels observed during blood tests.
Uncommon (may affect up to 1 in 100 people):
- Hypersensitivity reactions e.g skin rash or fever.
- Low blood pressure.
- Chest pain.
- Skin reactions (redness and swelling) at the infusion site, rash, itching.
- High blood pressure, shortness of breath, dizziness, anxiety, sleep disturbances, taste disturbance, tingling or numbness of the hands and feet, tremor, diarrhoea, constipation, stomach pain, indigestion, mouth ulcers, dry mouth, increased sweating, muscle cramps, feeling of weakness, swelling of the ankles, feet or fingers.
- Reduction in blood platelets leading to increased risk of bleeding or bruising.
- Reduction in the white cells of the blood increasing the risk of infection.
- Low level of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.
- Weight increase.
- Sleepiness.
- Blurred vision, tearing of the eye, eye sensitivity to light.
- Sudden coldness with fainting, limpness or collapse.
- Difficulty in breathing with wheezing or coughing.
- Urticaria.
- increased sensitivity of the senses (e.g. touch or hearing).
Rare (may affect up to 1 in 1,000 people):
- A rare type of anaemia in which red blood cells, white blood cells, and platelets are all reduced in number.
- High levels of blood sodium which can cause confusion, muscle twitching or abnormal heart rhythm.
- High levels of blood potassium which can cause abnormal heart rhythm.
- Slow heartbeat.
- Confusion.
- Unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may occur rarely. 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.
- Interstitial lung disease (inflammation of the tissue around the air sacks of the lungs).
- Flu-like symptoms including arthritis and joint swelling.
- Painful redness and/or swelling of the eye.
Very rare (may affect up to 1 in 10,000 people):
- Inflammation of the eye causing redness, watering and mild pain.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.
5. HOW TO STORE ZOLEDRONIC ACID
Your doctor, pharmacist or nurse knows how to
store Zoledronic Acid properly (see section 6).
• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
• The unopened vial does not require any special storage conditions.
• After first opening:
Chemical and physical stability has been demonstrated for 24 hours at 2°C - 8°C and at 25°C.
From a microbiological point of view, the solution for infusion 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°C -8°C. The refrigerated solution should then be equilibrated to room temperature prior to administration.
• Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Zoledronic Acid contains
- The active substance is zoledronic acid. One vial contains 4 mg zoledronic acid, corresponding to 4.26 mg zoledronic acid monohydrate.
- The other ingredients are:
mannitol (E421), sodium citrate (E331) water for injections.
What Zoledronic Acid looks like and the contents of the pack
Zoledronic Acid solution for infusion is a clear, colourless solution, free from visible particles. Zoledronic Acid is supplied as a solution in a vial. One vial contains 4 mg of zoledronic acid.
Zoledronic Acid 4mg/100ml solution for infusion is supplied as packs containing:
1 vial, 4 vials, 5 vials, 10 vials Not all pack sizes may be marketed.
Marketing Authorisation Holder
Beacon Pharmaceuticals Ltd., High Street, Tunbridge Wells, Kent, TN1 1YG
Manufacturer
Agila Specialties Polska Sp. Zo.o. 10, Daniszewska Str., 03-230 Warsaw, Poland or
Sanochemia Pharmazeutika AG, Landegger-strasse 33, 2491 Neufeld an der Leitha, Austria
This leaflet was last revised in 08/2016
AGXP265BND
SCXP265BND
^ PHARMACEUTICALS
Table 1: Preparation of reduced doses of Zoledronic Acid 4 mg/100 ml solution for infusion
|
Baseline Creatinine Clearance (ml/min) |
Remove the following Amount of Zoledronic Acid solution for infusion (ml) |
Replace with the following volume Of sterile sodium chloride 9 mg/ml (0.9%) or 5% glucose solution for injection (ml) |
Adjusted dose (mg zoledronic acid in 100 ml)* |
|
50-60 |
12.0 |
12.0 |
3.5 |
|
40-49 |
18.0 |
18.0 |
3.3 |
|
30-39 |
25.0 |
25.0 |
3.0 |
*Doses have been calculated assuming target AUC of 0.66 (mg^hr/l) (CLcr = 75 ml/min). The reduced doses for patients with renal impairment are expected to achieve the same AUC as that seen in patients with creatinine clearance of 75 ml/min.
- Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with zoledronic acid.
- Since no data are available on the compatibility of zoledronic acid with other intravenously administered substances, Zoledronic Acid must not be mixed with other medications/substances and should always be given through a separate infusion line.
How to store Zoledronic Acid
- Keep Zoledronic Acid out of the reach and sight of children.
- Do not use Zoledronic Acid after the expiry date stated on the pack.
- This medicinal product does not require any special storage conditions.
- The diluted Zoledronic Acid infusion solution should be used immediately in order to avoid microbial contamination.
Size: 148mm X 600mm Date: 31 Aug 16
Update: In line with Brand leader Colours: Black & Pantone 273 Designer: TC (AWG)
CCRF:15318