Zoledronic Acid 4 Mg/5 Ml Concentrate For Solution For Infusion
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Package leaflet: Information for the user
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 ornurse.
- If you get any side effects, talkto your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
□ What Zoledronic acid is and what it is used for
□ What you need to know before you are given Zoledronic acid
□ How Zoledronic acid is used
□ Possible side effects
□ How to store Zoledronic acid
□ Contents of the pack and other information
□ What Zoledronic acid is and what it is used for
The active substance 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, e.g. 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).
□ What you need to know before you are given Zoledronic acid
Follow carefully all instructions given to you byyourdoctor.
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:
- ifyou are breast-feeding.
- if you are allergic 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:
- ifyou have or have had a kidney problem.
- ifyou 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.
- ifyou 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 regularteeth 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 riskof 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. Ifyou 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 18years.
Other medicines and Zoledronic acid
Tell your doctor ifyou are taking, have recently taken or might take any other medicines. It is especially important that you tell yourdoctor if you arealso 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 calcium-lowering 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.
- Any other medicine that also contains zoledronic acid and is used to treat osteoporosis and other non-cancer diseases of the bone, 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 an increased risk of osteonecrosis of the jaw(ONJ).
Pregnancy and breast-feeding
You should not be given Zoledronic acid ifyou are pregnant or breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, askyour doctorfor advice before being given this medicine.
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.
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially'sodium-free'.
□ How Zoledronic acid is used
- 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 treatmentto 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 fourweeks.
- Ifyou are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic acid.
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.
Patients whose blood calcium levels are not too high will also be prescribed calcium and vitamin D supplements to be taken each day.
Ifyou are given more Zoledronic acid than you should be
Ifyou have received doses higher than those recommended,
INFORMATION FOR THE HEALTHCARE PROFESSIONAL
The following information is intended for medical or healthcare professionals only (see section 3):
How to prepare and administer Zoledronic acid
- To prepare an infusion solution containing 4 mg zoledronic acid, further dilute the Zoledronic acid concentrate (5.0 ml) with 100 ml of calcium-free or other divalent cation-free infusion solution. If a lower dose of Zoledronic acid is required, first withdraw the appropriate volume as indicated below and then dilute it further with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be eitherO.9% w/v sodium chloride or 5% w/vglucose solution.
Do not mix Zoledronic acid concentrate with calcium-containing or other divalent cation containing solutions such as
lactated Ringer's solution.
Instructions for preparing reduced doses of Zoledronic acid:
Withdraw the appropriate volume ofthe liquid concentrate, as follows:
- 4.4 ml for 3.5 mg dose
- 4.1 ml for 3.3 mg dose
- 3.8 ml for 3.0 mg dose
- 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 ofthe infusion.
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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.
Ifyou have any further questions on the use of this medicine, askyour doctor, pharmacist or nurse.
□ 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 afterashorttime.
Tell your doctor about any of the following serious side effects straight away:
Common (may affect upto 1 in 10 people):
- Severe kidney impairment (will normally be determined by your doctor with certain specific blood tests).
- Low level of calcium in the blood.
Uncommon (may affect up to 1 in 100 people):
- Pain in the mouth, teeth and/or jaw, swelling or nonhealing sores inside the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, 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 ifyou experience such symptoms afteryou have received zoledronicacid.
- Severe allergic reaction: shortness of breath, swelling mainly ofthe face and throat.
Rare (may affect upto 1 in 1,000 people):
- As a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia).
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 ifyou 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 phosphate in the blood.
Common (mayaffect upto 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.
- Conjunctivitis.
- Low level of red blood cells (anaemia).
Uncommon (may affect up to 1 in 100 people):
- Hypersensitivity reactions.
- 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 disturbances, trembling, tingling or numbness of the hands or feet, diarrhoea, constipation, abdominal pain, dry mouth.
- Low counts of white blood cells and blood platelets.
- Low level of magnesium and potassium in the blood. Your doctor will monitorthisandtakeany necessary measures.
- Weight increase.
- Increased sweating.
- 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.
Rare (may affect upto 1 in 1,000 people):
- Slow heart beat.
- Confusion.
- Unusual fracture ofthe 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 bean early indication of a possible fracture ofthe thigh bone.
- Interstitial lung disease (inflammation ofthe tissue around
the air sacks of the lungs)
- Flu-like symptoms including arthritisand joint swelling.
- Painfulrednessand/orswellingoftheeye.
Very rare (may affect up to 1 in 10,000 people):
- Faintingduetolowbloodpressure.
- Severe bone, joint and/or muscle pain, occasionally incapacitating.
Reporting of side effects
Ifyou 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 www.mhra.aov.uk/vellowcard. By reporting side effects, you can help provide more information on the safety of this medicine.
S How to store Zoledronic acid
Your doctor, pharmacist or nurse knows how to store Zoledronic acid properly (see section 6).
Keep this medicine out ofthe sight and reach of children.
Do not use this medicine after expiry date which is stated on the carton/bottle after "EXP". The expiry date refers to the last day of that month.
After dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C and room temperature (20-25°C).
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 should not be longer than 24 hours at 2°C- 8°C.The refrigerated solution should then be equilibrated to room temperature prior to administration.
□ 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 4.264 mg zoledronic acid monohydrate. One ml concentrate contains zoledronic acid (as monohydrate to 0.8 mg zoledronicacid (anhydrous)
— The other ingredients are: mannitol (E421), sodium citrate (E331), water for injections.
What Zoledronic acid looks like and contents ofthe pack
Zoledronic acid is supplied as a liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.
Each pack contains the vial with concentrate. Zoledronic acid is supplied as packs containing 1,4 or 10 vials. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Emcure Pharma UK Ltd 3 Howard Road Eaton Socon, St Neots Cambridgeshire PE19 8ETUK
Manufacturer:
Emcure Pharma UK Ltd Basepoint Business Centre 110 Butterfield, Great Marlings Luton
LU2 8DL, UK
United Kingdom Germany
Spain
Italy
France
Zoledronic acid Tillomed 4 mg/5 ml concentrate for solution for infusion Zoledronsaure Tillomed 4 mg/5 ml Konzentrat zur Herstellung einer Infusionslosung
Acido zoledronico Tillomed 4 mg/5 ml concentrado para solucion para perfusion EFG
Acido Zoledronico Tillomed 4 mg/5ml concentrato per soluzione per infusione
Acide zoledronique Tillomed 4 mg/5 ml, solution a diluer pour perfusion
- After dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C- 8°C and room temperature (20-25°C).
- 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 should not be longer than 24 hours at 2°C- 8°C.The refrigerated solution should then be equilibrated to room temperature prior to administration.
- The solution containing zoledronic acid 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.
- 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 ofthe reach and sight of children.
- Do not use Zoledronic acid after the expiry date stated on the pack.
- The unopened vial does not require any specific storage conditions.
- The diluted Zoledronic acid infusion solution should be used immediately in order to avoid
microbial contamination. * Pharma
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