Zoledronic Acid 4 Mg/100ml Solution For Infusion
Zoledronic Acid Amneal 4 mg/100 ml solution for infusion - UK - PIL Review - 3
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Package leaflet: Information for the user
Zoledronic Acid 4 mg/100 ml solution for infusion
Zoledronic acid
ead all of this leaflet carefully before you are iven this medicine because it contains important nformation 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
1. What Zoledronic Acid is and what it is used for
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 . 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).
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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 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.
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NFORMATION FOR THE HEALTHCARE PROFESSIONAL
The following information is intended for healthcare professionals only:
carefully all instructions given to you by your
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), 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 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 if you are pregnant. Tell your doctor if you are or think that you may be pregnant.
You must not be given Zoledronic Acid if you are breast-feeding.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking 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”.
3. 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 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.
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.
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How to prepare and administer Zoledronic Acid
- Zoledronic Acid 4 mg/100 ml solution for infusion contains 4 mg 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 solution for infusion should be used immediately, after first opening. 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 then 24 hours at 2°C - 8°C, unless dilution has taken place in controlled and validated aseptic conditions. The refrigerated solution should then 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 assure that they are adequately hydrated.
- Zoledronic Acid 4 mg/100 ml 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 bag and replace with an equal volume of sterile sodium chloride 9 mg/ml (0,9%) solution for injection, or 5% glucose solution for injection.
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Patients whose blood calcium levels are not too high will also be prescribed calcium and vitamin D supplements to be taken each day.
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.
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 serious 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).
- 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 sores inside the mouth, 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 if you experience such symptoms after you have received zoledronic acid.
- Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.
Very rare (may affect up to 1 in 10,000 people):
- As a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia), 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 phosphate in the blood.
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.
- Conjunctivitis.
- Low level of red blood cells (anaemia).
- 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 up to 1 in 1,000 people):
- Slow heart beat.
- 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):
- Fainting due to low blood pressure.
- Severe bone, joint and/or muscle pain, occasionally incapacitating.
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 MHRA Yellow Card Scheme, Website - 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).
6. Contents of the pack and other information
What Zoledronic Acid contains
- The active substance of Zoledronic Acid is zoledronic acid. One bag contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.
- The other ingredients are: mannitol (E-421), sodium citrate (E-331) and water for injections.
What Zoledronic Acid looks like and contents of the pack
Zoledronic Acid is supplied as a clear and colourless solution. It comes in 100 ml bags as a ready-to-use solution for infusion.
Zoledronic Acid is supplied as a unit pack containing one bag.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Amneal Pharma Europe Limited 70 Sir John Rogerson's Quay Dublin 2, Ireland
Manufacturer
Laboratorios NORMON, S.A.
Ronda de Valdecarrizo, 6 28760 Tres Cantos - Madrid SPAIN
This leaflet was last revised in July 2016
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 monitor this and take any necessary measures.
- Weight increase
- Increased sweating
- Sleepiness.
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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 Amneal 4 mg 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 this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the pack after EXP.
- The unopened bag does not require any special temperature storage conditions. Store in the original package.
- After opening the bag, the product should be used immediately in order to avoid microbial contamination. 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. Allow the refrigerated solution to reach room temperature before administration.
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Patient Reminder Card Zoledronic Acid
This reminder card contains important safety information that you need to be aware of before and during treatment with Zoledronic Acid injections for cancer-related conditions
Your doctor has recommended that you receive Zoledronic Acid injections to help prevent bone complications (e.g. fractures) caused by bone metastases, or bone cancers or to help reduce the amount of calcium in the blood in adult patients where it is too high due to the presence of a tumour.
A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported in very rare occasions in patients receiving Zoledronic Acid injections for cancer-related conditions. ONJ can also occur after stopping treatment. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take:
Before starting treatment:
• Ask your doctor to tell you about ONJ before you start treatment
• Check with your doctor whether a dental examination is recommended before you start treatment with Zoledronic Acid.
• Tell your doctor/nurse (health care professional) if you have any problems with your mouth or teeth.
Patients undergoing dental surgery (e.g. tooth extractions), who do not receive routine dental care or have gum disease, are smokers, who get different types of cancer treatments or who were previously treated with a bisphosphonate (used to treat or prevent bone disorders) may have a higher risk of developing ONJ.
While being treated:
• You should maintain good oral hygiene, make sure your dentures fit properly and receive routine dental check-ups.
• If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor and tell your dentist that you are being treated with Zoledronic Acid.
• Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw
Read the package leaflet for further information.