Zometa – Package Leaflet: InfoCons – Consumer Protection presents, in an accessible format, the official package leaflet of the medicine Zometa, as authorised in the European Union and published in the Union Register of medicinal products.
Before anything else
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 i n this leaflet 1. What Zometa is and what it is used for 2. What you need to know b efore you are given Zometa 3. How Zometa is used 4. Possible side effects 5. How to store Zometa 6. Contents of the pack and other information 1. What Zometa is and what it is used for The active substance in Zometa is z oledronic 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 patie nts 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) .
2. What you need to know before you are given Zometa Follow carefully all instructions given to you by your doctor.
Your doctor will carry out blood tests before you start treatment with Zometa and will check your response to treatment at regular intervals.
You should not be given Zometa: − if you are breast -feeding . − if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zometa belongs), or any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor b efore you are given Zometa: − 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 Zometa. − if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zometa and inform your doctor about your dental treatment .
While being treated with Zometa , you should maintain good oral hygiene (including regular teeth 86 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 Zometa. 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 lif e-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 Zometa. You will be given adequate calcium and vitamin D supplements.
Patients aged 65 years and over Zometa 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
Zometa is not recommended for use in adolescents and children below the age of 18 years.
Other medicines and Zometa
Tell your doctor if you are taking, have recently tak en or might take any other medicines . It is especially important that you tell your doctor if you are also taking :
- Aminoglycosides (medicine s 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.
- Aclasta (a 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 Zometa are unknown.
- Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zometa has been associated with an increased risk of osteonecrosis of the jaw (ONJ).
Pregnancy and breast -feeding You should not be given Zometa if you are pregnant. Tell your doctor if you are or think that you may be pregnant .
You must not be given Zometa i f 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 Zometa. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Zometa contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium free”. If your doctor uses a solution of common salt to dilute Zometa, the dose of sodium received 87 would be larger .
3. How Zometa is used − Zometa 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 f ollow all the other instructions given to you by your doctor, pharmacist or nurse.
How much Zometa 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 Zometa is given
- If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zometa 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 Zometa.
How Zometa is given
- Zometa is given as a drip (infusion) into a vein which should take at least 15 minute s 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.
If you are given more Zometa 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 det ermined 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 non- healing 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 Zometa 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 88 after you have received zoledronic acid. − Severe allergic reaction: shortness of breath, swelling mainly of the face and throat .
Rare (may affect up to 1 in 1,000 people)
− 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. − Osteonecrosis has also very rarely been seen occurring with other bones than the jaw, especially the hip or thigh. Tell your doctor immediately if you experience symptoms such as new onset or worsening of aches, pain or stiffness while being treated with Zometa or after stopping treatment .
Not known: frequency cannot be calculated from the available data
- Inflammation of the kidney (tubulointerstitial nephritis): signs and symptoms may include decreased volume of the urine, blood in the urine, nausea, feeling generally unwell .
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).
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. − Blurred vision, t earing of the eye, eye sensitivity to light. − Sudden coldness with fainting, limpness or collapse. − Difficulty in breathing with wh eezing or coughing . − Urticaria.
89 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 national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store Zometa Your doctor, pharmacist or nurse knows how to store Zometa properly (see section 6).
6. Contents of the pack and other information
What Zometa contains
− The active substance of Zometa is zoledronic acid. One vial contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate. − The other ingredients are mannitol, sodium citrate.
What Zometa looks like and contents of the pack
Zometa is supplied as a powder in a vial. One vial contains 4 mg of zoledronic acid.
Each pack contains the vial with powder, together with an ampoule of 5 ml water for injections, which is used to dissolve the powder.
Zometa is supplied as unit packs containing 1 or 4 vials and 1 or 4 ampoules , respectively , and as multi- packs containing 10 (10x 1+1) vials and ampoules . Not all pack sizes may be marketed.
Marketing Authorisation Holder
Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland
Manufacturer
Novartis Pharma GmbH Roonstrasse 25 D-90429 Nuremberg Germany 90 For any information about this medicin e, please contact the Marketing Authorisation Holder directly or, where available, the local representative:
BE, BG, CZ, DK, DE, EE, IE, HR, IT, CY, LV, LT, LU, HU, MT, NL, AT, PL, PT, RO, SI, SK, FI, SE and XI Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland Email: [email protected] Tel: +353 1 468 8900 ΕL Arriani Pharmaceuticals SA Lavriou Avenue 85 190 02 Paiania Attica Greece Tel: +30 210 6683000 ES EUROMED PHARMA SPAIN S.L C/Eduard Maristany, 430- 432 08919 Badalona (Barcelona) España Tel: + 34 932 684 208 Fax: + 34 933 150 469 FR Exploitant de l’autorisation de mise sur le marché :
EURODEP PHARMA 10 RUE ANTOINE DE SAINT EXUPERY ZAC DU PARC DE COMPANS 77290 MITRY MORY [email protected]
This leaflet was last revised i n
Other sources of information Detailed information on this medicine is available on the European Medicines Ag ency web site: http://www.ema.europa.eu 91 INFORMATION FOR THE HEALTHCARE PROFESSIONAL How to prepare and administer Zometa − To prepare an infusion solution containing 4 mg zoledronic acid , add 5 ml of water for injections from the ampoule supplied in the pack to the vial containing the Zometa powder under aseptic conditions. Shake the vial gently to dissolve the powder. − Further dilute the Zometa reconstituted solution (5 ml) with 100 ml of calcium- free or other divalent cation -free infusion solution. If a lower dose of Zometa is required, first withdraw the appropriate volume of the reconstituted solution (4 mg/5 ml) 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 either 0.9 % w/v sodium chloride or 5 % w/v glucose solution.
Do not mix Zometa reconstituted solution with calcium -containing or other divalent cation -containing solutions such as l actated Ringer’s solution.
Instructions for preparing reduced doses of Zometa:
Withdraw the appropriate volume of the reconstituted solution (4 mg/5 ml), 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 of the infusion.
− From a microbiological point of view, the reconstituted and 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 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 Zometa to assure that they are adequately hydrated. − Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zometa. − Since no data are available on the compatibility of Zometa with other intravenously administered substances, Zometa must not be mixed with other medications/substances and should always be given through a separate infusion line.
How to store Zometa − Keep Zometa out of the reach and sight of children. − Do not use Zometa after the expiry date stated on the pack. − The unopened vial doe s not require any specific storage conditions. − The diluted Zometa infusion solution should be used immediately in order to avoid microbial contamination .
92 Package leaflet: Information for the user Zometa 4 mg/5 ml concentrate for 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 i n this leaflet 1. What Zometa is and what it is used for 2. What you need to know b efore you are given Zometa 3. How Zometa is used 4. Possible side effects 5. How to store Zometa 6. Contents of the pack and other information 1. What Zometa is and what it is used for The active substance in Zometa 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) .
2. What you need to know before you are given Zometa Follow carefully all instructions given to you by your doctor.
Your doctor will carry out blood tests before you start treatment with Zometa and will check your response to treatment at regular intervals.
You should not be given Zometa: − if you are breast -feeding . − if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zometa 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 Zometa: − 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 Zometa. if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zometa and inform your doctor about your dental treatment.
While being treated with Zometa, you should maintain good oral hygiene (including regular teeth 93 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 Zometa. 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 Zometa. You will be given adequate calcium and vitamin D supplements.
Patients aged 65 years and over Zometa 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
Zometa is not recommended for use in adolescents and children below the age of 18 years.
Other medicines and Zometa
Tell your doctor if you are taking, have recently tak en or might take any other medicines . It is especially important that you tell your doctor if you are also taking :
- Aminoglycosides (medicine s 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.
- Aclasta (a 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 Zometa are unknown.
- Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zometa has been associated with an increased risk of osteonecrosis of the jaw (ONJ).
Pregnancy and breast -feeding You should not be given Zometa if you are pregnant. Tell your doctor if you are or think that you may be pregnant .
You must not be given Zometa 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 Zometa. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Zometa contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium free”. If your doctor uses a solution of common salt to dilute Zometa, the dose of sodium received 94 would be larger .
3. How Zometa is used − Zometa 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 f ollow all the other instructions given to you by your doctor, pharmacist or nurse.
How much Zometa 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 Zometa is given
- If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zometa 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 Zometa.
How Zometa is given
- Zometa 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.
If you are given more Zometa 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 non- healing 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 Zometa 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 95 after you have received zoledronic acid. − Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.
Rare (may affect up to 1 in 1,000 people)
− 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. − Osteonecrosis has also very rarely been seen occurring with other bones than the jaw, especially the hip or thigh. Tell your doctor immediately if you experience symptoms such as new onset or worsening of aches, pain or stiffness while being treated with Z ometa or after stopping treatment .
Not known: frequency cannot be calculated from the available data
- Inflammation of the kidney (tubulointerstitial nephritis): signs and symptoms may include decreased volume of the urine, blood in the urine, nausea, feeling generally unwell.
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).
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. − Blurred vision, t earing of the eye, eye sensitivity to light. − Sudden coldness with fainting, limpness or collapse. − Difficulty in breathing with wheezing or coughing. − Urticaria.
96 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 national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store Zometa Your doctor, pharmacist or nurse knows how to store Zometa properly (see section 6).
6. Contents of the pack and other information
What Zometa contains
− The active substance of Zometa is zoledronic acid. One vial contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate. − The other ingredients are mannitol, sodium citrate, water for injections.
What Zometa looks like and contents of the pack
Zometa is supplied as a liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.
Each pack contains the vial with concentrate. Zometa is supplied as unit packs containing 1 or 4 vials and as multi -packs containing 10 (10×1) vials . Not all pack sizes may be marketed.
Marketing Authorisation Holder
Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland
Manufacturer
LABORATORI FUNDACIÓ DAU Pol. Ind. Consorci Zona Franca. c/ C, 12- 14 08040 Barcelona Spain Or 97 Sanochemia Pharmazeutika GmbH Landegger -Straße 7 2491 Neufeld an der Leitha Burgenland Austria For any information about this medicin e, please contact the Marketing Authorisation Holder directly or, where available, the local representative:
BE, BG, CZ, DK, DE, EE, IE, HR, IT, CY, LV, LT, LU, HU, MT, NL, AT, PL, PT, RO, SI, SK, FI, SE and XI Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland Email: [email protected] Tel: +353 1 468 8900 ΕL Arriani Pharmaceuticals SA Lavriou Avenue 85 190 02 Paiania Attica Greece Tel: +30 210 6683000 ES EUROMED PHARMA SPAIN S.L C/Eduard Maristany, 430- 432 08919 Badalona (Barcelona) España Tel: + 34 932 684 208 Fax: + 34 933 150 469 FR Exploitant de l’autorisation de mise sur le marché :
EURODEP PHARMA 10 RUE ANTOINE DE SAINT EXUPERY ZAC DU PARC DE COMPANS 77290 MITRY MORY [email protected]
This leaflet was last revised in
Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu 98 INFORMATION FOR THE HEALTHCARE PROFESSIONAL How to prepare and administer Zometa − To prepare an infusion solution containing 4 mg zoledronic acid , further dilute the Zometa concentrate (5.0 ml) with 100 ml of calcium -free or other divalent cation- free infusion solution.
If a lower dose of Zometa 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 either 0.9 % w/v sodium chloride or 5% w/v glucose solution.
Do not mix Zometa concentrate with calcium -containing or other divalent cation – containing solutions such as lactated Ringer’s solution.
Instructions for preparing reduced doses of Zometa:
Withdraw the appropriate volume of the 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 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. T he 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 Zometa to ensure that they are adequately hydrated. − Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zometa. − Since no data are available on the compatibility of Zometa with other intravenously administered substances, Zometa must not be mixed with other medications/substances and should always be given through a separate infusion line.
How to store Zometa − Keep Zometa out of the reach and sight of children. − Do not use Zometa after the expiry date stated on the pack. − The unopened vial does not require any specific storage conditions. − The diluted Zometa infusion solution should be used immediately in order to avoid microbial contamination .
99 Package leaflet: Information for the user Zometa 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 i n this leaflet 1. What Zometa is and what it is used for 2. What you need to know b efore you are given Zometa 3. How Zometa is used 4. Possible side effects 5. How to store Zometa 6. Contents of the pack and other information
ℹ️ 1. What Zometa is and what it is used for
The active substance in Zometa 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) .
⚠️ 2. What you need to know before you are given Zometa
Follow carefully all instructions given to you by your doctor.
Your doctor will carry out blood tests before you start treatment with Zometa and will check your response to treatment at regular intervals.
You should not be given Zometa: − if you are breast -feeding. − if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zometa 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 Zometa: − 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 Zometa. − if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zometa and inform your doctor about your dental treatment.
While being treated with Zometa, you should maintain good oral hygiene (including regular teeth 100 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 p revent 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 Zometa. Irregular heart beat (cardiac arrhythmia), seizures, spasm and twitching (tetany) have been reported as secondary to severe hypocalcaemi a. 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 Zometa. You will be given adequat e calcium and vitamin D supplements.
Patients aged 65 years and over Zometa 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
Zometa is not recommended for use in adolescents and children below the age of 18 years.
Other medicines and Zometa
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 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.
- Aclasta (a 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 Zometa are unknown.
- Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zometa has been associated with an increased risk of osteonecrosis of the jaw (ONJ).
Pregnancy and breast -feeding You should not be given Zometa if you are pregnant. Tell your doctor if you are or think that you may be pregnant.
You must not be given Zometa 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 Zometa. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Zometa contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium free”. If your doctor uses a solution of common salt to dilute Zometa, the dose of sodium received 101 would be larger .
💊 3. How Zometa is used
− Zometa 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 Zometa 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 Zometa is given
- If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zometa 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 Zometa.
How Zometa is given
- Zometa 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.
If you are given more Zometa 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 f unction, 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 non- healing 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 Zometa 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 102 after you have received zoledronic acid. − Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.
Rare (may affect up to 1 in 1,000 people)
− 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. − Osteonecrosis has also very rarely been seen occurring with other bones than the jaw, especially the hip or thigh. Tell your doctor immediately if you experience symptoms such as new onset or worsening of aches, pain or stiffness while being treated with Z ometa or after stopping treatment .
Not known: frequency cannot be calculated from the available data
- Inflammation of the kidney (tubulointerstitial nephritis): signs and symptoms may include decreased volume of the urine, blood in the urine, nausea, feeling generally unwell .
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).
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. − Blurred vision, t earing 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 national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.
🌡️ 5. How to store Zometa
Your doctor, pharmacist or nurse knows how to store Zometa properly (see section 6).
After first opening, Zometa solution for infusion should preferably be used immediately. If the solution is not used immediately, it should be stored in a refrigerator at 2°C – 8°C.
📦 6. Contents of the pack and other information
What Zometa contains
− The active substance of Zometa is zoledronic acid. One bottle contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate. − The other ingredients are mannitol, sodium citrate and water for injections.
What Zometa looks like and contents of the pack
Zometa is supplied as a solution in a clear, colourless plastic bottle. One bottle contains 100 ml solution.
Zometa is supplied as a unit pack containing one bottle or as multipacks comprising 4 or 5 cartons, each containing 1 bottle. Not all pack sizes may be marketed.
Marketing Authorisation Holder
Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland
Manufacturer
LABORATORI FUNDACIÓ DAU Pol. Ind. Consorci Zona Franca. c/ C, 12- 14 08040 Barcelona 104 Spain Or Sanochemia Pharmazeutika GmbH Landegger -Straße 7 2491 Neufeld an der Leitha Burgenland Austria For any information about this medicine, please contact the Marketing Authorisation Holder directly or, where available, the local representative:
BE, BG, CZ, DK, DE, EE, IE, HR, IT, CY, LV, LT, LU, HU, MT, NL, AT, PL, PT, RO, SI, SK, FI, SE and XI Phoenix Labs Unlimited Company Suite 12, Bunkilla Plaza Bracetown Business Park Clonee, County Meath Ireland Email: [email protected] Tel: +353 1 468 8900 ΕL Arriani Pharmaceuticals SA Lavriou Avenue 85 190 02 Paiania Attica Greece Tel: +30 210 6683000 ES EUROMED PHARMA SPAIN S.L C/Eduard Maristany, 430- 432 08919 Badalona (Barcelona) España Tel: + 34 932 684 208 Fax: + 34 933 150 469 FR Exploitant de l’autorisation de mise sur le marché :
EURODEP PHARMA 10 RUE ANTOINE DE SAINT EXUPERY ZAC DU PARC DE COMPANS 77290 MITRY MORY [email protected]
This leaflet was last revised in
Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu 105 INFORMATION FOR THE HEALTHCARE PROFESSIONAL How to prepare and administer Zometa − Zometa 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 t hen 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 f ollowing administration of Zometa to assure that they are adequately hydrated. − Zometa 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 Zometa solution indicated from the bottle and replace with an equal volume of sterile sodium chloride 9 mg/ml (0,9%) solution for injection, or 5% glucose solution for injection.
Table 1 Preparation of reduced doses of Zometa 4 mg/100 ml solution for infusion Baseline creatinine clearance (ml/min) Remove the following amount of Zometa 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 Zometa. − Since no data are available on the compatibility of Zometa with other intravenously administered substances, Zometa must not be mixed with other medications/substances and should always be given through a separate infusion line.
106 How to store Zometa − Keep Zometa out of the reach and sight of children. − Do not use Zometa after the expiry date stated on the pack. − The unopened bottle does not require any special storage conditions. − After opening the bottle, the product should be used immediately in order to avoid microbial contamination.
📄 Package Leaflet – official source
This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Zometa (PDF, ec.europa.eu).
You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/01/176).
⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.