zoledronic acid: package leaflet

For patients

Package leaflet, verbatim

Aclasta

Package leaflet: Aclasta 5 mg solution for infusion / zoledronic acid

1. What Aclasta is and what it is used for

Aclasta contains the active substance zoledronic acid. It belongs to a group of medicines called bisphosphonates and is used to treat post-menopausal women and adult men with osteoporosis or osteoporosis caused by treatment with corticosteroids used to treat inflammation, and Paget’s disease of the bone in adults.

Osteoporosis
Osteoporosis is a disease that involves the thinning and weakening of the bones and is common in women after the menopause, but can also occur in men. At the menopause, a woman’s ovaries stop producing the female hormone oestrogen, which helps keep bones healthy. Following the menopause bone loss occurs, bones become weaker and break more easily. Osteoporosis could also occur in men and women because of the long term use of steroids, which can affect the strength of bones. Many patients with osteoporosis have no symptoms but they are still at risk of breaking bones because osteoporosis has made their bones weaker. Decreased circulating levels of sex hormones, mainly oestrogens converted from androgens, also play a role in the more gradual bone loss observed in men.
In both women and men, Aclasta strengthens the bone and therefore makes it less likely to break.
Aclasta is also used in patients who have recently broken their hip in a minor trauma such as a fall and therefore are at risk of subsequent bone breaks.

Paget’s disease of the bone
It is normal that old bone is removed and is replaced with new bone material. This process is called remodelling. In Paget’s disease, bone remodelling is too rapid and new bone is formed in a disordered fashion, which makes it weaker than normal. If the disease is not treated, bones may become deformed and painful, and may break. Aclasta works by returning the bone remodelling process to normal, securing formation of normal bone, thus restoring strength to the bone.

2. What you need to know before you are given Aclasta

Follow all instructions given to you by your doctor, pharmacist or nurse carefully before you are given Aclasta.

You must not be given Aclasta:
- if you are allergic to zoledronic acid, other bisphosphonates or any of the other ingredients of

this medicine (listed in section 6).
- if you have hypocalcaemia (this means that the levels of calcium in your blood are too low).
- if you have severe kidney problems.
- if you are pregnant.
- if you are breast-feeding.

Warnings and precautions
Talk to your doctor before you are given Aclasta:
- if you are being treated with any medicine containing zoledronic acid, which is also the active substance of Aclasta (zoledronic acid is used in adult patients with certain types of cancer to prevent bone complications or to reduce the amount of calcium).
- if you have a kidney problem, or used to have one.
- if you are unable to take daily calcium supplements.
- if you have had some or all of the parathyroid glands in your neck surgically removed.
- if you have had sections of your intestine removed.

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported in the post-marketing setting in patients receiving Aclasta (zoledronic acid) for osteoporosis. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving Aclasta treatment, tell your doctor, pharmacist or nurse if
- you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction;
- you do not receive routine dental care or have not had a dental check-up for a long time;
- you are a smoker (as this may increase the risk of dental problems);
- you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders);
- you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
- you have cancer.

Your doctor may ask you to undergo a dental examination before you start treatment with Aclasta.

While being treated with Aclasta, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or are due to undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Aclasta. 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 osteonecrosis of the jaw.

Monitoring test
Your doctor should do a blood test to check your kidney function (levels of creatinine) before each dose of Aclasta. It is important for you to drink at least 2 glasses of fluid (such as water), within a few hours before receiving Aclasta, as directed by your healthcare provider.

Children and adolescents
Aclasta is not recommended for anyone under 18 years of age.

Other medicines and Aclasta
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

It is important for your doctor to know all the medicines you are taking, especially if you are taking

any medicines known to be harmful to your kidneys (e.g. aminoglycosides) or diuretics (“waterpills”) that may cause dehydration.

Pregnancy and breast-feeding
You must not be given Aclasta if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby.

Ask your doctor, pharmacist or nurse for advice before taking this medicine.

Driving and using machines
If you feel dizzy while taking Aclasta, do not drive or use machines until you feel better.

Aclasta contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 ml vial of Aclasta, i.e., essentially “sodium free”.

3. How Aclasta is given

Follow carefully all instructions given to you by your doctor or nurse. Check with your doctor or nurse if you are not sure.

Osteoporosis
The usual dose is 5 mg given as one infusion per year into a vein by your doctor or nurse. The infusion will take at least 15 minutes.

In case you recently broke your hip, it is recommended that Aclasta is administered two or more weeks after your hip repair surgery.

It is important to take calcium and vitamin D supplements (for example tablets) as directed by your doctor.

For osteoporosis, Aclasta works for one year. Your doctor will let you know when to return for your next dose.

Paget’s disease
For the treatment of Paget’s disease, Aclasta should be prescribed only by physicians with experience in the treatment of Paget’s disease of the bone.

The usual dose is 5 mg, given to you as one initial infusion into a vein by your doctor or nurse. The infusion will take at least 15 minutes. Aclasta may work for longer than one year, and your doctor will let you know if you need to be treated again.

Your doctor may advise you to take calcium and vitamin D supplements (e.g. tablets) for at least the first ten days after being given Aclasta. It is important that you follow this advice carefully so that the level of calcium in your blood does not become too low in the period after the infusion. Your doctor will inform you regarding the symptoms associated with hypocalcaemia.

Aclasta with food and drink
Make sure you drink enough fluids (at least one or two glasses) before and after the treatment with Aclasta, as directed by your doctor. This will help to prevent dehydration. You may eat normally on the day you are treated with Aclasta. This is especially important in patients who take diuretics (“water pills”) and in elderly patients (age 65 years or over).

If you missed a dose of Aclasta
Contact your doctor or hospital as soon as possible to re-schedule your appointment.

Before stopping Aclasta therapy
If you are considering stopping Aclasta treatment, please go to your next appointment and discuss this with your doctor. Your doctor will advise you and decide how long you should be treated with Aclasta.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects related to the first infusion are very common (occurring in more than 30% of patients) but are less common following subsequent infusions. The majority of the side effects, such as fever and chills, pain in the muscles or joints, and headache, occur within the first three days following the dose of Aclasta. The symptoms are usually mild to moderate and go away within three days. Your doctor can recommend a mild pain reliever such as ibuprofen or paracetamol to reduce these side effects. The chance of experiencing these side effects decreases with subsequent doses of Aclasta.

Some side effects could be serious
Common (may affect up to 1 in 10 people)
Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving Aclasta for the treatment of postmenopausal osteoporosis. It is currently unclear whether Aclasta causes this irregular heart rhythm but you should report it to your doctor if you experience such symptoms after you have received Aclasta.

Uncommon (may affect up to 1 in 100 people)
Swelling, redness, pain and itching to the eyes or eye sensitivity to light.

Very rare (may affect up to 1 in 10,000 people)
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.

Not known (frequency cannot be estimated from the available data)
Pain in the mouth and/or jaw, swelling or non-healing sores in 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 Aclasta or after stopping treatment.

Kidney disorders (e.g. decreased urine output) may occur. Your doctor should do a blood test to check your kidney function before each dose of Aclasta. It is important for you to drink at least 2 glasses of fluid (such as water), within a few hours before receiving Aclasta, as directed by your healthcare provider.

If you experience any of the above side effects, you should contact your doctor immediately.

Aclasta may also cause other side effects
Very common (may affect more than 1 in 10 people)
Fever

Common (may affect up to 1 in 10 people)
Headache, dizziness, sickness, vomiting, diarrhoea, pain in the muscles, pain in the bones and/or joints, pain in the back, arms or legs, flu-like symptoms (e.g. tiredness, chills, joint and muscle pain), chills, feeling of tiredness and lack of interest, weakness, pain, feeling unwell, swelling and/or pain at the infusion site.

In patients with Paget’s disease, symptoms due to low blood calcium, such as muscle spasms, or

numbness, or a tingling sensation especially in the area around the mouth have been reported.

Uncommon (may affect up to 1 in 100 people)
Flu, upper respiratory tract infections, decreased red cell count, loss of appetite, sleeplessness, sleepiness which may include reduced alertness and awareness, tingling sensation or numbness, extreme tiredness, trembling, temporary loss of consciousness, eye infection or irritation or inflammation with pain and redness, spinning sensation, increased blood pressure, flushing, cough, shortness of breath, upset stomach, abdominal pain, constipation, dry mouth, heartburn, skin rash, excessive sweating, itching, skin reddening, neck pain, stiffness in muscles, bones and/or joints, joint swelling, muscle spasms, shoulder pain, pain in your chest muscles and rib cage, joint inflammation, muscular weakness, abnormal kidney test results, abnormal frequent urination, swelling of hands, ankles or feet, thirst, toothache, taste disturbances.

Rare (may affect up to 1 in 1,000 people)
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. Low levels of phosphate in the blood.

Not known (frequency cannot be estimated from the available data)
Severe allergic reactions including dizziness and difficulty breathing, swelling mainly of the face and throat, decreased blood pressure, dehydration secondary to acute phase reactions (post-dose symptoms such as fever, vomiting and diarrhoea).

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 Aclasta

Your doctor, pharmacist or nurse knows how to store Aclasta properly.

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 bottle after EXP.
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. 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.

6. Contents of the pack and other information

What Aclasta contains
- The active substance is zoledronic acid. Each bottle with 100 ml of solution contains 5 mg zoledronic acid (as monohydrate).
One ml solution contains 0.05 mg zoledronic acid (as monohydrate).
- The other ingredients are mannitol, sodium citrate and water for injections.

What Aclasta looks like and contents of the pack
Aclasta is a clear and colourless solution. It comes in 100 ml plastic bottles as a ready-to-use solution for infusion. It is supplied in packs containing one bottle as unit pack, or in multipacks comprising five packs, each containing one bottle. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz Pharmaceuticals d.d.
Verovškova ulica 57
1000 Ljubljana
Slovenia

Manufacturer
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany

LEK Pharmaceuticals d.d.,
Verovškova ulica 57,
1526 Ljubljana,
Slovenia

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97
Lietuva
Sandoz Pharmaceuticals d.d. filialas
Tel: +370 5 2636 037

България
Сандоз България КЧТ
Teл.: +359 2 970 47 47
Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 234 142 222

Magyarország
Sandoz Hungária Kft.
Bartók Béla út 43-47
H-1114 Budapest
Tel: +36 1 430 2890
Info.hungary@sandoz.com

Danmark
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
(Slovenia)
Tel: +35699644126

Deutschland
Hexal AG
Industriestr. 25
D-83607 Holzkirchen
Tel: +49 8024 908-0 service@hexal.com

Nederland
Sandoz B.V.
Hospitaaldreef 29
NL-1315 RC Almere
Tel: +31 (0)36 5241600 info.sandoz-nl@sandoz.com
Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 6652400

Norge
Sandoz A/S
Tlf: +45 63 95 10 00
Ελλάδα
SANDOZ HELLAS
ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Österreich
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Tel: +43(0)1 86659-0

España
Bexal Farmacéutica, S.A.
Centro Empresarial Parque Norte
Edificio Roble
C/ Serrano Galvache, 56
28033 Madrid
Tel: +34 900 456 856

Polska
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02 672 Warszawa
Tel.: +48 22 209 7000 maintenance.pl@sandoz.com
France
Sandoz SAS
Tél: + 33 1 49 64 48 00

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 211 964 000

Hrvatska
Sandoz d.o.o.
Maksimirska 120
10 000 Zagreb
Tel : +385 1 235 3111 upit.croatia@sandoz.com

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60
Ireland
Rowex Ltd., Bantry, Co. Cork, Ireland. P75 V009
Tel: + 353 27 50077 e-mail: patient.safety.ireland@sandoz.net

Slovenija
Lek farmacevtska družba d.d.
Verovškova 57
SI-1526 Ljubljana
Tel: +386 1 580 21 11
Info.lek@sandoz.com

Ísland
Sandoz A/S
Sími: +45 63 95 10 00

Slovenská republika
Sandoz d.d. - organizačná zložka
Žižkova 22B
811 02 Bratislava
Tel: +421 2 48 200 600 sk.regulatory@sandoz.com

Italia
Sandoz S.p.A.
Tel: +39 02 812 806 96
Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400
Κύπρος
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
(Ελλάδα)
Τηλ: +30 216 600 5000
Sverige
Sandoz A/S
Tel: +45 63 95 10 00

Latvija
Sandoz d.d. Latvia filiāle
K.Valdemāra 33 – 29
LV-1010 Rīga
Tel: +371 67892006

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

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

The following information is intended for healthcare professionals only (see section 3):

How to prepare and administer Aclasta

Aclasta 5 mg solution for infusion is ready for use.

For single use only. Any unused solution should be discarded. Only clear solution free from particles and discoloration should be used. Aclasta must not be mixed or given intravenously with any other medicinal product and must be given through a separate vented infusion line at a constant infusion rate. The infusion time must not be less than 15 minutes. Aclasta must not be allowed to come into contact with any calcium-containing solutions. If refrigerated, allow the refrigerated solution to reach room temperature before administration. Aseptic techniques must be followed during preparation of the infusion. The infusion must be conducted according to standard medical practice.

How to store Aclasta

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 bottle after EXP.
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. 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.

Zometa

Package leaflet: Zometa 4 mg powder and solvent for solution for infusion / zoledronic acid

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

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 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

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 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

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, 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.

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

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: info@phoenixlabs.ie
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 exploitant@eurodep.fr

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

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 lactated 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 does not require any specific storage conditions.
−
The diluted Zometa infusion solution should be used immediately in order to avoid microbial contamination.

Package leaflet: Zometa 4 mg/5 ml concentrate for solution for infusion / zoledronic acid

1. What Zometa is and what it is used for

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.

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

brushing) and receive routine dental check-ups.

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.

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.

would be larger.

3. How Zometa is used

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 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.

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.

after you have received zoledronic acid.
−
Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.

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.

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.

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 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 (10x1) 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

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:

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

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

−
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 then be equilibrated to room temperature prior to administration.

−
Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zometa.

How to store Zometa

Package leaflet: Zometa 4 mg/100 ml solution for infusion / zoledronic acid