Zoledronic acid Ennogen 4 mg/5 ml concentrate for solution for infusion

• 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.

1. What Zoledronic Acid Ennogen is and what it is used for
2. What you need to know before you are given Zoledronic Acid Ennogen
3. How Zoledronic Acid Ennogen is used
4. Possible side effects
5. How to store Zoledronic Acid Ennogen
6. Contents of the pack and other information

• if you are breast-feeding.
• if you are allergic to zoledronic acid monohydrate, another bisphosphonate (the group of substances to which Zoledronic Acid Ennogen belongs), or any of the other ingredients of this medicine (listed in section 6).

Talk to your doctor before you are given Zoledronic Acid Ennogen:

• if you have or have had a kidney problem.
• if you have or have had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth. Your doctor may recommend a dental examination before you start treatment with Zoledronic Acid Ennogen.
• if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zoledronic Acid Ennogen and inform your doctor about your dental treatment.

While being treated with Zoledronic Acid Ennogen, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of a condition called osteonecrosis of the jaw.

Patients who are undergoing chemotherapy and/or radiotherapy, who are taking steroids, who are undergoing dental surgery, who do not receive routine dental care, who have gum disease, who are smokers, or who were previously treated with a bisphosphonate (used to treat or prevent bone disorders) may have a higher risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood hypocalcaemia (sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with Zoledronic acid Ennogen. Irregular heart beat (cardiac arrhythmia), seizures, spasm and twitching (tetany) have been reported as secondary to severe hypocalcaemia. In some instances, the hypocalcaemia may be life-threatening. If any of these apply to you, tell your doctor straight away. if you have pre-existing hypocalcaemia, it must be corrected before initiating the first dose of Zoledronic acid Ennogen. You will be given adequate calcium and vitamin D supplements.

Zoledronic Acid Ennogen can be given to people aged 65 years and over. There is no evidence to suggest that any extra precautions are needed.

Zoledronic Acid Ennogen is not recommended for use in adolescents and children below the age of 18 years.

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 Zoledronic Acid Ennogen are unknown.
• Certain medicines to treat cancer (anti-angiogenic medicines), since the combination of these with Zoledronic Acid Ennogen has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

You should not be given Zoledronic Acid Ennogen if you are pregnant. Tell your doctor if you are or think that you may be pregnant.

You must not be given Zoledronic Acid Ennogen if you are breast-feeding.

Ask your doctor for advice before taking any medicine while you are pregnant or breast-feeding.

There have been very rare cases of drowsiness and sleepiness with the use of Zoledronic Acid Ennogen. You should therefore be careful when driving, using machinery or performing other tasks that need full attention

This medicinal product contains less than 1 mmol sodium (23 mg) per vial (5 ml),that is to say essentially “sodium-free”.

If your doctor uses a solution of common salt to dilute Zoledronic Acid Ennogen, the dose of sodium received would be larger.

• 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.

• If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zoledronic Acid Ennogen every three to four weeks.
• If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic Acid Ennogen.

• Zoledronic Acid Ennogen 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 have received doses higher than those recommended, you will be carefully monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphorous 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.

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 Zoledronic Acid Ennogen or after stopping treatment.
• Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving Zoledronic Acid Ennogen for postmenopausal osteoporosis. It is currently unclear whether Zoledronic Acid Ennogen causes this irregular heart rhythm but you should report it to your doctor if you experience such symptoms after you have received Zoledronic Acid Ennogen.
• 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 Zoledronic acid Ennogen or after stopping treatment.

Not known: frequency cannot be estimated 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

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 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.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance of Zoledronic Acid Ennogen is zoledronic acid monohydrate. 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.

Zoledronic Acid Ennogen is supplied as a liquid concentrate in a vial. It is a clear and colourless solution, practically free from visible particles. One vial contains 4 mg of zoledronic acid.

Each pack contains the vial with concentrate. Zoledronic Acid Ennogen is supplied as unit packs containing 1,4 or 10 vials. Not all pack sizes may be marketed.