Zoledronic Acid 5 mg/100ml 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 is and what it is used for
2. What you need to know before you are given Zoledronic Acid
3. How Zoledronic Acid is given
4. Possible side effects
5. How to store Zoledronic Acid
6. Contents of the pack and other information

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, Zoledronic Acid strengthens the bone and therefore makes it less likely to break. Zoledronic Acid 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.

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. Zoledronic Acid works by returning the bone remodelling process to normal, securing formation of normal bone, thus restoring strength to the bone.

• if you are allergic to zoledronic acid, other bisphosponates 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.

Talk to your doctor before you are given Zoledronic Acid:

• if you are being treated with any medicine containing zoledronic acid, which is also the active substance of Zoledronic Acid (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 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 you receive treatment with Zoledronic Acid, 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 Zoledronic acid.

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

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

Zoledronic Acid is not recommended for anyone under 18 years of age.

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 (“water pills”) that may cause dehydration.

You must not be given Zoledronic Acid 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.

If you feel dizzy while taking Zoledronic Acid, do not drive or use machines until you feel better.

This medicinal product contains less than 1 mmol sodium (23 mg) 100 ml vial of Zoledronic Acid, i.e. essentially ’sodium-free’.

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 Zoledronic Acid 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, Zoledronic Acid works for one year. Your doctor will let you know when to return for your next dose.

For the treatment of Paget’s disease, Zoledronic Acid 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. Zoledronic Acid 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 Zoledronic Acid. 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.

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

Contact your doctor or hospital as soon as possible to re-schedule your appointment.

If you are considering stopping Zoledronic Acid 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 Zoledronic Acid.

Common (may affect up to 1 in 10 people)

Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving Zoledronic Acid for the treatment of 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.

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 Zoledronic acid 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 Zoledronic Acid. It is important for you to drink at least 2 glasses of fluid (such as water), within a few hours before receiving Zoledronic Acid, as directed by your healthcare provider.

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

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 diarrhea).

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. Also, you can help make sure medicines remain as safe as possible by reporting any unwanted side-effects via Yellow Card Scheme 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 is zoledronic acid. Each vial with 100 ml of solution contains 5 mg of zoledronic acid (as monohydrate).
  One ml solution contains 0.05 mg of zoledronic acid anhydrous (as monohydrate).
• The other ingredients are mannitol (E421), sodium citrate (E331) and water for injections.

Zoledronic Acid is a clear and colourless solution.

It comes in 100 ml clear Type I silicon dioxide inner coated glass or type II soda-lime-silica glass vials capped with Type I bromobutyl rubber stopper and aluminium seal with a polypropylene flip-off cap clear outside and unlacquered inside, or Type II soda-lime-silica glass vials capped with Teflon coated chlorobutyl rubber stopper and aluminium seal with a polypropylene flip-off cap clear outside and unlacquered inside as a ready-to-use solution for infusion.

Zoledronic Acid 5 mg/100 ml solution for infusions is supplied in:

1 vial

4 vials

Not all pack sizes may be marketed.