How does it work?

Aclasta infusion contains the active ingredient zoledronic acid,which is a type of medicine called a bisphosphonate. Bisphosphonates aremedicines that reduce the turnover of bone.

Bone is not a static structure. It is continually shaped,reformed and rebuilt by cells called osteoblasts and osteoclasts. These cellscontinously deposit and remove calcium and phophorous, stored in a proteinnetwork that makes up the structure of the bone. Old bone is broken down by theosteoclasts and new bone is formed by the osteoblasts.

In Paget's disease of bone the normal metabolism of bone isdisturbed. There is an increase in bone breakdown by the osteoclasts andincreased and irregular formation of new bone by the osteoblasts. The normalbone marrow also becomes replaced with blood vessels and fibrous tissue. Inthis disease there are often no symptoms for many years, but over time thebones can become enlarged, deformed, painful, weak and prone to breaking. Theenlarged and deformed bones can also put pressure on nerves, causing pain andmuscle weakness.

In women at the menopause, blood levels of the female hormoneoestrogen start to decrease. This results in an increase in bone breakdown bythe osteoclasts, which can lead to a loss of bone density. Bone loss isparticularly rapid for the first ten years after the menopause and it may leadto the development of osteoporosis - a condition in which the bones become weakand brittle and break (fracture) more easily.

Osteoporosis can also occur in men and as a result of long-term treatment with corticosteroid medicines such as prednisolone.

Zoledronic acid works by binding very tightly to the bone andpreventing the calcium being removed by the osteoclasts. This stops theosteoclasts from breaking down the bone. The reduced bone turnover helps toreduce deformity and keep the bones strong and less likely to break.

As this medicine slows bone turnover and so prevents calciumbeing reabsorbed from the bones into the blood, it can cause the amount ofcalcium in your blood to fall too low. Your doctor may ask you to take calciumand vitamin D supplements before you have your infusion and, if you have Paget's disease, for at least tendays after it to prevent this.

Calcium andvitamin D are needed for strong bones and yourdoctor may ask you to continue to take supplements of these if your dietaryintake is too low, or you are at risk of deficiency.

What is it used for?

• Bone disease called Paget's disease, in which there is excessive breakdown of bone and increased and irregular formation of bone, causing the bones to become enlarged, deformed, painful, weak and prone to breaking.
• Treatment of osteoporosis in postmenopausal women at high risk of breaking a bone.
• Treatment of osteoporosis in men at high risk of breaking a bone.
• Treatment of osteoporosis caused by long-term treatment with corticosteroids such as prednisolone, in postmenopausal women and men at increased risk of breaking a bone.

How is it given?

• Aclasta is given via a drip into a vein (intravenous infusion) overat least 15 minutes.
• The medicine is given as a single dose for treating Paget'sdisease of bone. The treatment can be repeated if your disease flares ups again.
• For treating osteoporosisthis medicine is given as a single dose once a year.

Warning!

• Your doctor will want you to have a blood test before your infusion to check the level of calcium in your blood. After you have had your infusion, your doctor may also want you to have further blood tests to monitor the level of calcium in your blood. If you have Paget's disease your calcium level may drop in the first 10 days after your infusion, so your doctor will prescribe you calcium and vitamin D supplements to prevent this. (Vitamin D is needed by the body to help it absorb calcium.) If the amount of calcium in your blood falls too low, this may cause symptoms such as muscle spasms, numbness, or tingling sensations, especially in the area around the mouth. Tell your doctor if you get any of these symptoms.
• Your doctor will also want to check your kidney function before each dose of this medicine. This is particularly important if you have any existing problems with your kidneys, or you are also taking diuretic medicines or other medicines that can affect the kidneys. Your doctor may also want to continue monitoring your kidneys after you have had the infusion.
• It is important that you drink enough fluid both before and after your infusion to prevent dehydration. Follow your doctors instructions.
• If you have recently broken your hip it is recommended that this medicine is not given until at least two weeks after the hip is fully repaired.
• The class of medicines that zoledronic acid belongs to (bisphosphonates) has been associated with a rare condition called osteonecrosis of the jaw. The majority of cases of this condition have been in cancer patients treated with bisphosphonates by injection into a vein, and many of these people were also having treatment with chemotherapy or corticosteroids. However, the condition has also been seen in people taking bisphosphonates by mouth. The risk may also be increased by poor oral hygiene, dental problems such as gum disease or poorly fitting dentures, teeth extractions, oral surgery and smoking. For this reason, you should have a dental examination and, if necessary, appropriate preventive dentistry, before you start treatment with this medicine. Discuss this with your doctor. It is important to look after your mouth and teeth as much as possible while you are having treatment with this medicine. You should have regular check-ups with your dentist and get advice straight away if you have any problems with your mouth or teeth. When you see a dentist during treatment, make sure they know you are having this medicine. Invasive dental procedures such as tooth extraction or surgery should be avoided if possible.
• Some people being treated with bisphosphonates (mainly people having long-term treatment for osteoporosis) have experienced an unusual fracture of their thigh bone. For this reason it is important to let your doctor know if you get any pain in your thighs, hips or groin while you are having treatment with this medicine. These symptoms could be an early indication of a possible fracture.

Use with caution in

• Elderly people.
• Decreased kidney function.
• Dehydration.
• People receiving treatment with diuretic medicines.
• Disorders of the parathyroid gland (gland that produces hormones responsible for regulating calcium metabolism).
• Vitamin D deficiency.

Not to be used in

• People who are allergic to other bisphosphonate medicines.
• People with a low level of calcium in their blood (hypocalcaemia).
• People with severely decreased kidney function.
• Pregnancy.
• Breastfeeding.
• This medicine is not recommended for children and adolescents under 18 years of age.

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such an allergy.

If you feel you have experienced an allergic reaction, stopusing this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• The safety of this medicine for use during pregnancy has not been established. It should not be used during pregnancy and is not recommended for women who could get pregnant. Seek medical advice from your doctor.
• It is not known if this medicine passes into breast milk. It should not be given to women who are breastfeeding. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience that orany side effect.

Very common (affect more than 1 in 10 people)

• High temperature (fever).

Common (affect between 1 in 10 and 1 in 100 people)

• Flu-like symptoms. Your doctor may recommend that you take paracetamol or ibuprofen after your infusion to reduce these symptoms.
• Pain in the muscles or joints.
• Feeling weak or tired.
• Headache.
• Redness, swelling or pain at the infusion site.
• Low blood calcium level (hypocalcaemia). This may cause symptoms such as pins and needles or muscle spasms/twitches/cramps. Tell your doctor if you experience symptoms like these.
• Dizziness.
• Disturbances of the gut, such as diarrhoea, nausea and vomiting.
• Bone pain.
• Pain in the extremities, eg hands and feet.
• Red eyes.
• Irregular heartbeat (atrial fibrillation).

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Loss of appetite.
• Difficulty sleeping (insomnia).
• Anaemia.
• Sleepiness or lethargy.
• Tremor.
• Change in taste.
• Inflammation of the membrane lining the eye (conjunctivitis).
• Eye pain.
• Sensation of spinning (vertigo).
• Awareness of your heartbeat (palpitations).
• Increased blood pressure.
• Flushing.
• Cough.
• Shortness of breath.
• Indigestion.
• Acid reflux.
• Abdominal pain.
• Inflammation of the foodpipe (oesophagitis).
• Dry mouth.
• Skin reactions such as rash, sweating or itching.
• Swollen ankles caused by fluid retention.
• Feeling thirsty.

Unknown frequency

• Decreased kidney function.
• Osteonecrosis of the jaw (see warning section above).
• Unusual fractures of the thigh bone (see warning section above).

The side effects listed above may not include all of the sideeffects reported by the medicine's manufacturer.

For more information about any other possible risks associatedwith this medicine, please read the information provided with the medicine orconsult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines while being treated with this one, to make sure that thecombination is safe.

This medicine should be used with caution in people who aretaking medicines that can affect kidney function, for example aminoglycoside antibioticssuch as gentamicin or diuretics such asfurosemide. Medicines that affect kidney function could increase the chance of side effects from this medicine.

There may an increased chance of the amount of calcium in the blood falling too low if aminoglycoside antibiotics such as gentamicin are used in combination with this medicine.

Other medicines containing the same active ingredient