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PACKAGE LEAFLET: INFORMATION FORTHE USER

Zoledronic Acid 4mg/100ml Solution for Infusion

(Referred to as Zoledronic Acid Solution for Infusion in the remainder of this leaflet)

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 in this leaflet:

1.    WhatZoledronic Acid Solution for Infusion is and what it is used for

2.    What you need to know before you are given Zoledronic Acid Solution for Infusion

3.    How Zoledronic Acid Solution for Infusion is used

4.    Possible side effects

5.    How to store Zoledronic Acid Solution for Infusion

6.    Contents of the pack and other information

1. WHAT ZOLEDRONIC ACID SOLUTION FOR INFUSION IS AND WHAT IT IS USED FOR

The active substance in Zoledronic Acid Solution for Infusion is zoledronic acid, which belongs to a

group of substances called ispnosphonates. 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 tne 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 ZOLEDRONIC ACID SOLUTION FOR INFUSION

Follow carefully all instructions given to you by your doctor.

Your doctor will carry out blood tests before you start treatment with Zoledronic Acid Solution for Infusion and will check your response to treatment at regular intervals.

You should not be given Zoledronic Acid Solution for Infusion:

•    if you are breast-feeding.

•    if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which zoledronic acid 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 Zoledronic Acid Solution for Infusion

•    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.

•    if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you areDeing treated with Zoledronic Acid Solution for Infusion.

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 Solution for Infusion. 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 Solution for Infusion. You will be given adequate calcium and vitamin D supplements.

Patients aged 65 years and over

Zoledronic Acid Solution for Infusion 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

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

Other medicines and Zoledronic Acid Solution for Infusion

Tell your doctor if you are takinq, 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.

•    Other zoledronic acid products 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 Solution for Infusion are unknown.

•    Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zoledronic Acid Solution for Infusion has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

You should not be given Zoledronic Acid Solution for Infusion if you are pregnant. Tell your doctor if you are or think that you may be pregnant. Women of child-bearing potential should avoid becoming pregnant whilst taking Zolendronic Acid.

You must not be given Zoledronic Acid Solution for Infusion 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 Zoledronic Acid Solution for Infusion. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.

Important information about some of the ingredients of Zoledronic Add Solution for Infusion

This medicinal product contains less than 1 mmol sodium (23mg) per dose, i.e. essentially'sodium-free'.

3. HOW ZOLEDRONIC ACID SOLUTION FOR INFUSION IS USED

•    Zoledronic Acid Solution for Infusion 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 Zoledronic Acid Solution for Infusion 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 Zoledronic Acid Solution for Infusion is given

If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zoledronic Acid Solution for Infusion 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 Solution for Infusion.

How Zoledronic Acid Solution for Infusion is given

-    Zoledronic Acid Solution for Infusion 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

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INFORMATION FORTHE HEALTHCARE PROFESSIONAL Zoledronic Acid 4 mg/100 ml Solution for Infusion (Referred to as Zoledronic Add Solution for Infusion in the remainder of this section)

The following information is intended for healthcare professionals only. Please refer to the Summary of Product Characteristics (SmPC) for further details on this product.

How to prepare and administer Zoledronic Acid Solution for Infusion

•    Zoledronic Acid 4 mg/100 ml Solution for Infusion contains 4 mg zoledronic acid in 100 ml of infasion 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.

•    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 following administration of Zoledronic Acid Solution for Infusion to assure that they are adequately hydrated.

• Zoledronic Acid 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 Zoledronic Acid Solution for Infusion 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.

prescribed calcium and vitamin D supplements to be taken each day.

If you are given more Zoledronic Acid Solution for Infusion 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 sores inside the mouth, 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.

•    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).

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).

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 red swollen eyes with blurred vision and increased sensitivity to light.

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.

•    Red, irritated or "gritty" eyes.

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 systems listed below:

United Kingdom:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland:

HPRA Pharmacovigilance,

EarlsfortTerrace, IRL - Dublin 2;

Tel:+353 1 6764971;

Fax:+3531 6762517;

Website: www.hpra.ie; e-mail: medsafety@hpra.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOWTO STORE ZOLEDRONIC ACID SOLUTION FOR INFUSION

Your doctor, pharmacist or nurse knows how to store Zoledronic Acid Solution for Infusion 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 expiry date refers to the last day of that month.

The unopened bottle does not require any special storage conditions.

Diluted solutions may be stored for up to 24 hours in a refrigerator (2°C - 8°C).

6. CONTENTS OFTHE PACK AND OTHER INFORMATION

What Zoledronic Acid Solution for Infusion contains

•    The active substance of Zoledronic Acid Solution for Infusion is zoledronic acid. One bottle contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.

•    The other ingredients are: mannitol (E421), sodium citrate and water for injections.

What Zoledronic Acid Solution for Infusion looks like and contents of the pack

Zoledronic Acid Solution for Infusion is a clear, colourless solution; free from visible foreign matter. It is supplied in a clear plastic bottle containing 100 ml of solution. Each pack contains one bottle.

Marketing Authorisation Holder

Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF,UK.

Manufacturer

CP Pharmaceuticals Ltd, Ash Road North, Wrexham, LL13 9UF, UK.

This leaflet was last revised in 03/2015.

Other sources of information:

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK Only). Please be ready to give the following information:

Product name	UK Reference number
Zoledronic Acid 4mg/100ml Solution for Infusion	PL 29831/0536

This is a service provided by the Royal National Institute of Blind People.

For the Republic of Ireland please call UK+44 1978 669272.

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*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.

•    Chemical and physical in-use stability has been demonstrated for 48 hours at 2°C- 8°C when diluted to a concentration of 3mg/100ml with 0.9% w/v sodium chloride or 5%w/v glucose.

From a microbiological point of view, the diluted product 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 to 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.

•    Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zoledronic Acid Solution for Infusion.

intravenously administered substances, Zoledronic Acid Solution for Infusion must not be mixed with other medications/substances and should always be given through a separate infusion line.

How to store Zoledronic Acid

Solution for Infusion

•    Keep Zoledronic Acid Solution for Infusion out of the sight and reach of children.

•    Do not use Zoledronic Acid Solution for Infusion 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.

Marketing Authorisation Holder

Wockhardt UK Ltd

Ash Road North, Wrexham,

LL13 9UF, UK.

Marketing Authorisation Number

PL 29831/0536

PA 1339/32/2

Date of Revision of Text:

March 2015

220597^M %/OCKHARDT

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   Since no data are available on the compatibility of Zoledronic Acid Solution for Infusion with other