Zendractin 4mg/100ml, oplossing voor infusie

The active substance in Zendractin 4mg/100ml, oplossing voor infusie 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).

Follow carefully all instructions given to you by your doctor.

Your doctor will carry out blood tests before you start treatment with Zendractin 4mg/100ml, oplossing voor infusie and will check your response to treatment at regular intervals.

You should not be given Zendractin 4mg/100ml, oplossing voor infusie:

• if you are breast-feeding.
• if you are allergic (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which Zendractin 4mg/100ml, oplossing voor infusie belongs), or any of the other ingredients of this medicine (listed in section 6)

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Zendractin 4mg/100ml, oplossing voor infusie:

• 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 are being treated with Zendractin 4mg/100ml, oplossing voor infusie.

Patients aged 65 years and over

Zendractin 4mg/100ml, oplossing voor infusie 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

Zendractin 4mg/100ml, oplossing voor infusie is not recommended for use in adolescents and children below the age of 18 years.

Other medicines and Zendractin 4mg/100ml, oplossing voor infusie

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), 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 medicines that also contain zoledronic acid, or any other bisphosphonate, since the combined effects of these medicines taken together with Zendractin 4mg/100ml, oplossing voor infusie are unknown.
• Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zendractin 4mg/100ml, oplossing voor infusie has been associated with reports of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

You should not be given Zendractin 4mg/100ml, oplossing voor infusie if you are pregnant. Tell your doctor if you are or think that you may be pregnant.

You must not be given Zendractin 4mg/100ml, oplossing voor infusie if you are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking any medicine

Driving and using machines

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

Zendractin 4mg/100ml, oplossing voor infusie contains sodium citrate

This medicinal product contains less than 1 mmol sodium (23 mg) per dose (100ml), i.e. essentially ‘sodium-free’.

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

− Zendractin 4mg/100ml, oplossing voor infusie 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 Zendractin 4mg/100ml, oplossing voor infusie 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 Zendractin 4mg/100ml, oplossing voor infusie is given

• If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zendractin 4mg/100ml, oplossing voor infusie 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 Zendractin 4mg/100ml, oplossing voor infusie.

How Zendractin 4mg/100ml, oplossing voor infusie is given

• Zendractin 4mg/100ml, oplossing voor infusie 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 Zendractin 4mg/100ml, oplossing voor infusie 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.

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 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.

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 more 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 more 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, sleep disturbances, tingling or numbness of the hands or feet, diarrhoea.
• 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.
• Sleepiness.

• 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 more up to 1 in 1,000 people):

• Slow heartbeat.
• 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).

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

• Fainting due to low blood pressure.
• Severe bone, joint and/or muscle pain, occasionally incapacitating.
• Painful redness and/or swelling of the eye.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet.

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

Nederlands Bijwerkingen Centrum Lareb

Website: www.lareb.nl

Your doctor, pharmacist or nurse knows how to store Zendractin 4mg/100ml, oplossing voor infusie properly (see section 6).

• 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 vial after EXP. The expiry date refers to the last day of that month.
• The unopened vial does not require any special storage conditions.
• After first opening: Chemical and physical stability has been demonstrated for 24 hours at 2°C - 8°C and at 25°C. From a microbiological point of view, the 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.

• Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Zendractin 4mg/100ml, oplossing voor infusie contains

• The active substance is zoledronic acid. One vial contains 4 mg zoledronic acid, corresponding to 4.26 mg zoledronic acid monohydrate.
• The other ingredients are: mannitol (E421) sodium citrate (E331) water for injections.

What Zendractin 4mg/100ml, oplossing voor infusie contains looks like and the contents of the pack

Zendractin 4mg/100ml, oplossing voor infusie solution for infusion is a clear, colourless solution, free from visible particles.

Zendractin 4mg/100ml, oplossing voor infusie is supplied as a solution in a vial. One vial contains 4 mg of zoledronic acid.

Zendractin 4mg/100ml, oplossing voor infusie is supplied as packs containing: 1 vial

1. vials
2. vials

Not all pack sizes may be marketed.

Marketing Authorisation Holder

PharmaSwiss Česká republika

Praag 7, Holesovice, Jankovcova 1569/2c, PSC 17000

Tsjechische Republiek

Manufacturer

Agila Specialties Polska Sp. Zo.o.

10, Daniszewska Str., 03-230 Warschau

Polen

Sanochemia Pharmazeutica AG

Landeggerstrasse 7, A - 2491 Neufeld an der Leitha

Oostenrijk

Marketing authorization number

RVG 112512

This medicines product is authorised in the Member States of the EEA under the following names:

NL: Zendractin 4mg/100ml, oplossing voor infusie

CZ: ZENDRACTIN 4mg/100ml Infuzní roztok

EE: ZENDRACTIN

HU: ZENDRACTIN 4mg/100ml Oldatos infúzió

LT: ZENDRACTIN 4mg/100ml Infuzinis tirpalas

LV: ZENDRACTIN 4mg/100ml šķīdums infūzijām

PL: ZENDRACTIN

RO: ZENDRACTIN 4mg/100ml Soluţie perfuzabilă

SK: ZENDRACTIN 4mg/100ml

Deze bijsluiter is voor het laatst goedgekeurd in augustus 2013.

--------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

How to prepare and administer Zendractin 4mg/100ml, oplossing voor infusie

• Zendractin 4mg/100ml, oplossing voor infusie contains 4 mg of zoledronic acid in 100 ml of infusion 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.
• 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 be equilibrated to room temperature prior to administration.
• 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 Zendractin 4mg/100ml, oplossing voor infusie to ensure that they are adequately hydrated.
• Zendractin 4mg/100ml, oplossing voor infusie 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 Zendractin 4mg/100ml, oplossing voor infusie solution indicated from the vial and replace with an equal volume of sterile sodium chloride 9 mg/ml (0,9%) solution for injection, or 5% glucose solution for injection.

Table 1: Preparation of reduced doses of Zendractin 4mg/100ml, oplossing voor infusie

Baseline	Remove the	Replace with	Adjusted
creatinine	following	the	dose (mg
clearance	amount of	following	zoledronic
(ml/min)	<Product	volume of	acid in
	name>	sterile	100 ml)
	solution for	sodium
	infusion	chloride 9
	(ml)	mg/ml
		(0,9%) or 5%
		glucose
		solution for
		injection
		(ml)
50-60	12.0	12.0	3.5
40-49	18.0	18.0	3.3
30-39	25.0	25.0	3.0

*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.

• Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with zoledronic acid.
• Since no data are available on the compatibility of zoledronic acid with other intravenously administered substances, Zendractin 4mg/100ml, oplossing voor infusie must not be mixed with other medications/substances and should always be given through a separate infusion line.

How to store Zendractin 4mg/100ml, oplossing voor infusie

• Keep Zendractin 4mg/100ml, oplossing voor infusie out of the reach and sight of children.
• Do not use Zendractin 4mg/100ml, oplossing voor infusie after the expiry date stated on the pack.
• This medicinal product does not require any special storage conditions.
• The diluted Zendractin 4mg/100ml, oplossing voor infusie infusion solution should be used immediately in order to avoid microbial contamination.