Zoledronic acid Mylan

Package leaflet: Information for the user

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

Zoledronic acid
Please 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 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.

Contents of this leaflet:

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

1. What Acido zoledronico Mylan is and what it is used for

The active substance of Acido zoledronico Mylan is zoledronic acid, which belongs to a group of
substances called bisphosphonates. Zoledronic acid works by binding to bone and slowing down its
rate of metabolism. It is used:

• To prevent bone complications, such as fractures, in adult patients with bone metastases (spread of the tumour from the primary tumour site to the bones).
• To reduce the amount of calcium in the blood in adult patients in whom it is too high due to the presence of a tumour. Tumours can accelerate normal bone metabolism, resulting in increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you should know before being given Zoledronic Acid Mylan

Carefully follow all instructions given to you by your doctor.
Before starting treatment with Zoledronic Acid Mylan, your doctor will perform blood tests and will monitor your response to treatment at regular intervals.

Zoledronic Acid Mylan must not be given to you:

• if you are breastfeeding.
• if you are allergic to zoledronic acid, to any other bisphosphonate (the group of substances to which Zoledronic Acid Mylan belongs), or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before being given Zoledronic Acid Mylan:

• if you have or have had kidney problems.
• if you have or have had pain, swelling or numbness in the jaw/mandible or a sensation of heaviness in the jaw/mandible, or tooth loss. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Mylan.
• if you are currently undergoing dental treatments or need to undergo dental surgery, inform your dentist that you are being treated with Zoledronic Acid Mylan, and inform your doctor about your dental treatments.

During treatment with Zoledronic Acid Mylan, you must maintain good oral hygiene (including regular tooth cleaning) and undergo routine dental check-ups.
Immediately inform your doctor and dentist if you experience any problems in the mouth or with your teeth, such as tooth loss, pain, swelling, failure of wounds to heal, or discharge, as these may be signs of a condition called osteonecrosis of the jaw/mandible.
Patients receiving chemotherapy and/or radiotherapy, those taking steroids, those undergoing dental surgery, those not receiving routine dental care, those with gum disease, smokers, or those previously treated with bisphosphonates (used to treat or prevent bone disorders) have a higher risk of developing osteonecrosis of the jaw/mandible.
In patients treated with Zoledronic Acid Mylan, reduced levels of calcium in the blood (hypocalcaemia) have been reported, which may sometimes cause muscle cramps, dry skin, or a burning sensation. Cases of irregular heartbeat (cardiac arrhythmia), seizures, and muscle spasms or contractions (tetany) secondary to severe hypocalcaemia have also been reported. In some cases, hypocalcaemia may be life-threatening. If any of these conditions apply to you, inform your doctor immediately.
If you have pre-existing hypocalcaemia, it must be corrected before starting the first dose of zoledronic acid. You will be given adequate supplementation of calcium and vitamin D.

Patients aged 65 years and older
Zoledronic Acid Mylan can be administered to individuals aged 65 years and older. There is no evidence that additional precautions are required.

Children and adolescents
Zoledronic Acid Mylan is not recommended for use in adolescents and children under 18 years of age.

Other medicines and Zoledronic Acid Mylan
Inform your doctor if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious infections), calcitonin (a type of medicine used to treat postmenopausal osteoporosis and hypercalcaemia), loop diuretics (a type of medicine used to treat high blood pressure or oedema), or other medicines that lower calcium levels, as combining these with bisphosphonates may cause a significant decrease in blood calcium concentration.
• Thalidomide (a medicine used to treat certain types of blood cancers involving bones) or any other medicine that may be harmful to the kidneys.
• Other medicines containing zoledronic acid used for the treatment of osteoporosis and other non-oncological bone disorders, or any other bisphosphonate, since the combined effects of these medicines when taken together with Zoledronic Acid Mylan are unknown.
• Anti-angiogenic medicines (used to treat cancer), as their combination with Zoledronic Acid Mylan has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
Zoledronic Acid Mylan must not be given to you if you are pregnant. Inform your doctor if you are pregnant or suspect you may be pregnant.
Zoledronic Acid Mylan must not be given to you if you are breastfeeding.
Ask your doctor for advice before taking any medicine if you are pregnant or breastfeeding.

Driving and use of machines
Drowsiness and numbness have very rarely been reported with the use of zoledronic acid. Therefore, you should exercise maximum caution when driving, operating machinery, or performing other activities requiring full attention.

Zoledronic Acid Mylan contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is essentially “sodium-free”.

3. How Acido Zoledronico Mylan is used

• Acido zoledronico Mylan must be administered only by healthcare personnel trained in the use of intravenous bisphosphonates, i.e. through a vein.
• Your doctor will recommend that you drink sufficient water before each treatment to help prevent dehydration.
• Carefully follow all other instructions given by your doctor, pharmacist, or nurse.

How much Acido Zoledronico Mylan is administered

• The usual single dose is 4 mg of zoledronic acid.
• If you have kidney problems, your doctor will administer a reduced dose based on the severity of your renal impairment.

How often Acido Zoledronico Mylan is administered

• If you are being treated to prevent bone complications caused by bone metastases, you will receive an infusion of Acido Zoledronico Mylan every three to four weeks.
• If you are being treated to reduce the amount of calcium in your blood, you will normally receive a single infusion of Acido Zoledronico Mylan.

How Acido Zoledronico Mylan is administered

• Acido Zoledronico Mylan is administered intravenously as an infusion lasting at least 15 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients with not excessively high blood calcium levels may also be prescribed daily calcium and vitamin D supplements.
If you have been given more Acido Zoledronico Mylan than you should have
If you have received doses higher than those recommended, you must be closely monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphate, and magnesium) and/or changes in renal function, including severe kidney impairment. If your calcium levels drop too low, you may need to receive intravenous calcium supplementation.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. The most common ones are usually mild and may disappear after a short time.
Contact your doctor immediately if you experience any of the following side effects:
Common (may affect up to 1 in 10 people):

• Severe kidney failure (this will be diagnosed by your doctor through specific blood tests).
• Low levels of calcium in the blood.

Uncommon (may affect up to 1 in 100 people):

• Pain in the mouth, teeth and/or jaw, swelling or failure of mouth or jaw wounds to heal, discharge, numbness or heaviness in the jaw, or tooth loss. These may be signs of jaw damage (osteonecrosis). If you experience such symptoms during or after stopping treatment with zoledronic acid Mylan, inform your doctor and dentist immediately.
• In patients treated with zoledronic acid for postmenopausal osteoporosis, irregular heartbeat (atrial fibrillation) has been observed. It is currently unknown whether zoledronic acid causes this irregular heart rhythm, but you must report any such symptoms to your doctor after receiving zoledronic acid.
• Severe allergic reactions: difficulty breathing, swelling, especially of the face and throat.

Rare (may affect up to 1 in 1,000 people):

• As a consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia secondary to hypocalcemia).
• A kidney disorder known as Fanconi syndrome (usually diagnosed by your doctor through urine tests).

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

• As a consequence of low calcium levels: seizures, numbness, and tetany (secondary to hypocalcemia).
• Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These episodes could be signs of bone damage in the ear.
• Osteonecrosis has very rarely occurred in other bones besides the jaw, particularly in the hip or thigh. If you experience new or worsening pain, or stiffness during or after stopping treatment with zoledronic acid Mylan, inform your doctor immediately.

Contact your doctor as soon as possible if any of the following side effects occur:
Very common (may affect more than 1 in 10 people):

• Low levels of phosphate in the blood.

Common (may affect up to 1 in 10 people):

• Headache and a flu-like syndrome with fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is needed and symptoms disappear after a short time (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Low levels of red blood cells in the blood (anaemia).

Uncommon (may affect up to 1 in 100 people):

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Infusion site reactions (redness and swelling), rash, itching.
• High blood pressure, shortness of breath, dizziness, anxiety, sleep disturbances, taste disturbances, tremor, tingling or numbness in hands or feet, diarrhoea, constipation, abdominal pain, dry mouth.
• Low levels of white blood cells and platelets in the blood.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor these and take necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, eye lesions, light sensitivity.
• Sudden chills with fainting, weakness or collapse.
• Breathing difficulties with wheezing or cough.
• Hives.

Rare (may affect up to 1 in 1,000 people):

• Slow heart rate.
• Confusion.
• Rarely, an unusual femur fracture may occur, particularly in patients receiving long-term treatment for osteoporosis. Contact your doctor if you experience pain, weakness or discomfort in the thigh, hip, or groin, as this may be an early sign of a possible femur fracture.
• Interstitial lung disease (inflammation of lung tissue).
• Flu-like symptoms including arthritis and joint swelling.
• Painful redness and/or swelling of the eyes.

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 disabling.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoledronic acid Mylan

Your doctor, pharmacist, or nurse knows how to store Zoledronic acid Mylan appropriately.

6. Package Contents and Other Information

What Acido zoledronico Mylan Contains

• The active substance in Acido zoledronico Mylan is zoledronic acid. One vial contains 4 mg of zoledronic acid (as monohydrate).
• The other components are: sodium citrate, sodium hydroxide, hydrochloric acid, and water for injections.

Description of the Appearance of Acido zoledronico Mylan and Contents of the Package
Acido zoledronico Mylan is a clear, colourless concentrate for solution for infusion. The concentrate is supplied in a colourless glass vial with a rubber stopper and an aluminium cap with a plastic tear-off seal.
One vial contains 5 ml of concentrate.
Acido Zoledronico Mylan is available in packs of 1, 4 or 10 vials, or as a multiple pack containing 4 packs, each with 1 vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mylan Pharmaceuticals Limited
Damastown Industrial Park,
Mulhuddart, Dublin 15,
DUBLIN
Ireland

Manufacturer
Hikma Farmacêutica S.A.
Estrada do Rio da Mó, nº 8, 8-A and 8-B
Fervença, Terrugem SNT, 2705-906
Portugal
VIATRIS SANTE
1 Rue de Turin,
69007 Lyon
France
STERISCIENCE Sp. z o.o.
ul. Daniszewska 10
03-230 Warsaw
Poland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Mylan bvba/sprl Mylan Healthcare UAB
Tél/Tel: + 32 (0)2 658 61 00 Tel: +370 5 205 1288

България Luxembourg/Luxemburg
Майлан ЕООД Mylan bvba/sprl
Teл.: + 359 2 44 55 400 Tél/Tel: + 32 (0)2 658 61 00
(Belgique/Belgien)

Česká republika Magyarország
Viatris CZ s.r.o. Mylan EPD Kft.
Tel: +420 222 004 400 Tel.: 36 1 465 2100

Danmark Malta
Viatris ApS V.J. Salomone Pharma Ltd
Tlf: + 45 28 11 69 32 Tel: + 356 21 22 01 74

Deutschland Nederland
Viatris Healthcare GmbH Mylan B.V
Tel: +49 800 0700 800 Tel: +31 (0)20 426 3300

Eesti Norge
BGP Products Switzerland GmbH Eesti filiaal Viatris AS
Tel: + 372 6363 052 Tlf: + 47 66 75 33 00

Ελλάδα Österreich
Generics Pharma Hellas ΕΠΕ Arcana Arzneimittel GmbH
Τηλ: +30 210 993 6410 Tel: +43 1 416 2418

España Polska
Viatris Pharmaceuticals, S.L.U Mylan Healthcare Sp. z.o.o
Tel: + 34 900 102 712 Tel.: +48 22 546 64 00

France Portugal
Viatris Santé Tél: +33 4 37 25 75 00 Mylan, Lda.
Tel: + 351 214 127 200

Hrvatska România
Viatris Hrvatska d.o.o. BGP Products SRL
Tel: +385 1 23 50 599 Tel: +40 372 579 000

Ireland Slovenija
Mylan Ireland Limited Viatris d.o.o.
Tel: +353 1 8711600 Tel: +386 1 23 63 180

Ísland Slovenská republika
Icepharma hf. Viatris Slovakia s.r.o
Sími: +354 540 8000 Tel: +421 2 32 199 100

Italia Suomi/Finland
Mylan Italia S.r.l. Viatris Oy
Tel: + 39 02 612 46921 Puh/Tel: +358 20 720 9555

Κύπρος Sverige
Varnavas Hadjipanayis Ltd Viatris AB
Τηλ: +357 2220 7700 Tel: + 46 (08) 630 19 00

Latvija United Kingdom (Northern Ireland)
Mylan Healthcare SIA Mylan IRE Healthcare Limited
Tel: +371 676 055 80 Tel: +353 18711600

Other Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals:
How to Prepare and Administer Acido zoledronico Mylan

• To prepare an infusion solution containing 4 mg of zoledronic acid, further dilute the concentrate (5 ml) with 100 ml of a calcium-free infusion solution or one free of other bivalent cations. If a reduced dose of Acido zoledronico Mylan is required, first withdraw the appropriate volume as described below, then further dilute it in 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution (w/v).

Acido zoledronico Mylan concentrate must not be mixed with solutions containing calcium or other bivalent cations, such as lactated Ringer's solution.

Instructions for preparing reduced doses of Acido zoledronico Mylan:
Withdraw the appropriate volume of concentrate as follows:

• 4.4 ml for the 3.5 mg dose

• 4.1 ml for the 3.3 mg dose

• 3.8 ml for the 3.0 mg dose

• For single use only. Any unused solution must be discarded. Only use clear, particle-free, colourless solution. Aseptic techniques must be followed during the preparation of the infusion.

• From a microbiological standpoint, the diluted infusion solution should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C. Refrigerated solution must be brought to room temperature before administration. Chemical and physical stability during use has been demonstrated for 48 hours between 2°C and 8°C and at 25°C after dilution in 100 ml of 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution (w/v) (minimum concentration: 3 mg/100 ml; maximum concentration: 4 mg/100 ml).

• The solution containing zoledronic acid must be administered as a single infusion lasting 15 minutes via a separate infusion line. The hydration status of patients must be assessed before and after administration of Acido zoledronico Mylan to ensure adequate hydration.

• Studies using polyolefin bags (pre-filled with 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution (w/v)) have shown no incompatibility with Acido zoledronico Mylan.

• Since data on the compatibility of Acido zoledronico Mylan with other substances administered intravenously are not available, Acido zoledronico Mylan must not be mixed with other medicinal products and/or substances and must always be administered through a separate infusion line.

How to Store Acido zoledronico Mylan

• Keep Acido zoledronico Mylan out of the sight and reach of children.
• Do not use Acido zoledronico Mylan after the expiry date stated on the vial and packaging following "Exp.".
• The unopened vial does not require any special storage conditions.
• The storage conditions for the diluted solution are described in the previous section "How to Prepare and Administer Acido zoledronico Mylan".