ACIDO 4 mg /5 Ml Concentrate For Infusion Solution

Зміст інструкції

1. Zoledronic acid Mylan 4 mg/5 ml concentrate for solution for infusion
   1. What is Acido zoledronico Mylan and what is it used for
   2. What you need to know before you are given Zoledronic acid Mylan
   3. How Acido Zoledronico Mylan is used
   4. Possible side effects
   5. How to store Acido zoledronico Mylan
   6. Contents of the pack and other information

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

Zoledronic acid

Read 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, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. 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 you are given Zoledronic acid Mylan
• 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 is Acido zoledronico Mylan and what is it used for

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

• To prevent bone complications,such as fractures, in adult patients with bone metastases (spread of cancer from the primary tumor site to the bones).
• To reduce the amount of calciumin the blood in adult patients in whom it is too high following the presence of a tumor. Tumors can accelerate normal bone metabolism in such a way that the release of calcium from the bone is increased. This condition is known as neoplastic hypercalcemia (TIH).

2. What you need to know before you are given Zoledronic acid Mylan

Follow all instructions given to you by your doctor carefully.
Before starting treatment with Zoledronic acid Mylan, your doctor will perform blood tests and check 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, another bisphosphonate (the group of substances to which Zoledronic acid Mylan 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 Mylan:

• if you have or have had kidney problems.
• if you have or have had pain, swelling or numbnessof the jaw/lower jaw or a feeling of heaviness in the jaw/lower jaw or tooth loss. Your doctor may recommend that you have a dental examination before starting treatment with Zoledronic acid Mylan.
• if you are undergoing dental treatmentsor are going to have dental surgery, tell your dentist that you are being treated with Zoledronic acid Mylan and tell your doctor about your dental treatments.

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

Patients aged 65 years and over
Zoledronic acid Mylan can be given to people aged 65 years and over. No
evidence suggests that additional precautions are necessary.

Children and adolescents
Zoledronic acid Mylan is not recommended for use in adolescents and children under the age of
18 years.
Other medicines and Zoledronic acid Mylan
Tell your doctor if you are taking, have recently taken or might take any other
medicines. It is particularly important that you tell your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious infections), calcitonin (a type of medicine used to treat post-menopausal osteoporosis and hypercalcemia), loop diuretics (a type of medicine used to treat high blood pressure or edema) or other medicines that lower calcium levels, as the combination of these substances with bisphosphonates may cause a significant decrease in blood calcium concentration.
• Thalidomide (a medicine used to treat some types of blood cancers involving the bones) or any other medicine that may be harmful to the kidneys.
• Other medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines when taken together with Zoledronic acid Mylan are not known.
• Anti-angiogenic medicines (used to treat cancer), as the combination of these with Zoledronic acid Mylan has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
If you are pregnant, you must not be given Zoledronic acid Mylan. Tell your doctor if you are
pregnant or suspect you may be pregnant.
If you are breastfeeding, you must not be given Zoledronic acid Mylan.
Ask your doctor for advice before taking any medicine during pregnancy or if you are
breastfeeding.

Driving and operating machinery
Very rarely, drowsiness and lethargy have been reported with the use of zoledronic acid. You should therefore
be very careful when driving, operating machinery or performing other
activities that require 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 professionals trained in the use of bisphosphonates via the intravenous route, i.e., through a vein.
• The doctor will recommend that you drink sufficient water before each treatment to help prevent dehydration.
• Carefully follow all other instructions given by the 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, the doctor will administer a reduced dose based on the severity of the kidney problem.

How often is Acido Zoledronico Mylan administered

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

How is Acido Zoledronico Mylan administered

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

Patients with not very high blood calcium levels will also be prescribed
calcium and vitamin D supplements, to be taken daily.

If you have been given too much Acido Zoledronico Mylan
If you have been given doses higher than those recommended, you must be monitored with
particular attention by the doctor. This is because you may develop electrolyte abnormalities (e.g.
abnormal levels of calcium, phosphorus and magnesium) and/or changes in kidney function, including
severe kidney impairment. If calcium levels drop too low, you may need to
be given calcium supplementation by infusion.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most common are usually mild and, probably, will disappear in a short time.

Tell your doctor immediately if any of these side effects should occur:
Common(may affect up to 1 in 10 people):

• Severe kidney failure (will be ascertained by the 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/mandible, swelling or failure of sores inside the mouth or jaw/mandible to heal, secretion, numbness or feeling of heaviness in the jaw/mandible or tooth loss. These may be signs of damage to the jaw/mandible (osteonecrosis). If you experience these symptoms during or after stopping treatment with Acido zoledronico Mylan, tell your doctor and dentist immediately.
• In patients treated with zoledronic acid for postmenopausal osteoporosis, an irregular heartbeat (atrial fibrillation) has been observed. It is currently unknown whether zoledronic acid causes this irregular heartbeat, but you should report to your doctor if you have such symptoms after being given zoledronic acid.
• Severe allergic reactions: shortness of breath, 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 disorder of kidney function called Fanconi syndrome (will normally be established by the doctor with some urine tests).

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

• As a consequence of low calcium levels: convulsions, numbness and tetany (secondary to hypocalcemia).
• Contact your doctor if you experience ear pain, ear discharge and/or ear infection. These episodes may be signs of bone damage to the ear.
• Osteonecrosis has occurred very rarely in other bones besides the jaw/mandible, in particular in the hip or thigh. If you experience symptoms such as the onset or worsening of pain, pain or stiffness during or after stopping treatment with Acido zoledronico Mylan, tell your doctor immediately.

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

• Low levels of phosphates 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 pain in the bones, joints and/or muscles. In most cases, no specific treatment is necessary and the 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 (anemia).

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 disorders, taste disturbances, tremor, tingling or numbness in the hands or feet, diarrhea, 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. The doctor will monitor them and take necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, eye injury, sensitivity to light.
• Sudden cold chills with fainting, weakness or collapse.
• Difficulty breathing with wheezing or coughing.
• Urticaria.

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

• Slow heartbeat.
• Confusion.
• Rarely, an unusual fracture of the femur may occur, particularly in patients treated for a long time for osteoporosis. Contact your doctor if you experience pain, weakness or discomfort in the thigh, hip or groin, as this may be an early indication of a possible femur fracture.
• Interstitial lung disease (inflammation of the 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 pain in the bones, joints and/or muscles, occasionally disabling.

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 through 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 Acido zoledronico Mylan

The doctor, pharmacist or nurse knows how to store Acido zoledronico Mylan appropriately.

6. Contents of the pack and other information

What Acido zoledronico Mylan contains

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

Description of the appearance of Acido zoledronico Mylan and contents of the pack
Acido zoledronico Mylan is a clear and colourless concentrate for solution for infusion. The
concentrate is supplied in a colourless glass vial with a rubber stopper and a plastic tear-off cap.
One vial contains 5 ml of concentrate.
Acido Zoledronico Mylan is supplied in packs of 1, 4 or 10 vials or as a multiple pack containing 4 packs, each containing 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 e 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 on this medicinal product, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Mylan bvba/sprl

Lietuva
Mylan Healthcare UAB
Tel: +370 5 205 1288

България
Майлан ЕООД
Тел.: + 359 2 44 55 400

Luxembourg/Luxemburg
Mylan bvba/sprl
Tél/Tel: + 32 (0)2 658 61 00
(Belgique/Belgien)

Česká republika
Viatris CZ s.r.o.
Tel: +420 222 004 400

Magyarország
Mylan EPD Kft.
Tel.: 36 1 465 2100

Danmark
Viatris ApS
Tlf: + 45 28 11 69 32

Malta
V.J. Salomone Pharma Ltd
Tel: + 356 21 22 01 74

Deutschland
Viatris Healthcare GmbH
Tel: +49 800 0700 800

Nederland
Mylan B.V
Tel: +31 (0)20 426 3300

Eesti
BGP Products Switzerland GmbH Eesti filiaal
Tel: + 372 6363 052

Norge
Viatris AS
Tlf: + 47 66 75 33 00

Ελλάδα
Generics Pharma Hellas ΕΠΕ
Τηλ: +30 210 993 6410

Österreich
Arcana Arzneimittel GmbH
Tel: +43 1 416 2418

España
Viatris Pharmaceuticals, S.L.U
Tel: + 34 900 102 712

Polska
Mylan Healthcare Sp. z.o.o
Tel.: +48 22 546 64 00

France
Viatris SantéTél: +33 4 37 25 75 00

Portugal
Mylan, Lda.
Tel: + 351 214 127 200

Hrvatska
Viatris Hrvatska d.o.o.
Tel: +385 1 23 50 599

România
BGP Products SRL
Tel: +40 372 579 000

Ireland
Mylan Ireland Limited
Tel: +353 1 8711600

Slovenija
Viatris d.o.o.
Tel: +386 1 23 63 180

Ísland
Icepharma hf.
Sími: +354 540 8000

Slovenská republika
Viatris Slovakia s.r.o
Tel: +421 2 32 199 100

Italia
Mylan Italia S.r.l.
Tel: + 39 02 612 46921

Suomi/Finland
Viatris Oy
Puh/Tel: +358 20 720 9555

Κύπρος
Varnavas Hadjipanayis Ltd
Τηλ: +357 2220 7700

Sverige
Viatris AB
Tel: + 46 (08) 630 19 00

Latvija
Mylan Healthcare SIA
Tel: +371 676 055 80

United Kingdom (Northern Ireland)
Mylan IRE Healthcare Limited
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 a solution for infusion containing 4 mg of zoledronic acid, further dilute the concentrate (5 ml) with 100 ml of calcium-free or other bivalent cation-free infusion solution. If a reduced dose of Acido zoledronico Mylan is required, first draw up the appropriate volume as follows and then further dilute in 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be sodium chloride 9 mg/ml (0.9%) solution for injection or 5% w/v glucose solution.

Acido zoledronico Mylan concentrate must not be mixed with solutions containing calcium or
other bivalent cations such as Ringer's lactate solution.
Instructions for preparing Acido zoledronico Mylan at reduced doses:
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 clear, particle-free and colourless solution should be used. Aseptic techniques must be followed during the preparation of the infusion.
• From a microbiological point of view, the diluted infusion solution must be used immediately. If not used immediately, the storage times during use and the conditions prior to use are the responsibility of the user and should not normally exceed 24 hours at 2°C-8°C. The refrigerated solution must be brought to room temperature before administration. Chemical and physical stability has been demonstrated for 48 hours at 2  C-8  C and at 25  C after dilution in 100 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or with a 5% w/v glucose solution (minimum concentration: 3 mg/100 ml; maximum concentration: 4 mg/100 ml).
• The solution containing zoledronic acid must be administered as a single infusion over a period of 15 minutes in a separate infusion line. The hydration status of patients must be assessed before and after the administration of Acido zoledronico Mylan to ensure that they are adequately hydrated.
• Studies with polyolefin bags (pre-filled with sodium chloride 9 mg/ml (0.9%) injection solution or with a 5% w/v glucose solution) have not shown incompatibility with Acido zoledronico Mylan.
• Since there are no data on the compatibility of Acido zoledronico Mylan with other substances administered intravenously, 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 which is stated on the vial and the pack after Scad..
• The unopened vial does not require any special storage conditions.
• The storage conditions of the diluted solution are described in the
• previous paragraph “How to prepare and administer Acido zoledronico Mylan”.