ACIDO 4 mg /5 Ml Koncentrat Do Roztworu Infuzyjnego

Treść ulotki

1. Zoledronic Acid Tillomed 4 mg/5 ml concentrate for solution for infusion
   1. What is Acido Zoledronico Tillomed and what is it used for
   2. What you need to know before using Acido Zoledronico Tillomed
   3. How Acido Zoledronico Tillomed is used
   4. Possible side effects
   5. How to store Acido Zoledronico Tillomed
   6. Package Contents and Other Information

Zoledronic Acid Tillomed 4 mg/5 ml concentrate for solution for infusion

Zoledronic acid

Equivalent medicine

Read this leaflet carefully before you are given this medicine as 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 Tillomed is and what it is used for
• 2. What you need to know before you are given Zoledronic Acid Tillomed
• 3. How to use Zoledronic Acid Tillomed
• 4. Possible side effects
• 5. How to store Zoledronic Acid Tillomed
• 6. Contents of the pack and other information

1. What is Acido Zoledronico Tillomed and what is it used for

The active substance is zoledronic acid, belonging to a group of substances called bisphosphonates.
Zoledronic acid works by binding to the 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 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 using Acido Zoledronico Tillomed

Follow all the instructions carefully that have been given to you by your doctor.
Before starting treatment with Acido Zoledronico Tillomed, your doctor will perform blood tests and check your response to treatment at regular intervals.

Acido Zoledronico Tillomed must not be administered to you:

• if you are breastfeeding.
• if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Acido Zoledronico Tillomed 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 Acido Zoledronico Tillomed:

• if you have or have had kidney problems.
• if you have or have had pain, swellingor numbnessin the jaw/lower jaw or a feeling of heaviness in the jaw or tooth loss. Your doctor may recommend that you have a dental examination before starting treatment with Acido Zoledronico Tillomed.
• if you are undergoing dental treatmentsor need to have dental surgery, tell your dentist that you are being treated with Acido Zoledronico Tillomed and inform your doctor about your dental treatments.

During treatment with Acido Zoledronico Tillomed, you must maintain good oral hygiene
(including regular teeth cleaning) and have regular 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 failure of sores to 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 do not receive routine dental care, who have gum disease,
who are smokers, or who have previously been treated with bisphosphonates (used to treat or
prevent bone diseases) are at higher risk of developing osteonecrosis of the
jaw/lower jaw.
Decreased levels of calcium in the blood (hypocalcemia) have been reported in patients treated with Acido Zoledronico Tillomed, which can sometimes cause muscle cramps, dry skin,
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, inform
your doctor immediately. If a pre-existing condition of hypocalcemia is present, it must be treated
before starting the first dose of Acido Zoledronico Tillomed. You will be given adequate
calcium and vitamin D supplementation.

Patients aged 65 years and over
Acido Zoledronico Tillomed can be administered to people aged 65 years and over.
There is no evidence that additional precautions are necessary.

Children and adolescents
The use of Acido Zoledronico Tillomed is not recommended in adolescents and children under the age of 18 years.

Other medicines and Acido Zoledronico Tillomed
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 postmenopausal 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 high 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.
• Also other medicines that contain zoledronic acid and are used for the treatment of osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, given that the combined effects of these medicines when taken together with Acido Zoledronico Tillomed are not known.
• Anti-angiogenic medicines (used to treat cancer), as the combination of these with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw/lower jaw.

Pregnancy and breastfeeding
If you are pregnant, you must not be given Acido Zoledronico Tillomed. If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your
doctor for advice before being given this medicine.

Driving and using machines
Very rarely, drowsiness and dizziness have been reported with the use of Acido Zoledronico Tillomed.
You should therefore be careful when driving, using machines or performing other
activities that require full attention.

Acido Zoledronico Tillomed 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 Tillomed is used

• Acido Zoledronico Tillomed must only be administered by healthcare professionals experienced 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 Tillomed is administered

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

How often Acido Zoledronico Tillomed will be administered

• If you are being treated for the prevention of bone complications caused by bone metastases, you will be given an infusion of Acido Zoledronico Tillomed 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 Tillomed.

How Acido Zoledronico Tillomed is administered

• Acido Zoledronico Tillomed is administered into a vein 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 too 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 Tillomed
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 abnormalities in serum electrolytes (e.g.
abnormal levels of calcium, phosphorus and magnesium) and/or alterations in kidney function, including
severe kidney impairment. If calcium levels drop too low, you may need to
be given a calcium supplement by infusion.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most common ones are usually mild and disappear after a short time.

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

• Severe kidney damage (this will usually be detected 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/mandible, swelling or non-healing sores inside the mouth or jaw/mandible, 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 Tillomed Zoledronic Acid, inform your doctor and dentist immediately.
• An irregular heartbeat (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. It is currently unknown whether zoledronic acid causes this irregular heartbeat, but you should report it to your doctor if you experience these 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).

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).
• Tell your doctor if you experience ear pain, ear discharge, and/or an ear infection. These could be signs of damage to the ear bone.
• Osteonecrosis has very rarely occurred 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 zoledronic acid, inform your doctor immediately.

Tell 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 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.
• Reactions at the infusion site (redness and swelling), skin rash, itching.
• High blood pressure, shortness of breath, dizziness, anxiety, sleep disturbances, 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. Your doctor will monitor them and take necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, eye injuries, sensitivity to light.
• Sudden 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 femur fracture can occur, particularly in patients treated for osteoporosis for a long time. Contact your doctor if you experience pain, weakness or discomfort in the thigh, hip or groin, as this could be an early indication of a possible femur fracture.
• Interstitial lung disease (inflammation of the tissue around the air sacs in the lungs).
• 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 side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system at www.agenziafarmaco.gov.it/content/come-
segnalare-una-sospetta-reazione-avversa .
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Acido Zoledronico Tillomed

The doctor, pharmacist and nurse know how to store Acido zoledronico Tillomed
adequately (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 pack/vial after EXP.
The expiry date refers to the last day of that month.
After dilution: Chemical and physical stability during use has been demonstrated for 24 hours at 2-8°C and at
room temperature (20-25°C).
From a microbiological point of view, the diluted solution for infusion must be used
immediately. If not used immediately, the in-use storage times and conditions of
storage before use are the responsibility of the user and generally should not
exceed 24 hours at 2° C – 8° C. The solution stored in the refrigerator must then be brought back to
room temperature before administration.

6. Package Contents and Other Information

What Acido Zoledronico Tillomed Contains

• The active ingredient is zoledronic acid. One vial contains 4 mg of zoledronic acid, equivalent to 4.264 mg of zoledronic acid monohydrate. One ml of concentrate contains 0.8 mg of zoledronic acid as monohydrate to 0.8 mg of zoledronic acid (anhydrous).
• The other ingredients are: mannitol (E421), sodium citrate (E331) and water for injections.

Description of the Appearance of Acido Zoledronico Tillomed and Package Contents
Acido zoledronico Tillomed is supplied as a liquid concentrate in a vial. One vial
contains 4 mg of zoledronic acid.
Each pack contains the vial with the concentrate. Acido zoledronico Tillomed is
supplied in packs containing 1, 4 or 10 vials. Not all pack sizes may be
marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
TILLOMED ITALIA S.r.l. Viale G. Richard, 1-A, 20143 Milano, Italy (IT).

Manufacturer
Emcure Pharma UK Ltd
Basepoint Business Centre
110 Butterfield, Great Marlings
Luton
LU2 8DL
United Kingdom
Tillomed Pharma GmbH
Manhagener Allee 36
22926, Ahrensburg
Germany

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
United Kingdom Zoledronic acid 4 mg/5 ml concentrate for solution for infusion
Germany Zoledronsäure Tillomed 4 mg/5 ml Konzentrat zur Herstellung einer
Infusionslösung
Spain Ácido zoledrónico Tillomed 4 mg/5 ml concentrado para solución para
perfusión EFG
Italy Acido Zoledronico Tillomed
France Acide zoledronique Tillomed 4 mg/5 ml, solution à diluer pour perfusion

INFORMATION FOR HEALTHCARE PROFESSIONALS
The following information is intended exclusively for doctors or healthcare professionals (see section
3):

How to Prepare and Administer Acido Zoledronico Tillomed

• To prepare an infusion solution containing 4 mg of zoledronic acid, further dilute Acido Zoledronico Tillomed concentrate (5 ml) with 100 ml of infusion solution free from calcium or other divalent cations. If a reduced dose of Acido Zoledronico Tillomed is required, initially withdraw the appropriate volume as indicated below and then further dilute it in 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be 0.9% p/v sodium chloride solution or 5% p/v glucose solution.

The reconstituted solution of Acido Zoledronico Tillomed must not be mixed with solutions
containing calcium or other divalent cations such as Ringer's lactate solution.
Instructions for preparing Acido Zoledronico Tillomed at reduced dosages:
Withdraw the appropriate volume of the liquid 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 must be used. Aseptic techniques must be followed during the preparation of the infusion.
• After dilution: Chemical and physical stability during use has been demonstrated for 24 hours at 2-8°C and at room temperature (20-25°C).
• From a microbiological point of view, the diluted infusion solution must be used immediately. If not used immediately, the storage times in use and the conditions of storage before use are the responsibility of the user and should generally not exceed 24 hours at 2° C - 8° C. The solution stored in the refrigerator must then be brought back to room temperature before administration.
• 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 the administration of Acido Zoledronico Tillomed to ensure they are adequately hydrated.
• Since no data are available on the compatibility of Acido Zoledronico Tillomed with other substances administered intravenously, Acido Zoledronico Tillomed must not be mixed with other medicinal products and/or substances and must always be administered via a separate infusion line.

How to Store Acido Zoledronico Tillomed

• Keep Acido Zoledronico Tillomed out of the reach and sight of children.
• Do not use Acido Zoledronico Tillomed after the expiry date which is stated on the packaging.
• The unopened vial does not require any special storage conditions.
• The diluted infusion solution of Acido Zoledronico Tillomed must be used immediately to avoid microbiological contamination.