Zoledronic acid Hikma

Package leaflet: Information for the user

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

Zoledronic acid
Generic medicine
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, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

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

The active substance of Acido Zoledronico Hikma 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 tumour from the primary tumour site to the bones).
• To reduce the level of calcium in the blood in adult patients in whom it is too high due to the presence of cancer. 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 Hikma

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

Zoledronic Acid Hikma 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 Hikma 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 Hikma:

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

During treatment with Zoledronic Acid Hikma, you must maintain good oral hygiene (including regular tooth cleaning) and receive 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.
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.

Low levels of calcium in the blood (hypocalcaemia) have been reported in patients treated with Zoledronic Acid Hikma, 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 treated before the first dose of Zoledronic Acid Hikma is administered.
You will be given adequate supplementation of calcium and vitamin D.

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

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

Other medicines and Zoledronic Acid Hikma
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 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 marked decrease in blood calcium concentration.
• Thalidomide (a medicine used to treat certain types of blood cancers involving bone) or any other medicine that may be harmful to the kidneys.
• Aclasta (a medicine which also contains zoledronic acid and is used to treat osteoporosis and other non-oncological bone disorders), or any other bisphosphonate, since the combined effects of these medicines when taken together with Zoledronic Acid Hikma are unknown.
• Anti-angiogenic medicines (used to treat cancer), as their combination with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw.

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

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

3. How Acido Zoledronico Hikma is used

• Acido zoledronico Hikma must be administered only by healthcare personnel trained in the use of intravenous bisphosphonates, that is, 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 Hikma is administered

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

How often Acido zoledronico Hikma is administered

• If you are being treated to prevent bone complications due to bone metastases, you will receive an infusion of Acido zoledronico Hikma every three or four weeks.
• If you are being treated to reduce the level of calcium in your blood, you will normally receive a single infusion of Acido zoledronico Hikma.

How Acido zoledronico Hikma is administered

• Acido zoledronico Hikma 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 blood calcium levels not too high may also be prescribed daily calcium and vitamin D supplements.
If you have been given more Acido zoledronico Hikma than you should have
If doses higher than those recommended have been administered, 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 calcium levels drop too low, you may need to be given an intravenous calcium supplement.

4. Possible side effects

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

• Severe kidney impairment (this will be confirmed 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 healing of sores inside the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or tooth loss. These may be signs of damage to the jaw (osteonecrosis). If you experience any of these symptoms during or after stopping treatment with zoledronic acid Hikma, inform your doctor and dentist immediately.
• In patients being treated with zoledronic acid for postmenopausal osteoporosis, an irregular heart rhythm (atrial fibrillation) has been observed. It is currently unknown whether zoledronic acid causes this irregular heart rhythm, but you should 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 hypocalcaemia). 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 hypocalcaemia).
• Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These symptoms could be signs of bone damage in the ear.

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 symptoms such as fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required 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.

• Skin reactions (redness and swelling) at the infusion site, rash, itching.

• High blood pressure, shortness of breath, dizziness, anxiety, sleep disturbances, taste disturbances, tremor, tingling or numbness in the 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 coughing.

• 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 could be an early sign of a possible femur fracture.
• Interstitial lung disease (inflammation of the lung tissue).
• Influenza-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 effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoledronic Acid Hikma

Your doctor, pharmacist or nurse knows how to store Zoledronic Acid Hikma appropriately (see section 6).
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after the wording {EXP}. The expiry date refers to the last day of the month.

6. Package contents and other information

What Acido Zoledronico Hikma contains

• The active substance of Acido Zoledronico Hikma is zoledronic acid. One vial contains 4 mg of zoledronic acid, equivalent to 4.264 mg of zoledronic acid (monohydrate).
• The other ingredients are: mannitol, sodium citrate, water for injection.

Description of the appearance of Acido Zoledronico Hikma and package contents
Acido Zoledronico Hikma is supplied as a liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.
Each package contains the vial with the concentrate. Acido Zoledronico Hikma is available in packages containing 1, 4 or 10 vials. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó 8, 8A and 8B – Fervença
2705-906 Terrugem SNT, Portugal
Tel.: +351 219608410
Fax: +351 219615102
e-mail: [email protected]

This medicinal product is authorized in EEA Member States under the following names:
Austria: Zoledronsäure Hikma 4mg/5ml Konzentrat Zur Herstellung einer Infusionslösung
Germany: Ribometa 4mg/5ml Konzentrat zur Herstellung einer Infusionslösung
Italy: Acido Zoledronico Hikma 4mg/5ml
Portugal: Ácido Zoledrónico Hikma 4mg/5ml
Netherlands: Zoledroninezuur Hikma 4mg/5ml

The following information is intended exclusively for physicians or healthcare professionals:
Acido zoledronico Hikma 4 mg/5 ml concentrate for solution for infusion
Zoledronic acid

How to prepare and administer Acido Zoledronico Hikma

• To prepare an infusion solution containing 4 mg of Acido Zoledronico Hikma, further dilute Acido Zoledronico Hikma concentrate (5.0 ml) with 100 ml of an infusion solution free of calcium or other bivalent cations. If a reduced dose of Acido Zoledronico Hikma is required, first withdraw the appropriate volume as described 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% w/v sodium chloride solution or 5% w/v glucose solution.

Do not mix Acido Zoledronico Hikma concentrate with solutions containing calcium or other bivalent cations, such as lactated Ringer's solution.
Instructions for preparing reduced doses of Acido Zoledronico Hikma:
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 residue must be discarded. Only use a clear, particle-free, colorless 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 at 2°C–8°C. If refrigerated, the solution must be brought to room temperature before administration.

• The solution containing zoledronic acid must be administered as a single infusion lasting 15 minutes through a separate infusion line. The hydration status of patients must be assessed before and after administration of Acido Zoledronico Hikma to ensure they are adequately hydrated.

• Studies on different types of infusion lines made of polyvinyl chloride, polyethylene and polypropylene have shown no incompatibility with Acido Zoledronico.

• Since compatibility data with other substances administered intravenously are not available, Acido Zoledronico Hikma 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 Hikma

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