The active substance in Zoledronic acid Actavis 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.
One vial contains 4 mg zoledronic acid (as monohydrate).
Excipients/Inactive Ingredients: mannitol, sodium citrate and water for injections.
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).
How much Zoledronic acid Actavis is given: The usual single dose given is 4 mg.
If the patient has a kidney problem, the doctor will give the patient a lower dose depending on the severity of the kidney problem.
How often Zoledronic acid Actavis is given: If the patient is being treated for the prevention of bone complications due to bone metastases, he/she will be given one infusion of Zoledronic acid Actavis every three to four weeks.
If the patient is being treated to reduce the amount of calcium in the blood, he/she will normally only be given one infusion of Zoledronic acid Actavis.
How Zoledronic acid Actavis is given: Zoledronic acid Actavis 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 the patient received doses higher than those recommended, the patient must be carefully monitored by the doctor. This is because the patient 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 the level of calcium falls too low, the patient may have to be given supplemental calcium by infusion.
If the patient is allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic acid Actavis belongs), or any of the other ingredients of this medicine (listed in Description).
If the patient is breast-feeding.
Zoledronic acid Actavis is contraindicated in patients with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment due to an increased risk of renal failure.
Before the patient is given Zoledronic acid Actavis, tell the doctor: If the patient has or had a kidney problem. Zoledronic acid is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction or other risk factors. Renal function should be measured before each infusion of zoledronic acid. The following precautions should be taken into account to minimise the risk of renal adverse reactions: Monitoring of renal function after zoledronic acid infusion should be considered, particularly in at-risk patients such as those with pre-existing renal dysfunction, those of advanced age, those using concomitant nephrotoxic drugs or diuretic therapy, or those who are dehydrated.
Zoledronic acid should be used with caution when used concomitantly with medicines that could affect renal function.
Patients, especially elderly patients and those receiving diuretic therapy, should be appropriately hydrated before administration of zoledronic acid.
The duration of infusion of zoledronic acid should be at least 15 minutes.
If the patient has or had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth.
If the patient is having dental treatment or are due to undergo dental surgery, tell the dentist that the patient is being treated with Zoledronic acid Actavis.
Zoledronic acid Actavis for cancer treatment is not recommended for use in patients with creatinine clearance <30 mL/min, and should only be considered for the treatment of hypercalcaemia in cancer patients with severe renal impairment after evaluating the risk and benefits of treatment.
In patients who show evidence of renal deterioration during the treatment period, Zoledronic acid Actavis should be withheld and only resumed when serum creatinine returns to within 10% of baseline.
Osteonecrosis of the jaw (ONJ): ONJ has been reported in the post-marketing setting in patients receiving Zoledronic Acid Actavis.
The start of treatment or of a new course of treatment should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with Zoledronic Acid Actavis in patients with concomitant risk factors.
The following should be considered when evaluating a patient's risk of developing ONJ: Potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and cumulative dose of bone resorption therapy.
Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking.
Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck.
Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures, e.g. tooth extractions.
All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, non-healing of sores or discharge during treatment with Zoledronic Acid Actavis. While on treatment, invasive dental procedures should be performed with caution and avoided in close proximity to Zoledronic Acid Actavis treatment.
The management plan for patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ Temporary interruption of Zoledronic Acid Actavis should be considered until the condition resolves and contributing risk factors are mitigated where possible.
Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.
Zoledronic acid Actavis contains sodium: This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially "sodium free".
Driving and using machines: There have been very rare cases of drowsiness and sleepiness with the use of zoledronic acid. The patient should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Use in Elderly: Patients aged 65 years and over Zoledronic acid Actavis can be given to people aged 65 years and over. There is no evidence to suggest that any extra precautions are needed.
Use in Children: Zoledronic acid Actavis is not recommended for use in adolescents and children below the age of 18 years.
The patient should not be given Zoledronic acid Actavis if pregnant. Tell the doctor if the patient is or thinks that she might be pregnant.
The patient must not be given Zoledronic acid Actavis if breast-feeding.
Ask the doctor for advice before taking any medicine while the patient is pregnant or breast-feeding.
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 the doctor about any of the following serious side effects straight away: Common (may affect up to 1 in 10 people): Severe kidney impairment (will normally be determined by the 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 the doctor and dentist immediately if the patient experiences 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 the patient should report it to the doctor if such symptoms after receiving zoledronic acid is experienced.
Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.
Tell the 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 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.
Low level of red blood cells (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, 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. The 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 up to 1 in 1,000 people): Slow heart beat; confusion; unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may occur rarely. Contact the doctor if the patient experiences pain, weakness or discomfort in the 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 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 the patient gets any side effects, talk to the doctor, pharmacist or nurse. This includes any possible side effects not listed.
Tell the doctor if the patient is taking, has recently taken or might take any other medicines. It is especially important that the patient tells the doctor if he/she is 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 the kidneys.
Other medicines that contain zoledronic acid which are used to treat osteoporosis and other non-cancer diseases of the bone, or any other bisphosphonate, since the combined effects of these medicines taken together with Zoledronic acid Actavis are unknown.
Anti-angiogenic medicines (used to treat cancer), since the combination of these with zoledronic acid has been associated with reports of osteonecrosis of the jaw (ONJ).
How Zoledronic acid Actavis is used: Zoledronic acid Actavis must only be given by healthcare professionals trained in administering bisphosphonates intravenously, i.e. through a vein.
The doctor will recommend that the patient drink enough water before each treatment to help prevent dehydration.
Carefully follow all the other instructions given by the doctor, pharmacist or nurse.
Store below 30°C.
Keep Zoledronic acid Actavis out of the sight and reach of children.
Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C and at 25°C after dilution in 100 ml 0.9% w/v sodium chloride solution or 100 ml 5% w/v glucose. From a microbiological point of view, the solution for infusion should be used immediately after dilution. If not used immediately, inuse 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. If refrigerated, the solution must be allowed to reach room temperature before administration.
The solution containing zoledronic acid 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 Zoledronic acid Actavis to ensure that they are adequately hydrated.
Since no data are available on the compatibility of Zoledronic acid Actavis with other intravenously administered substances, Zoledronic acid Actavis must not be mixed with other medications/substances and should always be given through a separate infusion line.
How to prepare and administer Zoledronic acid Actavis: To prepare an infusion solution containing 4 mg Zoledronic acid Actavis, further dilute the Zoledronic acid Actavis concentrate (5.0 ml) with 100 ml of calcium-free or other divalent cation-free infusion solution. If a lower dose of Zoledronic acid Actavis is required, first withdraw the appropriate volume as indicated below and then dilute it further with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 0.9% w/v sodium chloride or 5% w/v glucose solution.
Do not mix Zoledronic acid Actavis concentrate with calcium-containing or other divalent cation containing solutions such as lactated Ringer's solution.
Instructions for preparing reduced doses of Zoledronic acid Actavis: Withdraw the appropriate volume of the liquid concentrate, as follows: 4.4 ml for 3.5 mg dose; 4.1 ml for 3.3 mg dose; 3.8 ml for 3.0 mg dose.
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.
M05BA08 - zoledronic acid ; Belongs to the class of bisphosphonates. Used in the treatment of bone diseases.
Zoledronic Acid Actavis conc for soln for infusion 4 mg/5 mL