Expiration date: 07/2025

The composition and form of issue: 

Solution for infusion 100 ml

of zoledronic acid monohydrate is 5.33 mg

(corresponds to 5 mg of zoledronic acid anhydrous) 

excipients: mannitol sodium citrate water for injections 

in polyethylene bottles of 100 ml in a cardboard pack 1 bottle.

Description pharmaceutical form:

Clear, colourless solution

Pharmacokinetics:

Pharmacokinetic data obtained after single and repeated 5 - and 15-minute infusions of 2, 4, 8 and 16 mg of zoledronic acid in 64 patients. Pharmacokinetic parameters do not depend on the dose. After the start of injection the concentration of zoledronic acid in the blood plasma increases rapidly, reaching a maximum at the end of the infusion. After the end of the infusion there is a rapid decrease in the content of zoledronic acid in the blood plasma (<10% of Cmax within 4 h and to <1% of Cmax in the 24 h), then for a long period in the blood plasma is maintained low concentration of the drug (not exceeding 0.1% of the Cmax).

Zoledronic acid is excreted by the kidneys in 3 phases: rapid biphasic elimination from the systemic blood circulation with a T1/2 of 0.24 h (&alpha-phase) and HR of 1.87 (&beta phase) and a long phase with a finite T1/2, amounting to 146 h (&gamma phase). A rapid decline of drug concentration (&alpha - and &beta-phase) in plasma, probably due to the rapid distribution of zoledronic acid in bone tissue and its excretion by the kidneys. Not marked drug accumulation after repeated administration every 28 days. Zoledronic acid is not metabolized and is excreted by the kidneys unchanged. During the first 24 h in the urine detected (39±16)% of the administered dose. The remainder of the drug is associated exclusively with the bone tissue, then there is a slow release of zoledronic acid back from bone into the systemic circulation and its renal excretion. The total plasma clearance of the drug is (5,04±2,5) l/h and does not depend on dose, sex, age, race and body mass of the patient. It is established that variability of plasma clearance of zoledronic acid from the same patient and different patients are respectively 36 and 34%. The increase in infusion time from 5 to 15 min leads to a decrease of the concentration of zoledronic acid at 30% at the end of the infusion, but does not affect the bioavailability of the drug. Binding of zoledronic acid to plasma proteins is low (43-55%) and does not depend on its concentration.

Pharmacokinetics in special clinical cases

The renal clearance of zoledronic acid correlates with Cl creatinine is (75±33)% of Cl creatinine, the average value of which was (84±29) ml/min (range 22-143 ml/min) in the 64 patients included in the pharmacokinetic study. A small increase in AUC (30-40%) for mild and moderate renal impairment, compared to the norm, and lack of drug accumulation with repeated administration irrespective of renal function, suggest that there is no need for dose adjustments of zoledronic acid in mild (Cl — creatinine 50-80 ml/min) and moderate (creatinine Cl — 30-50 ml/min) impaired renal function.

Description pharmacological action:

Zoledronic acid, a representative of the class aminobisphosphonates, acts primarily on bone tissue, inhibits osteoclast activity and bone resorption. Selective action of bisphosphonates on bone tissue is based on high affinity for mineralized bone. After the on/in the introduction of zoledronic acid rapidly redistributed to bone tissue and, like other bisphosphonates, is localized mainly in areas of remodeling. The main molecular target of zoledronic acid in osteoclasts is an enzyme of farnesylpyrophosphate (FPS) this does not exclude the possibility of other mechanisms of action of the drug.

Long period of action of the drug is determined by a high affinity to the active center of FPS and a strong affinity for mineralized bone. In experimental models of accelerated ostertibble shown that zoledronic acid significantly inhibits bone resorption without undesirable influence on formation, mineralization and mechanical properties of bone tissue, dose-dependent decreases osteoclast activity and activation frequency of new remodeling foci in trabecular and cortical (Giveraway) of the bone without formation of fibrous bone tissue and aberrant accumulation of osteoid. With the exception of high antiresorptive action, the effect of zoledronic acid on bone tissue is similar to that of the other bisphosphonates.

In applying the drug of Aclasta in patients with postmenopausal osteoporosis (value of T-criterion of mineral bone density of the femoral neck is less than 2.5) was observed statistically significant reduction in the risk of vertebral fractures by 70% by the end of the 3rd year of treatment and reducing the risk of developing one or more new/re-fractures and moderate/severe vertebral fractures by 60-70%. In patients with osteoporosis at the age of 75 years and older in drug treatment of Aclasta was reached reduces risk of vertebral fractures by 61%.

In drug treatment of Aclasta the relative risk of developing nevertebralnah fractures at any site (including fractures of the phalanges, and bones of the facial part of the skull) was reduced by 33%. In applying the drug for 3 years in patients with postmenopausal osteoporosis showed an increase of mineral bone density (BMD) of lumbar vertebrae and femur in General, in the region of the femoral neck and distal radius on average, 6.9 6 5 and 3.2%, respectively.

On the background of drug therapy of Aclasta for 1 year in patients with postmenopausal osteoporosis observed decrease in activity of bone isoenzyme of alkaline phosphatase, N-terminal propeptide of type I collagen (PINP) and &beta-C-terminal telopeptide blood to premenopauznom values. After repeated administration of the drug for 3 years, was not marked further reduction in blood markers of bone remodeling. The use of the drug Aclasta for 3 years significantly reduced the rate of loss growth patients, also contributed to the reduction of the period of immobilization in postmenopausal women with osteoporosis and vertebral fractures, including by reducing the intensity of pain.

With the introduction of the drug in patients (men and women) with fractures of the proximal femur (resulting from minimal injury and required surgical intervention), a decrease in the frequency of subsequent osteoporotic fractures at any site by 35% compared with placebo (clinically significant vertebral fractures by 46%, nevertebralnah fractures — 27%).

In applying the drug of Aclasta in these patients the relative risk of deaths (irrespective of cause) was reduced by 28%. Patients with femur fractures if the drug of Aclasta for 2 years had been an increase in the IPC of the femur and neck of femur by 5.4% and 4.3%, respectively.

In applying the drug 1 time per year in men with primary (senile) or secondary (when hypogonadism) osteoporosis within 2 years there has been a pronounced increase in the IPC of the lumbar vertebrae.

In patients with osteoporosis caused by the use of corticosteroids, drug therapy of Aclasta also has greatly increased the IPC without having a negative effect on the bone structure and mineralization. In applying the drug of Aclasta for the prevention of postmenopausal osteoporosis 1 every 2 years in women with osteopenia and postmenopausal duration less and more than 5 years there was an increase in the IPC of the lumbar vertebrae by 6.3 and 5.4%, respectively. With the introduction of the drug 1 time in 2 years the IPC of the femur increased by 4.7 and 3.2% in women with duration of menopause less than 5 years or more respectively.

In women with various duration of menopause with the introduction of the drug Aclasta 1 time in 2 years, a decrease in the concentration of &beta-C-terminal telopeptide blood 44-46% (premenopauznom level) and N-terminal propeptide of type I collagen (PINP) 55-40%.

In drug treatment of Aclasta patients with bone Paget's disease was a statistically significant, rapid and lasting therapeutic response, normalization of bone metabolism and the activity of alkaline phosphatase in the blood plasma.

The drug is also highly effective in patients who received prior treatment with oral bisphosphonates.

It is established that the majority of patients with the use of zoledronic acid therapeutic response was maintained for the entire period of treatment (about 2 years). Marked reduction of pain at 6 months after a single injection of the drug Aclasta at a dose of 5 mg comparable analgesic effects rizedronova acid at a dose of 30 mg/day.

In patients with postmenopausal osteoporosis and bone Paget's disease zoledronic acid does not affect quality as normal bone tissue, does not violate the processes of bone remodeling and mineralization and promotes the preservation of normal trabecular architecture of the bone.

Indications:

• postmenopausal osteoporosis (to reduce the risk of fractures of the femur, vertebrae and nevertebralnah fractures, to increase bone mineral density)
  
• prevention of new fractures in men and women with fractures of the proximal femur
  
• osteoporosis in men
  
• prevention and treatment of osteoporosis caused by the use of corticosteroids
  
• prevention of postmenopausal osteoporosis (patients with osteopenia)
  
• bone Paget's disease.
  

Contraindications:

• hypersensitivity of zoledronic acid, other bisphosphonates and other components of the drug
  
• pregnancy
  
• lactation (breastfeeding)
  
• childhood and adolescence till 18 years (since the safety and efficacy of the drug of Aclasta in this category of patients has not been studied)
  
• severe disorders of mineral metabolism including hypocalcaemia
  
• severe violations of kidney function (Cl creatinine <30 ml/min), because of sufficient clinical experience with the drug in these patients is not.
  

Application of pregnancy and breast-feeding:

Drug Aclasta contraindicated during pregnancy and lactation (breastfeeding).

Data on the use of zoledronic acid in pregnant women.

The pilot studies have shown the presence of teratogenic effects from one experimental species of rodents. The potential risk when used in humans is unknown.

Side effects:

Treatment of various forms of osteoporosis, bone Paget's disease and prevention of new fractures in men and women with fractures of the proximal femur. At/in the introduction of 5 mg of Aclasta 1 per year for the treatment of postmenopausal osteoporosis in women, osteoporosis in men, prevention of new fractures in men and women with fractures of the proximal femur for the prevention and treatment of osteoporosis caused by corticosteroids and for the treatment of bone Paget's disease most adverse events (AES) were mild or moderate. After the on/in the introduction of the drug Aclasta these patients most frequently observed AES with the following: a duration of usually no more than 3 days ("Posidonia" symptoms) — fever (18,1%), myalgia (9.4 percent), flu-like symptoms (7.8 per cent), arthralgia (6.8 percent), headache (6.5 percent). Most of the above AES observed for 3 days after drug administration were mild or moderate. With repeated administration of the drug the severity of the AE data are significantly decreased. Below are AES possibly associated (according to doctors) with use of the drug for the treatment of various types of osteoporosis, bone Paget's disease and prevention of new fractures in men and women with fractures of the proximal femur.

The frequency of development of these AES were assessed as follows: very common (&ge1/10) frequently (&GE. 1/100, <1/10) uncommon (&ge1/1000, <1/100) rare (&ge1/10000, <1/1000), very rare (<1/10000), including individual messages.

From the nervous system: often — headache, dizziness and sometimes lethargy*, paraesthesia, somnolence, tremor, syncope.

From the sensory organs: sometimes — conjunctivitis, eye pain, vertigo rarely uveitis*, episcleritis, iritis.

The respiratory system: sometimes — shortness of breath* coughing.

From the digestive system: often — nausea, vomiting, diarrhea, occasionally anorexia*, decreased appetite, dyspepsia*, abdominal pain*, dry mouth, oesophagitis*, oesophageal reflux, pain in upper abdomen, constipation.

The skin and subcutaneous tissue: sometimes — rash, hyperhydrosis*, pruritus, erythema.

On the part of the musculoskeletal system and connective tissue: often — arthralgia*, myalgia* bone pain, pain in the back and limbs and sometimes pain in the neck, swelling in the joints*, muscle spasms, pain in shoulders, pain in the chest* muscular-skeletal origin, muscle weakness, stiffness in the muscle* and joints*, arthritis, muscular-skeletal pain.

From the urinary system: sometimes — increased level of blood creatinine, pollakiuria, proteinuria.

On the part of the hemopoietic system: sometimes — anemia.

Of the cardiovascular system: sometimes- increased blood pressure, sudden reddening of the face.

Infections and infestations: sometimes influenza, nasopharyngitis.

From the body as a whole: very often — fever often, — flu-like symptoms, chills, fatigue*, asthenia, pain*, malaise uncommon — peripheral oedema, thirst*, irritability* chest pain (not related to heart disease).

*Note: in some studies, the incidence of AES data increased as follows: very often — myalgia, arthralgia, fatigue, pain often — lethargy, dyspnoea, dyspepsia, oesophagitis, abdominal pain, rash, stiffness in muscles, swelling in the joints, pain in the chest, musculo-skeletal origin, joint stiffness, anorexia, thirst, anxiety rarely, uveitis.

Through separate studies have reported the following AES, the incidence of which in the group of drug Aclasta was lower than in patients not treated with the drug: redness of the eyes, elevated levels of C-reactive protein, hypocalcemia, taste disorders, toothache, gastritis, sensation of strong heartbeat, reactions at the injection site.

In applying the drug of Aclasta in patients with postmenopausal osteoporosis, the overall incidence of atrial fibrillation on the background of drug therapy of Aclasta was 2.5% (96 out of 3862) compared to 1.9% (75 out of 3852 patients) in patients not treated with drug (placebo). 1.3% of patients (51 out of 3862 patient) receiving the drug Aclasta, and in 0.6% (22 out of 3852) in the placebo group this adverse event was considered serious. The reason for the increase in the frequency of atrial fibrillation on the background of drug therapy of Aclasta in this study is not established. Increased frequency of atrial fibrillation compared with placebo observed in this study was not detected in other clinical studies of zoledronovoj acid.

Prevention of postmenopausal osteoporosis

In applying the drug of Aclasta for the prevention of postmenopausal osteoporosis (PMO) the overall safety profile of the drug was comparable in the treatment of PMO, with the exception of AES that occurred within 3 days after infusion: pain, fever, chills, myalgia, nausea, headache, fatigue, arthralgia, frequency of which was higher in women receiving the drug for prevention of PMO. The majority of these AES were mild or moderate severity and were held for 3 days after symptoms. With repeated administration of the drug the severity of the AE data are significantly decreased.

Below are AES possibly associated with the use of the drug for prevention of PMO (according to doctors):

1) AES observed in more than 1 time with the introduction of the drug Aclasta for the prevention of PMO and was not using the drug for the treatment of various types of osteoporosis, bone Paget's disease and for prevention of new fractures in men and women with fractures of the proximal femur

2) AES, whose frequency was higher in women receiving the drug for prevention of PMO (compared to other categories of patients).

The frequency of development of these AES was assessed as follows: very common (&ge1/10) frequently (&GE. 1/100,<1/10) uncommon (&ge1/1000, <1/100).

Mental breakdown: sometimes — anxiety.

From the nervous system: very often — headache often — tremor, lethargy rare — reduced sensitivity, disorders of taste.

On the part of the organ of vision: often — conjunctivitis, eye pain, iritis infrequently — blurred vision.

From the digestive system: very often — nausea, often — anorexia, abdominal pain, pain in upper abdomen, constipation.

The skin and subcutaneous tissue: often — increased sweating at night.

On the part of the musculoskeletal system and connective tissue: very often — myalgia often, musculoskeletal pain, muscle spasm, pain in the chest musculoskeletal origin, pain in jaw, pain in the neck rarely, pain in the side.

From the side of the body and reactions in the injection site: often — pain, chills often — peripheral edema, reactions at the injection site, nikardipina pain in the chest.

The change in laboratory findings

In patients with postmenopausal osteoporosis on the background of the use of the drug Aclasta in 0.2% of cases, a decrease in the concentration of calcium (<1.87 mmol/l) in serum, clinical signs of hypocalcemia were not observed.

In applying the drug in patients with fractures of the femur, in osteoporosis in men and osteoporosis, caused by the GCS, there has been a decrease in the calcium concentration in blood plasma <1.87 mmol/L.

In applying the drug in patients for the prevention of postmenopausal osteoporosis was observed a decrease of calcium concentration in blood plasma <1.87 mmol/l in patients with Paget's disease about 1% of the cases showed transient hypocalcemia, accompanied by clinical manifestations.

Violations of functions of kidneys. At/in the introduction of bisphosphonates, including zoledronic acid, there have been cases of renal dysfunction, manifested by increased concentration of blood creatinine and in rare cases acute renal failure. The impaired renal function on the background of the use of zoledronic acid was observed in patients with either renal disease history or additional risk factors (e.g. cancer diseases that require chemotherapy, the use of nephrotoxic drugs, diuretics or severe dehydration). Most of these patients had received treatment of zoledronic acid at a dose of 4 mg every 3&ndash4 weeks, but in some cases the impaired renal function was noted after a single application of zoledronic acid. When drug therapy of Aclasta for 3 years in patients with postmenopausal osteoporosis, the frequency of increasing the content of creatinine in the blood plasma and the development of renal failure did not differ from that in the application of placebo. In patients, receiving the drug of Aclasta, was more often observed a transient increase of creatinine concentration in the blood for 10 days after infusion compared with placebo (1.8 and 0.8%, respectively).

In applying the drug of Aclasta within 2 years in men with osteoporosis the rate of change of creatinine clearance and the development of renal dysfunction was similar to that in the group of alendronova acid.

In patients with osteoporosis caused by the use of GCS during therapy with the drug of Aclasta rate of change of creatinine clearance and the development of renal dysfunction was similar to that in the group rizedronova acid.

Reactions at the injection site of the drug. In applying the drug of Aclasta in patients with postmenopausal osteoporosis in 0.7% of cases showed redness, swelling and /or tenderness at the injection site.

Patients with femur fractures incidence of reactions at the injection site of the drug was comparable to that in the placebo group. In the treatment of osteoporosis in men the incidence of reactions at the injection site of the drug Aclasta was 2.6% (compared with 1.4% in the group of alendronova acid). In patients with osteoporosis caused by the use of GCS, there were no reactions in the injection site. When using the drug for prevention of postmenopausal osteoporosis the incidence of reactions at the injection site of the drug Aclasta was 1.1% (compared with 2.0% in the placebo group).

The osteonecrosis of the jaw. Cases of osteonecrosis (most often &ndash jaw) took place mostly in cancer patients receiving bisphosphonates treatment after tooth extraction or other dental procedures. Most of the patients had symptoms of local infectious-inflammatory process, including osteomyelitis. In clinical studies in patients with osteoporosis case of osteonecrosis of the jaw occurred in 1 patient who took the drug Aclasta, and in 2 patients who received a placebo. In all three cases it was noted the resolution process. In applying the drug of Aclasta in patients with fractures of the femur, in osteoporosis in men and osteoporosis, caused by the GCS, and also using the drug for prevention of postmenopausal osteoporosis, there were no cases of osteonecrosis of the jaw.

Anecdotal reports of adverse events

On the background of drug therapy of Aclasta in clinical practice, the following was stated NYA no indication of a causal relationship with the drug (incidence of AES is not installed): hypersensitivity reactions, including in rare cases, bronhoobstrukcia, urticaria, angioedema and isolated reports of the development of anaphylactic reactions, including anaphylactic shock. In rare cases, the use of the drug Aclasta in clinical practice, the patients had renal dysfunction, including renal failure requiring hemodialysis, especially in patients with renal disease or a history or additional risk factors (such as concomitant therapy with nephrotoxic drugs, diuretics and in severe dehydration).

In very rare cases it was reported about the development of the following AES: dehydration due to fever, vomiting, and diarrhea that occur after drug administration marked reduction in blood pressure in patients with risk factors, osteonecrosis of the jaw, scleritis and inflammation of the orbit.

Drug interactions:

Special studies on the interaction of zoledronic acid with other drugs have not been conducted. Zoledronic acid is not subject to systemic metabolism and does not affect the cytochrome P450 isoenzymes of the person in vitro.

Zoledronic acid is characterized by a low degree of binding with plasma proteins (approximately 43-55%) interaction due to the displacement of drugs with a high degree of binding with proteins from bonding unlikely.

Zoledronic acid is excreted by the kidneys. Caution should be exercised with simultaneous use of the drug Aclasta with drugs that can have a significant impact on renal function (e.g. aminoglycosides), agents that cause dehydration (e.g., diuretics). In patients with impaired renal function if the drug is of Aclasta together with drugs that are excreted largely by the kidneys, may increase the systemic bioavailability data of medicines.

Pharmaceutical interoperability and compatibility

The solution of Aclasta incompatible with solutions containing calcium (e.g. in one system for in/drip in the introduction).

Method of application and dose:

In/in, using the valve infusion system that provides a constant rate of infusion, for at least 15 min Before administration of the drug Aclasta should be ensure adequate hydration of the body. This is especially important for patients older than 65 years and in patients, receiving treatment dioretikami.

For the treatment of postmenopausal osteoporosis in women and osteoporosis in men the recommended dose of Aclasta is 5 mg (contents of one bottle — 100 ml solution) in/in 1 once a year. If the intake of calcium and vitamin D from food is insufficient, patients should also prescribe calcium and vitamin D.

For the prevention of recurrent fractures in patients with fractures of the proximal femur recommended dose of Aclasta is 5 mg (contents of one bottle — 100 ml solution) in/in 1 once a year. Patients with recent (within 90 days) fractured proximal femur is recommended 2 weeks prior to infusion of the drug Aclasta once to take vitamin D in high doses (50000 to 125000 ME oral or I/m). After a single application of vitamin D in high doses, the patient is recommended within 14 days before infusion of the drug Aclasta daily ingest calcium supplements (1000 mg/day) and vitamin D (800 IU/day). After infusion during the year, patients should also take calcium and vitamin D.

According to clinical studies, the best results, increasing mineral density of bone tissue was achieved with the introduction of the drug Aclasta in the period from 6 to 12 weeks after surgery for a fracture of the femur. For the treatment of osteoporosis caused by the use of corticosteroids, the recommended dose of Aclasta is 5 mg (contents of one bottle — 100 ml solution) in/in 1 once a year. If the intake of calcium and vitamin D from food is insufficient, patients with osteoporosis should also prescribe calcium and vitamin D.

For the prevention of postmenopausal osteoporosis the recommended dose of Aclasta is 5 mg (contents of one bottle — 100 ml solution) in/in 1 once in 2 years. For decision-making about the need for re-infusion should be carried out annual assessment of the risk of fractures and assessment of the clinical response to therapy.

For the prevention of postmenopausal osteoporosis, it is very important that sufficient intake of calcium and vitamin D. if dietary intake is insufficient, it is recommended additional intake of calcium and vitamin D.

For the treatment of bone Paget's disease is recommended that a single administration of 5 mg of Aclasta V/V. as the bone Paget's disease is characterized by a high level of bone metabolism, all patients with this disease are advised to take daily intake of calcium (at least 500 mg of elemental calcium 2 times a day) and vitamin D during the first 10 days after administration of Aclasta.

Repeated drug treatment of Aclasta bone of Paget's disease. Currently, specific recommendations for re-treatment of bone Paget's disease is not available. In patients that responded to therapy with the drug of Aclasta, after its single administration was observed for a long period of remission.

The possibility of reintroduction of the drug Aclasta may be considered in case of detection of patients with disease recurrence on the basis of the following criteria: absence of normalization of the activity of alkaline phosphatase in serum, enhancing its activity in the dynamics and the presence of clinical signs of bone Paget's disease, detected during a medical examination after 12 months after the first dose of the drug Aclasta.

Patients with impaired renal function. Patients with Cl creatinine >35 ml/min is not required correction doses of the drug.

Patients with impaired liver function. Patients with impaired liver function is not required correction doses of the drug.

Elderly patients (>65 years). The dosage adjustment is not required as the bioavailability, distribution and excretion of the drug in patients of different ages have similar character.

Instructions for use of the drug. In preparing and conducting the infusion should comply with the rules of asepsis. Before the introduction of the drug Aclasta should visually assess the quality and the color of the solution. Do not use this drug if you change the color or appearance of undissolved visible particles. Drug Aclasta should not be mixed or put together with any other drugs. Avoid contact of the drug Aclasta with any solutions containing calcium or any other divalent cations. To administer the drug, you should always use a separate system for infusion. At the end of the drug infusion of Aclasta unused solution remaining in the vial cannot be used.

The solution of Aclasta it is desirable to use directly after opening the bottle. From unused solution can be stored in the refrigerator at 2-8 °C for no longer than 24 hours if the solution is cooled before introduction it should be kept indoors until reaching room temperature.

Overdose:

Currently, there are limited clinical data on cases of overdose. Patients who received a dose that exceeds the recommended should be under medical supervision.

Symptoms: in acute overdose of zoledronic acid (limited data), violations of renal function, including renal failure, hypocalcaemia, hypophosphatemia, hypomagnesemia.

Treatment: in case of drug overdose, accompanied by clinical symptoms (numbness, tingling, particularly in the area of the mouth, muscle spasms, etc.), shown in/with the introduction of solutions containing ions of calcium, magnesium and phosphates.

Special instructions:

The physician should inform patients about the basic manifestations of hypocalcemia and to provide regular monitoring of patients belonging to the risk group.

Therapy the drug of Aclasta in patients with osseous Paget's disease should be done only by qualified physicians with experience in the treatment of this disease.

To reduce the frequency of some AES observed during 3 days after administration of the drug can be prescribe paracetamol or ibuprofen immediately after the infusion of Aclasta.

Zoledronic acid is an active substance like a drug Aclasta and the drug zometa (a drug for the treatment of oncological patients), however, these drugs are not interchangeable and should not be applied simultaneously. In the presence of hypocalcemia before administration of the drug of Aclasta necessary to carry out a treatment with adequate doses of calcium and vitamin D. You should also conduct therapy other disorders of mineral metabolism (such as encountered after operations on the thyroid and parathyroid glands, with hypoparathyroidism or decreased calcium absorption in the intestine) and to provide regular monitoring of patients with hypocalcemia.

Violations of kidney function. To reduce the risk of developing kidney disorders should comply with the following instructions:

Drug Aclasta is not recommended in patients with severe impairment of nights (Cl creatinine <35 ml/min) as there are limited data on the safety of the drug in these patients.

Caution should be exercised with simultaneous use of the drug Aclasta with drugs that can have a significant impact on renal function (see section "Interactions ").