Aclasta infusion solution 5mg/100ml vial, 100ml

Composition

1 bottle (100 ml) contains:

Active ingredient:

5 mg zoledronic acid monohydrate;

Auxiliary substances:

mannitol;

sodium citrate;

water for injection.

Pharmacological action

Pharmacodynamics

Zoledronic acid, a representative of the class of aminobisphosphonates, acts mainly on bone tissue, suppresses the activity of osteoclasts and bone resorption. The selective effect of bisphosphonates on bone tissue is based on a high affinity for mineralized bone tissue.

After intravenous use, zoledronic acid is rapidly redistributed into bone tissue and, like other bisphosphonates, is localized mainly in the sites of remodeling. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthetase (FPS); however, the possibility of other mechanisms of action of the drug is not excluded.

The long period of action of the drug is determined by a high affinity for the active center of the FPS and a pronounced affinity for mineralized bone tissue. Using experimental models of accelerated osteoresorption, it was shown that zoledronic acid significantly inhibits bone resorption without undesirable effects on the formation, mineralization and mechanical properties of bone tissue, dose-dependently reduces the activity of osteoclasts and the frequency of activation of new remodeling foci in both the trabecular and cortical (Haversa) parts of the bone, without causing the formation of fibrous bone tissue and aberrant accumulation of osteoid. Except for the high antiresorptive effect, the effect of zoledronic acid on bone tissue is similar to that of other bisphosphonates.

When using Aklasta in patients with postmenopausal osteoporosis (values of the T-criterion of bone mineral density of the femoral neck — less than 2.5), there was a statistically significant reduction in the risk of vertebral fractures by 70% by the end of the 3rd year of treatment, as well as a 60-70% reduction in the risk of developing one or more new/repeated fractures and moderate/severe vertebral fractures. In patients with osteoporosis aged 75 years and older, treatment with Aklasta resulted in a 61% reduction in the risk of vertebral fractures.

When treated with Aklasta, the relative risk of developing non-vertebral fractures of any localization (including fractures of the phalanges of the fingers and bones of the facial part of the skull) was reduced by 33%. When using the drug for 3 years, patients with postmenopausal osteoporosis showed an increase in bone mineral density (BMD) of the lumbar vertebrae, femur in general, in the femoral neck and distal radius on average, by 6.9,6,5 and 3.2%, respectively.

Patients with postmenopausal osteoporosis treated with Aklasta for 1 year showed a decrease in the activity of bone isoenzyme ALP, N-terminal type I collagen propeptide (PINP), and beta-C-terminal blood telopeptides to premenopausal values. With repeated use of the drug for 3 years, there was no further decrease in the blood content of markers of bone remodeling.

The use of Aklasta for 3 years significantly reduced the rate of growth loss in patients, and also helped to reduce the period of immobilization in postmenopausal women with osteoporosis and vertebral fractures, including by reducing the intensity of pain syndrome.

When the drug was administered to patients (men and women) with fractures of the proximal femur (resulting from minimal trauma and requiring surgical intervention), the frequency of subsequent osteoporotic fractures of any localization decreased by 35% compared to placebo (of which clinically significant vertebral fractures — by 46%, non — vertebral fractures-by 27%).

When using the drug Aklasta in this category of patients, the relative risk of fatal outcomes (regardless of their cause) decreased by 28%. In patients with femoral fractures, when using Aklasta for 2 years, there was an increase in the BMD of the femur as a whole and in the femoral neck area by 5.4 and 4.3%, respectively.

When using the drug 1 time a year in men with primary (senile) or secondary (with hypogonadism) osteoporosis for 2 years, a pronounced increase in the BMD of the lumbar vertebrae was noted.

In patients with corticosteroid-induced osteoporosis, Aclasta therapy also significantly increased BMD without adversely affecting bone structure and mineralization. When using the drug Aklasta for the prevention of postmenopausal osteoporosis 1 time in 2 years, women with osteopenia and postmenopausal duration of less than and more than 5 years showed an increase in BMD of the lumbar vertebrae by 6.3 and 5.4%, respectively. When the drug was administered once every 2 years, the BMD of the femur increased by 4.7 and 3.2% in women with a postmenopausal duration of less than and more than 5 years, respectively.

In women with different postmenopausal durations, the use of Aklasta 1 time in 2 years showed a decrease in the concentration of beta-C-terminal telopeptides in the blood by 44-46% (up to the premenopausal level) and N-terminal propeptide of collagen type I (PINP) by 55-40%.

Patients with Paget’s bone disease treated with Aklasta showed a statistically significant, rapid and long-term therapeutic response, normalization of bone metabolism and ALP activity in blood plasma.

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

It was found that the majority of patients treated with zoledronic acid have a therapeutic response that persists throughout the entire treatment period (about 2 years). The marked reduction in pain syndrome at 6 months after a single use of Aklasta at a dose of 5 mg is comparable to the analgesic effect of risedronic acid at a dose of 30 mg / day.

In patients with postmenopausal osteoporosis and Paget’s bone disease, zoledronic acid does not affect the qualitative state of normal bone tissue, does not interfere with the processes of bone remodeling and mineralization, and contributes to the preservation of normal trabecular bone architectonics.

Pharmacokinetics

Pharmacokinetic data were 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 of the drug. After starting the drug use, 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 blood plasma (to a level <10% of Cmax – after 4 hours and up to

Zoledronic acid is excreted by the kidneys in 3 stages: rapid two-phase elimination from the systemic circulation with a T1/2 of 0.24 hours (alpha-phase) and 1.87 hours (beta-phase) and a long phase with a final T1/2 of 146 hours (gamma-phase).

A rapid decrease in the concentration of the drug (alpha-and beta-phases) in blood plasma may be associated with the rapid distribution of zoledronic acid in bone tissue and its excretion by the kidneys. No accumulation of the drug was observed with repeated injections every 28 days. Zoledronic acid is not metabolized and is excreted unchanged by the kidneys.

During the first 24 hours in the urine is detected (39±16)% of the administered dose. The remaining amount of the drug binds exclusively to bone tissue, after which there is a slow release of zoledronic acid back from the bone tissue into the systemic circulation and its excretion by the kidneys. The total plasma clearance of the drug is (5.04±2.5) l / h and does not depend on the dose, gender, age, race and body weight of the patient.

It was found that the variability of plasma clearance of zoledronic acid in the same patient and in different patients is 36 and 34%, respectively. An increase in the infusion time from 5 to 15 minutes leads to a 30% decrease in the concentration of zoledronic acid at the end of the infusion, but does not affect the bioavailability of the drug. The binding of zoledronic acid to plasma proteins is low (43-55%) and does not depend on its concentration.

Pharmacokinetics in special clinical cases

Renal clearance of zoledronic acid correlates with creatinine clearance and is (75±33)% of creatinine clearance, with mean values of (84±29) ml / min (range: 22-143 ml / min) in 64 patients included in the pharmacokinetic study.

A small increase in AUC (30-40%) in mild and moderate renal impairment, compared with the norm, and the absence of accumulation of the drug with repeated use, regardless of renal function, suggest that there is no need to adjust the dose of zoledronic acid in mild (creatinine clearance — 50-80 ml/min) and moderate (creatinine clearance — 30-50 ml/min) renal impairment.

The testimony of

• postmenopausal osteoporosis (to reduce the risk of fractures of the femur, vertebrae and nevertebrate 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 (in patients with osteopenia);
• bone Paget’s disease.

Use during pregnancy and lactation

The drug Aklasta is contraindicated during pregnancy and lactation (breastfeeding).

There are no data on the use of zoledronic acid in pregnant women.

Experimental studies have shown the presence of teratogenic effects in one of the experimental rodent species.

The potential risk of human use is unknown.

Contraindications

• hypersensitivity of zoledronic acid, other bisphosphonates and other components of the drug Aklast;
• pregnancy;
• lactation (breastfeeding);
• childhood and adolescence to 18 years (since the safety and efficacy of the drug of Aklast in this category of patients has not been studied);
• severe disorders of mineral metabolism, including hypocalcaemia;
• severe impairment of renal function (Cl creatinine less than 30 ml/min), because of sufficient clinical experience with the drug in this category of patients there.

Side effects

Treatment of various types of osteoporosis, Paget’s bone disease and prevention of new fractures in men and women with fractures of the proximal femur.

With intravenous use of 5 mg of Aklasta once a year for the treatment of postmenopausal osteoporosis in women, osteoporosis in men, for the prevention of new fractures in men and women with fractures of the proximal femur, for the prevention and treatment of osteoporosis caused by the use of corticosteroids and for the treatment of Paget’s bone disease, most adverse events (AES) were mild or moderate.

After intravenous use of Aklasta, these patients most frequently experienced the following AES: usually lasting no more than 3 days (“post-dose” symptoms) — fever (18.1%), myalgia (9.4%), flu-like syndrome (7.8%), arthralgia (6.8%), headache (6.5%). Most of the above-mentioned AES observed within 3 days after drug use were mild or moderate.

With repeated use of the drug, the severity of these AES significantly decreased. Below are AES that may be associated (according to the attending physicians) with the use of the drug for the treatment of various types of osteoporosis, Paget’s bone disease and for the prevention of new fractures in men and women with fractures of the proximal femur.

From the nervous system: often-headache, dizziness; sometimes-lethargy*, paresthesia, drowsiness, tremor, fainting.

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

From the respiratory system: sometimes-shortness of breath*, cough.

From the digestive system: often — nausea, vomiting, diarrhea; sometimes — anorexia*, loss of appetite, dyspepsia*, abdominal pain*, dry mouth, esophagitis*, gastroesophageal reflux, upper abdominal pain, constipation.

From the skin and subcutaneous tissue: sometimes-rash, hyperhidrosis*, pruritus, erythema.

Musculoskeletal and connective tissue disorders: often-arthralgia*, myalgia*; bone pain, back and limb pain; sometimes-neck pain, joint swelling*, muscle spasms, shoulder girdle pain, chest pain* of musculoskeletal origin, muscle weakness, stiffness in the muscles* and joints*, arthritis, musculoskeletal pain.

From the urinary system: sometimes-increased blood creatinine, pollakiuria, proteinuria.

From the hematopoietic system: sometimes-anemia.

From the cardiovascular system: sometimes-increased blood pressure, sudden redness of the face.

Infections and infestations: sometimes-flu, nasopharyngitis.

On the part of the body as a whole: very often — fever; often — flu — like syndrome, chills, fatigue*, asthenia, pain*, general malaise; infrequently-peripheral edema, thirst*, increased excitability*, chest pain (not related to heart disease).

*Note: in some studies, the frequency of these AES increased as follows: very often-myalgia, arthralgia, increased fatigue, pain; often-lethargy, shortness of breath, dyspepsia, esophagitis, abdominal pain, hyperhidrosis, muscle stiffness, joint edema, chest pain of musculoskeletal origin, joint stiffness, anorexia, thirst, increased excitability; infrequently-uveitis.

In separate studies, the following AES were reported, the frequency of which in the Aklasta group was lower than in patients who did not receive the drug: redness of the eyes, increased C-reactive protein content, hypocalcemia, taste disorders, toothache, gastritis, palpitations, reactions at the injection site.

When using Aclasta in patients with postmenopausal osteoporosis, the overall incidence of atrial fibrillation during treatment with Aclasta was 2.5% (96 out of 3,862 patients) compared to 1.9% (75 out of 3,852 patients) in patients who did not receive treatment with the drug (placebo group). In 1.3% of patients (51 patients out of 3,862) treated with Aklasta, and in 0.6% (22 people out of 3,852) in the placebo group, this adverse event was considered serious. The reason for the increased frequency of atrial fibrillation during therapy with Aklasta was not established in this study. The increase in the frequency of atrial fibrillation compared to placebo noted in this study was not found in other clinical studies of zoledronic acid.

Prevention of postmenopausal osteoporosis

When using Aklasta for the prevention of postmenopausal osteoporosis (PMO), the overall safety profile of the drug was comparable to that in the treatment of PMO, with the exception of AES that occurred within 3 days after the infusion: pain, fever, chills, myalgia, nausea, headache, fatigue, arthralgia, the frequency of which was higher in women receiving the drug for the prevention of PMO. Most of these AES were mild to moderate in severity and resolved within 3 days of onset. With repeated use of the drug, the severity of these AES significantly decreased.

The following are AES that may be associated with the use of the drug for the prevention of PMO (according to the attending physicians)::

1) adverse events observed in more than 1 time with the introduction of the drug Aklast for the prevention of PMO and is not registered when using the drug to treat 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) S, the frequency of which was higher in women receiving the drug for prevention of PMO (compared to other categories of patients).

Mental disorders: sometimes-anxiety.

From the nervous system: very often — headache; often-tremor, lethargy; infrequently-decreased sensitivity, taste disorders.

From the side of the organ of vision: often-conjunctivitis, eye pain, iritis; infrequently-blurred vision.

From the digestive system: very often-nausea; often-anorexia, abdominal pain, upper abdominal pain, constipation.

From the skin and subcutaneous tissue: often-increased sweating at night.

Musculoskeletal and connective tissue disorders: very often-myalgia; often-musculoskeletal pain, muscle spasm, chest pain of musculoskeletal origin, pain in the jaw, pain in the neck; infrequently-pain in the side.

On the part of the body as a whole and reactions at the injection site: very often — pain, chills; often — peripheral edema, reactions at the injection site, non-cardiac pain in the chest.

Changing the results of laboratory tests

Patients with postmenopausal osteoporosis who were treated with Aclasta showed a decrease in serum calcium concentration (less than 1.87 mmol/l) in 0.2% of cases, but no clinical signs of hypocalcemia were observed.

When using the drug in patients with femoral fractures, in men with osteoporosis and osteoporosis caused by taking corticosteroids, there was no decrease in the concentration of calcium in the blood plasma less than 1.87 mmol/l.

When using the drug in patients for the prevention of postmenopausal osteoporosis, there was no decrease in the concentration of calcium in blood plasma less than 1.87 mmol/l. In patients with Paget’s disease, approximately 1% of cases showed transient hypocalcemia, accompanied by clinical manifestations.

Impaired renal function. With intravenous use of bisphosphonates, including zoledronic acid, there were cases of impaired renal function, manifested by an increase in blood creatinine concentration and, in rare cases, acute renal failure. Impaired renal function associated with the use of zoledronic acid was observed in patients with either a history of renal pathology or additional risk factors (for example, cancer requiring chemotherapy, the use of nephrotoxic drugs, diuretics, or severe dehydration). Most of these patients received zoledronic acid therapy at a dose of 4 mg every 3-4 weeks, but in some cases, renal dysfunction was observed after a single dose of zoledronic acid. When treated with Aklasta for 3 years in patients with postmenopausal osteoporosis, the frequency of increased plasma creatinine and the development of renal failure did not differ from that with placebo. Patients treated with Aclasta were slightly more likely to have a transient increase in blood creatinine concentration within 10 days after the infusion compared to placebo (1.8 and 0.8%, respectively).

When using Aklasta for 2 years in men with osteoporosis, the frequency of changes in creatinine clearance and the development of renal dysfunction was similar to that in the alendronic acid group.

In patients with corticosteroid-induced osteoporosis treated with Aclasta, the frequency of changes in creatinine clearance and the development of renal dysfunction was similar to that in the risedronic acid group.

Reactions at the injection site. When using Aklasta in patients with postmenopausal osteoporosis, redness, swelling and /or soreness at the injection site were observed in 0.7% of cases.

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

Osteonecrosis of the jaw. Cases of osteonecrosis (most often in the jaw) occurred mainly in cancer patients treated with bisphosphonates, after tooth extraction or other dental manipulations. Most of the patients had symptoms of a local infectious and inflammatory process, including osteomyelitis. In clinical trials in patients with osteoporosis, a case of osteonecrosis of the jaw occurred in 1 patient taking Aklasta and in 2 patients taking placebo. In all three cases, the process was resolved. When using Aklasta in patients with femoral fractures, in men with osteoporosis and osteoporosis caused by corticosteroids, as well as when using the drug for the prevention of postmenopausal osteoporosis, there were no cases of osteonecrosis of the jaw.

Individual reports of undesirable events

The following AES have been reported in clinical practice with Aclasta without evidence of a causal relationship with the use of the drug (the frequency of AES has not been established): hypersensitivity reactions, including in rare cases bronchial obstruction, urticaria, angioedema, and isolated reports of anaphylactic reactions, including anaphylactic shock. In rare cases, patients with Aclasta in clinical practice have experienced impaired renal function, including renal failure requiring hemodialysis, especially in patients with either a history of renal pathology or additional risk factors (for example, with concomitant therapy with nephrotoxic drugs, diuretics, or severe dehydration).

In very rare cases, the following AES have been reported: dehydration due to fever, vomiting and diarrhoea occurring after use of the drug; a marked decrease in blood pressure in patients with risk factors, osteonecrosis of the jaw, scleritis and inflammation in the eye socket.

Interaction

Special studies on the interaction of zoledronic acid with other drugs have not been conducted. Zoledronic acid does not undergo systemic metabolism and does not affect human cytochrome P 450 isoenzymes in vitro.

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

Zoledronic acid is excreted by the kidneys. Caution should be exercised when using Aclasta concomitantly with drugs that may have a significant effect on renal function (for example, aminoglycosides) and drugs that cause dehydration (for example, diuretics). In patients with impaired renal function, when using Aklasta together with drugs that are mainly excreted by the kidneys, the systemic bioavailability of these drugs may increase.

Pharmaceutical interaction and compatibility

The solution of Aklasta is incompatible with solutions containing calcium (for example, in one system for intravenous drip use).

How to take, course of use and dosage

Intravenously, using a valvular infusion system that provides a constant infusion rate, for at least 15 minutes. Adequate hydration of the body should be ensured before use of Aklasta. This is especially important for patients over the age of 65, as well as in patients receiving diuretic therapy.

For the treatment of postmenopausal osteoporosis in women and osteoporosis in men, the recommended dose of Aklasta is 5 mg (the content of one bottle of the drug is 100 ml of solution) intravenously once a year. If dietary intake of calcium and vitamin D is insufficient, patients should be additionally prescribed calcium and vitamin D supplements.

For the prevention of repeated fractures in patients with fractures of the proximal femur, the recommended dose of Aklasta is 5 mg (the contents of one bottle of the drug — 100 ml of solution) intravenously once a year. Patients with a recent (up to 90 days) fracture of the proximal femur are recommended to take a single dose of vitamin D in high doses (from 50,000 to 125,000 IU orally or intramuscularly) 2 weeks before the infusion of Aklasta. After a single dose of vitamin D in high doses, patients are recommended to take daily oral calcium supplements (1000 mg/day) and vitamin D supplements (800 IU/day) for 14 days before the infusion of Aklasta. After the infusion, patients should also take calcium and vitamin D supplements for a year.

According to clinical studies, the best results in increasing bone mineral density were achieved with the introduction of the drug Aklasta in the period from 6 to 12 weeks after surgery for a femoral fracture. For the treatment of osteoporosis caused by the use of corticosteroids, the recommended dose of Aklasta is 5 mg (the content of one bottle of the drug is 100 ml of solution) intravenously once a year. If dietary intake of calcium and vitamin D is insufficient, patients with osteoporosis should be additionally prescribed calcium and vitamin D supplements.

For the prevention of postmenopausal osteoporosis, the recommended dose of Aklasta is 5 mg (the content of one bottle of the drug is 100 ml of solution) intravenously 1 time in 2 years. To make a decision on the need for repeated infusion, an annual assessment of the risk of fractures and an assessment of the clinical response to therapy should be carried out.

Adequate intake of calcium and vitamin D is essential for the prevention of postmenopausal osteoporosis. If their intake with food is insufficient, additional intake of calcium and vitamin D preparations is recommended.

For the treatment of Paget’s bone disease, a single injection of 5 mg of Aklasta intravenously is recommended. Since Paget’s bone disease is characterized by a high level of bone metabolism, all patients with this disease are recommended to take a daily allowance of calcium (at least 500 mg of elemental calcium 2 times a day)and vitamin D for the first 10 days after use of Aklasta.

Repeated treatment with Aklasta for Paget’s bone disease. Currently, there are no specific recommendations for repeated treatment of Paget’s bone disease. Patients who responded to Aclasta therapy experienced a long period of remission after a single dose.

The possibility of repeated use of the drug Aklasta can be considered if a relapse of the disease is detected in patients based on the following criteria: the absence of normalization of serum alkaline phosphatase activity, an increase in its activity in dynamics, as well as the presence of clinical signs of Paget’s bone disease, detected during a medical examination 12 months after the first dose of Aklasta.

Patients with impaired renal function. No dose adjustment is required in patients with creatinine clearance >35 ml / min.

Patients with impaired liver function. Patients with impaired liver function do not need to adjust the dose of the drug.

Elderly patients (>65 years). No dose adjustment is required, since the bioavailability, distribution and elimination of the drug in patients of different ages are similar.

Instructions for use of the drug. When preparing and conducting the infusion, follow the rules of asepsis. Before use of Aklasta, the quality and color of the solution should be visually evaluated. The drug should not be used if the color changes or undissolved visible particles appear.

The drug Aklasta should not be mixed or administered together with any other drugs. Do not allow Aklasta to come into contact with any solutions containing calcium or any other divalent cations. A separate infusion system should always be used to administer the drug. At the end of the infusion of Aklasta, the unused solution remaining in the vial should not be used.

It is advisable to use the solution of the drug Aklasta immediately after opening the bottle. Unused immediately solution can be stored in the refrigerator at a temperature of 2-8 °C for no more than 24 hours. If the solution is cooled, it should be kept indoors until room temperature is reached before use.

Overdose

Currently, there are limited clinical data on drug overdose cases.Patients who receive a dose of the drug that exceeds the recommended dose should be monitored by a doctor.

Symptoms: acute overdose of zoledronic acid (limited data) has been associated with impaired renal function, including renal failure, hypocalcemia, hypophosphatemia, hypomagnesemia.

Treatment: in case of overdose of the drug, accompanied by clinical symptoms (numbness, tingling sensation, especially in the mouth, muscle spasms, etc. ), intravenous use of solutions containing calcium, magnesium and phosphate ions is indicated.

Special instructions

The doctor should inform patients about the main manifestations of hypocalcemia and ensure regular monitoring of patients at risk.

Aklasta therapy in patients with Paget’s bone disease should only be performed by qualified physicians with experience in the treatment of this disease.

Paracetamol or ibuprofen may be prescribed immediately after the Aclasta infusion to reduce the frequency of some AES that occurred within 3 days after use.

Zoledronic acid is the active ingredient of both Aklasta and Zometa (a drug for the treatment of cancer patients), but these drugs are not interchangeable and should not be used simultaneously. In the presence of hypocalcemia, adequate doses of calcium and vitamin D should be used before starting the use of Aklasta. Other existing mineral metabolic disorders (such as those that occur after thyroid and parathyroid surgery, hypoparathyroidism, or decreased intestinal calcium absorption) should also be treated, and patients with hypocalcemia should be monitored regularly.

Impaired renal function. To reduce the risk of developing kidney disorders, the following guidelines should be followed::

Aclasta is not recommended for use in patients with severe renal impairment (creatinine clearance less than 35 ml / min), as there are limited data on the safety of the drug in this category of patients.

Caution should be exercised when concomitantly using Aklasta with drugs that may have a significant effect on renal function.

Before use of the drug, it is necessary to determine the content of creatinine in the blood plasma. During therapy with the drug in patients with a history of impaired renal function, a transient increase in plasma creatinine may be higher than in patients with normal renal function. When using the drug Aklasta in patients with risk factors for renal disorders, the determination of creatinine in blood plasma should be carried out regularly.

Adequate hydration of the body should be ensured before use of Aklasta. This is especially important for patients aged >65 years, as well as in patients receiving diuretic therapy.

The dose of the drug for a single intravenous infusion should not exceed 5 mg, while the use of Aklasta should be carried out for at least 15 minutes.

Osteonecrosis of the jaw. Risk factors for osteonecrosis include cancer, concomitant therapy (for example, chemotherapy, radiation therapy, corticosteroid therapy), and the presence of other concomitant diseases (for example, anemia, coagulopathy, infections, and a history of dental diseases). Although a causal relationship between osteonecrosis of the jaw and bisphosphonate use has not been established, dental surgery should be avoided, since the recovery time after these operations may increase. Before starting treatment with bisphosphonates, it is necessary to conduct a dental examination and perform the necessary preventive procedures in advance in patients with risk factors (cancer, chemotherapy, treatment with corticosteroids, non-compliance with oral hygiene). With the development of osteonecrosis of the jaw against the background of bisphosphonate therapy, dental operations can worsen the condition of patients. There is no evidence that discontinuing bisphosphonate treatment prior to dental intervention reduces the risk of osteonecrosis of the jaw. The treatment strategy of a particular patient should be based on an individual assessment of the risk / benefit ratio.

Influence on the ability to drive vehicles and work with mechanisms. There are no data on the effect of the drug Aklasta on the ability to drive vehicles and work with mechanisms, but due to the possibility of side effects (including blurred visual perception, lethargy, etc. ), care should be taken when driving vehicles and working with mechanisms.

Form of production

Solution for infusions

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Zoledronic acid

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Paget’s Disease, Cancer