Aclasta solution for infusion bottles 100 ml
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Active ingredients
Zoledronic acid
Release form
Solution
Composition
1 tablet contains 500 mg of chondroitin sodium sulfate and 500 mg of glucosamine hydrochloride.
Pharmacological effect
Bone tissue resorption inhibitor, a representative of bisphosphonates. Zoledronic acid belongs to the class of aminobisphosphonates, acts primarily on bone, inhibits 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 iv administration, zoledronic acid is rapidly redistributed to the bone and, like other bisphosphonates, is localized predominantly at the sites of bone remodeling. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthetase (FPS), and this does not exclude the possibility of other mechanisms of drug action. 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. Experimental models of accelerated osteoresorption have shown that zoledronic acid significantly inhibits bone resorption without an undesirable effect on bone formation, mineralization and mechanical properties, decreases the activity of osteoclasts and the frequency of activation of new remodeling sites both trabecular and cortical (Gaversoy) bone, not causing the formation of fibrous bone and the aberrant accumulation of osteoid. With the exception of a high antiresorptive effect, the effect of zoledronic acid on bone is similar to that of other bisphosphonates. When using Aclasta in patients with postmenopausal osteoporosis (T-test values for bone density of the femoral neck are less than 2.5), a statistically significant reduction in the risk of vertebral fractures by 70% by the end of 3 years of treatment was noted, as well as a decrease in the risk of developing one or more new / subsequent fractures and moderate / severe vertebral fractures by 60-70%. In patients with osteoporosis aged 75 years and older, the treatment of Aclasta reduced the risk of developing vertebral fractures by 61%.In the treatment of Aklasty, 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) decreased by 33%, respectively. When Aklasty was used for 3 years in patients with postmenopausal osteoporosis, there was an increase in bone mineral density (BMD) of the lumbar vertebrae, the femur as a whole, the femoral neck and the distal radial bone by an average of 6.9%, 6%, 5% and 3.2 %, respectively. During treatment with Aclasta for 1 year, patients with postmenopausal osteoporosis experienced a decrease in the bone isoenzyme level of alkaline phosphatase, N-terminal propeptide type I collagen (PINP) and? -C-terminal blood telopeptides to premenopausal level. With repeated administrations of the drug for 3 years, there was no further decrease in the level of bone remodeling markers in the blood. The use of Aklasts for 3 years significantly reduced the rate of growth loss in patients, and also contributed to an increase in physical activity in postmenopausal women with osteoporosis and vertebral fractures. When the drug was administered to patients (men and women) with fractures of the proximal femur (caused by minimal trauma and requiring surgical intervention), there was a decrease in the frequency of subsequent osteoporotic fractures of any localization by 35% compared with placebo (of them clinically significant vertebral fractures - by 46 %, non-vertebral fractures - by 27%). In patients with femoral fractures, the use of Aklasts for 2 years resulted in an increase in BMD of the proximal femur as a whole and the neck of the femur by 5.4% and 4.3%, respectively. In the treatment of Aclasta, patients with Pedzhet's bone disease showed a statistically significant, rapid and long-lasting therapeutic response, normalization of bone metabolism and alkaline phosphorus concentration in plasma. The drug is also highly effective in patients who have previously received treatment with oral bisphosphonates. It has been established that in the majority of patients with the use of zoledronic acid, the therapeutic response persists throughout the entire period of treatment (about 2 years). The marked decrease in pain at 6 months after a single injection of Aklasty at a dose of 5 mg is comparable to the analgesic effect of risedronate at a dose of 30 mg.In patients with postmenopausal osteoporosis and Paget's disease of bone, zoledronic acid does not affect the quality of normal bone, does not interfere with bone remodeling and mineralization, and contributes to the preservation of normal trabecular bone architectonics.
Pharmacokinetics
Data on pharmacokinetics 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 the start of infusions of Aklasts, the concentration of zoledronic acid in plasma increases rapidly, reaching a peak at the end of the infusions, followed by a rapid decrease in concentration by 10% from the peak after 4 hours and by less than 1% from the peak after 24 hours with a sequentially prolonged period of low concentrations, not exceeding 0.1% of Cmax. Zoledronic acid, introduced into / in, is excreted by the kidneys in 3 stages: rapid two-phase elimination of the drug from systemic blood flow with a T1 / 2 of 0.24 h (? -Phase) and 1.87 h (? -Phase) and a long phase with a final T1 / 2 constituting 146 h (? -Phase). The rapid decrease in the concentration of the drug (? - and? -Phase) in the blood plasma is probably due to the rapid distribution of zoledronic acid in the bone tissue and its excretion by the kidneys. No marked cumulation of the drug with repeated injections every 28 days. Zoledronic acid is not metabolized, excreted by the kidneys unchanged. During the first 24 hours, 39 ± 16% of the administered dose is detected in the urine. The rest of the drug is associated exclusively with bone tissue. Then, slowly, the back release of zoledronic acid back from the bone tissue into the systemic circulation and 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 is shown 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 min leads to a decrease in the concentration of zoledronic acid by 30% at the end of the infusion, but does not affect the bioavailability. The binding of zoledronic acid to plasma proteins is low (43-55%) and does not depend on its concentration. Pharmacokinetics in special clinical situations Renal clearance of zoledronic acid is positively correlated with CC and is 75 ± 33% of creatinine clearance, averaging 84 ± 29 ml / min (range 22-143 ml / min) in 64 patients included in the study.A slight observed increase in bioavailability (30–40%) in case of impaired renal function from mild to moderate, compared with patients with normal renal function, and the lack of cumulation of the drug after repeated administration, regardless of renal function, suggest that there is no need to adjust the dose of zoledronic acid with mild (CK 50-80 ml / min) and moderate (CK 30-50 ml / min) impaired renal function.
Indications
Postmenopausal osteoporosis (to reduce the risk of fractures of the femur, vertebrae and non-vertebral fractures, to increase bone mineral density). Prevention of new osteoporotic fractures in men and women with proximal femur fractures. Osteoporosis in men. Prevention and treatment of osteoporosis caused by GCS. Prevention of postmenopausal osteoporosis (in patients with osteopenia). Pedzhet's bone disease.
Contraindications
- severe violations of mineral metabolism, including hypocalcemia; - pregnancy; - lactation period (breastfeeding); - children and adolescents up to 18 years of age (since the safety and efficacy of using Aklasts in this category of patients has not been studied); - Hypersensitivity to zoledronic acid, or to any other component of the drug, or to any bisphosphonates. Aclasta is not recommended for use in patients with severely impaired renal function (CC less than 30 ml / min).
Precautionary measures
Use for violations of liver functionPatients with impaired liver function does not require dose adjustment of the drug. Use for impaired renal functionPatients with impaired renal function with QC more than 30 ml / min do not require dose adjustment of the drug. Aclasta is not recommended for patients with severely impaired renal function (QC. The physician should inform patients about the main manifestations of hypocalcemia and ensure regular monitoring of patients at risk. Aklast's therapy in patients with Paget's disease of the bone should be carried out only by experienced doctors of this disease. To reduce the incidence of adverse reactions that occur within 3 days after drug administration, you can assign paracetamol or iibuprofen immediately after e infusion Aklasty.Zoledronovaya acid is the active substance as a Aklasty,and Zometa (drug for the treatment of cancer patients), however, these drugs are not interchangeable and should not be used simultaneously. In the presence of hypocalcemia, before starting the use of Aklasty, it is necessary to treat with adequate doses of calcium and vitamin D. Other available mineral metabolism disorders should also be treated (for example, occurring after operations on the thyroid and parathyroid glands, hypoparathyroidism or decrease calcium absorption in the intestine) and ensure regular monitoring of patients with hypocalcemia. To reduce the risk of kidney function disorders Observe the following guidelines: Aclasta is not recommended for use in patients with severely impaired renal function (KKS should be careful with one Belt application of Aclasta with drugs that can have a significant impact on kidney function. Before administration of the drug, creatinine levels should be determined in the blood plasma. Against the background of drug therapy in patients with a history of renal impairment, a transient increase in plasma creatinine may be higher in patients with normal renal function. When using Aclasta in patients with risk factors for the occurrence of renal impairment, determination of plasma creatinine should be take place regularly. Before the introduction of Aclasta should ensure adequate hydration of the body. This is especially important for patients over the age of 65 years, as well as in patients receiving diuretic therapy. The dose of the drug in a single IV infusion should not exceed 5 mg, while the administration of Aclasta should be carried out for at least 15 minutes. osteonecrosis is cancer, concomitant therapy (for example, chemotherapy, radiation therapy, treatment of GCS) and the presence of other comorbid diseases (for example, anemia, coagulopathy, infections, diseases of the teeth in history). Osteonecrosis of the jaw with the administration of bisphosphonates has not been established; dental operations should be avoided, since recovery times after these operations may be extended.Before starting treatment with bisphosphonates, it is necessary to conduct a dental examination and perform the necessary preventive procedures in advance for patients with risk factors (cancer, chemotherapy, treatment with glucocorticosteroids; lack of oral hygiene). During osteonecrosis of the jaw during the treatment with bisphosphonates, dental surgery may worsen the condition of patients . There is no evidence that interrupting treatment with bisphosphonates prior to dental interventions reduces the risk of osteonecrosis of the jaw. Tactics of treating a particular patient should be based on an individual assessment of the risk / benefit ratio. Impact on the ability to drive motor vehicles and control mechanisms There are no data on the impact of Aklasty on the ability to drive motor vehicles and work with mechanisms, but because of the possibility of side effects (including blurred visual perception, inhibition ) Care should be taken when driving and working with machinery.
Use during pregnancy and lactation
The drug Aclasta is contraindicated during pregnancy and lactation (breastfeeding). Data on the use of zoledronic acid in pregnant women are not available. In experimental studies showed the presence of teratogenic effects in one of the experimental species of rodents. The potential risk of use in humans is unknown, so Aklast's drug is contraindicated during pregnancy and during breastfeeding.
Dosage and administration
The drug is administered in the form of / in infusion. The drug should be administered using a valve infusion system that provides a constant infusion rate for at least 15 minutes. Before the introduction of Aklasty should ensure adequate hydration of the body. This is especially important for patients over the age of 65, as well as for patients receiving diuretic therapy. For the treatment of postmenopausal osteoporosis in women and osteoporosis in men, the recommended dose of Aklasty is 5 mg (1 bottle - 100 ml of solution) i / v once a year. If the intake of calcium and vitamin D with food is not enough, patients with osteoporosis should also be given calcium and vitamin D drugs.For the prevention of recurrent fractures in patients with proximal femur fractures, the recommended dose of Aklasty is 5 mg (1 bottle - 100 ml of solution) i / v once a year. Patients with a recent (up to 90 days) fracture of the proximal femur are recommended 2 weeks before the infusion of Aklasty once to take vitamin D in high doses (from 50 000 to 125 000 ME orally or intramuscularly). After a single dose of vitamin D in high doses, it is recommended that patients take 14 days prior to the infusion of Aklasty with calcium supplements (1000 mg /) and vitamin D (800 ME /) daily. After infusion of Aklasty during the year, patients should also take calcium and vitamin D preparations. According to clinical studies, the best results in increasing bone mineral density were achieved with the introduction of Aklasty between 6 and 12 weeks after surgery for a femur fracture. For the treatment of osteoporosis caused by the use of corticosteroids, the recommended dose of Aklasty is 5 mg (1 bottle - 100 ml of solution) i.v. once a year. If the intake of calcium and vitamin D with food is not enough, patients with osteoporosis should also be prescribed calcium and vitamin D drugs. 2 years. An annual assessment of the risk of fractures and an assessment of the clinical response to therapy must be carried out to decide on the need for a re-infusion. For the prevention of postmenopausal osteoporosis, sufficient intake of calcium and vitamin D is very important. In case their dietary intake is insufficient, an additional intake of calcium and vitamin D drugs is recommended. . Since Paget's bone disease is characterized by a high level of bone metabolism, all patients with this disease are advised to take a daily intake of calcium (at least 500 mg of elemental calcium 2) and vitamin D during the first 10 days after the introduction of Aklasty. Repeated treatment of Akad's bone disease of Pedzhet. Currently, there are no special recommendations for re-treating Paget's disease of the bone. In patients who responded to Aklasta's therapy, after a single injection, a long period of remission was observed.The possibility of re-introduction of Aclasta can be considered if a disease recurrence is found in patients based on the following criteria: the lack of normalization of serum alkaline alkaline phosphatase level, its increase in dynamics, as well as the presence of clinical signs of Paget's disease detected during medical examination 12 months after the first dose Aklasty. In case of impaired renal function. With CC ≥ 35 ml / min, no dose adjustment is required. With abnormal liver function No dose adjustment required. In elderly patients Since bioavailability, distribution and elimination are of a similar nature in patients of different ages, elderly patients 65 years of age and older do not need to adjust the dose of the drug. Rules for infusion When preparing and conducting infusions should follow the rules of asepsis. Before the introduction of Aklasty, the quality and color of the solution should be visually assessed. The drug can not be used when changing color or the appearance of undissolved visible particles. Aclasta should not be mixed or administered with any other drugs. Do not allow Aclasta to contact with any solutions containing calcium or any other divalent cations. For the introduction of the drug should always use a separate system for infusion. At the end of the infusion Aklasty unused solution remaining in the vial, can not be used. After opening the bottle, the solution is chemically and physically stable for 24 hours at a temperature of 2 ° to 8 ° C. Aklasty solution is desirable to use immediately after opening the bottle. The solution that is not used immediately can be stored in a refrigerator at a temperature of 2 ° to 8 ° C for no more than 24 hours. If the solution is cooled, it should be kept indoors prior to its introduction until it reaches room temperature.
Side effects
In the treatment of various types of osteoporosis, Pedzhet's bone disease and prevention of new fractures in men and women with proximal femur fractures. With intravenous administration of 5 mg Aklasty 1 time per year for the treatment of postmenopausal osteoporosis in women, osteoporosis in men to prevent 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 disease of the bone, most adverse events were mild or moderate. After the on / in the introduction of Aklasty, the following adverse events were most often noted with a duration of usually 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 these reactions were mild or moderate. With repeated administration of the drug, the severity of adverse events significantly decreased. Below are the adverse events 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 disease of the bone and for the prevention of new fractures in men and women with fractures of the proximal femur. The frequency of development of these adverse events was estimated as follows: Very often (≥ 1/10). Often (≥1 / 100, less than 1/10). Infrequently / sometimes (≥1 / 1 000, less than 1/100). Rarely (≥1 / 10 000, less than 1/1 000). Very rarely (less than 1/10 000), including individual messages. From the side of the central nervous system and peripheral nervous system Often - headache, dizziness. Sometimes - lethargy *, paresthesia, drowsiness, tremor, syncope. From the senses Sometimes - conjunctivitis, pain in the eyes, vertigo. Rarely - uveitis *, episcleritis, iritis. Respiratory system. Sometimes - shortness of breath *, cough. Of the digestive system Often - nausea, vomiting, diarrhea. Sometimes - anorexia *, loss of appetite, dyspepsia *, abdominal pain *, dry mouth, esophagitis *, gastroesophageal reflux, pain in the upper abdomen, constipation. Dermatological reactions Sometimes - rash, hyperhidrosis *, pruritus, erythema. From the musculoskeletal system Often - arthralgia *, myalgia *, pain in the bones, pain in the back and limbs. Sometimes - pain in the neck, swelling in the joints *, muscle spasms, pain in the shoulder girdle, pain in the chest * musculoskeletal origin, weakness in muscles, stiffness in muscles and joints, arthritis, musculoskeletal pain. On the part of the urinary system Sometimes - increased serum creatinine, pollakiuria, proteinuria. From the hemopoietic system Sometimes - anemia. Since the cardiovascular system Sometimes - increased blood pressure, sudden reddening of the face. Infections and invasions Sometimes - flu, nasopharyngitis. On the part of the body as a whole. Very often - a temperature increase. Often - flu-like syndrome, chills, fatigue *, asthenia, pain *, general malaise.Infrequently - peripheral edema, thirst *, irritability *, chest pain (not associated with heart disease). * - In some studies, the frequency of these adverse events increased as follows: Very often - myalgia, arthralgia, fatigue, pain. Often - lethargy, shortness of breath, dyspepsia, esophagitis, abdominal pain, hyperhidrosis, stiffness in muscles, swelling in the joints, pain in the chest of musculoskeletal origin, stiffness in the joints, anorexia, thirst, increased excitability. Infrequently - uveitis. In the course of separate studies, the following adverse events were registered, the development rate of which in the Aclasta group was lower than in patients who did not receive the drug: Red eyes. Increasing the content of C-reactive protein. Hypocalcemia. Taste disorders. Toothache. Gastritis. Feeling of palpitations. Reactions at the injection site. When using Aclasta in patients with postmenopausal osteoporosis, the overall incidence of atrial fibrillation during treatment with Aklasty was 2.5% (96 people out of 3862) compared with 1.9% (75 out of 3852 patients) in patients not treated with the drug (placebo group). In 1.3% of patients (51 patients from 3862) who received Aclasta, and 0.6% (22 people from 3852) in the placebo group, this undesirable phenomenon was regarded as serious. The reason for the increase in the frequency of atrial fibrillation during therapy with Aklastaya in this study has not been established. The increased incidence of atrial fibrillation compared with placebo, noted in this study, was not found in other clinical studies of zoledronic acid. When using Aclasta for the prevention of postmenopausal osteoporosis, the overall safety profile of the drug was comparable to that in the treatment of postmenopausal osteoporosis, with the exception of adverse events that occurred within 3 days after the infusion: pain, fever, chills, myalgia, nausea, headache, increased fatigue, arthralgia whose frequency was higher in women who received the drug for the prevention of postmenopausal osteoporosis. Most of these adverse events were mild or moderate in severity and occurred within three days after onset.With repeated administration of the drug, the severity of these adverse events was significantly reduced. The following are undesirable effects, possibly associated with the use of the drug for the prevention of postmenopausal osteoporosis (in the opinion of the attending physicians): 1 - adverse events that were observed more than 1 time with the introduction of Aclasta for the prevention of postmenopausal osteoporosis and not registered when using the drug to treat various types of osteoporosis Paget's bone disease and for the prevention of new fractures in men and women with proximal femur fractures; 2 - adverse events, the frequency of which was higher in women who received the drug for the prevention of postmenopausal osteoporosis (compared with other categories of patients). The frequency of development of these adverse events was estimated as follows: Very often (more than 1/10) Often (more than 1/100, less than 1/10). Infrequently (more than 1/1 000, less than 1/100). Mental disorders Sometimes - anxiety. From the nervous system Very often - a headache. Often - tremor, lethargy. Infrequently - reduced sensitivity, taste disturbances. On the part of the organ of vision Often - conjunctivitis, pain in the eyes, iritis. Infrequently - blurred vision. On the part of the digestive system. Very often - nausea. Often - anorexia, abdominal pain, pain in the upper abdomen, constipation. On the part of the skin and subcutaneous tissue Often - excessive sweating at night. From the musculoskeletal system Very often - myalgia. Often - musculoskeletal pain, muscle spasm, pain in the chest 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. Very often - pain, chills. Often - peripheral edema, reactions at the injection site, non-cardiac pain in the chest. On the part of laboratory parameters Patients with osteoporosis while using Aclasta in 0.2% of cases showed a decrease in calcium concentration (When using the drug in patients with femur fractures, osteoporosis in men and osteoporosis caused by GCS, there was no decrease in plasma calcium concentration When using the drug in patients for the prevention of postmenopausal osteoporosis, there was no decrease in plasma calcium concentration. In patients with Paget's disease in approximately 1% of cases detected there was transient hypocalcemia, accompanied by clinical manifestations.On the part of the urinary system With the on / in the introduction of bisphosphonates, including zoledronic acid, there were cases of impaired renal function, manifested by increased levels of serum creatinine and in rare cases, acute renal failure. Impaired renal function with zoledronic acid was observed in patients with a history of either renal disease or additional risk factors (for example, cancer, concomitant chemotherapy, use of nephrotoxic drugs, diuretics, or severe dehydration). Most of these patients received therapy with zoledronic acid at a dose of 4 mg every 3-4 weeks, but in some cases renal failure was noted after a single use of zoledronic acid. During treatment with Aclasta for 3 years in patients with postmenopausal osteoporosis, the frequency of elevated blood creatinine levels and the development of renal failure did not differ from that with placebo in patients who received placebo. In patients receiving Aclasta, a transient increase in the level of creatinine was somewhat more frequent within 10 days after the infusion compared with placebo (1.8% and 0.8%, respectively). When Aklasty was used for 2 years in men with osteoporosis, the incidence of changes in creatinine clearance and the development of renal dysfunction was similar to that in the alendronic acid group. In patients with osteoporosis caused by the use of corticosteroids, during treatment with Aklasty, the frequency of changes in creatinine clearance and the development of renal dysfunction was similar to that in the risedronic acid group. Local reactions When using Aclasta in patients with postmenopausal osteoporosis, in 0.7% of cases, redness, swelling and / or pain were observed at the injection site. In patients with femoral fractures, the incidence of local reactions at the injection site was comparable to that in the placebo group. In the treatment of osteoporosis in men, the frequency of development of reactions at the site of injection of Aklasty was 2.6% (compared with 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 development of reactions at the injection site of Aklasty was 1.1% (compared to 2.0% in the placebo group).Other Cases of osteonecrosis (most often jaws) occurred mainly in cancer patients receiving treatment with bisphosphonates, after tooth extraction or other dental procedures. The majority of these patients showed symptoms of a local inflammatory process, including osteomyelitis. In clinical studies in patients with osteoporosis, a case of osteonecrosis of the jaw occurred in 1 patient who took Aclasta, and in 2 patients who took placebo. In all 3 cases, the resolution of the process was noted. When using Aclasta in patients with femoral fractures, with osteoporosis in men and osteoporosis caused by taking GCS, as well as when using the drug for the prevention of postmenopausal osteoporosis, there were no cases of osteonecrosis of the jaw. During treatment with Aclasta, the following adverse events were noted in clinical practice without an indication of a causal relationship with the use of the drug (frequency not established): hypersensitivity reactions, including rare cases of bronchial obstruction, urticaria, angioedema, and individual reports on the development of anaphylactic reactions, in t. h anaphylactic shock. In rare cases, when using Aclasta in clinical practice, patients had impaired renal function, including renal failure, requiring hemodialysis, especially in patients with a history of either renal disease or additional risk factors (for example, with concomitant therapy with nephrotoxic drugs, diuretics, or with severe dehydration). In very rare cases, the development of the following adverse events has been reported: dehydration due to fever, vomiting and diarrhea that occur after drug administration; pronounced decrease in blood pressure in patients with risk factors, osteonecrosis of the jaw, scleritis and inflammation in the orbital area.
Overdose
Currently, there are limited clinical data on cases of drug overdose. Patients who received the drug in a dose that exceeds the recommended should be under the supervision of a physician. Symptoms: in acute overdose of zoledronic acid (limited data), renal dysfunction was noted, including renal failure, hypocalcemia, hypophosphatemia, hypomagnesaemia. Clinical symptoms: numbness, tingling sensation, especially in the area of the mouth, muscle spasms. Treatment: in / in the introduction of solutions containing calcium ions, magnesium and phosphates.
Interaction with other drugs
Solution Aklasty should not be mixed with infusion solutions containing calcium ions (for example, in one system for IV drip).
special instructions
The physician should inform patients of the main manifestations of hypocalcemia and ensure regular monitoring of patients at risk. Aklast's therapy in patients with Paget's disease of the bone should be performed only by qualified doctors with experience in treating this disease. Before the appointment of the drug trace