Composition, form of production and packaging
Solution for infusions is transparent, colorless.
100 ml
zoledronic acid monohydrate 5.33 mg,
which corresponds to the content of zoledronic acid (anhydrous) 5 mg
Excipients: mannitol - 4950 mg, sodium citrate dihydrate - 30 mg, water d / and - up to 100 ml.
100 ml - polyethylene bottles (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Inhibitor of bone resorption, bisphosphonate.
Zoledronic acid belongs to the class of nitrogen-containing bisphosphonates, it acts predominantly on the bone, suppresses the activity of osteoclasts and resorption of bone tissue.
Selective action of bisphosphonates on bone tissue is based on a high affinity for mineralized bone tissue. After intravenous administration, zoledronic acid is rapidly redistributed into bones and, like other bisphosphonates, is localized primarily at bone remodeling sites.
The main molecular target of zoledronic acid in osteoclast is the enzyme farnesyl pyrophosphate synthetase (FPS), while the possibility of other mechanisms of action of the drug is not ruled out. The long period of action of the drug is determined by a high affinity for the active center of FBS and a pronounced affinity for the mineralized bone tissue.
Against the backdrop of using the drug Aklast, there is a rapid decrease in bone turnover from elevated postmenopausal values ​​to the lowest acceptable level (by day 7 for bone resorption and by 12 weeks for bone formation). Subsequently, bone exchange rates stabilize within pre-menopausal values.
Experimental models of accelerated osteorectomy showed that zoledronic acid significantly inhibits bone resorption without undue influence on the formation, mineralization and mechanical properties of bone tissue, dose-dependently decreases the activity of osteoclasts and the frequency of activation of new foci of remodeling both in trabecular (spongy) and cortical (compact ) of bone tissue without causing the formation of fibrous bone and aberrant accumulation of the osteoid, as well as bone mineralization defects.
With the exception of high antiresorptive action, the effect of zoledronic acid on bone tissue is similar to that of other bisphosphonates.
When using the drug Aklasta in patients with postmenopausal osteoporosis (values ​​of 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 3 years of treatment, as well as a reduction in the risk of developing one or more new / repeated fractures and moderate / severe fractures of the vertebrae by 60-70%. In patients with osteoporosis at the age of 75 years and older, the risk of developing vertebral fractures was reduced by 61% when treated with the drug Aklast.
In the treatment with Aklast, the relative risk of developing femoral fractures by the 3rd year of therapy was reduced by 40%. In the treatment with Aklast, the relative risk of developing any clinical fractures, non-vertebral fractures of any location (excluding fractures of phalanges of fingers and bones of the facial part of the skull) decreased by 33% and 25%, respectively. With the use of Aklasty for 3 years in patients with postmenopausal osteoporosis, there was 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.
On the background of therapy with Aklasta for 1 year in patients with postmenopausal osteoporosis, there was a decrease in the level of bone isoenzyme of AP, N-terminal propeptide of type I collagen (PINP) and ОІ-C-terminal telopeptides of blood to pre-menopausal values. With repeated injections of the drug for 3 years, there was no further decrease in the blood content of markers of bone remodeling.
The use of Aklasty for 3 years significantly reduced the rate of loss of growth in patients, and also increased physical activity in postmenopausal women with osteoporosis and vertebral fractures.
When the drug was administered to patients (men and women) with recent (within 90 days) fractures of the proximal femur (caused by minimal trauma and requiring surgical intervention), a decrease in the incidence of subsequent osteoporotic fractures of any localization by 35% compared with placebo clinically significant vertebral fractures - by 46%, non-vertebral fractures - by 27%). When applying the drug Aklasta in this category of patients, the relative risk of deaths (regardless of their cause) decreased by 28%. In patients with fractures of the femur, the use of the drug Aklasta for 2 years resulted in an increase in the BMD of the proximal femur in general and in the femoral neck region by 5.4% and 4.3%, respectively.
When applying the drug once a year, in men with primary (senile) or secondary (with hypogonadism) osteoporosis within 2 years, there was a marked increase in the lumbar spine of the lumbar spine.
In patients with osteoporosis caused by the use of GCS, Aklast therapy during the year also significantly increased BMD (lumbar vertebrae, cervix, trochanter, radius), without adversely affecting bone structure and mineralization.
With the use of the drug Aklasta for the prevention of postmenopausal osteoporosis, every 2 years in women with osteopenia and postmenopausal duration less than 5 years and more, an increase in the MIC of the lumbar vertebrae by 6.3% and 5.4%, respectively. With the introduction of the drug once in 2 years, the BMD of the femur increased by 4.7% and 3.2% in women with a postmenopause duration of less than 5 years, respectively.
In women with different postmenopausal durations, with the introduction of Aklasty, a decrease in the concentration of ОІ-C-terminal telopeptides of blood by 44-46% (before the premenopausal level) and N-terminal propeptide of collagen type I (PINP) by 55-40% .
In the treatment of Aklastoy, patients with bone disease of Paget had a statistically significant, rapid and long-term therapeutic response, normalization of bone metabolism and activity of AP in the blood plasma.
The drug is also highly effective in patients who received previous treatment with oral bisphosphonates. Therapeutic response in the application of Aklasty lasts longer than with the use of Residronic acid (7.7 years compared with 5.1 years). The marked reduction of the pain syndrome at 6 months after a single injection of the drug Aklasta at a dose of 5 mg is comparable to the analgesic effect of risedron 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 disturb the processes of bone remodeling and mineralization, and contributes to the preservation of normal architectonics of the trabecular bone.
PHARMACOKINETICS
Pharmacokinetics 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.
Distribution
After the start of the drug, the concentration of zoledronic acid in the blood plasma increases rapidly, reaching a maximum at the end of the infusion. After the infusion, a rapid decrease in the level of zoledronic acid in the blood plasma (to <10% of C max after 4 h and up to <1% of C max after 24 h), then a low concentration of the drug remains for a long period in blood plasma not exceeding 0.1% of C max ).
Increasing the infusion time from 5 to 15 min leads to a 30% decrease in the concentration of zoledronic acid at the end of the infusion, but does not affect the AUC .
The binding of zoledronic acid with plasma proteins is low (43-55%) and does not depend on its concentration.
During the first 24 hours, 39 В± 16% of the administered dose is detected in the urine. The rest of the drug binds solely to bone tissue, after which a very slow release of zoledronic acid back from the bone tissue into the systemic circulation and its excretion by the kidneys.
There was no cumulation of the drug with repeated administration every 28 days.
Metabolism and excretion
Zoledronic acid is not metabolized. It is excreted by the kidneys unchanged in 3 stages: rapid two-phase elimination from the systemic blood stream with T 1/2 0.24 h (? -phase) and 1.87 h (? -phase) and a long phase with a finite T 1/2 of 146 h (? - phase). Rapid reduction in the concentration of the drug (? And? Phase) in blood plasma is probably associated with a rapid distribution of zoledronic acid in bone tissue and excretion by the kidneys.
The total plasma clearance of the drug is 5.04 В± 2.5 l / h and does not depend on the dose, sex, 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.
Pharmacokinetics in special clinical cases
The renal clearance of zoledronic acid correlates with QC and is 75 В± 33% of the CK, the mean of which is 84 В± 29 ml / min (range 22-143 ml / min) in 64 patients included in the pharmacokinetic study.
A slight increase in AUC 0-24 (30-40%) for mild and moderate renal dysfunction, as compared to the norm, and the absence of cumulation of the drug with repeated administration regardless of renal function, suggest that there is no need to correct the dose of zoledronic acid at lung (KK 50-80 ml / min) and moderate (KK 35-50 ml / min) renal dysfunction.
The use of the drug in patients with severe renal dysfunction (CK <35 ml / min) is contraindicated because of the increased risk of renal failure.
INDICATIONS
- postmenopausal osteoporosis (to reduce the risk of fracture of the femur, vertebra and extraratinal fractures, to increase bone mineral density);
- prevention of subsequent (new) osteoporotic fractures in men and women with fractures of the proximal femur;
osteoporosis in men;
- prevention and treatment of osteoporosis caused by the use of SCS;
- prevention of postmenopausal osteoporosis (in patients with osteopenia);
- Paget's bone disease.
DOSING MODE
The drug is administered as an IV infusion. The administration of the drug should be carried out with the help of a valvular infusion system, providing a constant infusion rate, for at least 15 minutes.
Before the introduction of the drug Aklast should provide adequate hydration of the body. This is especially important for elderly patients (? 65 years), as well as for patients receiving diuretic therapy.
For the treatment of postmenopausal osteoporosis in women and osteoporosis in men, the recommended dose of Aklast is 5 mg (1 vial - 100 ml solution) iv once a year. If intake of calcium and vitamin D with food is not enough, patients with osteoporosis should additionally be prescribed calcium and vitamin D.
To prevent subsequent fractures in patients with fractures of the proximal femur, the recommended dose of Aklast is 5 mg (1 vial - 100 ml solution) iv once a year.
Patients with a recent (up to 90 days) fracture of the proximal femur are recommended to take single vitamin D at high doses (from 50,000 to 125,000 IU orally or IM) two weeks before the first infusion of the drug Aklast. With a single application of the drug Aklast, patients are recommended to take calcium preparations (1000 mg / day) and vitamin D (800 IU / day) every day for 14 days before the infusion. After infusion of the drug Aklasta throughout the year, patients should also take calcium and vitamin D.
To prevent subsequent fractures in patients with fractures of the proximal femur, the first infusion of the drug should be performed 2 or more weeks after the operation.
For the treatment of osteoporosis caused by the use of GCS , the recommended dose of Aklast is 5 mg (1 vial - 100 ml solution) iv once a year. If intake of calcium and vitamin D with food is not enough, patients with osteoporosis should additionally be prescribed calcium and vitamin D.
For the prevention of postmenopausal osteoporosis, the recommended dose of Aklasty is 5 mg (the contents of one vial of the drug - 100 ml of solution) iv once every 2 years.
An annual assessment of the risk of fracture and an evaluation of the clinical response to therapy should be conducted to determine whether a re-infusion is necessary.
For the prevention of postmenopausal osteoporosis, sufficient intake of calcium and vitamin D is very important. In case their intake with food is insufficient, an additional intake of calcium and vitamin D preparations is recommended.
For the treatment of Paget's bone disease , a single IV dose of 5 mg is recommended. Paget's bone disease is characterized by a high level of bone metabolism. Due to the rapid onset of the effect on bone metabolism, after the application of the drug Aklast, within the first 10 days after the infusion, the development of transient hypocalcemia is possible. Against the background of the use of the drug Aklast recommended taking a sufficient dose of vitamin D. In addition to this, it is strictly recommended to take an adequate dose of calcium (not less than 500 mg of elemental calcium 2 times / day) for at least the first 10 days after the administration of the drug Aklasta.
Repeated treatment with drug Aklasta bone disease Paget. After a single application of the drug Aklasta with bone disease Paget, patients had a long (about 7.7 years on average) remission. Because Paget's bone disease is a chronic disease, repeated use of the drug is recommended. Repeated use of the drug in Paget's disease consists in its iv administration in a dose of 5 mg after 1 year or more from the start of treatment. The interval between injections of the drug Aklasta should be determined individually based on the effectiveness of treatment and the results of the study of the level of alkaline phosphatase, which must be done every 6-12 months. In the absence of clinical signs of deterioration, such as bone pain and compression symptoms, and / or radiologic signs of disease progression, the next infusion of the drug Aklast can be performed no earlier than 12 months after the first.
Patients with impaired renal function with QC? 35 ml / min no dose adjustment is required.
Patients with impaired liver function do not need a dose adjustment.
Patients of the elderly (65 years and older) do not need a dose adjustment; bioavailability, distribution and excretion of zoledronic acid are similar in patients of different ages.
Instructions for use
When preparing and conducting infusions, you should follow the rules of asepsis.
Before the introduction of the drug, Aklast should visually assess the quality and color of the solution. The drug can not be used when changing color or the appearance of undissolved visible particles.
The drug Aklast should not be mixed or injected with any other drugs. Do not allow the contact of the drug Aklast with any solutions containing calcium or any other divalent cations.
To administer the drug, you should always use a separate system for infusion.
After the infusion of the drug Aklast, the unused solution remaining in the vial can not be used.
A solution of the drug Aklast should be used immediately after opening the vial. Unused immediately solution can be stored in the refrigerator at a temperature of 2 В° to 8 В° C for not more than 24 hours. If the solution is cooled, it must be kept in the room before it reaches room temperature.
SIDE EFFECT
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 injection of the drug Aklasta in a dose of 5 mg once a year for the treatment of postmenopausal osteoporosis in women, osteoporosis in men, for the prevention of subsequent fractures in men and women with fractures of the proximal femur, for the prevention and treatment of osteoporosis caused by the use of GCS and for the treatment of Paget's bone disease, most of the adverse events were mild or moderate.
After IV injection of the drug Aklast, the following undesirable events lasting usually not more than 3 days ("postdose" symptoms) were most often observed: 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 the repeated administration of the drug, the severity of adverse events decreased significantly.
Below are the adverse events possibly related (in the opinion of the attending physicians) with the use of the drug for treatment of various types of osteoporosis, Paget's disease of bone and to prevent new fractures in men and women with fractures of the proximal femur.
The incidence of these adverse events was assessed as follows: very common (1/10?); common (1/100, <1/10?); infrequently (1/1, 000, <1/100?); rare (? 1/10 000, <1/1 000), very rare (<1/10 000), the frequency is unknown (on separate reports from clinical practice).
From the nervous system: often - headache, dizziness; infrequently - * lethargy, paresthesia, somnolence, tremor, syncope, dysgeusia.
From the senses:often - redness of the sclera; infrequently - conjunctivitis, eye pain, vertigo; rarely - * uveitis, episcleritis, iritis, the frequency is unknown - an inflammation of the sclera and eye socket.
The respiratory system: rarely - shortness of breath *, cough.
From the digestive system: often - nausea, vomiting, diarrhea; infrequently - * anorexia, decreased appetite, dyspepsia *, abdominal pain *, dry mouth, oesophagitis *, gastroesophageal reflux disease, pain in the upper abdomen, constipation, gastritis (in patients receiving GCS), toothache.
Skin and subcutaneous tissue: rare - rash, rash *, pruritus, erythema.
On the part of the musculoskeletal system and connective tissue:often - arthralgia * * myalgia, bone pain, pain in the back and limbs; infrequently - a pain in the neck, swelling in the joints *, muscle cramps, pain in the shoulder girdle, pain in the chest * musculoskeletal origin, muscle weakness, stiffness in muscles * and joints *, arthritis, musculoskeletal pain; the frequency is unknown - osteonecrosis of the jaw.
From the urinary system: rarely - increase in blood creatinine, pollakiuria, proteinuria; frequency is unknown - kidney failure.
From hemopoiesis system: rarely - anemia.
Cardio-vascular system: often - atrial fibrillation; infrequently -increased blood pressure, sudden reddening of the face, palpitations; the frequency is unknown - marked reduction of blood pressure (in patients with risk factors).
Mental disorders: rarely - insomnia.
Infections and infestations: rare - influenza, nasopharyngitis.
On the part of the body in general and violations at the injection site: very often - fever; often - flu-like symptoms, chills, fatigue *, asthenia, pain *, malaise, infusion site reactions; infrequently -peripheral edema, thirst *, acute phase reaction *, chest pain (not associated with heart disease); frequency is unknown - dehydration (develops secondary to a postinfuzionnymi symptoms such as fever, vomiting, and diarrhea).
* - In some studies, the frequency of adverse events data, increased as follows: very often - myalgia, arthralgia, fatigue, pain; often - lethargy, shortness of breath, indigestion, esophagitis, abdominal pain, rash, muscle stiffness, swelling in the joints, pain in the chest musculoskeletal origin, stiffness in the joints, anorexia, thirst, acute phase reaction; infrequently - uveitis.
eye redness, elevated levels of C-reactive protein, hypocalcemia, dysgeusia, toothache, gastritis, palpitations, reactions: In the individual studies the following adverse events, the incidence of which Aklasty group was lower than in patients not receiving the drug have been reported at the site of injection.
In applying the drug Aklasta patients with post-menopausal osteoporosis overall incidence of atrial fibrillation during therapy drug Aklasta was 2.5% (96 out of 3862) compared to 1.9% (75 out of 3852 patients) in patients not treated with drug (placebo group) . In 1.3% of patients (patient 51 of 3862), receiving Aklastu, and 0.6% (22 patients out of 3852) in the placebo group, this adverse event was regarded as serious. The reason for increased incidence of atrial fibrillation on the background of therapy with Aklasta not established in this study. Increasing the frequency of atrial fibrillation in comparison with placebo, noted in this study was not detected in other clinical trials of zoledronic acid.
Prevention of postmenopausal osteoporosis
In applying Aklasta drug for post-menopausal osteoporosis prevention overall safety profile was comparable to that in the treatment of post-menopausal osteoporosis, except undesirable phenomena occurring within 3 days after infusion (pain, fever, chills, myalgia, nausea, headache, fatigue, arthralgia) whose frequency was higher in women who received the drug for prevention of postmenopausal osteoporosis. The majority of these adverse events were mild or moderate severity and took place within 3 days after presentation. With repeated drug administration data severity of adverse events is significantly decreased.
Below are undesirable phenomena, possibly related to use of the drug for prevention of postmenopausal osteoporosis (according to the attending physicians): 1) adverse events noted more than one time when administered Aklasta drug for prevention of postmenopausal osteoporosis, and is not registered in the application of a drug for treating various types of osteoporosis , bone Paget's disease and for the prevention of new fractures in men and women with fractures of the proximal femur; 2) undesirable phenomena whose frequency was higher in women who received the drug for prevention of postmenopausal osteoporosis (in comparison with other categories of patients).
The incidence of adverse events data, estimated as follows: very common (1/10?); common (1/100, <1/10?); infrequently (? 1/1000, <1/100).
Mental disorders: rare - anxiety.
From the nervous system: very often - headache; often - tremor, confusion; infrequently - decreased sensitivity, dysgeusia.
From a sight organ: often - conjunctivitis, eye pain, iritis, rarely - blurred vision.
From the digestive system: very often - nausea; often - anorexia, abdominal pain, pain in the upper abdomen, constipation.
Skin and subcutaneous tissue: often - increased sweating at night.
On the part of the musculoskeletal system and connective tissue: very often - myalgia; often - muscle spasm, pain in the chest musculoskeletal origin, pain in jaw, pain in the neck; infrequently - the pain in his side.
On the part of the body in general and violations at the injection site: very often - pain, chills; often - peripheral edema, reaction at the site of administration, non-cardiac pain in the chest area.
Changes in laboratory results
In patients with post-menopausal osteoporosis Aklasta against application of the drug in 0.2% of cases there was a decrease of calcium concentration (<1.87 mmol / l) in serum hypocalcemia clinical signs were not observed in this case.
In applying the drug in patients with fractures of the femur, in men with osteoporosis and osteoporosis caused by GCS, there was no decrease in calcium concentration in blood plasma of <1.87 mmol / L.
In applying the drug in patients for the prevention of post-menopausal osteoporosis is not observed decrease in plasma calcium concentration <1.87 mmol / L.
In patients with Paget's disease of bone in approximately 1% of cases detected transient hypocalcemia, accompanied by clinical symptoms.
Renal function
on / in administration of bisphosphonates, including zoledronic acid, there were cases of impaired renal function with an increase in serum creatinine concentration, and in rare cases with acute renal failure.
Impaired renal function during treatment with zoledronic acid was observed in patients with the presence or renal disease history, any additional risk factors (e.g. advanced age, concomitant use of nephrotoxic drugs, diuretics, cancer patients receiving chemotherapy or severe dehydration) with predominance in patients receiving the drug at a dose of 4 mg every 3-4 weeks.
Thus in patients with impaired renal function or any of the above risk factors renal failure requiring dialysis, or resulting in death, is rare. Caution must be exercised when using the drug Aklasta in patients with concomitant diseases and cancer chemotherapy due to increased risk of developing renal failure.
When therapy with Aklasta for 3 years in patients with postmenopausal osteoporosis, increase incidence of creatinine in the blood plasma and renal failure was similar to that with placebo. Patients receiving Aklasta drug somewhat more often observed a transient increase in serum creatinine during 10 days after the infusion as compared to placebo (1.8% and 0.8% respectively).
In applying the drug Aklasta for 2 years in men with osteoporosis frequency changes QC and development of renal dysfunction was similar to that in the group of alendronic acid.
Patients with osteoporosis caused by the use of SCS, during therapy drug Aklasta frequency changes QC and development of renal dysfunction was similar to that in the group receiving risedronic acid.
In applying the drug in patients with fractures of the femur changes the frequency of QC and renal function disorders was similar to that in the placebo group. In applying the drug in patients for the prevention of postmenopausal osteoporosis frequency changes QC and developmental disorders nochek function was similar to that in the placebo group.
Reactions at the site of administration
In applying Aklasta drug in patients with post-menopausal osteoporosis in 0.7% of cases were marked redness, swelling and / or soreness at the injection site. Patients with hip fracture incidence of local reactions at the injection site was comparable to that in the placebo group.
In the treatment of osteoporosis in men incidence of reactions at the injection site Aklasta was 2.6% (compared with 1.4% in alendronic acid group).
In patients with osteoporosis caused by the use of corticosteroids, there was no reaction at the injection site.
In applying the drug for prevention of postmenopausal osteoporosis incidence of injection site reactions in Aklasta preparation was 1.1% (compared with 2.0% in the placebo group).
osteonecrosis of the jaw
Cases of osteonecrosis (most frequently - jaw) were primarily in cancer patients treated with bisphosphonates (including zoledronic acid - rarely) in most cases after tooth extraction or other dental procedures. Most of these patients had signs of local infection-inflammation, including osteomyelitis. In clinical studies in patients with osteoporosis case of osteonecrosis of the jaw occurred in 1 patient, which took Aklastu, and in 1 patient the placebo. In both cases it mentioned resolution process.
In applying the drug Aklasta in patients with fractures of the femur, osteoporosis in men and osteoporosis caused by taking corticosteroids, as well as the use of the drug for the prevention of postmenopausal osteoporosis were no cases of osteonecrosis of the jaw.
Anecdotal reports of adverse events
on background therapy with Aklasta in clinical practice were observed following adverse events were no indications of a causal relationship with the drug (the frequency of adverse events has not been established): hypersensitivity reactions, including rare cases of bronchoconstriction, urticaria, angioedema, and individual on the development of communication anaphylactic reactions / shock.
In rare cases, when using the drug Aklasta in clinical practice, patients had impaired renal function, including renal failure requiring dialysis, or cases of death, particularly in patients with the presence or renal disease history, any additional risk factors (e.g. advanced age , concomitant therapy with nephrotoxic drugs, diuretics or severe dehydration).
CONTRAINDICATIONS
- severe disorders of mineral metabolism, including hypocalcemia;
- severe renal impairment (creatinine clearance <35 mL / min);
- Pregnancy;
- lactation period (breastfeeding);
- child and adolescence to 18 years (since the safety and efficacy of Aklasty in these patients has not been studied);
- hypersensitivity to zoledronic acid or any other component of the formulation;
- Hypersensitivity to any bisphosphonates.
With caution should be prescribed to patients with impaired renal mild and moderate severity function; patients in a state of severe dehydration; patients with concomitant diseases and cancer chemotherapy in history; patients with "aspirin" asthma history; simultaneously with drugs able to exert a significant influence on renal function (e.g., aminoglycoside antibiotics-or diuretic causing dehydration).
PREGNANCY AND LACTATION
Data on the use of zoledronic acid in pregnant women are missing.
Potential risk in human use is not known, so the drug Aklasta is contraindicated in pregnancy and during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function in QA> 35 ml / min is required dose correction. Aklastu not recommended for patients with severe renal impairment (creatinine clearance <35 mL / min) due to lack of sufficient clinical experience with the drug in these patients.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with impaired liver function is not required dose correction.
APPLICATION FOR CHILDREN
Contraindicated: childhood and adolescence to 18 years (since the safety and efficacy of Aklasty in these patients has not been studied).
APPLICATION IN ELDERLY PATIENTS
Since the bioavailability, distribution and elimination are similar in character in patients of all ages, elderly patients aged 65 and older do not need dose adjustment.
SPECIAL INSTRUCTIONS
The physician should inform the patient about the main manifestations of hypocalcemia and ensure regular monitoring of patients at risk.
Therapy with Aklasta in patients with Paget's disease of bone should be performed only by qualified physicians experienced in the treatment of this disease.
To reduce the occurrence of adverse events noted for 3 days after administration of the drug can be assigned to paracetamol or ibuprofen shortly after infusion Aklasta preparation.
Zoledronic acid is an active substance like Aklasta drug and drug Zometa В® (a treatment for cancer patients), but medicaments data are not interchangeable and need not be applied simultaneously.
In the presence of hypocalcemia before drug application necessary to carry out treatment Aklasta adequate doses of calcium and vitamin D. It should also hold other existing therapies disorders of mineral metabolism (e.g., occurring after operations on the thyroid and parathyroid glands, gipoparatireoze or reducing calcium absorption in the gut) and provide regular monitoring of patients
