Comparison of the effectiveness of Aklasta and Zometa
The effectiveness of Aklasta is quite similar to Zometa - this means that the ability of the drug substance to provide the maximum possible effect is similar.
For example, if the therapeutic effect of Aklasta is more pronounced, then using Zometa even in large doses will not achieve this effect.
Also, the speed of therapy - an indicator of the speed of therapeutic action - is approximately the same for Aklasta and Zometa. And bioavailability, that is, the amount of a drug reaching its site of action in the body, is similar. The higher the bioavailability, the less it will be lost during absorption and use by the body.
Comparison of safety of Aklasta and Zometa
The safety of a drug includes many factors.
At the same time, in Aklasta it is quite similar to Zometa. It is important where the drug is metabolized: drugs are excreted from the body either unchanged or in the form of products of their biochemical transformations. Metabolism occurs spontaneously, but most often involves major organs such as the liver, kidneys, lungs, skin, brain and others. When assessing metabolism in Aklasta, as well as in Zometa, we look at which organ is the metabolizing organ and how critical the effect on it is.
The risk-benefit ratio is when the prescription of a drug is undesirable, but justified under certain conditions and circumstances, with the obligatory observance of caution in use. At the same time, Aklasta does not have any risks when used, just like Zometa.
Also, when calculating safety, it is taken into account whether only allergic reactions occur or possible dysfunction of the main organs. In other matters, as well as the reversibility of the consequences of using Aklasta and Zometa.
Aklasta solution for infusion 5 mg/100 ml bottle 100 ml 1 pc. in Moscow
Treatment of various types of osteoporosis, Paget's disease of bone and prevention of new fractures in men and women with fractures of the proximal femur.
With intravenous administration 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 GCS and for treatment of Paget's disease of bone, most adverse events (AEs) were mild or moderate. After intravenous administration of the drug Aklasta, the following AEs were most often observed in these patients: usually lasting no more than 3 days (“post-dose” symptoms) - fever (18.1%), myalgia (9.4%), influenza-like syndrome (7. 8%), arthralgia (6.8%), headache (6.5%). Most of the above-mentioned AEs observed within 3 days after drug administration were mild or moderate. With repeated administration of the drug, the severity of these AEs decreased significantly. Below are AEs that may be associated (in the opinion of the treating physicians) with the use of the drug for the treatment of various types of osteoporosis, Paget's disease of bone and for the prevention of new fractures in men and women with fractures of the proximal femur.
The incidence of these AEs was assessed as follows: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated reports.
From the nervous system:
often - headache, dizziness; sometimes - lethargy*, paresthesia, drowsiness, tremor, fainting.
From the senses:
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, pain in the upper abdomen, constipation.
From the skin and subcutaneous tissue:
sometimes - rash, hyperhidrosis*, itching, erythema.
From the musculoskeletal system and connective tissue:
often - arthralgia*, myalgia*; bone pain, 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* of musculoskeletal origin, muscle weakness, stiffness in the muscles* and joints*, arthritis, musculoskeletal pain.
From the urinary system:
sometimes - increased blood creatinine levels, 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.
From the body as a whole:
very often - increased temperature; often - flu-like syndrome, chills, increased fatigue*, asthenia, pain*, general malaise; Uncommon: peripheral edema, thirst*, increased excitability*, chest pain (not associated with heart disease).
*Note:
in some studies, the frequency of these AEs increased as follows: very often - myalgia, arthralgia, fatigue, pain; often - lethargy, shortness of breath, dyspepsia, esophagitis, abdominal pain, hyperhidrosis, muscle stiffness, swelling in the joints, pain in the chest area of musculoskeletal origin, stiffness in the joints, anorexia, thirst, increased excitability; infrequently - uveitis.
In separate studies, the following AEs were recorded, the incidence of which in the Aklasta group was lower than in patients who did not receive the drug: redness of the eyes, increased levels of C-reactive protein, hypocalcemia, taste disturbances, toothache, gastritis, palpitations , reactions at the injection site.
When using Aklasta in patients with postmenopausal osteoporosis, the overall incidence of atrial fibrillation during treatment with Aklasta was 2.5% (96 out of 3862 people) compared to 1.9% (75 out of 3852 patients) in patients not treated with the drug (placebo group). In 1.3% of patients (51 out of 3862 patients) receiving Aklasta, and in 0.6% (22 out of 3852) in the placebo group, this adverse event was assessed as serious. The reason for the increased incidence of atrial fibrillation during therapy with Aclasta was not established in this study. The increased incidence of atrial fibrillation compared with placebo observed 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 infusion: pain, fever, chills, myalgia, nausea, headache, fatigue , arthralgia, the frequency of which was higher in women receiving the drug to prevent PMO. Most of these AEs were mild or moderate and resolved within 3 days of onset. With repeated administration of the drug, the severity of these AEs decreased significantly.
The following are AEs possibly associated with the use of the drug for the prevention of PMO (according to the attending physicians):
1) AEs that were observed more than once during the administration of Aklasta for the prevention of PMO and were not registered when using 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;
2) AEs, the frequency of which was higher in women receiving the drug to prevent PMO (compared to other categories of patients).
The incidence of these AEs was assessed as follows: very common (≥1/10); often (≥1/100,<1/10); uncommon (≥1/1000, <1/100).
Mental disorders:
sometimes - anxiety.
From the nervous system:
very often - headache; often - tremor, lethargy; infrequently - decreased sensitivity, taste disturbances.
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, pain in the upper abdomen, constipation.
From the skin and subcutaneous tissue:
often - increased sweating at night.
From the musculoskeletal system and connective tissue:
very often - myalgia; often - musculoskeletal pain, muscle spasm, pain in the chest area of musculoskeletal origin, pain in the jaw area, pain in the neck area; infrequently - pain in the side.
From the body as a whole and reactions at the site of drug administration:
very often - pain, chills; often - peripheral edema, reactions at the injection site, non-cardiac pain in the chest area.
Changes in laboratory results
In patients with postmenopausal osteoporosis, while using Aklasta, a decrease in calcium concentration (<1.87 mmol/l) in the blood serum was observed in 0.2% of cases; clinical signs of hypocalcemia were not observed.
When using the drug in patients with femoral fractures, osteoporosis in men and osteoporosis caused by taking corticosteroids, there was no decrease in the concentration of calcium in the blood plasma <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 the blood plasma <1.87 mmol/l. In patients with Paget's disease, transient hypocalcemia accompanied by clinical manifestations was found in approximately 1% of cases.
Renal dysfunction.
With intravenous administration of bisphosphonates, including zoledronic acid, there have been cases of renal dysfunction, manifested by an increase in blood creatinine concentrations and, in rare cases, acute renal failure. Impaired renal function with the use of zoledronic acid has been observed in patients with either a history of renal pathology or additional risk factors (for example, cancer requiring chemotherapy, use of nephrotoxic drugs, diuretics or severe dehydration). Most of these patients were treated with zoledronic acid 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 incidence of increased plasma creatinine and the development of renal failure did not differ from that when using placebo. Patients receiving Aklasta were slightly more likely to experience a transient increase in blood creatinine concentrations within 10 days after 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 osteoporosis caused by the use of corticosteroids, during therapy with Aklasta, 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 pain at the injection site were noted in 0.7% of cases.
In patients with femoral fractures, the incidence 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 Aclasta was 2.6% (compared to 1.4% in the alendronic acid group). In patients with osteoporosis caused by the use of corticosteroids, no reactions were observed at the injection site. When using the drug for the prevention of postmenopausal osteoporosis, the incidence 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 of the jaw) occurred mainly in cancer patients receiving bisphosphonate treatment after tooth extraction or other dental procedures. Most patients had symptoms of a local infectious and inflammatory process, including osteomyelitis. In clinical studies 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, resolution of the process was noted. When using the drug Aklasta in patients with femoral fractures, with osteoporosis in men and osteoporosis caused by taking corticosteroids, as well as when using the drug for the prevention of postmenopausal osteoporosis, there were no cases of osteonecrosis of the jaw.
Isolated reports of adverse events
During therapy with Aklasta, the following AEs were observed in clinical practice without indication of a cause-and-effect relationship with the use of the drug (the frequency of AEs has not been established): hypersensitivity reactions, including in rare cases broncho-obstruction, urticaria, angioedema and isolated reports of the development of anaphylactic reactions, in incl. anaphylactic shock. In rare cases, when using Aklasta in clinical practice, patients have experienced renal dysfunction, including renal failure requiring hemodialysis, especially in patients with a history of either renal pathology or additional risk factors (for example, with concomitant therapy with nephrotoxic drugs, diuretics or with severe dehydration).
In very rare cases, the following AEs have been reported:
dehydration due to fever, vomiting and diarrhea occurring after administration of the drug; a pronounced decrease in blood pressure in patients with risk factors, osteonecrosis of the jaw, scleritis and inflammation in the orbital area.
Comparison of addiction in Aklasta and Zometa
Like safety, addiction also involves many factors that must be considered when evaluating a drug.
So, the totality of the values of such parameters as “o syndrome” in Aklasta is quite similar to the similar values in Zometa. Withdrawal syndrome is a pathological condition that occurs after the cessation of intake of addictive or dependent substances into the body. And resistance is understood as initial immunity to a drug; in this it differs from addiction, when immunity to a drug develops over a certain period of time. The presence of resistance can only be stated if an attempt has been made to increase the dose of the drug to the maximum possible. At the same time, in Aklasta the meaning of “syndrome” is quite small, however, the same as in Zometa.
Comparison of side effects of Aklasta and Zometa
Side effects or adverse events are any adverse medical event that occurs in a subject after administration of a drug.
Aklasta has more adverse effects than Zometa. This implies that the frequency of their occurrence is low in Aklasta and low in Zometa. Frequency of manifestation is an indicator of how many cases of an undesirable effect from treatment are possible and registered. The undesirable effect on the body, the strength of influence and the toxic effect of drugs are different: how quickly the body recovers after taking it and whether it recovers at all. When using Aklasta, the body’s ability to recover faster is higher than that of Zometa.
Aclasta solution for infusion 5 mg/100 ml 100 ml
Zoledronic acid, a member of the class of nitrogen-containing bisphosphonates, acts primarily on bone tissue, inhibiting osteoclast activity and bone resorption. The selective effect of bisphosphonates on bone tissue is based on their high affinity for mineralized bone tissue. Following intravenous administration, zoledronic acid is rapidly redistributed into bone tissue and, like other bisphosphonates, is localized primarily at sites of bone 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 substance is not excluded. The long period of action of the drug is determined by its high affinity for the active center of the FPS and pronounced affinity for mineralized bone tissue. With the use of Aklasta, there is a rapid decrease in bone turnover from elevated postmenopausal values to the minimum acceptable level (by day 7 for bone resorption and by week 12 for bone formation). Subsequently, bone turnover indicators stabilize within premenopausal values. Experimental models of accelerated osteoresorption with long-term use of zoledronic acid have 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 foci of remodeling in both trabecular (spongy) and and in cortical (compact) bone tissue, without causing the formation of fibrous bone tissue and aberrant accumulation of osteoid, as well as defects in bone mineralization. With the exception of its high antiresorptive effect, the effects of zoledronic acid on bone tissue are similar to those of other bisphosphonates. When using Aklasta in patients with postmenopausal osteoporosis (T-criterion values for femoral neck bone mineral density 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 decrease in the risk of one or more new ones. recurrent fractures and moderate/severe vertebral fractures by 60-70%. In patients with osteoporosis aged 75 years and older, treatment with Aclasta achieved a 61% reduction in the risk of vertebral fractures. When treated with Aklasta, the relative risk of femoral fractures by the 3rd year of therapy decreased by 40%. When treated with Aklasta, the relative risk of any clinical fractures, non-vertebral fractures of any location (excluding fractures of the phalanges of the fingers and bones of the facial part of the skull) decreased by 33% and 25%, respectively. When using the drug for 3 years in patients with postmenopausal osteoporosis, there was an increase in bone mineral density (BMD) of the lumbar vertebrae, femur as a whole, in the area of the femoral neck and distal radius by an average of 6.9%, 6 %, 5% and 3.2% respectively. During treatment with Aklasta for 1 year, patients with postmenopausal osteoporosis experienced a decrease in the activity of the bone isoenzyme alkaline phosphatase, N-terminal propeptide of type I collagen (PINP) and β-C-terminal telopeptides of the blood to premenopausal levels. With repeated administrations of the drug over 3 years, no further decrease in the content of bone remodeling markers in the blood was observed. The use of Aklasta for 3 years significantly reduced the rate of height loss in patients, and also contributed to an increase in physical activity in postmenopausal patients with osteoporosis and vertebral fractures. When administered to patients (men and women) with recent (within 90 days) fractures of the proximal femur (resulting from minimal trauma and requiring surgical intervention), there was a 35% reduction in the incidence of subsequent osteoporotic fractures of any location by 35% compared with placebo (from of which clinically significant vertebral fractures - by 46%, non-vertebral fractures - by 27%). When using Aklasta in this category of patients, the relative risk of deaths (regardless of their cause) decreased by 28%. In patients with femoral fractures, when using Aklasta for 2 years, there was an increase in BMD of the femur as a whole and in the femoral neck by 5.4% and 4.3%, respectively. When using the drug once a year in men with primary (senile) or secondary (hypogonadism) osteoporosis, a marked increase in BMD of the lumbar vertebrae was observed for 2 years. In patients with osteoporosis caused by the use of glucocorticosteroids, treatment with Aklasta for a year also significantly increased BMD (lumbar vertebrae, femoral neck, trochanter, radius), without having a negative effect on bone structure and mineralization. When using the drug Aklasta for the prevention of postmenopausal osteoporosis once every 2 years in women with a postmenopausal duration of less than and more than 5 years, an increase in BMD of the lumbar vertebrae was observed by 6.3% and 5.4%, respectively. When the drug was administered once every 2 years, femoral BMD 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 durations of postmenopause, when administered with Aklasta once every 2 years, there was a decrease in the concentration of α-C-terminal telopeptides in the blood by 44-46% (to premenopausal levels) and N-terminal propeptide of type I collagen (PINP) by 55-40 %. When treated with Aklasta in patients with Paget's disease of bone, a statistically significant, rapid and long-term therapeutic response, normalization of bone metabolism and alkaline phosphatase activity in the blood plasma were observed. The drug is also highly effective in patients previously treated with oral bisphosphonates. The therapeutic response with Aklasta lasts longer than with risedronic acid (7.7 years compared to 5.1 years). A pronounced decrease in pain at 6 months after a single administration of Aklasta at a dose of 5 mg is comparable to the analgesic effect of risedronic acid at a dose of 30 mg per day. In patients with postmenopausal osteoporosis and Paget's disease of bone, zoledronic acid does not affect the qualitative state of normal bone tissue, does not disrupt the processes of bone remodeling and mineralization, and helps maintain the normal architecture of trabecular bone tissue.