Pharmacodynamics and pharmacokinetics
The use of this drug allows you to dissolve and prevent the formation of uric acid stones by alkalizing urine to optimal pH values of 6.6-6.8. As is known, at a urine pH of 6.6-6.8, there is a significant increase in the dissolution of salts in uric acid. Calcium excretion is also reduced , the solubility of calcium oxalate in urine is improved, and the formation of crystals is inhibited, which prevents the appearance of calcium oxalate stones.
The bioavailability of this drug is almost 100%. Removal of substances from the body occurs through the kidneys.
Pharmacological properties
Pharmacodynamics.
When effervescent tablets of blemarene are dissolved in water, potassium-sodium hydrocitrate is formed and carbon dioxide is released. in this case, residual alkaline ions are formed, which are excreted by the kidneys. thus, the pH of urine increases (depending on the dose, it is neutralized or alkalized). this increases the degree of dissociation and at the same time the degree of dissolution of uric acid and cystine. confirmation of litholysis of uric acid stones is performed radiographically. When taking the drug, the excretion of citrates increases and the excretion of calcium in the urine decreases. Alkalinization of urine, increased excretion of citrates and decreased excretion of calcium lead to a decrease in the amount of calcium oxalate in the urine, since in a weak alkaline environment citrate forms stable complex compounds with calcium. In addition, the citrate ion should be considered an effective physiological inhibitor of crystal formation and accumulation of calcium oxalate and calcium phosphate.
Pharmacokinetics. After a one-day use of the drug Blemaren, effervescent tablets, the administered amount of sodium and potassium is excreted from the body by the kidneys for 24–48 hours. With prolonged use of the drug, the daily excretion of potassium and sodium corresponds to the daily intake. There are no significant changes in blood gases or electrolytes in the blood or plasma. This means that due to the renal regulation of alkalization, the acid-base balance in the body is maintained, and the accumulation of sodium and potassium does not occur with normal kidney function.
Indications for use of the drug
Treatment with Blemaren is prescribed when necessary:
- dissolve uric acid and calcium oxalate stones and prevent their formation;
- dissolve mixed uric acid-oxalate stones , with an oxalate content of up to 25%;
- perform urine alkalinization in patients who receive cytostatics and agents that can increase the excretion of uric acid;
- carry out symptomatic treatment of skin porphyria.
Contraindications for use
The main contraindications to taking Blemaren are:
- hypersensitivity;
- metabolic alkalosis;
- acute and chronic forms of renal failure ;
- urinary tract infections , caused by microorganisms that break down urea ;
- adherence to a strict salt-free diet, for example, with severe arterial hypertension;
- urine pH level is more than 7;
- The age of patients is less than 12 years, since clinical experience for this age group has not been studied.
Overdose
With normal renal function, no undesirable effect of the drug on changes in physiological metabolic parameters was noted either at the usual recommended dose or at a higher one, since the release of excess alkalis by the kidneys is a natural mechanism for regulating the acid-base balance in the body.
The upper limit of the urine pH range indicated above should not be exceeded for several days, since due to the increase in pH (pH factor 7.8) there is an increased risk of phosphate crystallization; furthermore, an overtly alkaline metabolic status is not considered a long-term problem.
A possible overdose can be corrected by reducing the dose of the drug. If necessary, measures can be taken to treat metabolic alkalosis.
Blemaren, instructions for use (Method and dosage)
The tablets are intended to be taken orally after eating. To do this, the medicine is dissolved in 200 ml of any liquid - tea, fruit juice or water.
According to the instructions for use of Blemaren, the daily dosage can be 2-6 tablets , the intake of which should be evenly distributed throughout the day. Correctly selected dosage allows you to maintain the pH throughout the day within 6.2-7 - if you need to dissolve uric acid stones, 7.5-8.5 when dissolving cystine stones, at least 7 - therapy with cytostatics , 7.2-7.5 – treatment of porphyria. When the urine pH value is less than specified, the dosage is increased, and when the pH value is high, it is reduced. The average duration of treatment can be 4-6 months.
During therapy, it is necessary to monitor the effectiveness, that is, determine the urine pH at least 3 times a day, before taking each dose, using indicator paper. The results on paper need to be compared with the scale and the indicator entered into the control calendar.
The effectiveness of using the citrate mixture "Blemaren" for uric acid nephrolithiasis
I.A. Aboyan, V.A. Sknar, S.V. Pavlov Municipal budgetary healthcare institution “Clinical Diagnostic, Rostov-on-Don”, Russia
Urolithiasis (UCD) has a high medical and social significance, which is due to a fairly high incidence, reaching 10% in the world, its annual growth in many countries and the defeat of the most able-bodied part of the population [1].
In the Russian Federation in 2012, the incidence of urolithiasis was 550.5 people per 100 thousand population, and its increase over the period from 2002 to 2012 exceeded 25% [2]. The prevalence of uric acid stones worldwide varies from 5 to 40% and varies geographically, so in North America it ranges from 5 to 10%, and in Israel it is 40% [3-5].
In the structure of the incidence of urolithiasis, there is an increase in the frequency of uric acid nephrolithiasis to 20-30%, which may be due to an increase in people's life expectancy, physical inactivity leading to impaired purine metabolism, and increased consumption of protein foods and alcohol.
The ratio of uric acid stones according to the results of a study of the composition of uroliths in recent years was 11.9-30.5% [7-10].
Numerous studies indicate the high efficiency of litholysis of uric acid stones using citrate mixtures (Blémaren and others) [11-17].
According to the recommendations of the European Association of Urology, the method of choice for non-invasive surgical treatment of stones up to 2 cm can be external shock wave lithotripsy (ESW) [11,18].
Most authors indicate that the effectiveness of this procedure depends on the size and density of the stone [6,14,17,19], along with some negative assessments of such a correlation [21].
In recent years, increasing attention has been paid to the effect of citrate drugs on stone density and the results of a subsequent course of extracorporeal lithotripsy (ESLT). Most studies have noted an increase in efficiency and a reduction in the duration of a course of DLT as a result of the use of citrates [14,16,19, 21].
The purpose of the study is to study the effectiveness of litholysis and the dynamics of the density of uric acid and mixed stones during therapy using citrate mixtures.
MATERIALS AND METHODS
We conducted a study of a group of 30 patients (14 women and 16 men aged 27-64 years) with uric acid nephrolithiasis. The size of the stones ranged from 8 mm to 22 mm, there were no signs of obstructive uropathy. Multislice computed tomography (MSCT) of the kidneys was performed on Siemens Somatom Difinition AS 64 and AS 40 devices in all patients before the start of therapy, after 3 months and after the end of the 6-month course of treatment (if a stone was present after 3 months according to MSCT).
The diagnosis of uric acid (urate) nephrolithiasis was established if the patient had a low stone density (138-600 NU) on MSCT of the kidneys; X-ray negative stones on plain urography or when performing a topographic image before MSCT of the kidneys, the results of X-ray phase analysis (XRF) of urinary stones that had passed earlier or were obtained as a result of lithotripsy, lithoextraction or surgical treatment before the current course of treatment, the presence of hyperuricemia and/or hyperuricuria. All patients received the Blemaren citrate mixture 3 times a day, in an individual pH-dependent dose from 0.5 tablets to 1.5 - 2 tablets 3 times a day during the course of litholysis (3-6 months).
In the presence of hyperuricemia and/or hyperuricuria, allopurinol 100–200 mg per day was also prescribed during the course of litholysis, usually in one dose. Some patients were recommended to take allopurinol twice a day if they had complaints of discomfort in the stomach with a single dose of the drug. In this case, the daily dose of allopurinol depended on the degree of hyperuricemia and/or hyperuricuria and was the minimum necessary to normalize the level of uric acid in the blood and/or urine.
RESULTS AND DISCUSSION
Complete dissolution of stones occurred in 22 patients (73.3%). In 6 cases (20%) there was a decrease in the size of the stone (Table 1). Of these, in three patients the stones decreased in size and passed naturally. The three remaining patients with a decrease in stone size underwent EBRT of stones. We noted greater efficiency in dissolving calculi when their size is less than 1 cm.
Table 1. Results of litholysis of uric acid stones using Blemaren
Result | n | % |
Complete dissolution | 22 | 73,3 |
Partial dissolution | 6 | 20 |
No dissolution | 2 | 6,7 |
Total | 30 | 100 |
As for two cases of lack of effect from the course of litholysis, in one case DLT was successfully performed. The density of this stone after the course of litholysis decreased slightly (by 6 HU units). Analysis of stone fragments showed a combination of uric acid dihydrate and apatite in a ratio of 70% and 30%. The second patient underwent laser nephrolithotripsy. XRF of this calculus revealed the presence of uricite and insoluble sodium urate in a ratio of 60%:40%. The density of the stone in this case also decreased slightly - by 3 units. HU.
In the study group, we studied the relationship between the effectiveness of treatment, stone density before and after treatment and the degree of reduction in stone density depending on the composition of stones according to X-ray phase analysis. The density and composition of stones from patients who had complete stone dissolution after 3 months are presented in Table 2.
Table 2. Initial density and composition of stones in patients who had complete stone dissolution after 3 months.
№ | patient no. | Density of stones | Composition of stones (XRF) |
1 | 1 | 296 | |
2 | 2 | 370 | 80–90% uricite (anhydrous uric acid) and 10–20% uric acid dihydrate |
3 | 4 | 382 | contains approximately equal amounts of uricite and uric acid dihydrate |
4 | 6 | 138 | |
5 | 7 | 218 | |
6 | 10 | 290 | 60% uric acid dihydrate and 40% uricite |
7 | 12 | 390 | 80% uricite and 20% uric acid dihydrate |
8 | 13 | 196 | |
9 | 18 | 384 | 90% uricite and 10% uric acid dihydrate |
10 | 25 | 210 | |
11 | 30 | 282 | |
Average stone density НU | 286,9 |
The initial composition of stones and the degree of reduction in the density of stones in patients who had complete stone dissolution after 6 months are presented in Table 3.
Table 3. Composition of stones and the degree of reduction in the density of stones in patients who had complete stone dissolution after 6 months.
No. | patient no. | Density of stones | Stone density after treatment | Degree of stone density reduction | Composition of stones (XRF) |
1 | 3 | 420 | 300 | 120 | uric acid dihydrate, about 90%, a little uricite, about 10%; uricite 90% and ammonium urate 10%, possible admixture of uric acid dihydrate |
2 | 5 | 484 | 320 | 164 | |
3 | 9 | 388 | 240 | 148 | uricite and some uric acid dihydrate, possible traces of calcium urate |
4 | 14 | 226 | 136 | 90 | uricite |
5 | 15 | 290 | 150 | 140 | |
6 | 16 | 328 | 180 | 148 | 80% uricite and 20% uric acid dihydrate |
7 | 21 | 324 | 220 | 104 | |
8 | 22 | 388 | 234 | 154 | |
9 | 23 | 412 | 303 | 109 | |
10 | 28 | 340 | 310 | 30 | |
11 | 29 | 360 | 308 | 52 | |
Average stone density НU | 360 | 245,5 | |||
Average degree of stone density reduction | 114,5 |
The density, the degree of its reduction and the composition of the stones of patients in whom partial dissolution of the stones was noted are presented in Table 4.
Table 4. Density, degree of density reduction and composition of stones from patients with partial dissolution of stones
No. | patient no. | Density of stones | Stone density after treatment | Degree of stone density reduction | Composition of stones (XRF) |
1 | 11 | 510 | 450 | 60 | uric acid dihydrate 85-90% and 10-15% apatite |
2 | 17 | 524 | 518 | 6 | uric acid dihydrate 50% and apatite 50% |
3 | 19 | 530 | 450 | 80 | uricite and 5-10% wewellite (calcium oxalate monohydrate); after 800 °C – residue about 5–10%, calcium oxide |
4 | 20 | 580 | 510 | 70 | uricite and 10% wewellite (calcium oxalate monohydrate) + calcium urate 5% |
5 | 24 | 580 | 510 | 70 | 85% uricite+and 15% wewellite (calcium oxalate monohydrate) |
6 | 26 | 536 | 477 | 59 | uric acid dihydrate 85% + veddelite 5% + apatite 10% |
Average stone density НU | 543,3 | 485,8 | |||
Average degree of stone density reduction | 52,5 |
The density, the degree of its reduction and the composition of the stones of patients in whom stone dissolution was not noted are presented in Table 5. These patients are characterized by a relatively high density of stones and a low degree of reduction in the density of stones.
Table 5. Density, degree of density reduction and composition of stones from patients in whom stone dissolution was not noted
No. | patient no. | Density of stones | Stone density after treatment | Degree of stone density reduction | Composition of stones (XRF)* |
1 | 8 | 524 | 518 | 6 | uric acid dihydrate 50% and apatite 50% |
2 | 27 | 390 | 387 | 3 | 60% uricite and 40% sodium urate |
Average stone density НU | 457 | 452,5 | |||
Average degree of stone density reduction | 4,5 |
As can be seen from tables 2-5, the best results were observed with litholysis of monophasic uric acid stones. As the density of stones increases, the proportion of patients with successful litholysis decreases and the duration of the dissolution process lengthens.
Table 6 shows the dynamics of stone density during litholysis in patients receiving the Blemaren citrate mixture for 6 months (complete dissolution, partial dissolution and no dissolution).
Table 6. Dynamics of stone density during litholysis in patients receiving the citrate drug Blemaren for 6 months (complete dissolution, partial dissolution and no dissolution)
No. | patient no. | Stone density before treatment (HU) | Density of stones after 6 months. treatment (HU) | Degree of stone density reduction (HU) |
1 | 3 | 420 | 300 | 120 |
2 | 5 | 484 | 320 | 164 |
3 | 8 | 524 | 518 | 46 |
4 | 9 | 388 | 240 | 148 |
5 | 11 | 510 | 450 | 60 |
6 | 14 | 226 | 136 | 90 |
7 | 15 | 290 | 150 | 140 |
8 | 16 | 328 | 180 | 148 |
9 | 17 | 524 | 518 | 6 |
10 | 19 | 530 | 450 | 80 |
11 | 20 | 580 | 510 | 70 |
12 | 21 | 324 | 220 | 104 |
13 | 22 | 388 | 234 | 154 |
14 | 23 | 412 | 303 | 109 |
15 | 24 | 580 | 510 | 70 |
16 | 26 | 536 | 477 | 59 |
17 | 27 | 390 | 387 | 3 |
18 | 28 | 340 | 310 | 30 |
19 | 29 | 360 | 308 | 52 |
Average stone density НU | 432 | 343,2 | ||
Average degree of stone density reduction | 87 (31,6%) |
As can be seen from the table, during the treatment the density of stones decreased significantly, by an average of 89 units. НU (31.6%).
During the study, we noted a decrease in the level of stone density during therapy with the citrate drug Blemaren in all patients, while the stone density according to MSCT in all patients with successful litholysis was less than 500 NU.
Figure 1 shows the relationship between the average density of stones and the results of litholysis (the degree and timing of stone dissolution).
Rice. 1. Relationship between the average density of stones and the results of litholysis
Our study also revealed a directly proportional relationship between the average degree of reduction in stone density during treatment and the results of litholysis, that is, the degree and timing of stone dissolution (Fig. 2).
Rice. 2. Average degree of reduction in the density of calculi during litholysis
CONCLUSIONS
Litholysis of uric acid stones using a citrate mixture (Blemaren) is a highly effective non-traumatic method of treating patients.
During treatment, a significant decrease in the density of uric acid and mixed stones was noted
The noted decrease in density turned out to be more pronounced when performing litholysis of monophasic (single-component) uric acid stones.
In addition, we noted that this type of treatment turned out to be highly effective when the stone density according to MSCT data is less than P 500 NU.
LITERATURE
- Yasui T, Ando R, Okada A. Et al. Epidemiology of urolithiasis for improving clinical practice. Hinyokika Kiyo. 2012. Vol. 58, (12):697-701.
- Apolikhin O.I., Sivkov A.V., Moskaleva N.G., Solntseva T.V., Komarova V.A. Analysis of uronephrological morbidity and mortality in the Russian Federation for a ten-year period (2002-2012) according to official statistics. // Experimental and clinical urology. 2014; (2):2-12
- Gutman AB, Yu TF. Uric acid nephrolithiasis. Am J Med 1968; 45:756.
- Hesse A, Schneider HJ, Berg W, Hienzsch E. Uric acid dihydrate as urinary calculus component. Invest Urol 1975; 12:405.
- Scholz D, Schwille PO, Ulbrich D. et al. Composition of renal stones and their frequency in a stone clinic: relationship to parameters of mineral metabolism in serum and urine. Urol Res 1979; 7:161.
- Grenabo L, Hedelin H, Pettersson S. The severity of infection stones compared to other stones in the upper urinary tract. Scand J Urol Nephrol 1985; 19:285.
- Konstantinova O.V., Shaderkina V.A. Epidemiological assessment of urolithiasis in outpatient urological practice. Experimental and clinical urology. 2015;(1): 11-14
- Sknar V.A., Aboyan I.A., Shukaev I.L., Pavlov S.V., Zolotukhin D.A. Investigation of the composition of 2200 urinary stones using advanced X-ray diffraction analysis: our experience. Materials of the 1st scientific and practical conference of urologists of the North-Western Federal District of the Russian Federation “Current issues of urology”, St. Petersburg. 2015.s. 111
- SpivacowFR, Del Valle EE, Lores E. et al. Kidney stones: Composition, frequency and relation to metabolic diagnosis., Medicina 2016;76(6):343-346
- D'Alessandro M., Gennaro G., Tralongo P. et al. Fourier Transform Infrared Analysis of Urinary Calculi and Metabolic Studies in a Group of Sicilian Children, Iranian J Kid Dis. 2017;(3)209-216
- Pytel Yu. A. Zolotarev I. I. Urate nephrolithiasis, Moscow, Medicine, 1995. 90 p.
- S. H. Al-Shukri, M. N. Slesarevskaya, I. V. Kuzmin. Litholytic therapy of urate nephrolithiasis, Urology. 2016;(2): 23-27
- Slesarevskaya M. N., I. V. Kuzmin, Al-Shukri S. Kh. Litholytic therapy of urolithiasis. Urological Journal 2015;(1):112-11319.
- Rudenko V. I., Rapoport L. M., Kuzmicheva G. M. Modern aspects of citrate litholysis. Effective pharmacotherapy, 2017; 24, S. 10-12.
- Alyaev Yu. G., Kuzmicheva G. M., Rapoport L. M., Rudenko V. I. Modern aspects of citrate therapy in patients with urolithiasis. Medical class, 2004;4. S.. 20-24.
- Chistik T. Citrate therapy in outpatient practice of urolithiasis: focus on Blemaren®. Kidneys 2015; 4 (14): 71-74.
- Glybochko P. V., Blumberg B. I., Osnovin O. V., Soldatenko M. V., Rossolovsky A. N., Maksimova A. V., The influence of stone density and size on the effectiveness of external lithotripsy using Dornier Compact Delta and Sonolit devices . Saratov Scientific and Medical Journal, 2011;7,(S2):208.
- Neisius A, et al. Shock wave lithotripsy: the new phoenix? World J Urol 2015 Feb; 33 (2): 213-221.
- Alyaev Yu. G., Rapoport L. M., Rudenko V. I. Citrate therapy to prepare for extracorporeal lithotripsy. Urology and Nephrology 2002;(4):20-23
- Chekhonatskaya M. L., Rossolovsky A. N., Bobylev D. A. The relationship between the density and size of stones in patients with nephrolithiasis and the effectiveness of treatment using external shock wave lithotripsy, Saratov Journal of Medical Scientific Research, 2017;13(1):77 -81
- Alyaev Yu. G., Rapoport L. M., Rudenko V. I. Citrate therapy to prepare for extracorporeal lithotripsy. - Urology 2002;(4):20-23
The article was published in the journal “Experimental and Clinical Urology” No. 2 2021, pp. 44-49
Topics and tags
Urolithiasis disease
Magazine
Journal "Experimental and Clinical Urology" Issue No. 2, 2018
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Interaction
The combination of Blemaren and products that contain citrates and aluminum sometimes causes increased absorption of aluminum. In this case, it is necessary to maintain an interval between doses of about 2 hours.
cardiac glycosides may be weakened , since Blemaren contains a substance such as potassium.
Concomitant use of drugs that lower blood pressure, such as aldosterone antagonists, potassium-sparing diuretics, ACE blockers or NSAIDs and analgesics , can reduce potassium excretion.
special instructions
The average daily dosage is 4 tablets and contains almost 0.9 g of sodium and 1.5 mg of potassium, so this must be taken into account when treating patients whose salt intake is limited.
Taking Blemaren is allowed in case of chronic renal failure, unless potassium ion retention is established.
During the dissolution of uric acid stones, it is necessary to strictly adhere to the daily dose, since an increase in pH above 7 leads to the precipitation of phosphates on uric acid crystals, preventing their subsequent dissolution.
It is also recommended to limit the consumption of foods rich in proteins or purine bases, ensuring adequate fluid intake - about 1.5-2 liters.
Treatment does not have a particular effect on the ability to drive vehicles or operate machinery that require increased attention.
Special instructions for the use of the drug Blemaren
When dissolving urate stones, prolonged excessive alkalization of urine (pH 7.8) should not be allowed, given the possible appearance of a sediment of phosphate salts on the surface of the stone, which may prevent its further dissolution. The drug can be used for compensated renal failure, which is not accompanied by potassium retention in the body. Before use, it is necessary to determine the level of electrolytes in the blood serum and check renal function. If renal tubular acidosis is suspected, a COR study should be performed. Patients with heart failure should take into account that 1 effervescent tablet or measuring spoon of the drug contains 380 mg or 9.7 mmol of potassium, which can affect the action of cardiac glycosides (an increase in the extracellular concentration of potassium reduces the effectiveness of glycosides, and a decrease increases the arrhythmogenic effect). For patients with uric acid metabolism disorders, it is recommended to combine the drug with allopurinol. Persons who follow a sodium-restricted diet should take into account that 1 effervescent tablet of Blemaren contains 220 mg or 9.7 mmol of sodium. During therapy with Blemaren, it is recommended to follow a low-protein diet, limiting the consumption of foods rich in purines (meat, sausages, offal, sardines). Every day you need to drink 2-3 liters of fluid in the form of tea, fruit juice or alkaline mineral water in order to reduce the risk of stone formation by producing a sufficient amount of urine. The drug does not contain carbohydrates and can be used to treat patients with diabetes. Changes in color of unused test strips do not affect pH results. When using the drug in accordance with the instructions, no negative effects were observed during pregnancy and lactation.
Analogs
Level 4 ATC code matches:
Phytolit
Cyston
Uronephron
Rowatinex
The main analogues of Blemaren are K-Na hydrogen citrate and Soluran .
There are also drugs with a similar effect, for example: Urolesan, Cystenal, Phytolysin, Uronephron and others.
Reviews about Blemarin
This drug is actively used in clinical practice. At the same time, patient reviews of Blemaren report that its effectiveness is manifested in cases where they strictly adhered to the therapeutic regimen prescribed by a specialist.
Many patients report that they were prescribed this drug to treat kidney stones due to a shift in pH towards acidity. It was course therapy with this medicine that helped completely eliminate this disease.
There are also reviews of Blemaren for gout, when patients tried to get rid of the problem on their own. However, they were subsequently forced to see a doctor and after treatment with this drug they experienced significant relief.
More than one forum is dedicated to reviews of Blemaren, where you can find a detailed description of therapeutic regimens using this drug and mineral water. This treatment helps restore the pH level of urine and normalize health.
Blemarin price, where to buy
The drug can be bought in Moscow in pharmacies without a prescription at a cost of 635-990 rubles for 80 pieces.
The price of Blemarin in Ukraine varies between 288-350 UAH.
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- Online pharmacies in UkraineUkraine
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Note!
Description of the drug Blemaren table. thorn. No. 80 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.