Blemaren

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BLEMAREN®

Composition:

Active substances: anhydrous citric acid, anhydrous trisodium citrate, potassium hydrogencarbonate;

One tablet contains: anhydrous citric acid 1197 mg; anhydrous trisodium citrate 835.5 mg; potassium hydrogencarbonate 967.5 mg;

Excipients: lactose monohydrate, mannitol (E 421), lemon flavoring, sodium saccharin, adipic acid, polyethylene glycol.

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white, round tablets with a score line, lemon-scented.

Pharmacotherapeutic group.
Agents used for dissolution of urinary calculi. ATC code G04BC.

Pharmacological Properties

Pharmacodynamics

When Blemaren® effervescent tablets are dissolved in water, potassium-sodium hydrocitrate is formed and carbon dioxide is released.

Residual alkaline ions are generated, which are excreted by the kidneys. Thus, the pH level of urine increases (depending on the dosage, urine is either neutralized or alkalinized).

This increases the degree of dissociation and, simultaneously, the solubility of uric acid/cystine. Radiographic imaging confirms the litholytic effect on uric acid stones.

The drug enhances excretion of citrates and reduces calcium excretion in urine. Alkalinization of urine, increased citrate excretion, and decreased calcium excretion lead to reduced urinary calcium oxalate levels, since in a weakly alkaline environment citrate forms stable complex compounds with calcium. Furthermore, the citrate ion should be considered the most effective physiological inhibitor of crystal formation and accumulation of calcium oxalate and calcium phosphate.

Pharmacokinetics

After single-day administration of Blemaren® effervescent tablets, the administered amounts of sodium and potassium are excreted from the body via the kidneys within 24–48 hours. With prolonged use of the drug, daily excretion of potassium and sodium corresponds to daily intake. In blood or blood serum, no significant changes in blood gases or electrolytes are observed. This indicates that, due to renal regulation, acid-base balance in the body is maintained, and accumulation of sodium and potassium does not occur with normal kidney function.

Clinical characteristics.

Indications.

Blemaren® is used in the treatment of urolithiasis for:

• alkalinization of urine in patients with urate concrements, with or without accompanying calcium concrements;
• metaphylaxis of calcium concrements (prevention of recurrence of new concrements and/or growth of residual fragments).

Contraindications.

• Hypersensitivity to the components of the drug.
• Renal insufficiency.
• Urinary tract infections caused by urea-splitting bacteria (risk of struvite stone formation).
• Metabolic alkalosis.
• Episodic hereditary adynamia.

Interaction with other medicinal products and other types of interactions.

Interaction studies were conducted only in adults. Concomitant administration of substances containing citrate and aluminum may lead to increased aluminum absorption; therefore, a two-hour interval between the administration of such agents and Blemaren® is recommended.

The drug enhances the therapeutic effect of allopurinol.

Certain antihypertensive agents (aldosterone antagonists and other low-potassium diuretics such as triamterene, spironolactone, and amiloride), ACE inhibitors, sartans, as well as analgesic and anti-inflammatory medicinal products (nonsteroidal anti-inflammatory drugs and peripheral analgesics) may reduce potassium excretion, which should be considered when co-administered with Blemaren® (increased risk of hyperkalemia). Increased extracellular potassium concentration reduces the efficacy of cardiac glycosides, whereas decreased potassium concentration enhances the arrhythmogenic effect of cardiac glycosides.

With prolonged use of Blemaren®, accumulation of quinidine in the body may occur if administered concomitantly, as well as reduced efficacy of nitrofurantoin (due to alkaline environment), salicylates, and lithium preparations (accelerated elimination).

Special precautions.

In conditions predisposing to urinary stone formation (e.g., parathyroid adenoma, uric acid stones associated with malignancy), etiological therapy should be implemented.

During dissolution of uric acid stones, prolonged excessive alkalization of urine (pH above 7.8) should be avoided due to the possible precipitation of phosphate salts on the surface of uric acid stones, which may hinder their further dissolution. In addition, prolonged and pronounced alkaline metabolic state is undesirable.

Before administration, serum electrolyte levels should be determined and renal function assessed. In suspected renal tubular acidosis, additional monitoring of acid-base balance parameters is required.

During treatment, regular monitoring of blood and urine parameters is necessary. Special attention should be paid to acid-base balance.

In patients with heart failure, the effect of potassium on myocardial excitability should be considered: one tablet of Blemaren® contains 380 mg of potassium ions, or 9.7 mmol of potassium, which may influence the effect of cardiac glycosides (increased extracellular potassium concentration reduces glycoside efficacy, while decreased concentration enhances their arrhythmogenic effect).

In patients with impaired uric acid metabolism, administration of the drug should be combined with allopurinol.

Patients on a sodium-restricted diet, particularly those with hypertension, should consider the high sodium content of this medicinal product (one tablet contains 220 mg of sodium ions, or 9.7 mmol of sodium, equivalent to 0.57 g of salt).

One effervescent tablet contains 9.7 mmol (380 mg) of potassium. This should be taken into account when treating patients with hepatic insufficiency or those on a potassium-restricted diet.

During therapy with this drug, a low-protein diet is recommended, i.e., limiting intake of foods rich in purines (e.g., meat, sausages, animal offal, sardines), as well as restricting salt consumption.

Daily fluid intake of 2–3 liters in the form of tea, fruit juice, or alkaline mineral water is recommended.

The drug is carbohydrate-free and can be used in the treatment of diabetic patients.

Blemaren® should be administered to patients with severe hepatic insufficiency only under strict monitoring.

Do not use in patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

When used according to instructions, no adverse effects have been observed during pregnancy or breastfeeding.

Ability to influence reaction rate while driving or operating machinery. No effect.

Method of Administration and Dosage.

The average daily dose is determined individually based on the measurement of urine pH.

Effervescent tablets should be taken dissolved in liquid (water or fruit juice). The liquid may appear slightly cloudy and may contain some undissolved particles.

The daily dose can be taken once in the evening or divided into 3 equal portions taken throughout the day (e.g., at 8:00, 14:00, 21:00). If the required daily dose exceeds 3 tablets, it is recommended to take one tablet in the morning, one during the day, and the remainder at night.

Monitoring the effectiveness of the drug is performed by measuring the pH of fresh urine 3 times daily, just before the next dose. Standard indicator strips included in each package should be used for this purpose. The indicator area of the test strip should be briefly immersed in urine, then removed from the liquid, and after 2 minutes the resulting color of the test strip should be compared with the color scale printed on the indicator strip container; the determined pH values should be recorded in the control calendar. The dosage is considered correctly established if the pH values measured 3 times daily remain within the recommended ranges for each specific pathology. Color changes in unused indicator strips do not affect the pH measurement results.

For the dissolution of uric acid (urate) stones, urine pH should be maintained within the range of 7.0–7.2.

If the daily pH profile is below 7.0, the dose should be increased; if it exceeds 7.2, the dose should be decreased.

For maintenance therapy in patients with nephrolithiasis associated with calcium-containing stones, urine pH should be maintained within the range of 6.2–6.8.

If the daily pH profile is below 6.2, the dose should be increased; if it exceeds 6.8, the dose should be decreased.

For the dissolution of mixed urate-oxalate stones and for prophylaxis of calcium-oxalate stone formation, urine pH should be maintained at 6.8–7.4 for a certain period.

Blemaren® should be used prior to extracorporeal shock wave lithotripsy (ESWL) in cases of mixed (radiolucent) stones to enhance treatment efficacy, reduce stone structural density, and decrease the number of repeat sessions. The duration of citrate therapy prior to ESWL should be at least 3 weeks.

For urinary alkalinization in patients with cystine stones, urine pH should be maintained between 7.5 and 8.5. This requires a higher dose of the drug.

During cytostatic therapy, urine pH should not fall below 7.0; in the treatment of late cutaneous porphyria, urine pH should be maintained between 7.2 and 7.5.

Uricosuric therapy, as well as treatment of urate stones, should be performed with urine pH maintained between 7.0 and 7.2.

The pH values that can be determined using standard indicator strips range from 5.4 to 7.4. In cases where monitoring of urine pH is required in patients with cystine stones or late cutaneous porphyria, special indicator strips capable of measuring pH within the range of 7.2–9.7 should be used.

The duration of treatment for stone dissolution (depending on their size and composition) ranges from 4 weeks to 6 months. For prevention of nephrolithiasis recurrence, the drug should be administered in courses, with duration and frequency individually determined for each patient.

Children.

The efficacy and safety of the drug in children have not been sufficiently studied; therefore, Blemaren® is not recommended for use in children (under 18 years of age).

Overdose.

With normal kidney function, no adverse effects of the drug on physiological metabolic parameters are observed, either at the usual recommended dose or at higher doses, since the excretion of excess base by the kidneys is a natural mechanism for regulating acid-base balance in the body.

The upper limit of the urine pH range specified above should not be exceeded for several consecutive days, as elevated pH (pH factor >7.8) increases the risk of phosphate crystallization. In addition, a pronounced alkaline metabolic state is not suitable for long-term maintenance.

Possible overdose can be corrected by reducing the dose of the drug. If necessary, standard measures for treating metabolic alkalosis may be applied.

Adverse Reactions.

Hypersensitivity reactions are possible in individuals with hypersensitivity to any component of the drug. In some cases, tablet intake may cause gastrointestinal disturbances in predisposed patients. Reports include belching, heartburn, abdominal pain, flatulence, diarrhea, nausea, and vomiting.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach of children.

Packaging.

20 effervescent tablets in a polypropylene container; 4 or 5 containers in a cardboard box together with indicator paper and a control calendar labeled in Ukrainian.

Supply classification. Over-the-counter.

Manufacturer.

Laboratorios Medicamentos Internacionales, S.A., Spain

Manufacturer's address

Calle Solana, 26, Torrejón de Ardoz, 28850, Madrid, Spain

Marketing authorization holder.

Esparma GmbH, Germany.

Address of the marketing authorization holder.

Bielefelder Strasse 1, 39171 Sülzetal, Germany.