CITROCAS

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYTROKAS (CYTROKAS)

Composition:

Active substance: potassium citrate;

1 sachet of powder contains 3 g of potassium citrate;

Excipients: aspartame (E 951); calcium phosphate; colloidal anhydrous silicon dioxide; orange flavoring (contains butylhydroxyanisole (E 320)).

Pharmaceutical form. Oral powder for solution.

Main physicochemical properties: transparent white granules without any visible inclusions, with a characteristic orange odor.

Pharmacotherapeutic group.

Agents promoting dissolution of urinary calculi.

ATC code G04B C.

Pharmacological Properties

Pharmacodynamics

Potassium citrate reduces the saturation of urine with calcium salts by binding calcium and decreasing the concentration of calcium ions. Due to this alkalinizing effect, it also enhances the dissociation of uric acid, thereby reducing the amount of poorly soluble, undissociated acid, and decreasing the tendency for stone formation. The drug regulates the pH of urine and maintains a long-lasting shift toward alkaline conditions within the pH range of 6.2–7.5, at which uric acid salts remain in solution and do not form concretions.

Potassium citrate prevents the crystallization of calcium salts that form kidney stones through two mechanisms: citrate forms complexes with calcium, reducing the concentration of free calcium ions, thereby decreasing the saturation of urine with oxalate—the driving force behind crystallization of these salts; it also directly inhibits oxalate crystallization. Potassium citrate does not affect the saturation of calcium phosphate salts because citrate-calcium complex formation may not occur due to increased pH, which leads to greater phosphate dissociation. Calcium phosphate stones are more stable in an alkaline environment. It has been demonstrated that citrate inhibits spontaneous calcium oxalate precipitation and slows down the agglutination of already formed calcium oxalate crystals.

Pharmacokinetics

Under normal conditions, the majority of orally administered potassium citrate is absorbed. Nearly all absorbed citrate is oxidized under normal physiological conditions, while potassium ions remain free, thereby generating an alkaline load. The formation of this alkaline load increases urinary pH and elevates the amount of citrate in urine; hence, only a small fraction of absorbed citrate remains unoxidized and is excreted in urine. Approximately 75% of citrate filtered by the kidneys is reabsorbed, while 25% is eliminated in urine.

In cases of hypokalemia, potassium ions themselves increase urinary citrate excretion, correcting intracellular acidosis.

Clinical characteristics.

Indications.

Litholysis of uric acid stones in the urinary tract and prevention of their primary and recurrent formation (single-phase calcium, oxalate, urate, and mixed-phase calcium oxalate and calcium phosphate stones). Urinary alkalinization during cytostatic therapy, when using uricosuric agents, and in the treatment of patients with cystine stones (as adjunctive therapy). As an adjuvant in combined symptomatic therapy of late cutaneous porphyria.

Contraindications.

Hypersensitivity to the components of the drug. Impaired renal excretory function, acute and chronic renal failure; acute acid-base balance disorders (metabolic alkalosis); urinary tract infections caused by urea-splitting bacteria (risk of struvite stone formation); urinary tract obstruction; hypernatremia; adrenocortical insufficiency; hyperkalemia; hypochlorhydria; metabolic or respiratory alkalosis; active peptic ulcer; intestinal obstruction; concomitant anticholinergic therapy; cardiac diseases whose course may worsen with potassium intake; strict salt-free diet (e.g., in severe forms of arterial hypertension); periodic hyperkalemic paralysis; phenylketonuria (contains a source of phenylalanine – aspartame).

Special precautions.

When dissolving uric acid stones, prolonged excessive urinary alkalinization (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 further dissolution. In addition, prolonged and pronounced alkaline metabolic state is undesirable.

The drug may be used in compensated renal insufficiency not associated with potassium retention in the body. Prior to administration, serum electrolyte levels should be determined and renal function assessed. In suspected renal tubular acidosis, acid-base balance parameters should be additionally monitored.

Patients with heart failure should consider the effect of potassium on myocardial excitability.

In patients with impaired potassium excretion, such as those with renal failure, there is a risk of developing life-threatening hyperkalemia.

Dosage recommendations must not be violated, as this may harm health.

A complete blood count and determination of blood electrolytes (sodium, potassium, and chloride) and creatinine are recommended every four months.

Patients taking Citrocas are advised to switch to a salt-free diet and increase fluid intake.

Interaction with other medicinal products and other types of interactions.

Concomitant administration of substances containing citrate and aluminum may increase aluminum absorption; therefore, a two-hour interval between the intake of such drugs is recommended.

The drug enhances the therapeutic effect of allopurinol.

Medicinal products that increase blood potassium levels (including ACE inhibitors, cyclosporines, and penicillins), potassium-sparing diuretics, as well as analgesics and anti-inflammatory drugs (nonsteroidal anti-inflammatory agents and peripheral analgesics), may reduce potassium excretion, which should be considered when prescribing them concomitantly with Citrocas.

Concomitant use with methenamine should be avoided.

Urinary alkalinization, related to the ion-trapping mechanism, may enhance the excretion of medicinal products such as salicylates, tetracyclines, and barbiturates. On the other hand, it may prolong the half-life of certain sympathomimetic and stimulant drugs (e.g., amphetamines). Additionally, interaction between potassium citrate and nitrofurantoin or methenamine may reduce their antibacterial activity.

Medicinal products with antimuscarinic effects (spasmolytics, etc.) may delay gastric emptying, potentially increasing gastrointestinal toxicity of potassium salts.

The drug should be used with caution in patients receiving cardiac glycosides, as the activity of the latter may, in some cases, depend on serum potassium ion concentration.

Special precautions for use.

Use during pregnancy or breastfeeding.

When using the drug in pregnant women, the expected benefit to the woman and the potential risk to the fetus should be carefully weighed.

During lactation, a decision should be made whether to discontinue breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

Does not affect.

Method of Administration and Dosage.

To prepare one dose, dissolve 1 sachet in 200 ml of water.

For calcium stones associated with hypocitraturia: in moderate hypocitraturia – 1 dose twice daily; in severe hypocitraturia (associated with chronic diarrheal syndrome or renal tubular acidosis) – 2 doses twice daily.

For calcium stones associated with hyperuricosuria: 1–2 doses daily in two divided doses. For calcium stones without uricosuria: 1/2 sachet twice daily.

For dissolution of calculi (depending on their size and composition), treatment duration ranges from 4 weeks to 6 months. To prevent recurrences of nephrolithiasis, the drug is administered in courses; the duration and frequency of which are determined individually for each patient.

Children.

Do not use in children (under 18 years of age).

Overdose.

With normal kidney function, undesirable effects of the drug on physiological parameters of metabolism are not observed, either at the usual recommended dose or at higher doses, since renal excretion of excess alkali is a natural mechanism regulating acid-base balance in the body.

Prolonged use of the drug in patients with impaired potassium excretion may lead to hypernatremia, which in turn may cause muscle paralysis and cardiovascular collapse. Excessive intake of citrate may have a laxative effect.

Overdose can be prevented by reducing the drug dose. If necessary, treatment measures for metabolic alkalosis may be employed.

Recommended initial treatment of overdose. For patients with hypernatremia, it is recommended to administer intravenously a 10% dextrose solution containing 10–20 units of insulin per 1000 ml of solution.

Treatment of potential acidosis may be carried out by intravenous administration of sodium bicarbonate and peritoneal dialysis.

Side effects.

Mild gastrointestinal disturbances such as abdominal discomfort, belching, heartburn, nausea, abdominal pain, flatulence, vomiting, and diarrhea. These symptoms may be reduced by taking the medication with food.

If any adverse reactions occur, consult a physician.

Shelf life.

3 years.

Storage conditions. Store in a place protected from light and moisture at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging. 20 or 60 sachets per cardboard box.

Classification.

Over-the-counter (without prescription).

Manufacturer.

Laboratorios Casasco A.P.T.T. / Laboratorios Casasco S.A.I.C.

Manufacturer's address and location of operations.

Boyaca No. 229/37/49/63/65, Terrero No. 250/52/60, Bacacay No. 1843/45 (Zip Code C1406BHC), City of Buenos Aires, Argentine Republic, and Calle 5 No. 186, Industrial Park of Pilar, Pilar District, Province of Buenos Aires, Argentine Republic / Av. Boyaca No. 229/37/41/49/63/65, Terrero No. 250/52/60, Bacacay No. 1843/45 (Zip Code C1406BHC), of the City of Buenos Aires, Argentine Republic, and Calle 5 No. 186, Industrial Park of Pilar, Province of Buenos Aires, Argentine Republic.

Marketing Authorization Holder.

Laboratorios Casasco A.P.T.T. / Laboratorios Casasco S.A.I.C.

Address of the Marketing Authorization Holder.

Av. Boyaca 237 (Zip Code C1406BHC), City of Buenos Aires, Argentine Republic / Av. Boyaca 237 (Zip Code C1406BHC), of the City of Buenos Aires, Argentine Republic.