- For dissolution of uric acid stones

- For metaphylaxis (prevention of recurrent formation) of calcium stones and uric acid stones and/or mixed calcium oxalate and uric acid stones or mixed calcium oxalate and calcium phosphate stones.

NOTE:

This product should only be used as part of a general concept of metaphylaxis (e.g. diet, increased fluid uptake, etc.).

Posology

a) Dissolution and metaphylaxis of uric acid stones

In general, it is recommended to take 4 measuring spoonfuls (= 10 g of granules,equivalent to 88 mmol of alkali) daily, divided into three doses, after meals. One measuring spoonful shall be taken in the morning, 1 measuring spoonful at noon and 2 measuring spoonfuls in the evening.

The pH value of the freshly voided urine should be within the range of:

Uric acid stones: pH 6.2 – 6.8.

If the pH value is below the specified range, the daily dose should be increased by half a measuring spoonful of Uralyt-U® (11 mmol of alkali) in the evening. If the pH is above the specified range, the daily dose should be reduced by half a measuring spoonful (11 mmol of alkali) in the evening.

The correct dosage has been reached if the pH value of the freshly voided urine, measured before taking the dose of Uralyt-U®, is within the specified range.

For metaphylaxis of uric acid stones, regular checks of the urine pH levels are recommended.

 

b) Metaphylaxis of calcium-containing kidney stones:

The recommended daily dose is 2-3 measuring spoonfuls (= 5-7.5 g of granules, equivalent to 44-66 mmol of alkali) and should be taken in a single dose in the evening.

If needed, i.e. if the measured pH value is too low, 3-4.5 measuring spoonfuls (= 7.5 g-11.25 g of granules, equivalent to 66 to 99 mmol of alkali) should be taken in 2-3 doses divided over the day, after meals.

A neutral pH value should be aimed at. The pH value should not be lower than 6.2 and should not exceed pH 7.4.

Citrate levels and/or urine pH values should be regularly checked and the individual dose (see above) be adjusted accordingly.

 

Method of administration:

The granules shall be dissolved in a glass of water and drunk.

Measurement of the urine pH value:

Immediately before taking each dose, a test strip of the indicator paper provided in the pack should be wetted with freshly voided urine using the clamp also supplied in this pack.

 

The colour of the wet test strip shall then be compared with the colour chart, and the pH value printed below the corresponding colour can be read off.

This pH reading as well as the number of measuring spoonfuls of granules taken should be noted in the control calendar. The patient shall bring along this calendar every time he/she visits the doctor.

 

Paediatric population

No data are available.

In the patient information leaflet it is pointed out to the patient that Uralyt-U® should not be used in cases of: - Impaired renal excretory function - Metabolic alkalosis - Hyperkalaemia - Adynamia episodica hereditaria - Chronic urinary tract infections with urea-splitting bacteria (danger of formation of struvit stones) - Low sodium diet - Hypersensitivity to potassium sodium hydrogen citrate, Yellow Orange S (E 110), or to any of the excipients. Note: The treatment of children less than 12 years of age is not recommended as there is insufficient clinical experience for this age group.

 

Before starting treatment, all circumstances or diseases which may be in favour of urinary stones and for which well-targeted therapy is available (such as adenoma of parathyroid glands, malignancy associated with uric acid stones etc.) should be ruled out.

The maximum recommended daily dose is 11.25 g of granules (4.5 measuring spoonfuls). This is equivalent to 1.86 g of potassium and 1.09 g of sodium, i.e. 47.5 mmol of potassium and 47.5 mmol of sodium. This should be considered in particular when treating the elderly and in case of concomitant therapy with potassium-saving diuretics, aldosterone antagonists, ACE inhibitors, angiotensin receptor antagonists, non-steroidal anti-inflammatory drugs or peripheral analgesics.

Interaction with these medicinal products can lead to hyperkalaemia.

Before taking the first dose, the serum electrolytes should be determined and renal function should be monitored. Moreover, the acid-base status should be checked when renal tubular acidosis (RTA) is suspected.

 

Uralyt-U® should be used with caution in patients with severely impaired liver function.

This medicinal product contains the colouring agent Yellow Orange S (E 110) which may induce allergic reactions including asthma in sensitized persons. Allergy is more often seen in people reacting to 2-acetoxybenzoic acid (acetylsalicylic acid).

 

 

Any increase in extracellular potassium concentration will weaken the effect of cardiac glycosides, while any decrease will potentiate the arrhythmogenic effect of cardiac glycosides. Aldosterone antagonists, potassium-saving diuretics, ACE inhibitors, angiotensin receptor antagonists, non-steroidal anti-inflammatory drugs and peripheral analgesics reduce renal potassium excretion. Attention should be paid to the fact that 1.0 g of potassium sodium hydrogen citrate contains 0.172 g or 4.4 mmol of potassium.

 

When prescribing a low sodium diet it should be remembered that 1.0 g of potassium sodium hydrogen citrate contains 0.1 g or 4.4 mmol of sodium (equivalent to 0.26 g of sodium chloride).

 

Concomitant administration of substances containing citrate and aluminium can lead to increased aluminium absorption; if such medicines need to be taken, an interval of at least 2 hours must be allowed between taking each kind of product.

 

There is no adequate clinical data from the use of Uralyt-U® in pregnant women.

Experimental studies in animals did not indicate any teratogenic or embryotoxic effects.

As the active substance is a combination of physiologically occurring substances, Uralyt-U® may be used in pregnancy and lactation under the specified dose recommendations.

 

No indications of harmful effects during pregnancy and lactation have been noted.

Uralyt-U® has no or negligible influence on the ability to drive or use machines.

 

The rating for side effects is based on the following frequency convention:

Very common > 1/10

Common > 1/100 - < 1/10

Uncommon > 1/1,000 - < 1/100

Rare > 1/10,000 - < 1/1,000

Very rare < 1/10,000

Not known Frequency cannot be estimated from the available data.

Gastrointestinal disorders:

Mild gastric or abdominal pain are common. In rare cases, mild diarrhoea and nausea may occur.

 

Other possible undesirable effects:

Yellow Orange S (E 110) may provoke allergic reactions.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via

 

Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

Fax: +966-11-205-7662

SFDA Call Center: 19999

E-mail:npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa/

Other Countries:

Please contact the relevant competent authority.

 

Overdose can lead to hyperkalaemia (potassium-plasma level >5 mmol/l), in particular in patients with simultaneous acidosis or renal failure.

Provided that renal function is adequate, there is no likelihood of any unwanted effects on normal metabolic physiological parameters, even after taking doses higher than those recommended, since the excretion of any base excess via the kidney provides a natural regulatory mechanism which ensures maintenance of the acid-base balance.

 

It should be avoided that the specified urine pH range will be exceeded for several days, since considerably elevated pH values are related with an increased risk of phosphate crystallisation. On the other hand, the long-term establishment of a marked alkalotic metabolic state shall not be achieved. Inadvertent overdosage can be corrected at any time by reducing the dose; if necessary, appropriate measures for the treatment of metabolic alkalosis may be considered.

 

Pharmacotherapeutic group: Alkali citrates, agents for urolithiasis

ATC code: G04BC01

Salts of strong bases with weak acids are suitable for alkalinization (neutralization therapy), and the acid component is assumed to be metabolizable. The citrate ion from alkali citrates undergoes almost complete oxidative metabolic breakdown to CO2 or bicarbonate. The base excess resulting from the remaining alkali ions is eliminated via the kidneys and produces an increase in urine pH value.

Neutralisation or alkalinization of the urine can be achieved by oral administration of alkali citrates, the response being dose-dependent.

1 g of potassium sodium hydrogen citrate (8.8 mmol of alkali) causes the urine pH value to increase by 0.2–0.3 units. As a result, the dissociation rate increases and thus the solubility of uric acid. Litholysis of uric acid stones has been radiologically demonstrated.

Serum concentration of bicarbonate (negatively charged base excess) is the regulator of citrate excretion. Negatively charged base excess induces alkalosis via a shift in intracellular pH value.

 

This leads to alkalosis-induced inhibition of renal tubular metabolism of citrate what results in reduced reabsorption of citrate and increased citrate excretion. At the same time, alkalosis has an influence on renal calcium flux by significantly reducing urinary calcium excretion.

Alkalisation of urine, increased excretion of citrate and reduced excretion of calcium lead to a decrease in the activity product of calcium oxalate, as citrate in weak alkalotic milieu forms stable complexes with calcium. Moreover, the citrate ion must be regarded as the most effective physiological inhibitor of calcium oxalate (and calcium phosphate) crystallisation and aggregation of these crystals.

 

To assess the usefulness of urinary alkalisation in the following kinds of illness, data from systematic trials are lacking. Observations in single cases as well as theoretical considerations speak for a therapeutic effect:

- Cystinuria and cystine stone formation: Alkalisation of urine increases the solubility of cystine. However, urinary pH should arrive at values ranging between 7.5 and 8.5.

- Treatment with cytostatics: Alkalisation of urine in order to eliminate the rise in uric acid makes sense during a treatment with cytostatics. This is in line with the prophylaxis of uric acid stones, claimed as therapeutic indication. In addition, a protective effect of alkalotic urinary pH value is claimed because of reduced aggressivity of cytostatic metabolites (e.g. oxazaphosphorin cytostatics) and their increased solubility (e.g. methotrexate), respectively. For this purpose, urinary pH level

should be regulated to a value of 7.0 at least.

- Porphyria cutanea tarda: In porphyria cutanea tarda, an uroporphyrinogen

decarboxylase deficiency exists which metabolises uroporphyrinogen to

coproporphyrinogen. The objective of metabolic alkalisation is to prevent back diffusion of coproporphyrin through renal tubuli so that the coproporphyrin clearance will increase. As a consequence of the increased coproporphyrinogen excretion, the synthesis of coproporphyrinogen from uroporphyrinogen is believed to increase and is consequently accompanied by a decrease in circulating uroporphyrin. Urinary pH levels

should be adjusted to range between 7.2 - 7.5.

 

Citrate undergoes almost complete metabolic breakdown. Only 1.5% to 2% of the original administered dose appears unchanged in the urine.

Intake of 10 g of potassium sodium hydrogen citrate yields approximately 36 mmol of citrate; this is equivalent to less than 2% of the daily turnover of citrate involved in energy metabolism within the body.

After a one-day intake of potassium sodium hydrogen citrate, the equivalent amounts of sodium and potassium are quantitatively excreted via the kidneys within 24 - 48 hours.

During long-term administration, daily excretion of sodium and potassium is in equilibrium with the daily intake.

No significant changes in blood gases or in serum electrolytes have been observed.

This indicates that by virtue of renal regulation of alkalinization the acid-base balance of the body remains intact and that, provided renal function is adequate, any possibility of accumulation of sodium or potassium can be excluded.

 

According to the results obtained from investigations in animals, potassium sodium hydrogen citrate (6:6:3:5) has no toxicological potential in the prescribed dosage.

Chronic tests in rats revealed that oral doses between 1 g / kg and less than 3 g / kg of bodyweight were safe.

Toxicological tests on reproduction in rats and rabbits at 2 g / kg of bodyweight revealed no teratogenic or embryotoxic/fetotoxic effects.

When observing the contraindications and notes, no cancerogenic and mutagenic effects are to be expected for the intended mode and duration of use.

 Aroma: Lemon oil; Coloring agent: Yellow Orange S (E 110).

 Not applicable.

3 years

 Do not store above 30°C

Original pack containing 280 g of granules.

The pack also contain indicator paper and control calendars.

 No special requirements.