Potassium sulfate, Magnesium sulfate, Sodium sulfate

Pharmacological properties

the drug is an osmotic laxative. its mechanism of action is mainly based on a limited and saturated process of active sulfate transfer. due to saturation during the gastrointestinal transfer, sulfate remains in the intestine. The osmotic effect of unabsorbed ions when taken with a large amount of water causes profuse watery stools. during clinical trials, the average time until the appearance of frequent stools was about 6.3 hours with an interval between doses of 12 hours and about 2.8 hours when used with an interval of 1 hour.

Pharmacokinetics Sulfate absorption is a limited and saturated process of active transfer; Absorbed sulfate is excreted mainly by the kidneys. After the clinical use of the drug with the same sulfate content as the drug Eziclen, in 6 healthy volunteers in accordance with the divided dose regimen, that is, the use of two doses with an interval of 12 hours, C_max plasma sulfate was achieved approximately 16 hours after the first half of the dose and 5 hours after the second dose [C_max: 499.5 μmol / L (CV: 33.03%) compared with the initial values ​​of 141-467 μmol / L, average 335 μmol / L (CV: 34.4%)]. After this, the plasma concentration decreased with T_½ 8.5 hours (CV: 53.76%). The main way to remove sulfate is excretion with feces (about 70% of the dose taken).

Systemic exposure (AUC and C_max) sulfate after taking the drug was also compared in healthy volunteers, 6 patients with moderate renal impairment (creatinine clearance - 30–49 ml / min) and 6 patients with minor or moderate hepatic impairment (Child-Pugh score A (n = 5) and B (n = 1)), respectively. Impaired renal function led to a decrease in urinary sulfate excretion. As a result, the average values ​​of AUC and C_max were approximately 50% higher compared with those in patients with normal renal function. Impaired liver function did not affect the systemic effect of sulfate. The concentration of sulfate in blood plasma returned to baseline values ​​on the 6th day after taking the drug in all 3 studied groups. In this study, the use of the drug did not result in clinically significant hypersulfatemia in patients with impaired liver or kidney function.

Indications

The drug is prescribed for adults to cleanse the intestines before any procedure requiring this (for example, imaging of the intestine, including endoscopy and radiology, or surgical procedures).

The drug is not a treatment for constipation.

Application

Doses

Adults For proper bowel cleansing, use the contents of 2 bottles of the drug. Before use, the contents of each bottle should be diluted in water using a cup, which is attached, until a total volume of about 0.5 l is obtained; after use, 1 liter of water or a clear liquid should be used additionally for 2 hours.

Transparent liquids are allowed: water, tea or coffee (without milk or non-dairy cream), carbonated or non-carbonated soft drinks, juices from mashed fruits without pulp (not red and not purple), broth or soup filtered in such a way as to eliminate solid fragments .

The total volume of fluid that must be taken to cleanse the intestines is about 3 liters, which must be taken orally before the procedure. This drug can be taken in divided doses (within 2 days, while the content of one bottle is taken in the evening before the procedure, and the second one the next morning) or as a one-day dose, as described below (see Method of use). The exact dosage and dosage of the drug is determined by the doctor.

If this allows you to increase the duration of the procedure, the divided dose regimen should be preferred over the one-day regimen. A single daily dosing regimen is a potentially useful alternative regimen.

Mode of application

The divided dose regimen (two-day)

The day before the procedure. In the early evening before the procedure (for example, at 18:00):

• the contents of one bottle of the drug should be poured into a cup, which is in the package, and diluted with water to the measuring line (i.e., about 0.5 l);
• the patient should drink this diluted solution, washing it down with two additional glasses of water or a clear liquid filled with a measured line (i.e., about 1 liter), for 2 hours.

The day of the procedure. In the morning before the procedure (10-12 hours after the evening dose):

• the contents of the second bottle of the drug should be poured into a glass and diluted with water to the measuring line (that is, about 0.5 l);
• the patient should drink this diluted solution, washing it down with two additional glasses of water or a clear liquid filled with a measured line (i.e., about 1 liter), for 2 hours.

Reception of the whole diluted solution of a medicine and additional liquid (water or a clear liquid) should be completed:

• in the absence of anesthesia - at least one hour before the start of the procedure;
• in case of anesthesia, at least 2 hours before the start of the procedure in accordance with the instructions of the anesthetist.

One-day dosage regimen (alternative dosage regimen, which can be used depending on the clinical requirements of the patient)

The evening before the procedure. Early in the evening before the procedure (for example, at 18:00):

• the contents of one bottle of the drug should be poured into a glass and diluted with water to a measuring line (about 0.5 l);
• the patient should drink this diluted solution, washing it down with two additional glasses of water or a clear liquid filled with a measured line (i.e., about 1 liter), for 2 hours.

About 2 hours after the start of the first dose (for example, at 20:00):

• the contents of the second bottle of the drug should be poured into a glass and diluted with water to a measuring line (about 0.5 l);
• the patient should drink this diluted solution, washing it down with two additional glasses of water or a clear liquid filled with a measured line (i.e., about 1 liter), for 2 hours.

Reception of the whole diluted solution of a medicine and additional liquid (water or a clear liquid) should be completed:

• in the absence of anesthesia - at least one hour before the start of the procedure;
• in case of anesthesia, at least 2 hours before the start of the procedure in accordance with the instructions of the anesthetist.

Whatever method is chosen, the following steps should be followed for both the first and second modes:

1. Open a bottle that is not accessible for children to open by pressing the lid and turning it counterclockwise.

2. Pour the contents of one bottle of the drug into a cup with a measuring line.

3. Add water to the drug until the level reaches the measuring line on the cup.

4. Drink all the liquid in a glass (within 0.5–1 h).

5. Important: drink 2 more glasses of water or a clear liquid. Each time, fill the cup with water or a clear liquid to the measuring line.

6. Drink all the liquid in each cup (within 0.5 h).

Steps 1–6 should take about 2 hours and should be repeated for the second part of the plan.

Whatever the plan, it should be completed at least 1 hour before the procedure.

After the procedure. In order to recover fluid lost during preparation for the procedure, patients should be advised to take a sufficient amount of fluid after the procedure in order to maintain an adequate level of hydration.

Nutritional restrictions. A light breakfast is allowed on the day before the procedure.After this, the patient should use only clear liquids for lunch, dinner and any other meals, until the procedure is performed. Red and purple fluids, milk, and alcohol should be avoided.

Special populations

Elderly patients. There were no differences in safety or effectiveness for the elderly and other categories of patients during the clinical development of the drug. There is no need for dose adjustment for elderly patients, however, special precautions should be taken for this population, as for any other population with an increased level of risk.

Patients with impaired renal function. There is insufficient data for this population. Dose adjustment for patients with impaired renal function of mild to moderate severity is not required, however, special precautions should be taken for this population, as for any other group of patients with an increased level of risk. The drug should not be taken in patients with severe impaired renal function.

Patients with impaired liver function. There is insufficient data for this population. Dose adjustment for patients with impaired liver function is not required, however, special precautions should be taken for this population, as for any other group of patients with an increased level of risk.

Contraindications

The use of the drug is contraindicated in patients with the following conditions:

• hypersensitivity to the active substance or any of the excipients;
• known or suspected gastrointestinal obstruction;
• perforation of the intestinal wall;
• violation of gastric emptying (e.g. gastroparesis);
• intestinal obstruction;
• toxic colitis or toxic megacolon;
• profuse vomiting;
• severe dehydration;
• congestive heart failure;
• ascites;
• severe renal failure (glomerular filtration rate of 30 ml / min / 1.73 m²);
• active inflammatory bowel disease (e.g., Crohns disease, ulcerative colitis).

Side effects

On the part of the immune system (data from post-registration studies): hypersensitivity (including urticaria, itching, rash, erythema, shortness of breath, sensation of constriction in the throat).

From the nervous system: infrequently - headache.

From the digestive tract: very often - bloating, abdominal pain, nausea, vomiting; infrequently - anorectal discomfort, dry mouth.

From the urinary system: infrequently - dysuria.

General disorders: very often - discomfort; infrequently - chills.

On the part of laboratory indicators and instrumental data: infrequently - increasing the level of AsAT; increased levels of CPK in the blood; increased LDH in the blood; hyperbilirubinemia; violations of the chemical composition of the blood, including hyponatremia, hypokalemia and hyperuricemia.

special instructions

Electrolyte disturbances and dehydration

Given the potential risk of severe electrolyte abnormalities, the risk / benefit ratio of the drug should be carefully analyzed before starting treatment for high-risk patients. When prescribing a medicine, special attention should be paid to known contraindications and special instructions for use, including the importance of a sufficient level of hydration.

All patients should be advised to take a sufficient amount of fluid before, during and after the use of the drug. If a patient develops severe vomiting or signs of dehydration after using the drug, rehydration measures must be taken to avoid the potential risks of developing severe complications associated with fluid and electrolyte disturbances (such as convulsions or arrhythmias).In addition, you should consider the possibility of conducting laboratory tests before the procedure (electrolytes, creatinine and blood urea nitrogen). The patient should be advised to take additional water or a clear liquid in the amount necessary to maintain an adequate level of hydration.

Risk patients

In debilitated patients, the elderly, patients with clinically significant impaired renal, liver or heart function, as well as patients for whom there is a risk of electrolyte imbalance, the doctor should consider the possibility of an initial and post-therapeutic study of electrolytes and kidney function.

Patients with manifestations of dehydration or persons with electrolyte disorders should be eliminated before using the drug to cleanse the intestines. In addition, caution should be exercised in patients with conditions that increase the risk of developing fluid and electrolyte disturbances, or are taking medications that increase the risk of developing water-electrolyte disturbances (including hyponatremia and hypokalemia) or who may increase the risk of potential complications. In this case, patients require proper monitoring.

There is a theoretical risk of lengthening the Q – T interval due to electrolyte imbalance.

Use with caution:

• patients with a violation of the gag reflex, as well as persons prone to belching or aspiration. Such patients require observation during the use of the drug to cleanse the intestines;
• patients with hypokinetic disorders of the gastrointestinal tract or medical conditions or operations on the gastrointestinal tract in history, causing the development of hypokinetic disorders.

Hyperuricemia The drug may cause a temporary minor or moderate increase in uric acid levels. Before using the drug, the potential for increasing uric acid levels in patients with a history of gout or hyperuricemia should be considered.

Additional Information:

• the drug is not intended for undiluted administration. Direct administration of undiluted solution may increase the risk of nausea, vomiting, dehydration and electrolyte disturbances. The contents of each bottle should be diluted with water and taken with additional water, as recommended, in order to ensure tolerability of the drug;
• the drug contains 247.2 mmol (or 5.683 g) of sodium per bottle. Information should be considered for patients following a diet with a limited sodium content;
• the drug contains 35.9 mmol (or 1.405 g) of potassium per bottle. Information should be considered in patients with impaired renal function or those on a low potassium diet.

Use during pregnancy and lactation. There are no data on the use of this drug in pregnant women. The use of the drug during pregnancy is not recommended. It is not known whether the drug passes into breast milk. The risk to newborns / infants cannot be ruled out. During drug therapy, breast-feeding should be discontinued until 48 hours after taking the second dose.

Fertility. There are no data on fertility effects.

Children. The safety and effectiveness of the drug for children (i.e. patients under the age of 18) have not yet been established. Data on the use in children are not available.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The drug does not affect the ability to drive vehicles and work with other mechanisms.

Interactions

As with any other bowel cleansing medicine:

• use with caution in patients taking calcium channel blockers, diuretics, lithium preparations or drugs that can affect the level of electrolytes;
• caution is advised when using drugs for which it is known that they tend to lengthen the Q – T interval;
• loose stool is the expected result; concomitant oral medications that are taken for 1–3 hours from the start of treatment until the end of the cleaning process can be washed out of the digestive tract and not absorbed properly. The therapeutic effect of regularly used oral drugs with a narrow therapeutic range or short half-life (such as oral contraceptives, antiepileptic drugs, antidiabetic drugs, antibiotics, levothyroxine, digoxin, etc.) can be particularly affected.

Incompatibility. This medicine should not be mixed with other medicines.

Overdose

In case of overdose or improper use (for example, drug non-dilution and / or insufficient water consumption), nausea, vomiting, diarrhea and electrolyte disturbances are expected. usually conservative measures are enough; oral rehydration therapy should be given. in the unlikely event that an overdose leads to a serious metabolic disorder, iv rehydration should be performed.

Storage conditions

In the original packaging to protect from the effects of light.

It does not require special storage conditions.

It should not be stored after the first opening of the package and / or dilution.