Eziclen^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Ipsen Consumer Healthcare SAS (France)

Manufactured By

Beaufour Ipsen Industrie (France)

ATC Code

A06AD10 (Mineral salts in combination)

Active Substances

Sodium sulphate, anhydrous (Ph.Eur.)

Magnesium sulphate (Ph.Eur.)

Potassium sulphate (Ph.Eur.)

Dosage Form

Eziclen®

Concentrate for preparation of solution for oral administration 17.51 g+3.276 g+3.13 g/1 bottle: bottle 176 ml 2 pcs. in set with measuring cup

Dosage Form, Packaging, and Composition

Concentrate for preparation of solution for oral administration as a clear or slightly opalescent liquid with a fruity odor.

Excipients: sodium benzoate – 0.098 g/1 bottle (0.196 g/2 bottles), anhydrous citric acid – 0.315 g/1 bottle (0.63 g/2 bottles), malic acid – 0.315 g/1 bottle (0.63 g/2 bottles), sucralose – 0.3025 g/1 bottle (0.605 g/2 bottles), fruit and berry cocktail flavor* – 0.7875 g/1 bottle (1.575 g/2 bottles), purified water – 169.641 g/1 bottle (339.282 g/2 bottles).

* Fruit and berry cocktail flavor consists of a mixture of natural and synthetic flavors, propylene glycol (E1520), ethyl alcohol, acetic acid, and benzoic acid (E210).

176 ml – transparent dark brown polyethylene terephthalate bottles with a capacity of 180 ml (2) in a set with a polypropylene measuring cup – cardboard packs.

Clinical-Pharmacological Group

Laxative drug with osmotic properties

Pharmacotherapeutic Group

Osmotic laxative

Pharmacological Action

The mechanism of action of the drug is primarily due to the saturable process of active transport of sulfates. When the absorption saturation threshold is reached, sulfates remain in the intestinal lumen.

The osmotic effect of non-absorbed sulfates and the oral intake of a significant volume of water causes water retention in the intestine, which provides a laxative effect, causing profuse watery diarrhea, and leads to bowel cleansing.

Pharmacokinetics

Sulfate absorption is a saturable active transport process. Absorbed sulfates are excreted primarily by the kidneys. In clinical studies after administration of a drug similar in sulfate content to Eziclen^®, in 6 healthy volunteers (in a split-dose regimen, i.e., taking 2 doses with a 12-hour break), the C_max of sulfates in serum was observed approximately 16 hours after the 1st dose and 5 hours after the 2nd dose and was 499.5 µmol/L, compared to the baseline value of 141-467 µmol/L, on average – 335 µmol/L. Then the serum sulfate concentration decreased with a T_1/2 of 8.5 hours.

The main route of sulfate excretion is intestinal excretion (about 70% of the administered amount).

Systemic exposure to sulfates: AUC and C_max after administration of Eziclen^® were studied in a comparative study in healthy volunteers, in 6 patients with moderate renal impairment (CrCl from 30 to 49 ml/min) and in 6 patients with mild or moderate hepatic impairment (according to the Child-Pugh scale: A (N=5) and B (N=1), respectively). Renal impairment led to a decrease in the amount of sulfates excreted by the kidneys. The mean AUC and C_max values of sulfates were approximately 50% higher in patients with renal impairment compared to healthy volunteers. The systemic effect of the drug on sulfate concentrations was independent of hepatic impairment. In all 3 study groups, serum sulfate concentrations returned to baseline on day 6 after administration of Eziclen^®. In this study, administration of Eziclen^® did not lead to a clinically significant increase in blood sulfate concentrations in patients with hepatic or renal impairment.

Indications

Cleansing of the colon in adult patients in preparation for

• Endoscopic and radiological examination of the colon;
• Surgical interventions requiring the absence of contents in the colon.

ICD codes

Dosage Regimen

For oral administration.

The drug can only be used in adult patients.

For proper bowel cleansing, the intake of 2 bottles of Eziclen^®® is required.

Before administration, the contents of each bottle must be diluted with water. The patient should drink the resulting diluted solution and two more cups filled to the mark with water or an approved clear liquid (i.e., approximately 1 L) over the next 2 hours, as described below in the “Administration Regimen” and “Dilution and Administration Scheme” sections.

Permitted clear liquids are water, tea or coffee (without milk or non-dairy creamer), carbonated or non-carbonated soft drinks, clear fruit juices (without pulp, not red or purple), broths or soups strained from solid ingredients.

In total, at least 3 L of fluid must be drunk to cleanse the bowel before the procedure.

The solution after dilution must be used immediately.

Administration Regimen

The drug is taken either in a split-dose regimen (the 1st bottle is taken in the evening on the day before the procedure, and the 2nd – the next morning), or in a single-dose regimen (administration on the day before the procedure).

The appropriate regimen for taking Eziclen^® may be determined by the doctor.

If the scheduled procedure time allows, the split-dose regimen is preferable to the single-dose regimen on the day before the procedure. The single-dose regimen on the day before the procedure is potentially suitable as an alternative regimen.

Split-dose regimen

Day before the procedure

The following instructions must be followed

• The contents of one bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Day of the procedure

On the day of the procedure (10-12 hours after taking the first bottle of the drug), it is necessary to repeat the actions according to the instructions for the previous day

• The contents of the 2nd bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Intake of the full volume of the diluted Eziclen^® solution and the additional amount of water or clear liquid must be completed at least 2 hours and no later than 4 hours before the start of the procedure.

The exact regimen and time of taking Eziclen^® is determined by the doctor.

Single-dose regimen

(a regimen for use depending on individual patient needs, as well as depending on the time of the procedure).

Single-step evening scheme

Examination time – until 14:00.

Evening before the procedure

• The contents of one bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Approximately 2 hours after starting the 1st dose

• The contents of the 2nd bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Intake of the full volume of the diluted Eziclen^® solution and the additional amount of water or clear liquid must be completed at least 2 hours and no later than 4 hours before the start of the procedure.

Single-step morning scheme

Examination time – 14:00 and later.

Before the procedure

• The contents of one bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Approximately 2 hours after starting the 1st dose:

• The contents of the 2nd bottle of Eziclen^® should be poured into the supplied measuring cup and diluted with water to the mark (i.e., to a volume of 0.5 L);
• Over the next 2 hours, the patient should drink the resulting solution and an additional 2 measuring cups of water or clear liquid (i.e., about 1 L).

Intake of the full volume of the diluted Eziclen^® solution and the additional amount of water or clear liquid must be completed at least 2 hours and no later than 4 hours before the start of the procedure.

In case of procedures under general anesthesia

For the two-step, single-step morning and single-step evening dosing schemes, intake of Eziclen^® and other liquids (according to the list of permitted ones – see above) must be stopped at least 2 hours before the start of the procedure.

In case of procedures without anesthesia

For the two-step, single-step morning and single-step evening dosing schemes, intake of Eziclen^® and other liquids (according to the list of permitted ones – see above) must be stopped at least 1 hour before the start of the procedure.

Drug dilution and administration scheme

• Open the bottle by pressing the cap and turning it counterclockwise;
• Pour the contents of one bottle into the supplied measuring cup;
• Dilute the drug with water to the mark (i.e., to a volume of 0.5 L);
• Slowly drink all the liquid from the cup, within 30-60 minutes;
• it is important to drink another 2 measuring cups of water or clear liquid, each time filling the cup to the mark;
• Slowly drink the liquid from each cup within 30 minutes (2 x 30 minutes).

Completing the above steps takes about 2 hours.

All steps should be repeated with the 2nd bottle of Eziclen^®.

After the procedure

To replenish the fluid lost during the preparation for the procedure, patients should drink a sufficient amount of it to maintain an appropriate level of hydration.

Dietary restrictions

A light breakfast is allowed on the day before the procedure. Thereafter, the patient may only consume clear liquids as a meal until the procedure. Intake of red and purple liquids, milk, and alcoholic beverages should be avoided.

Special patient groups

Elderly patients

In clinical studies of the drug, no difference in the efficacy and safety of Eziclen^® was found in elderly patients and patients of other age groups. No dose adjustment is required for elderly patients, however, caution should be exercised when using the drug in such patients, as in any other high-risk population.

Patients with renal impairment

There are limited data for this patient group. No dose adjustment is required for patients with mild or moderate renal impairment, however, caution should be exercised when using the drug in such patients, as in any other high-risk population. Eziclen^® is contraindicated in patients with severe renal impairment.

Patients with hepatic impairment

There are limited data for this patient group. No dose adjustment is required for patients with hepatic impairment, however, caution should be exercised when using the drug in such patients, as in any other high-risk population.

Pediatric population

The safety and efficacy of Eziclen^® in patients under 18 years of age have not yet been established. No data available.

Adverse Reactions

Diarrhea occurring after taking Eziclen^® is an expected effect during bowel cleansing in preparation for procedures and occurs in most patients. The most frequently reported adverse reactions in clinical studies and post-marketing surveillance were: discomfort, abdominal bloating, abdominal pain, nausea and vomiting.

During clinical studies, reports of vomiting were received more frequently with the use of the single-dose regimen than with the use of the split-dose regimen.

The frequency of adverse reactions with the use of Eziclen^® is classified as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data).

Additional information for special patient groups

During clinical studies, a temporary increase in uric acid concentration was found. For patients with a history of clinical manifestations of gout or hyperuricemia, see information in the “Special Instructions” section.

In clinical studies, no difference in the safety of taking Eziclen^® was found in elderly patients and patients of other age groups. Caution should be exercised when using the drug in such patients, as in any other high-risk population (see the “Special Instructions” section).

Contraindications

• Hypersensitivity to the active substances or to any of the components of the drug;
• Gastrointestinal obstruction or suspicion of gastrointestinal obstruction or stenosis;
• Known or suspected perforation of the intestinal wall (intestinal perforation);
• Impaired gastric emptying (including gastroparesis, gastrostatis);
• Intestinal obstruction (ileus);
• Toxic colitis or toxic megacolon;
• Nausea and vomiting;
• Serious deterioration of health (such as severe dehydration);
• Congestive heart failure;
• Ascites;
• Severe renal failure (GFR<30 ml/min/1.73m²);
• Active phase of inflammatory bowel diseases (such as Crohn’s disease, ulcerative colitis);
• Acute abdominal diseases requiring surgical intervention (e.g., acute appendicitis);
• Pregnancy;
• Breastfeeding period;
• Age under 18 years.

With caution

• Elderly age;
• Mild or moderate renal impairment;
• Hepatic impairment;
• Concomitant use of drugs affecting electrolyte concentrations (calcium channel blockers, diuretics, lithium preparations or other drugs of similar action);
• Concomitant use of drugs that prolong the QT interval;
• Decreased gastrointestinal motility (including in history), presence of gastrointestinal surgeries that led to impaired motility;
• In patients with impaired gag reflex, prone to regurgitation and aspiration;
• In debilitated, weakened patients;
• In patients with clinically significant cardiac dysfunction;
• In patients at high risk of developing water-electrolyte disorders (including hyponatremia and hypokalemia), manifestations of gout or hyperuricemia.

Use in Pregnancy and Lactation

Pregnancy

Reproductive function studies in animals using sodium, magnesium and potassium sulfates have not been conducted.

There are no data on the use of Eziclen^® in pregnant women.

The use of Eziclen^® during pregnancy is not recommended.

Breastfeeding

It is not known whether Eziclen^® is excreted in breast milk.

The risk to the newborn/infant cannot be ruled out.

Breastfeeding should be discontinued during the period of taking Eziclen^® and up to 48 hours after taking the second dose.

Fertility

No data on the effect on fertility are available.

Use in Hepatic Impairment

Use with caution in patients with hepatic impairment, no dose adjustment is required.

Use in Renal Impairment

Use with caution in patients with mild or moderate renal impairment, no dose adjustment is required. Eziclen^® is contraindicated in patients with severe renal failure (GFR<30 ml/min/1.73m²).

Pediatric Use

The use of the drug in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

No dose adjustment is required for elderly patients, however, caution should be exercised when using the drug in this category of patients.

Special Precautions

The drug Eziclen^® is not used for the treatment of constipation.

Electrolyte disorders and dehydration

Given the potential risk of developing serious electrolyte disturbances, the benefit/risk ratio must be carefully evaluated before using the drug Eziclen^® in high-risk groups. Contraindications for its use must be ruled out before administering the drug Eziclen^®. Particular attention should be paid to the implementation of special precautions, including the need to maintain adequate hydration.

All patients should be warned about the need to maintain an adequate level of hydration before, during, and after taking the drug Eziclen^®. If a patient develops profuse vomiting or signs of dehydration after taking the drug, rehydration measures should be taken to avoid the potential risk of serious complications associated with water-electrolyte imbalance (such as seizures and cardiac arrhythmia). Furthermore, preliminary laboratory tests (determination of electrolyte concentrations, creatinine, and blood urea nitrogen) are recommended. Patients should be advised to drink as much water or clear fluids as possible to maintain an appropriate level of hydration.

High-risk patients

In debilitated, weakened patients, elderly patients, patients with clinically significant impairments of renal, hepatic, or cardiac function, as well as in patients at high risk of developing electrolyte disturbances, biochemical tests with determination of serum electrolyte concentrations and assessment of renal function should be performed before and after the use of the drug.

Patients with dehydration or water-electrolyte imbalances require appropriate therapy to correct these conditions before taking the bowel cleansing preparation. Furthermore, caution should be exercised when using the drug in patients with pathological conditions or in patients taking medications that increase the risk of water-electrolyte imbalances (including hyponatremia and hypokalemia) or increase the risk of potential complications. Such patients require monitoring.

There is a theoretical risk of QT interval prolongation, which may occur as a result of electrolyte disturbances.

Caution is required when using the drug in the following patient groups

• The drug should be used with caution and only under the supervision of medical personnel in patients with an impaired gag reflex and in patients prone to regurgitation and aspiration;
• Decreased gastrointestinal motility, including a history of gastrointestinal surgeries that led to reduced motility.

Hyperuricemia

Taking the drug Eziclen^® may cause a temporary mild or moderate increase in uric acid concentration. The possibility of an increase in uric acid concentration should be considered before prescribing the drug to patients with manifestations of gout or hyperuricemia.

Ischemic colitis

Osmotic laxatives can cause aphthous ulcers of the colonic mucosa. Post-marketing rare cases of ischemic colitis, including serious cases requiring hospitalization, have been reported. This diagnosis should be considered in case of abdominal pain with or without proctorrhagia (rectal bleeding) after taking the drug Eziclen^®. The drug Eziclen^® should be used with caution in patients with known risk factors for ischemic colitis. If the symptoms mentioned above occur, a doctor should be consulted immediately.

Additional information

The drug must be diluted with water before use. Taking the undiluted solution may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances. Each bottle of the drug must be diluted with water, and the recommended additional amount of water should also be consumed to ensure good tolerability of the drug in the patient.

The medicinal product contains 247.1 mmol (or 5.684 g) of sodium per bottle. This must be taken into account in patients who are on a sodium-controlled diet.

The medicinal product contains 35.9 mmol (or 1.405 g) of potassium per bottle. This must be taken into account in patients with reduced renal function or in patients who are on a potassium-controlled diet.

After opening the bottle and/or dilution with water, the solution must be used immediately.

Effect on ability to drive vehicles and operate machinery

Taking the drug Eziclen^® does not affect the ability to drive a car or operate machinery.

Overdose

In case of overdose or improper use (for example, using the undiluted drug and/or taking an insufficient volume of water), nausea, vomiting, diarrhea, and electrolyte disturbances may occur. Symptomatic therapy, including oral fluid intake, is usually applied in this case. In rare cases of overdose accompanied by severe metabolic disturbances, intravenous rehydration is recommended.

Drug Interactions

Use with caution in patients receiving therapy with drugs that affect electrolyte concentrations (for example, slow calcium channel blockers, diuretics, lithium preparations, or other drugs of similar action).

Caution should be exercised when taking drugs that prolong the QT interval concomitantly.

Diarrhea is an expected effect; oral intake of other medicinal products within 1-3 hours after starting the drug Eziclen^® and until the end of the bowel cleansing process may lead to their washing out from the gastrointestinal tract and impaired absorption. The therapeutic effect of regularly taken oral drugs, those with a narrow therapeutic range or a short T_1/2 (for example, oral contraceptives, antiepileptic drugs, hypoglycemic drugs, antibiotics, levothyroxine sodium, digoxin, etc.), may be altered.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

After opening the bottle and/or dilution with water, the solution must be used immediately.

Do not use after the expiration date.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.