Iziklin concentrate for oral solution bottle 176 ml with measuring cup No. 2

Instructions for use Iziklin concentrate for oral solution, 176 ml bottle with measuring cup No. 2

Composition

active ingredients: 1 bottle contains: sodium sulfate anhydrous 17.510 g, magnesium sulfate, heptahydrate 3.276 g, potassium sulfate 3.130 g;

excipients: sodium benzoate (E 211), anhydrous citric acid, malic acid, sucralose, fruit and berry flavoring (mixture of natural and synthetic flavors, propylene glycol (E 1520), diluted ethanol, acetic acid and benzoic acid (E 210)), purified water.

Dosage form

Concentrate for oral solution.

Main physicochemical properties: clear to slightly cloudy liquid with a fruity aroma.

Pharmacotherapeutic group

Osmotic laxatives. Combination of mineral salts.

ATX code A06A D10.

Pharmacological properties

Pharmacodynamics

The drug is an osmotic laxative. Its mechanism of action is mainly based on a limited and saturable active transport process of sulfate. Due to saturation in the gastrointestinal transport process, sulfate remains in the intestine. The osmotic effect of unabsorbed ions when taken with large amounts of water causes copious watery stools. In clinical studies, the average time to frequent bowel movements was about 6.3 hours with a 12-hour dosing interval and about 2.8 hours with a 1-hour dosing interval.

Pharmacokinetics

Absorption of sulfate is a limited and saturable active transport process; absorbed sulfate is excreted primarily by the kidneys. After clinical administration of a medicinal product with the same sulfate content as in Iziklin in six healthy volunteers according to a divided-dose regimen, i.e. administration of two doses 12 hours apart, the maximum serum sulfate concentration was observed approximately 16 hours after the first dose and 5 hours after the second dose [Cmax: 499.5 μmol/l (CV: 33.03%) compared to baseline values of 141–467 μmol/l, mean value 335 μmol/l (CV: 34.4%)]. Thereafter, serum concentrations declined with a half-life of 8.5 hours (CV: 53.76%). The main route of sulfate excretion was faecal excretion (approximately 70% of the administered dose).

The systemic exposure (AUC and Cmax) of sulfate after drug administration was also compared in healthy volunteers, six patients with moderate renal impairment (creatinine clearance 30–49 mL/min), and six patients with mild or moderate hepatic impairment (Child-Pugh scores A (N=5) and B (N=1), respectively). Impaired renal function resulted in reduced urinary excretion of sulfate. As a result, mean AUC and Cmax values were approximately 50% higher compared with those in patients with normal renal function. Impaired hepatic function did not affect the systemic exposure of sulfate. Serum sulfate concentrations returned to baseline values by day 6 after drug administration in all three study groups. In this study, drug administration did not result in clinically significant hypersulfatemia in patients with hepatic or renal impairment.

Indication

The drug is prescribed to adults to cleanse the intestines before any procedure that requires it (for example, visualization of the intestines, including endoscopy and radiology, or surgical procedures).

The medicine is not intended for the treatment of constipation.

Contraindication

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

hypersensitivity to the active substances or to any of the excipients;

congestive heart failure;

serious deterioration in general health, including severe dehydration;

active inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis);

acute gastrointestinal disorders requiring surgery, including acute appendicitis;

known or suspected or history of gastrointestinal obstruction or stenosis;

known or suspected perforation of the stomach or intestinal wall;

gastric emptying disorders (e.g. gastroparesis, gastrostasis);

known or suspected or history of paralytic ileus;

toxic colitis or toxic megacolon;

nausea or vomiting;

ascites;

severe renal failure (glomerular filtration rate <30 ml/min/1.73 m2).

Special safety measures.

Given the potential risk of serious electrolyte disturbances, the risk-benefit ratio of the medicinal product should be carefully considered before initiating treatment in patients at increased risk. When prescribing the medicinal product, special attention should be paid to the known contraindications and special precautions for use, including the importance of adequate hydration.

All patients should be advised to drink sufficient fluids before, during and after administration of the medicinal product. If the patient develops severe vomiting or signs of dehydration after administration of the medicinal product, rehydration measures should be taken to avoid the potential risks of serious complications associated with fluid and electrolyte disturbances (such as seizures or cardiac arrhythmias). In addition, pre-procedure laboratory tests (electrolytes, creatinine and blood urea nitrogen) should be considered. The patient should be advised to drink additional water or clear fluids in the amount necessary to maintain adequate hydration.

Patients at risk

In debilitated patients, elderly patients, patients with clinically significant renal, hepatic or cardiac dysfunction, and patients at risk of electrolyte imbalance, the physician should consider conducting electrolyte and renal function tests before and after administration of the medicinal product.

Patients with signs of dehydration or electrolyte disturbances should have these corrected before using a bowel cleansing agent. In addition, caution should be exercised in patients who either have conditions at risk of fluid and electrolyte disturbances or are taking medications that increase the risk of fluid and electrolyte disturbances (including hyponatremia and hypokalemia) or may increase the risk of potential complications. Such patients require appropriate monitoring.

There is a theoretical risk of QT prolongation due to electrolyte imbalance.

Use with caution.

Patients with impaired gag reflex, as well as patients prone to regurgitation or aspiration. Such patients require supervision during the use of the drug for bowel cleansing.

Patients with hypokinetic gastrointestinal disorders or a history of medical conditions or gastrointestinal surgery that contribute to hypokinetic disorders.

Hyperuricemia

The drug may cause a temporary slight to moderate increase in uric acid levels. The potential for an increase in uric acid levels should be considered before using the drug in patients with a history of gout or hyperuricemia.

Ischemic colitis

Osmotic laxatives may cause aphthous ulcers of the colonic mucosa. In the post-marketing period, cases of ischemic colitis have been reported, including serious cases requiring hospitalization. Patients who develop sudden abdominal pain, with or without rectal bleeding, or other symptoms of ischemic colitis after using Iziclin should seek immediate medical attention.

Additional information

The medicinal product is not intended for administration undiluted. Direct administration of the 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 to ensure tolerability of the medicinal product.

This medicinal product contains 247.1 mmol (or 5.684 g) sodium per bottle. This information should be taken into consideration by patients on a controlled sodium diet.

This medicinal product contains 35.9 mmol (or 1.405 g) of potassium per bottle. This information should be taken into account by patients with impaired renal function or patients on a controlled potassium diet.

Interaction with other medicinal products and other types of interactions

As with any other bowel cleansing medication:

Use with caution in patients taking calcium channel blockers, diuretics, lithium preparations, or medications that may affect electrolyte levels.

Caution is advised when using medicinal products known to prolong the QT interval.

Diarrhea is an expected consequence; concomitant oral medications taken within 1–3 hours of starting treatment and before the cleansing process is complete may be flushed from the gastrointestinal tract and not absorbed properly. The therapeutic effect of regularly administered oral medications with a narrow therapeutic range or short half-life (such as oral contraceptives, antiepileptics, antidiabetics, antibiotics, levothyroxine, digoxin, etc.) may be particularly affected.

Use during pregnancy or breastfeeding

There are no data on the use of this medicine in pregnant women.

The use of the drug during pregnancy is not recommended.

It is not known whether the drug is excreted in breast milk.

Breastfeeding should be discontinued until 48 hours after the second dose of Iziclin.

Fertility.

There are no data on the effect on fertility.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug does not affect the ability to drive vehicles and work with other mechanisms.

Method of administration and doses

Adults

For proper bowel cleansing, the contents of 2 bottles of Iziclin should be used. Before use, the contents of each bottle should be diluted in water using the enclosed cup to obtain a total volume of approximately 0.5 l; after use, an additional 1 liter of water or clear liquid should be taken within 2 hours.

Clear liquids allowed: water, tea or coffee (without milk or non-dairy creamer), carbonated or non-carbonated soft drinks, juices from pureed fruit without pulp (not red or purple in color), broth or soup strained until clear.

The total volume of fluid required for bowel cleansing is approximately 3 liters, which should be taken orally before the procedure. This medicine can be taken in divided doses (over two days; the contents of the first bottle are taken the evening before the procedure and the second the following morning) or in one day, as described below (see "Method of administration"). The exact dosage regimen and frequency of administration will be determined by the doctor.

If time permits, a divided-dose regimen should be preferred over a once-daily regimen. The once-daily dosing regimen is a potentially useful alternative regimen.

Method of application

SPLIT DOSE REGIME (bi-daily)

The day before the procedure:

Early evening before the procedure (for example at 6:00 PM):

Pour the contents of 1 bottle of the medicine into the cup included in the package and dilute with water to the measuring line (i.e. about 0.5 l).

The patient should drink this diluted solution, followed by two glasses of water or clear liquid filled to the measuring line (i.e. approximately 1 liter), within 2 hours.

Procedure day

In the morning before the procedure (10–12 hours after the evening dose):

The contents of the second bottle of medicine should be poured into the cup included in the package and diluted with water to the measuring line (i.e. about 0.5 l).

The patient should drink this diluted solution, followed by two glasses of water or clear liquid filled to the measuring line (i.e. approximately 1 liter), within 2 hours.

The entire diluted medicinal product solution and additional fluid (water or clear liquid) should be taken:

– in the absence of anesthesia – at least an hour before the start of the procedure;

– in case of anesthesia – at least 2 hours before the start of the procedure, according to the anesthesiologist's instructions.

ONE-HOUR DOSAGE REGIME (alternative dosage regimen that may be used depending on the individual clinical needs of the patient)

The evening before the procedure:

Early evening before the procedure (for example at 6:00 PM):

The contents of one bottle of the medicine should be poured into the cup included in the package and diluted with water to the measuring line (approximately 0.5 l).

The patient should drink this diluted solution, followed by two glasses of water or clear liquid filled to the measuring line (i.e. approximately 1 liter), within two hours.

Approximately 2 hours after starting the first dose (for example at 8:00 PM):

The contents of the second bottle of medicine should be poured into the cup included in the package and diluted with water to the measuring line (approximately 0.5 l).

The patient should drink this diluted solution, followed by two glasses of water or clear liquid filled to the measuring line (i.e. approximately 1 liter), within 2 hours.

The entire diluted medicinal product solution and additional fluid (water or clear liquid) should be taken:

– in the absence of anesthesia – at least an hour before the start of the procedure;

– in case of anesthesia – at least 2 hours before the start of the procedure, according to the anesthesiologist's instructions.

The necessary steps for both modes are described below:

Steps 1–6 should take about 2 hours and should be repeated for the divided dose regimen.

After the procedure

To replace fluids lost during preparation for the procedure, patients should be advised to consume sufficient fluids after the procedure to maintain adequate hydration.

A light breakfast is allowed the day before the procedure. After that, the patient should drink only clear liquids instead of lunch, dinner, and any other meals until the procedure is performed. Red and purple liquids, milk, and alcoholic beverages should be avoided.

Special populations

Elderly patients

Overall, no differences in safety or efficacy were observed between elderly patients and other patients during clinical development of the medicinal product. No dose modification is required for elderly patients, but special precautions should be taken for this population, as for any other population at increased risk.

Patients with renal impairment

There are insufficient data for this population. There is no need for dose modification in patients with mild to moderate renal impairment, however, special precautions should be taken in this population, as for any other population at increased risk. The drug should not be used in patients with severe renal impairment.

Patients with hepatic impairment

There are insufficient data for this population. There is no need for dose modification in patients with hepatic impairment, however, special precautions should be taken for this population, as for any other population at increased risk.

Children

The safety and efficacy of the medicinal product in children (i.e. patients under 18 years of age) have not yet been established. There are no data on use in children.

Overdose

In case of overdose or incorrect administration (e.g., not diluting the medicinal product and/or not drinking enough water), nausea, vomiting, diarrhea, and electrolyte disturbances are to be expected. Conservative oral rehydration is usually sufficient. In the unlikely event of serious metabolic disturbances due to overdose, intravenous rehydration should be performed.

Adverse reactions

The frequency of adverse reactions is classified as follows: very common (≥1/10); common (≥1/100 to ≤1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

The table lists adverse reactions from clinical trials and isolated cases. In addition, adverse reactions reported during post-marketing surveillance are listed.

Transient increases in uric acid levels have been observed in clinical trials. For patients with gout or a history of hyperuricemia, see Special Precautions.

There were no differences in safety data between the elderly population and other patients during clinical development. However, elderly patients should be treated as any high-risk group (see "Special precautions").

For patients with renal or hepatic impairment, see Contraindications and Special Precautions.

Reporting of adverse reactions

Post-marketing adverse reaction reporting is important. This ensures continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Expiration date

3 years.

After first opening the bottle and/or dilution in water, the solution should be used immediately.

Storage conditions

Store in the original packaging to protect from light.

Does not require a special storage temperature.

Do not store after first opening the bottle and/or dilution.

Incompatibility.

The medicine should not be mixed with other medicines.

Packaging

Approximately 176 ml of concentrate for oral solution in a bottle with a child-resistant screw cap with a multi-layer sealing system; 2 bottles complete with one measuring cup in a cardboard box.

Vacation category

According to the recipe.

Producer

BOFUR IPSAIN INDUSTRIES.

Location of the manufacturer and its business address.

Applicant

IPSEN CONSUMER HELSKEA

Simplified joint-stock company

Location of the applicant and/or applicant's representative

65 Quai Georges Gors 92100 Boulogne-Billancourt, France