PICOLPREPP

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PICO PREP (PICOPREP)

Composition:

Active substances: 1 sachet contains sodium picosulfate 10 mg; light magnesium oxide 3.5 g; anhydrous citric acid 12 g;

Excipients: potassium bicarbonate; sodium saccharin; natural orange flavor containing gum arabic (E 414), lactose monohydrate, ascorbic acid (E 300), butylhydroxyanisole (E 320).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white crystalline powder with a faint orange odor.

Pharmacotherapeutic group. Stimulant laxatives. Sodium picosulfate combinations.

ATC code A06AB58.

Pharmacological properties

Pharmacodynamics

The active ingredients of the PicoPrep preparation are sodium picosulfate and magnesium citrate.

Sodium picosulfate is a locally acting substance which stimulates the mucosa; after being cleaved by colonic bacteria, it is converted into its active laxative form, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which acts as a local irritant in both the colon and rectum.

Magnesium citrate exerts an osmotic and laxative effect, promoting fluid secretion into the intestinal lumen.

The action of the preparation results in a strong cleansing effect, combined with stimulation of intestinal peristalsis.

The preparation is not intended for use as a regular laxative.

Pharmacokinetics

Sodium picosulfate and magnesium citrate, the two components of the preparation, are locally active with minimal systemic exposure.

After administration of PicoPrep (2 sachets taken 6 hours apart), picosulfate reached mean peak plasma concentrations (Cmax) of 2.3 and 3.2 ng/mL at median times (Tmax) of 2 and 8 hours after the first and second sachet, respectively.

Magnesium plasma concentrations reached levels of 0.90 and 0.95 mmol/L at 4 and 10 hours, respectively. The baseline value was 0.75 mmol/L.

Plasma levels of BHPM remained consistently low or undetectable, and urine samples showed that most of the excreted BHPM was in glucuronide-conjugated form.

Clinical studies on bowel cleansing prior to colonoscopy demonstrated an increase in serum magnesium levels from baseline to the time of colonoscopy of approximately 0.11 mmol/L (from 0.86 to 0.97 mmol/L).

All changes in serum magnesium levels were transient and within the normal range, including in patients with mild to moderate renal impairment.

The mean terminal elimination half-life of picosulfate was 7.4 hours. The fraction of the sodium picosulfate dose excreted unchanged in urine was 0.11%.

Both active components act locally in the colon, and neither is absorbed in any detectable amounts.

Preclinical safety data

Preclinical data revealed no special hazard for humans based on standard repeated-dose toxicity and genotoxicity studies.

Due to the very short duration of treatment, long-term animal studies were not conducted.

Reproductive studies showed no potential to impair fertility or harm the fetus when sodium picosulfate or PicoPrep was administered.

In an animal study on pre- and postnatal development, the no-observed-adverse-effect level (NOAEL) was determined to be a mean dose of 750 mg/kg twice daily.

At a dose of 2000 mg/kg twice daily in animals (approximately 8 times the recommended human dose), adverse effects were observed, including death of pups between days 2 and 4 of lactation due to maternal toxicity.

Effects observed in reproductive toxicity and developmental animal studies with sodium picosulfate alone occurred only at doses greatly exceeding the maximum recommended human dose, indicating limited relevance for clinical use.

Clinical characteristics.

Indications.

For bowel cleansing prior to radiological examinations, endoscopy, or prior to surgical procedures.

Contraindications.

Hypersensitivity to any component of the drug, congestive heart failure, gastric outlet obstruction, gastrointestinal ulcers, toxic colitis, toxic megacolon, intestinal obstruction, nausea and vomiting, acute abdominal conditions requiring surgical intervention such as acute appendicitis, as well as diagnosed or suspected gastrointestinal obstruction or perforation, severe dehydration, rhabdomyolysis, hypermagnesemia, active inflammatory bowel disease, severe renal impairment (creatinine clearance less than 30 mL/min), since hypermagnesemia may develop. In patients with significantly impaired renal function, magnesium accumulation in blood plasma is possible. In such cases, another drug should be used.

Interaction with other medicinal products and other forms of interaction.

Since PicoPrep is a laxative, it increases gastrointestinal transit rate. Therefore, administration of the drug may alter the absorption of other oral medicinal products (e.g., antiepileptic and antidiabetic agents, contraceptives, and antibiotics).

Antibiotics of the tetracycline and fluoroquinolone classes, iron, digoxin, chlorpromazine, and penicillamine should be administered no later than 2 hours before or 6 hours after PicoPrep administration to prevent chelation with magnesium.

The efficacy of PicoPrep is reduced when used concomitantly with laxatives that increase intestinal content volume.

PicoPrep should be used with caution in patients who are already taking medicinal products that may cause hypokalemia (such as diuretics or corticosteroids), as well as drugs associated with a particular risk of developing hypokalemia (e.g., cardiac glycosides). PicoPrep should also be prescribed with caution to patients taking nonsteroidal anti-inflammatory drugs or drugs that induce syndrome of inappropriate antidiuretic hormone secretion, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, and carbamazepine, as they may increase the risk of water retention and/or electrolyte imbalance.

PicoPrep should also be used with caution in patients who are already taking drugs that increase the risk of fluid and electrolyte imbalance or may increase the risk of seizures, arrhythmias, or prolonged QT interval in the context of fluid or electrolyte disturbances.

Special precautions for use.

Bowel cleansing should only be performed when clear preoperative indications are present, as clinical benefit of bowel preparation prior to elective colorectal surgery cannot be established. The risk-benefit ratio must be carefully evaluated depending on the procedure used.

Inadequate or excessive oral intake of water and electrolytes may lead to clinically significant fluid and electrolyte imbalances, especially in debilitated patients. Therefore, children, elderly patients, debilitated individuals, and patients at risk of developing hypokalemia or hyponatremia should be under medical supervision. Patients showing signs of hypokalemia or hyponatremia may require prompt corrective measures to restore fluid and electrolyte balance.

Drinking water alone to replace fluid losses may result in electrolyte imbalance.

The drug should be used with particular caution after recent gastrointestinal surgical procedures, and in patients with impaired renal function, cardiac disease, or a history of inflammatory bowel disease.

Picolprep should be administered with caution to patients taking medications that may affect fluid and/or electrolyte balance, such as diuretics, corticosteroids, or lithium.

Picolprep may alter the absorption of concomitantly administered medicinal products intended for regular oral use. Therefore, Picolprep should be used cautiously in such cases. There have been isolated reports of seizures in patients taking antiepileptic drugs that previously provided effective control of epilepsy.

Use Picolprep with caution in patients with impaired renal function or in patients concurrently taking medications that may affect kidney function (e.g., diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or nonsteroidal anti-inflammatory drugs). In these patients, there may be an increased risk of kidney injury. Isolated reports of serious arrhythmias associated with the use of ionic osmotic laxatives for bowel preparation have been reported. Exercise caution when prescribing Picolprep to patients at increased risk of arrhythmias (e.g., history of prolonged QT interval, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathies). An ECG should be performed before taking the drug and after completion of colonoscopy in patients at increased risk of serious cardiac arrhythmias.

There have been isolated reports of ischemic colitis requiring hospitalization. However, a causal relationship between these cases of ischemic colitis and the use of Picolprep has not been established.

Patients with impaired vomiting reflex or those prone to regurgitation or aspiration should be closely monitored when using Picolprep. The drug should be used with caution in such patients.

The bowel cleansing period should not exceed 24 hours, as longer duration may increase the risk of disturbances in fluid or electrolyte balance.

Each sachet contains 5 mmol (or 195 mg) of potassium. This information should be taken into account when prescribing the drug to patients with impaired renal function or those on a potassium-restricted diet.

The product contains lactose and therefore should not be used in patients with hereditary disorders of galactose metabolism, such as Lapp lactase deficiency or glucose-galactose malabsorption.

The drug is not intended for use as a general laxative.

Use during pregnancy or breastfeeding.

Fertility.

Animal studies have not shown embryofetotoxic effects or impaired fertility with Picolprep. However, studies with sodium picosulfate alone have shown embryofetotoxic effects in rats and rabbits after administration of very high doses. Animal fertility studies do not always predict human response; therefore, this drug should be used during pregnancy only if clearly needed.

Pregnancy.

There is no clinical experience with the use of Picolprep during pregnancy. For safety reasons, this drug should not be used during pregnancy, as sodium picosulfate exerts a laxative effect that stimulates peristalsis.

Breastfeeding.

There is no clinical experience with the use of Picolprep during breastfeeding. However, considering the pharmacokinetic properties of the drug, Picolprep may be used in breastfeeding women if clinically necessary.

Ability to affect reaction speed when driving or operating machinery.

During treatment with the drug, patients should avoid activities requiring rapid psychomotor responses, due to the possibility of seizures or confusion.

Method of Administration and Dosage

The medication should be taken orally.

A low-residue diet is recommended starting one day prior to hospitalization. On the day of the procedure, a clear liquid diet is recommended. To avoid dehydration, it is important to follow fluid intake recommendations during treatment with PicoPrep until the effect of the medication has ceased. In addition to fluids consumed as part of the treatment regimen (PicoPrep plus additional fluids), normal thirst should be satisfied with clear liquids.

Clear liquids should include pulp-free fruit juices, non-carbonated beverages, broth, tea, coffee (without milk, soy, or cream), and water. Do not drink water only.

Instructions for dissolving the powder for use in adults (including elderly individuals)

Dissolve the contents of one sachet in a glass of cold water (approximately 150 mL). Mix the solution for 2–3 minutes. The resulting solution will be whitish, cloudy, and have a mild orange odor. This solution is ready for consumption. If the solution has warmed, wait until it cools to a drinkable temperature.

Adults, including elderly individuals (if the examination/surgery is scheduled for the second half of the following day, the split-dose regimen is recommended)

Split-dose regimen (evening before and on the day of the procedure)

Administer the first dose in the evening before the procedure and the second dose on the morning of the procedure.

Day before the procedure – first dose:

• Dissolve the contents of one sachet in water as described above and take in the evening, approximately between 17:00 and 21:00, one day before the procedure. After administration, drink at least 5 glasses (250 mL each) of clear liquids.

Day of the procedure – second dose:

• Dissolve the contents of one sachet in water as described above and take in the morning (5–9 hours before the procedure). After administration, drink at least 3 glasses (250 mL each) of clear liquids.

Clear liquids may be consumed no later than 2 hours before the procedure.

or

Evening-only regimen (only the evening before the procedure)

Administer the first dose in the afternoon or early evening and the second dose approximately 6 hours later at night.

Day before the procedure – 2 sachets:

• First dose: Dissolve the contents of one sachet in water as described above and take in the afternoon or early evening (e.g., 16:00–18:00). After administration, drink at least 5 glasses (250 mL each) of clear liquids.
• Second dose: Dissolve the contents of one sachet in water as described above and take late in the evening (22:00–24:00). After administration, drink at least 3 glasses (250 mL each) of clear liquids.

Clear liquids may be consumed no later than 2 hours before the procedure.

Children

The medication should be administered to children under 9 years of age under medical supervision in a hospital setting.

Instructions for dissolving the powder for use in children

The medication is supplied with a measuring spoon. Fill the spoon with powder. It is recommended to level the powder with a flat edge (e.g., the back of a knife) to obtain a flat surface (1 measuring spoon contains 4 g of powder (1/4 sachet)).

Dissolve the required amount of powder in a glass of water (approximately 50 mL of water per spoonful of powder). Mix the solution for 2–3 minutes. The resulting solution will be whitish, cloudy, and have a mild orange odor. This solution is ready for consumption. If the solution has warmed, wait until it cools to a drinkable temperature.

Any remaining contents of the sachet should be discarded.

Administration to children

Dissolve the powder in water as described above. Administer the first dose before 8:00 AM on the day of the procedure. Administer the second dose 6–8 hours after the first dose.

Children aged 1–2 years: ¼ sachet, or 1 measuring spoon of powder, in the morning (first dose); ¼ sachet, or 1 measuring spoon of powder, during the day (second dose).

Children aged 2–4 years: ½ sachet, or 2 measuring spoons of powder, in the morning (first dose); ½ sachet, or 2 measuring spoons of powder, during the day (second dose).

Children aged 4–9 years: 1 sachet of powder in the morning (first dose); ½ sachet, or 2 measuring spoons of powder, during the day (second dose). (For instructions on dissolving a full sachet for children aged 4–9 years, refer to the instructions for dissolving the powder for adult use.)

Children aged 9 years and older: dosage as for adults.

Children

The medication may be administered to children from 1 year of age (see section "Method of Administration and Dosage").

Overdose

Overdose may lead to profuse diarrhea.

Treatment of overdose consists of general supportive measures and correction of fluid and electrolyte imbalances.

Adverse Reactions.

The most commonly reported adverse reactions during clinical trials are nausea, headache, and vomiting.

Adverse reactions are listed by system organ classes and frequency of occurrence:

frequent (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency not known (available data do not allow estimation of frequency).

Immune system disorders.
Uncommon: anaphylactoid reactions, hypersensitivity.

Metabolism and nutrition disorders.
Uncommon: hyponatremia, hypokalemia.

Psychiatric disorders.
Frequent: sleep disorders.

Nervous system disorders.
Frequent: headache.
Uncommon: epilepsy, clonic-tonic seizures, seizures, confusion, dizziness.

Gastrointestinal disorders.
Frequent: dry mouth, nausea, bloating, anal discomfort, proctalgia.
Uncommon: vomiting, abdominal pain, aphthous ulcers of the ileum*.
Frequency not known: diarrhea, fecal incontinence, flatulence.

Skin and subcutaneous tissue disorders.
Uncommon: rash (including erythematous and maculopapular rashes), urticaria, pruritus, purpura.

Vascular disorders:
Uncommon: orthostatic hypotension.

General disorders and administration site conditions.
Frequent: thirst, fatigue; frequency not known: pain.

*Isolated cases of mild reversible aphthous ulcers of the ileum have been reported.

Diarrhea and fecal incontin游戏副本