Guttalax® picosulfate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GUTTALAX® PICOSULFATE (GUTTALAX® PICOSULFATE)

Composition:

Active substance: sodium picosulfate monohydrate;

1 ml contains 7.5 mg of sodium picosulfate monohydrate;

Excipients: sodium benzoate (E 211); sorbitol solution, non-crystallizing (E 420); citric acid monohydrate; sodium citrate dihydrate; purified water.

Pharmaceutical form. Drops.

Main physical and chemical properties: clear solution, from colorless to slightly yellowish or slightly yellowish-brown, slightly viscous liquid with a faint odor.

Pharmacotherapeutic group. Stimulant laxatives. ATC code A06AB08.

Pharmacological properties.

Pharmacodynamics.

Sodium picosulfate, the active ingredient of GUTTALAX**®** PICOSULFATE, is a locally-acting laxative of the triarylmethane group. After bacterial cleavage in the colon, it stimulates the colonic mucosa, accelerating peristalsis and promoting accumulation of water and electrolytes in the lumen of the colon. This results in stimulation of defecation, reduced transit time, and softening of stool.

Sodium picosulfate acts in the colon and directly stimulates evacuation of fecal matter from this section of the gastrointestinal tract. Therefore, it does not affect digestion or absorption of calories and essential nutrients in the small intestine.

In a randomized, double-blind, parallel-group study involving 367 patients with chronic constipation, daily administration of GUTTALAX**®** PICOSULFATE resulted in a significant increase in the number of successful defecations per week compared to placebo, starting from the first week of treatment. The superiority of GUTTALAX**®** PICOSULFATE over placebo was demonstrated throughout all 4 weeks of treatment (p < 0.0001). At the end of the study, serum potassium levels remained unchanged (4.4 mM) and within the physiological normal range (3.6 – 5.3 mM).

Pharmacokinetics.

Absorption and distribution. After oral administration, sodium picosulfate reaches the colon without significant absorption.

Metabolism. Sodium picosulfate is converted into the active compound responsible for the laxative effect—bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)—via bacterial cleavage in the distal segment of the intestine.

Elimination. Only a small portion of BHPM is absorbed after conversion. After oral administration of 10 mg sodium picosulfate, 10.4% of the total dose is excreted as the glucuronide of BHPM in urine within 48 hours. Additionally, BHPM is excreted in bile as a glucuronide conjugate.

Relationship between pharmacokinetics and pharmacodynamics. The onset of action typically occurs 6–12 hours after administration, depending on the release of the active metabolite (BHPM). The laxative effect of the drug does not correlate with plasma levels of the active metabolite.

Clinical characteristics.

Indications.

Constipation or conditions requiring facilitation of defecation.

Like other laxatives, GUTTALAX**®** PICOSULFATE should not be used daily or for prolonged periods without a complete diagnostic evaluation to determine the cause of constipation.

Contraindications.

• Hypersensitivity to the active substance, other triarylmethanes, or to any of the excipients of the medicinal product.
• Dynamic or mechanical intestinal obstruction.
• Severe abdominal diseases with pain syndrome and/or elevated body temperature (e.g., appendicitis), which may be accompanied by nausea and vomiting.
• Acute inflammatory bowel diseases.
• Severe dehydration.
• Rare hereditary intolerance to any of the excipients of the medicinal product (see section "Special precautions for use").

GUTTALAX**®** PICOSULFATE must not be prescribed to children under 4 years of age.

GUTTALAX**®** PICOSULFATE must not be used in patients with rare hereditary fructose intolerance.

GUTTALAX**®** PICOSULFATE should be taken under medical supervision in conditions associated with disturbances in fluid and electrolyte balance (e.g., severe renal function impairment).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of high doses of GUTTALAX**®** PICOSULFATE and diuretics or corticosteroids may increase the risk of electrolyte imbalance, which could lead to increased sensitivity to cardiac glycosides.

Concomitant use with antibiotics may reduce the laxative effect of GUTTALAX**®** PICOSULFATE.

Special precautions for use

In patients suffering from chronic constipation, a complete diagnostic evaluation should be performed to determine the cause of constipation.

Prolonged and excessive use of GUTTALAX® PICOSULFATE may lead to disturbances in fluid and electrolyte balance and to hypokalemia. Discontinuation of GUTTALAX® PICOSULFATE may result in recurrence of symptoms. If GUTTALAX® PICOSULFATE has been used for chronic constipation over a prolonged period, any recurrence of constipation symptoms may be more pronounced.

Cases of dizziness and/or syncope temporally associated with administration of sodium picosulfate have been reported. Available data suggest that these events were related to defecation-induced syncope (associated with the Valsalva maneuver) or vasovagal response to abdominal pain.

This medicinal product contains approximately 450 mg of sorbitol (corresponding to approximately 600 mg of sorbitol when the maximum recommended daily dose for adults is used) and 2 mg of sodium benzoate per 1 ml of solution.

If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicinal product.

Patients with the rare hereditary fructose intolerance should not take GUTTALAX® PICOSULFATE.

This medicinal product contains less than 1 mmol (or 23 mg) of sodium per dose. Caution should be exercised when administering this product to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Pregnancy

Adequate clinical studies in pregnant women have not been conducted. Animal studies have demonstrated reproductive toxicity of the drug when administered at daily doses of 10 mg/kg and higher. For safety reasons, GUTTALAX® PICOSULFATE should be avoided during pregnancy if possible.

Breastfeeding

Clinical data indicate that neither the active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), nor its glucuronides are excreted in breast milk. Therefore, GUTTALAX® PICOSULFATE may be used during breastfeeding.

Fertility

Clinical studies on the effect of the drug on human fertility have not been conducted. Animal studies did not demonstrate any effect of the drug on fertility.

Ability to affect reaction speed when driving or operating machinery

No studies on the effect of the drug on the ability to drive or operate machinery have been conducted.

However, patients should be warned about the possible occurrence of adverse effects such as dizziness and/or syncope due to vasovagal reactions (e.g., in response to abdominal cramps). If abdominal cramps occur, patients should avoid potentially hazardous activities such as driving or operating machinery.

Method of Administration and Dosage.

Dosing. Unless otherwise prescribed, the dose for adults is 10–18 drops (corresponding to 5–10 mg of sodium picosulfate). The dose for children aged 4 years and older is 5–9 drops (corresponding to 2.5–5 mg of sodium picosulfate).

It is recommended to start with the lowest dose. The dose may be adjusted up to the maximum recommended dose to achieve regular bowel movements. The maximum daily dose must not be exceeded, which is 18 drops for adults or 9 drops for children aged 4 years and older.

GUTTALAX**®** PICOSULFATE should not be used continuously (daily) or for prolonged periods without determining the cause of constipation.

Method of Administration. Oral use. GUTTALAX**®** PICOSULFATE is preferably taken in the evening. The drops may be taken with liquid or without. Bowel movement usually occurs approximately 10–12 hours after administration.

Children.

The product should be used in children aged 4 years and older only on medical advice.

Overdose.

Overdose may lead to watery stools (diarrhea), abdominal cramps, and clinically significant loss of fluid, potassium, and other electrolytes.

In acute overdose, the consequences may be minimized or eliminated by induced emesis or gastric lavage shortly after ingestion. Consideration may be given to replacement fluid therapy and correction of electrolyte imbalances. Antispasmodic agents may be used.

Ischemia of the colonic mucosa has been reported in isolated cases following administration of sodium picosulfate doses significantly higher than those recommended for the treatment of constipation.

Chronic overdose of GUTTALAX**®** PICOSULFATE (as with other laxatives) may result in chronic diarrhea, abdominal pain, hypokalemia, secondary hyperaldosteronism, and kidney stone formation. With prolonged abuse of laxatives, renal tubular damage, metabolic alkalosis, and muscle weakness due to hypokalemia have been reported.

Side effects

Side effects are listed by frequency of occurrence: 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), frequency not known (cannot be estimated from available data).

Skin and subcutaneous tissue disorders:

Frequency not known: skin reactions (angioneurotic edema, drug toxicoderma, rash, itching).

Immune system disorders:

Frequency not known: allergic reactions.

Nervous system disorders:

Uncommon: dizziness;

Frequency not known: syncope.

Available data suggest that dizziness and syncope are due to vasovagal reactions (e.g., in response to abdominal cramps or defecation) (see also section "Special precautions").

Gastrointestinal disorders:

Very common: diarrhea;

Common: abdominal discomfort, abdominal pain, abdominal cramps;

Uncommon: nausea, vomiting.

Prolonged and excessive use of GUTTALAX**®** PICOSULFATE may lead to loss of fluid, potassium, and other electrolytes. This may result in muscle weakness and impaired cardiac function, particularly when GUTTALAX**®** PICOSULFATE is used concomitantly with diuretics or corticosteroids.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions to the State Expert Centre of the Ministry of Health of Ukraine.

Shelf life

3 years. Use within 12 months after first opening of the bottle.

Storage conditions

Store out of reach and sight of children, at a temperature not exceeding 25 °C.

Packaging

15 ml or 30 ml in a bottle; 1 bottle in a cardboard box.

Pharmaceutical classification

Over-the-counter (without prescription).

Manufacturer

Istituto de Angeli S.r.l., Italy

Manufacturer's address and place of business

Località Prulli, 103/c - 50066 Reggello (FI), Italy

Marketing Authorization Holder

LLC "Opella HealthCare Ukraine", Ukraine

Address of the Marketing Authorization Holder and/or its representative

48-50A Zhylianska St., Kyiv, 01033, Ukraine