Gutclear

Lactitol Monohydrate Syrup 66.67% w/v

Each 15 ml syrup contains:

Lactitol Monohydrate USP 10 g

Benzoic Acid USP 0.0225 g

Syrup

10 g/15ml in 100/200 ml bottles

4.1 Therapeutic indications

Gutclear® Syrup is indicated for treatment of chronic constipation and prevention of hepatic encephalopathy.

4.2 Posology and method of administration

In the treatment of constipation, the recommended dose of Gutclear® Syrup is as follows

Adults:

The recommended adult dosage of Gutclear® Syrup is 30 ml (20 grams) orally once daily, preferably with meals.

Reduce the dosage to 15 ml (10 grams) once daily for persistent loose stools.

Pediatrics: 250-400 mg/kg/day

Gutclear® Syrup is given as a single dose with the morning or evening meal, subsequently adjusted to produce one stool daily.

In the treatment of hepatic encephalopathy, Gutclear® Syrup is given in usual oral doses of 500 to 700 mg/kg daily in 3 divided doses at meal times. The dose is subsequently adjusted to produce 2 soft stools daily.

Administration Instructions

Doses should be mixed with food or liquid, and it is recommended to drink 1 to 2 glasses of liquid with the meal.

Administer other oral medications at least 2 hours before or 2 hours after Gutclear® Syrup.

4.3 Contraindications

Gutclear® Syrup is contraindicated in:

• Patients with the undiagnosed abdominal pain, colic, bleeding or vomiting
• Patients with intestinal obstruction, ileostomy, colostomy, appendicitis or diverticulitis
• Patients with galactosemia
• Patients hypersensitive to the drug or any other component of the formulation

4.4 Special warnings and precautions for use

• It is suggested that individuals taking Gutclear® Syrup have their fluid and salt (electrolyte) balance monitored regularly especially in elderly patients on long term treatment.
• Treatment with Gutclear® Syrup may cause accumulation of hydrogen in the bowel; patient should be advised to have a thorough bowel cleansing with a non-fermentable solution.

4.5 Interaction with other medicinal products and other forms of interaction

Reduced Absorption of Other Oral Medications Gutclear® Syrup may reduce the absorption of concomitantly administered oral medications. Administer oral medications at least 2 hours before or 2 hours after Gutclear® Syrup [see Dosage and Administration] Gutclear® Syrup should not be administered with other laxatives.

Caution may be exercised in using Gutclear® Syrup with drugs causing potassium loss like loop diuretics.

Gutclear® Syrup can increase digitalis toxicity.

Reduction in acidification effect can be observed if broad spectrum antibacterial agents or antacids are administered along with Gutclear® Syrup.

4.6 Pregnancy and lactation

Pregnancy

Lactitol is minimally absorbed systemically following oral administration, and it is unknown whether maternal use will result in fetal exposure to the drug. Available data from case reports on lactitol use in pregnant women are insufficient to evaluate for any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of lactitol to rats and rabbits during organogenesis at doses much higher than the maximum recommended human dosage. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Gutclear® Syrup should be prescribed only if the potential benefits outweigh the risks to the fetus.

Animal Data

Reproduction studies have been performed in pregnant rats at oral doses of lactitol up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) and in pregnant rabbits at oral doses up to 1 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) administered during the period of organogenesis. These studies did not reveal any evidence of harm to the fetus due to lactitol.

In a pre-and postnatal development study in rats, lactitol, administered from gestation day 6 to lactation day 20, did not cause any adverse effect on pre and postnatal development up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area).

Lactation

There are no data on the presence of lactitol in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Lactitol is minimally absorbed systemically following oral administration. It is unknown whether the minimal systemic absorption of lactitol by adults will result in a clinically relevant exposure to breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Gutclear® Syrup and any potential adverse effects on the breastfed infant from Gutclear® Syrup or from the underlying maternal condition.

No studies are available on the secretion of lactitol in breast milk.

4.7 Effects on ability to drive and use machines

Lactulose has no or negligible influence on your ability to drive safely or use machines.

Undesirable effects

The most commonly observed adverse effects with Gutclear® Syrup are abdominal cramps, distensionor flatulence during the first 10 days of treatment which are likely to disappear after continued administration. The other less frequent side effects are abdominal pain, diarrhoea, nausea and vomiting, anal pruritus, borborygmii or steatorrhea.

Reporting of suspected adverse reactions

• Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com
• Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.8 Overdose

No data on overdosage of Lactitol is available. If a patient consumes large amount of Lactitol, symptoms of abdominal pain and diarrhea may appear. There may also be electrolyte imbalance. There is no specific antidote known for Lactitol over dosage. Gastric lavage may be instituted at the earliest to remove the remnant drug from the stomach. Patient should be treated symptomatically and electrolyte levels should be monitored periodically.

5.1 Pharmacodynamic properties

Mechanism of action

Once ingested, Lactitol is neither hydrolysed nor absorbed in the small intestine. It is passed undigested to the colon and a substantial proportion of orally ingested lactitol becomes substrate for the resident colonic microflora where it is slowly fermented and is converted into short-chain fatty acids (SCFAs). The liberation of short-chain fatty acids causes a fall in pH of the right colon. The fall in pH results in the formation of an acidic media.

The reduction in intra-luminal pH increases the intra-luminal osmolality. This promotes retention of water within the bowel lumen, softening the stool and increasing the bowel volume. Hydration of the gut content and reduction in intra-luminal pH also results in shorter transit time and the establishment of laxation.

Lactitol decreases blood ammonia concentration by inhibiting both the production and the absorption of ammonia by reducing intestinal pH and shortening the residence time of intestinal contents in the intestinal tract and hence improves hepatic encephalopathy. Lactitol also favors the growth of saccharolytic (healthy) bacteria in the gut.

5.2 Pharmacokinetic Properties

Following a single oral dose of 20-gram Lactitol in healthy adult subjects under fed conditions, the mean ± SD peak serum concentration (Cmax) is 776 ± 253 ng/mL, and the mean ± SD area under the curve (AUC) is 6,019 ± 1,771 ng*hr/mL.

Absorption

Lactitol is minimally absorbed systemically following oral administration. The mean ± SD time to reach peak serum concentration (Tmax) is 3.6 ± 1.2 hours following a single oral dose of 20-gram Lactitol in healthy adult subjects under fed conditions.

Effect of Food

Cmax and AUC values increase greater than 2-fold under fasted conditions compared to fed conditions.

Elimination

The mean half-life of lactitol is 2.4 hours.

Excretion

6.1 Preclinical safety data

A perinatal and postnatal study of lactitol, a hepatic encephalopathy drug was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats per level were allowed to deliver naturally for postnatal examination of their offspring. The high dose caused diarrhea or soft stool in dams. The high dose suppressed the body weight of dams during the perinatal period. The food consumption of dams decreased in the intermediate and high dose groups. The water consumption of dams increased in the high dose group. The high dose caused enlargement of cecum and increase of weights of cecum in dams. The drug failed to affect the delivery of dams and gestation index. However, high dose caused prolongation of gestation period. Two dams in the high dose group failed to nurse their all newborns during early lactation. The drug did not affect the number of live newborns, birth index, external appearance, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that the no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 2.65 g/kg for reproductive function in mother animals, and 10 g/kg for their offspring.

Lactitol is an osmotic laxative for oral use. Lactitol is a simple monosaccharide sugar alcohol. It is a dry, free flowing, white to off-white powder, readily soluble in aqueous solutions. As shown by the structure diagrams, it is an analog of the disaccharide lactulose. Its chemical name is 4-O-β-dGalactopyranosyl-d-glucitol lactitol.

Molecular Formula C₁₂H₂₄O₁₁

Molecular Weight 344.31

Gutclear® Syrup ® (lactitol) for oral solution is available in multi-dose bottles.

8.1 List of excipients

Benzoic Acid and Purified water

8.2 Incompatibilities

Gutclear® Syrup may reduce the absorption of concomitantly administered oral medications. Administer oral medications at least 2 hours before or 2 hours after Gutclear® Syrup

8.3 Shelf life

36 months

8.4 Special precautions for storage

Store below 30°C. Protect from light. Do not freeze

8.5 Nature and contents of container

100 ml or 200 ml filled in amber colour pet bottle of 200 ml with a silver pp cap with ep wad and 15 ml measuring cup. One such pack is placed along with a leaflet in a carton.

8.6 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

Persistent Loose Stools Advise patients to stop Gutclear® Syrup ® Syrup and contact their healthcare provider if they experience persistent loose stools.