LACTULOSE SOLUTION solution

Drug Details [pdf]

For Oral Administration
Rx only
DESCRIPTION

Lactulose is a synthetic disaccharide in solution form for oral administration. Each 15 mL of lactulose solution contains: 10 g lactulose (and less than 1.6 g galactose, less than 1.2 g lactose, and 1.2 g or less of other sugars). Also contains water. The pH range is 2.5 to 6.5.

Lactulose is a colonic acidifier which promotes laxation.

The chemical name for lactulose is 4-O-β-D-galactopyranosyl-D-fructofuranose. The molecular formula is C12H22O11. It has the following structural formula:

The molecular weight is 342.30. It is freely soluble in water.
CLINICAL PHARMACOLOGY

Lactulose is poorly absorbed from the gastrointestinal tract and no enzyme capable of hydrolysis of this disaccharide is present in human gastrointestinal tissue. As a result, oral doses of lactulose reach the colon virtually unchanged. In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents. This in turn causes an increase in stool water content and softens the stool.

Since lactulose does not exert its effect until it reaches the colon, and since transit time through the colon may be slow, 24 to 48 hours may be required to produce the desired bowel movement.

Lactulose given orally to man and experimental animals resulted in only small amounts reaching the blood. Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.
INDICATIONS AND USAGE

For the treatment of constipation. In patients with a history of chronic constipation, lactulose solution therapy increases the number of bowel movements per day and the number of days on which bowel movements occur.
CONTRAINDICATIONS

Since lactulose solution contains galactose (less than 1.6 g/15 mL), it is contraindicated in patients who require a low galactose diet.
WARNINGS

A theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of H2 gas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of CO2 as an additional safeguard may be pursued but is considered to be a redundant measure.
PRECAUTIONS

General

Since lactulose solution contains galactose (less than 1.6 g/15 mL) and lactose (less than 1.2 g/15 mL) it should be used with caution in diabetics.

Information for Patients

In the event that an unusual diarrheal condition occurs, contact your physician.

Laboratory Tests

Elderly, debilitated patients who receive lactulose for more than six months should have serum electrolytes (potassium, chloride, carbon dioxide) measured periodically.

Drug Interactions

Results of preliminary studies in humans and rats suggest that non-absorbable antacids given concurrently with lactulose may inhibit the desired lactulose-induced drop in colonic pH. Therefore, a possible lack of desired effect of treatment should be taken into consideration before such drugs are given concomitantly with lactulose solution.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There are no known human data on long-term potential for carcinogenicity, mutagenicity, or impairment of fertility.

There are no known animal data on long-term potential for mutagenicity.

Administration of lactulose solution in the diet of mice for 18 months in concentrations of 3 and 10 percent (v/w) did not produce any evidence of carcinogenicity.

In studies of mice, rats, and rabbits, doses of lactulose solution up to 6 or 12 mL/kg/day produced no deleterious effects in breeding, conception, or parturition.

Pregnancy

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in mice, rats, and rabbits at doses up to 3 or 6 times the usual human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to lactulose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lactulose solution is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.
ADVERSE REACTIONS

Precise frequency data are not available.

Initial dosing may produce flatulence and intestinal cramps, which are usually transient. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia.

Nausea and vomiting have been reported.

To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
OVERDOSAGE

Signs and Symptoms: There have been no reports of accidental overdosage. In the event of overdosage, it is expected that diarrhea and abdominal cramps would be the major symptoms. Medication should be terminated.

Oral LD50: The acute oral LD50 of the drug is 48.8 mL/kg in mice and greater than 30 mL/kg in rats.

Dialysis: Dialysis data are not available for lactulose. Its molecular similarity to sucrose, however, would suggest that it should be dialyzable.
DOSAGE AND ADMINISTRATION

The usual dose is 1 to 2 tablespoonfuls (15 to 30 mL, containing 10 g to 20 g of lactulose) daily. The dose may be increased to 60 mL daily if necessary. Twenty-four to 48 hours may be required to produce a normal bowel movement.

Note: Some patients have found that lactulose solution may be more acceptable when mixed with fruit juice, water or milk.
HOW SUPPLIED

Lactulose Solution is a colorless to amber syrupy liquid. It is available in 100 mL (NDC: 70436-003-10), 120 mL (NDC: 70436-003-11), 200 mL (NDC: 70436-003-13), 300 mL (NDC: 70436-003-14), 500 mL (NDC: 70436-003-16), and 1000 mL (NDC: 70436-003-18) bottles.

Lactulose Solution USP contains 667 mg/mL (10 g/15 mL).

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not freeze. Keep tightly closed.

Under recommended storage conditions, a normal darkening of color may occur. Such darkening is characteristic of sugar solutions and does not affect therapeutic action. Prolonged exposure to temperatures above 30°C (86°F) or to direct light may cause extreme darkening and turbidity which may be pharmaceutically objectionable. If this condition develops, do not use.

Prolonged exposure to freezing temperatures may cause change to a semi-solid, too viscous to pour. Viscosity will return to normal upon warming to room temperature.

Dispense in original container or in a tight, light-resistant container as defined in the USP, with a child-resistant closure.

Manufactured and Packaged by: LIFEPharma FZE, Jebel Ali Free Zone, Dubai, United Arab Emirates

Distributed by: Slate Run Pharmaceuticals, LLC, Columbus, Ohio 43215

Rev. August 2017

10000013/01
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

NDC: 70436-003-10, 100 mL Bottle

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Package/Label Display Panel

NDC: 70436-003-11, 120 mL Bottle

$T:\SPL Documents\Lactulose Solution USP\Life Approved 0002 version\0002 version\spl\lactulosesolution120mlv010.jpg$
Package/Label Display Panel

NDC: 70436-003-13, 200 mL Bottle

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Package/Label Display Panel

NDC: 70436-003-14, 300 mL Bottle

$T:\SPL Documents\Lactulose Solution USP\Life Approved 0002 version\0002 version\spl\lactulosesolution300mlv010.jpg$
Package/Label Display Panel

NDC: 70436-003-16, 500 mL Bottle

$T:\SPL Documents\Lactulose Solution USP\Life Approved 0002 version\0002 version\spl\lactulosesolution500mlv011.jpg$
Package/Label Display Panel

NDC: 70436-003-18, 1000 mL Bottle

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INGREDIENTS AND APPEARANCE

LACTULOSE SOLUTION
lactulose solution solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 70436-003
Route of Administration	ORAL

Ingredient Name	Basis of Strength	Strength
Active Ingredient/Active Moiety
LACTULOSE (UNII: 9U7D5QH5AE) (LACTULOSE - UNII:9U7D5QH5AE)	LACTULOSE	10 g in 15 mL

Ingredient Name	Strength
Inactive Ingredients
GALACTOSE (UNII: X2RN3Q8DNE)
LACTOSE, UNSPECIFIED FORM (UNII: J2B2A4N98G)
WATER (UNII: 059QF0KO0R)

#	Item Code	Package Description	Marketing Start Date
Packaging
1	NDC: 70436-003-10	100 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019
2	NDC: 70436-003-11	120 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019
3	NDC: 70436-003-13	200 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019
4	NDC: 70436-003-14	300 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019
5	NDC: 70436-003-16	500 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019
6	NDC: 70436-003-18	1000 mL in 1 BOTTLE; Type 0: Not a Combination Product	04/01/2019

Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Marketing Information
ANDA	ANDA209517	04/01/2019

Labeler - Slate Run Pharmaceuticals LLC (039452765)

Registrant - LIFEPharma FZE (851194279)

Name	Address	ID/FEI	Business Operations
Establishment
LIFEPharma FZE		851194279	MANUFACTURE(70436-003)

LACTULOSE SOLUTION solution

Lactulose Solution by

Drug Labeling and Warnings

Drug Details [pdf]

General

Information for Patients

Laboratory Tests

Drug Interactions

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Nursing Mothers

Pediatric Use