Lactulose

A06A - Drugs for constipation ATC A06AD11 Small molecule approved 1976 Oral Topical Natural product

JFDA label: Ramlac syrup

Mechanism of Action

— Colonic bacteria substrate

Indications

Approved

Constipation (Constulose, Kristalose)
Portal systemic encephalopathy (Enulose, Generlac)

Off-label

Subclinical (minimal) hepatic encephalopathy

Contraindications

Source: Lexicomp

Patients requiring a low galactose diet Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Metabolism and nutrition disorders (3)

Not Known Dehydration · hypernatremia · hypokalemia

Gastrointestinal disorders (8)

Not Known Abdominal cramps · abdominal distention · abdominal distress · diarrhea (excessive dose) · eructation · flatulence · nausea · vomiting

Dosing

Source: Lexicomp

Constipation: Oral: 10 to 20 g (15 to 30 mL or 1 to 2 packets) daily; may increase to 40 g (60 mL or 2 to 4 packets) daily if necessary Portal systemic encephalopathy (PSE), prevention: Oral: 20 to 30 g (30 to 45 mL) 3 to 4 times daily; adjust dose every 1 to 2 days to produce 2 to 3 soft stools/day PSE treatment: Oral: 20 to 30 g (30 to 45 mL) every 1 hour to induce rapid laxation; reduce to 20 to 30 g (30 to 45 mL) 3 to 4 times daily after laxation is achieved to produce 2 to 3 soft stools/day Rectal administration (retention enema): 200 g (300 mL) via rectal balloon catheter; retain for 30 to 60 minutes; may repeat every 4 to 6 hours; transition to oral treatment prior to discontinuing rectal administration Overt hepatic encephalopathy (OHE) episodes, treatment: Route not specified: 16.7 g (25 mL) every 1 to 2 hours until at least 2 soft or loose bowel movements are produced daily; titrate to maintain 2 to 3 bowel movements daily (AASLD [Vilstrup 2014]). Subclinical (minimal) hepatic encephalopathy (off-label use): 20 to 40 g (30 to 60 mL) daily in 2 to 3 divided doses to maintain 2 to 3 bowel movements daily for up to 3 months (Dhiman 2000; Watanabe 1997; Prasad 2007)

(For additional information see "Lactulose: Pediatric drug information") Note: Doses in pediatric patients may be expressed in volume (mL) or weight (g); use extra precaution. Portal systemic encephalopathy (PSE), prevention: Oral: Infants: 1.7 to 6.7 g/day (2.5 to 10 mL/day) in divided doses; adjust dosage to produce 2 to 3 stools/day Children and Adolescents: 26.7 to 60 g/day (40 to 90 mL/day) in divided doses; adjust dosage to produce 2 to 3 stools/day Constipation (off-label dose): Infants, Children, and Adolescents: Oral: 1 to 2 g/kg/day (1.5 to 3 mL/kg/day) once daily or in 2 divided doses (NASPGHAN [Tabbers 2014]); maximum daily dose: 60 mL/day in adults.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Electrolyte imbalance

Monitor periodically for electrolyte imbalance when lactulose is used >6 months or in patients predisposed to electrolyte abnormalities (eg, elderly, debilitated patients). Hepatic disease may predispose patients to electrolyte imbalance. Infants receiving lactulose may develop hyponatremia and dehydration. Disease-related concerns:

Diabetes

Use with caution in patients with diabetes mellitus; solution contains galactose and lactose. Other warnings/precautions:

Electrocautery procedures

During proctoscopy or colonoscopy procedures involving electrocautery, a theoretical risk of reaction between H2 gas accumulation and electrical spark may exist; thorough bowel cleansing with a nonfermentable solution is recommended.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies. Lactulose is poorly absorbed following oral administration. Use of dietary fiber or bulk-forming laxatives along with increased fluid intake is generally considered first line therapy for treating constipation in pregnant women. Short-term use of lactulose is also considered to be safe/low risk when therapy is needed; however, side effects may limit its use (Cullen, 2007; Mahadevan, 2006; Prather, 2004; Wald, 2003).

Lactation

It is not known if lactulose is excreted in breast milk; however, lactulose is poorly absorbed following oral administration. The manufacturer recommends that caution be exercised when administering lactulose to nursing women.

Monitoring

Clinical pearl	Blood pressure, standing/supine; serum electrolytes, serum ammonia; bowel movement patterns, fluid status

Chemistry & Properties

Formula	C12H22O11
Molecular weight	342.3 g/mol
IUPAC name	(2S,3R,4S,5R,6R)-2-[(2R,3S,4S,5R)-4,5-dihydroxy-2,5-bis(hydroxymethyl)oxolan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol
CAS	4618-18-2
PubChem CID	11333
InChIKey	`JCQLYHFGKNRPGE-FCVZTGTOSA-N`
logP	-5.4 (XLogP -4.3)
Polar surface area	189.53 Å²
H-bond acceptors / donors	11 / 8
Drug-likeness (QED)	0.24
Lipinski violations	2

SMILES

OC[C@H]1O[C@@H](O[C@@H]2[C@@H](CO)O[C@](O)(CO)[C@H]2O)[C@H](O)[C@@H](O)[C@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.406 h
Volume of distribution	0.33 L/kg
Protein binding	27.3%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abarelix	moderate
Abiraterone	moderate
Acetazolamide	moderate
Alfuzosin	moderate
Alimemazine	moderate
Amiloride	moderate
Amiodarone	moderate
Amisulpride	moderate
Anagrelide	moderate
Apalutamide	moderate
Apomorphine	moderate
Arsenic trioxide	moderate
Asenapine	moderate
Astemizole	moderate
Atomoxetine	moderate
Azithromycin	moderate
Bedaquiline	moderate
Bendroflumethiazide	moderate
Benzthiazide	moderate
Bepridil	moderate
Betamethasone	moderate
Bicalutamide	moderate
Bisacodyl	moderate
Bosutinib	moderate
Bumetanide	moderate
Buprenorphine	moderate
Cabozantinib	moderate
Castor oil	moderate
Ceritinib	moderate
Chlorothiazide	moderate
Chlorpromazine	moderate
Chlorthalidone	moderate
Cilostazol	moderate
Ciprofloxacin	moderate
Cisapride	moderate
Citalopram	moderate
Clarithromycin	moderate
Clofazimine	moderate
Clozapine	moderate
Corticotropin	moderate

Showing 40 of 100+.

Registered Products (10)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Ramlac syrup	Syrup 67 g/100 ml	100 ml pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	1.000
Lactulax Syrub	Suspension 3.33 g/5 ml	100 ml pack varies	Al-Gadeed Pharmaceutical Industries/JORDAN	1.140
Ramlac syrup	Syrup 67 g/100 ml	150 ml pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	1.710
Ramlac syrup	Syrup 67 g/100 ml	200 ml pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	1.860
Lactulax Syrub	Suspension 3.33 g/5 ml	200 ml pack varies	Al-Gadeed Pharmaceutical Industries/JORDAN	2.170
Laxodad Syrup	Syrup 10 g/15 ml	200 ml	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.170
Ezilax Syrup	Syrup 10 g/15 ml	300 ml	Sukhtian Group	2.740
Ramlac syrup	Syrup 67 g/100 ml	300 ml pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	2.740
Duphalac Oral Solution	Solution 667 g/L	20 sachet pack varies	Abu Sheikha Drug Store	3.500
Duphalac Oral Solution	Solution 667 g/L	300 ml pack varies	Abu Sheikha Drug Store	4.200