Lactulose

Evidence Level: L5

Predicted Indications: 8

Lactulose

Pharmacist Assessment Report

Lactulose: From Hepatic Encephalopathy to Obstructive Jaundice

One-Sentence Summary

Lactulose is a non-absorbable sugar originally used to treat hepatic encephalopathy, hepatic coma and constipation. The TxGNN model’s top-scoring prediction is acute urate nephropathy, but this has no supporting studies, so this report focuses on the best-supported prediction, obstructive jaundice. That prediction currently has 0 registered clinical trials and 20 publications, mostly older or preclinical.

Quick Overview

Item	Content
Original Indication	Hepatic encephalopathy, hepatic coma, constipation (the Health Canada licence records contain no indication text)
Predicted New Indication	Obstructive jaundice (the highest-ranked prediction, acute urate nephropathy, has no evidence and is not featured here)
TxGNN Prediction Score	0.9953 (obstructive jaundice); 0.9989 for acute urate nephropathy
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 5 of 6; dormant: 1)
Number of DINs	6 (marketed: 5)
Recommended Decision	Hold (research question only)

Other predictions and their evidence levels:

Predicted Indication	Score	Evidence Level
Acute urate nephropathy	0.9989	L5
Nephrolithiasis	0.9978	L5
Obstructive jaundice	0.9953	L3
Bile duct disease	0.9947	L3
Biliary tract disease	0.9938	L5
Hyperphosphatemia	0.9937	L5
Exercise-induced malignant hyperthermia	0.9914	L5
Bile duct neoplasm	0.9912	L5

Why is This Prediction Reasonable?

Detailed mechanism of action data is not currently available. Based on known information, lactulose is a non-absorbable disaccharide that acts in the gut as an osmotic laxative. It acidifies the colon and traps ammonia, which is why it works in hepatic encephalopathy and constipation.

In obstructive jaundice, bile salts are absent from the gut. This promotes bacterial overgrowth, a leaky intestinal barrier and endotoxaemia, which in turn contribute to kidney dysfunction and infections after surgery. Lactulose has been reported to reduce gut endotoxin absorption and to help restore barrier function. That gives a plausible gut-mediated link to its existing liver and bowel uses.

Several cautions apply. Most of the evidence is old, and perioperative care for this condition has changed since. Only titles and short abstracts were available, so study designs and effect sizes could not be confirmed. A review (PMID 9145459) notes that kidney protection from lactulose has not been conclusively shown in clinical studies.

The other predictions have little or no mechanistic support. For acute urate nephropathy and exercise-induced malignant hyperthermia, no link to lactulose’s gut action is apparent, and the high scores likely reflect TxGNN model (deep learning) artefacts.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Selected publications for obstructive jaundice. Study types are as classified in the compiled data, with some designs still unverified.

PMID	Year	Type	Journal	Key Findings
2032107	1991	Prospective randomized study (multicentre)	Br J Surg	102 patients with obstructive jaundice were randomized to preoperative oral lactulose, oral sodium deoxycholate, or no specific treatment, to prevent postoperative renal failure. Results are not shown in the available text.
3768644	1986	Experimental and clinical study	Br J Surg	In 24 surgical patients, 12 given oral lactulose before operation had significantly less endotoxaemia than 12 controls.
12957136	2003	Experimental study (rabbit)	J Surg Res	Evaluated lactulose for preventing bacterial translocation and endotoxaemia after bile duct ligation.
12598962	2002	Animal study (rat)	Pediatr Surg Int	Effects of melatonin and lactulose on liver and kidney injury in 30 rats with obstructive jaundice.
9231859	1997	Animal study (rat)	Eur J Surg	Tested whether lactulose prevents bacterial translocation caused by obstructive jaundice.
10576346	1999	Animal study (rat)	Hepatogastroenterology	Compared sodium deoxycholate, lactulose and glutamine for bacterial translocation after bile duct ligation.
2311978	1990	In vitro study	Gut	Lactulose inhibited endotoxin-induced tumour necrosis factor production by monocytes.
23297639	2012	Clinical study	Zh Mikrobiol Epidemiol Immunobiol	Studied gut microecology after bile duct decompression combined with lactulose in obstructive jaundice.
9145459	1997	Review/commentary	Scand J Gastroenterol Suppl	Kidney protection by lactulose after biliary surgery was hypothesized but has not been conclusively shown in clinical studies.
15782993	2005	Review	Hepatogastroenterology	Argues for adequate preoperative hydration and lactulose to prevent postoperative renal dysfunction in acute obstructive jaundice.

For the other predictions, only indirect literature was found:

Bile duct disease and biliary tract disease: mostly overlap with the papers above, plus a review of lactulose and fibre effects on bile and gallstones (PMID 9145452).
Hyperphosphatemia: one review of constipation in chronic kidney disease (PMID 37814433), which does not show phosphate lowering.
Bile duct neoplasm: only supportive perioperative papers, none showing lactulose as the tested agent.
Acute urate nephropathy, nephrolithiasis, exercise-induced malignant hyperthermia: no literature.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02331551	TEVA-LACTULOSE	Not available	Not available
02469391	PMS-LACTULOSE-PHARMA	Not available	Not available
02247383	PHARMA-LACTULOSE	Not available	Not available
00854409	RATIO-LACTULOSE	Not available	Not available
02295881	JAMP-LACTULOSE	Not available	Not available

A sixth licence, DIN 02412268 (LACTULOSE), is also valid. All six are valid single-ingredient products, and none are cancelled.

Safety Considerations

Package insert warnings and contraindications were not available for this report, so please refer to the package insert for safety information.

Contraindication signals from the knowledge graph (not label text):

Diabetes mellitus and diabetic ketoacidosis
Galactosemia
Glycogen storage disease
G6PD deficiency
Cystinuria
Glucose-galactose malabsorption
Appendicitis

Drug interactions: 100 interactions were recorded. The 20 reviewed here are mostly moderate, with one minor. Examples include:

Abiraterone
Tramadol
Acetazolamide
Hydrocortisone
Salbutamol
Hydrochlorothiazide
Amiloride
Amiodarone
Propofol
Triamcinolone
Arsenic trioxide

Several of these are QT-prolonging drugs or drugs affecting electrolytes. Lactulose can cause diarrhoea and electrolyte loss, so that may be relevant, but this is not stated in the data and should be checked against the package insert.

Conclusion and Next Steps

Decision: Hold

Rationale:

Obstructive jaundice has a plausible gut-barrier and endotoxin mechanism and some older clinical and animal reports (L3), but no registered trials. The one randomized study’s results and the overall benefit are unconfirmed, and a review notes that kidney protection was never conclusively shown. The other seven predictions are supported only by indirect evidence or none (L4–L5).
Health Canada package insert data are missing, and the safety screening cannot proceed without them.

To proceed, the following is needed:

The package insert warnings and contraindications from Health Canada, which block safety screening
Detailed mechanism of action data
Full-text review of PMID 2032107 and 3768644 to confirm design, outcomes and effect sizes
A check of whether more recent studies (the existing evidence is mostly from 1986–2005) support lactulose in current perioperative care for obstructive jaundice
Review of the diabetes-related and galactosemia contraindication signals before any use in affected patients
No further work is warranted on acute urate nephropathy, nephrolithiasis or exercise-induced malignant hyperthermia without a supporting mechanistic rationale
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.