Drug Interaction Report

Lactulose and Phenprocoumon: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Lactulose

Cholac® Constilac® Syrup Constulose Constulose® Enulose Enulose® Evalose® Syrup Generlac
+

Phenprocoumon

No brand names on record
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 9 documented Lactulose interactions, 7 are rated moderate — including this one.
Onset
delayed
Evidence
probable
Severity
Moderate

What happens

Elevated International Normalized Ratio serum values with potentiation of anticoagulation effects

Interaction Deep Dive

Coadministration of lactulose with phenprocoumon or acenocoumarol resulted in a significantly higher risk of excessive anticoagulation in patients receiving prophylactic anticoagulation therapy (adjusted relative risk=3.4; 95% confidence interval=2.2, 5.3)1.

Why it happens (mechanism)

Reduced intestinal absorption of vitamin K

Literature reports

1 report — tap to read

a) Coadministration of lactulose with either phenprocoumon or acenocoumarol resulted in a significantly higher risk of excessive anticoagulation in patients receiving prophylactic anticoagulation therapy. In a population-based retrospective cohort study, patients receiving anticoagulation therapy with phenprocoumon or acenocoumarol (n=1124) were evaluated for a correlation between laxative use and the incidence of excessive anticoagulation (indicated by an International Normalized Ratio (INR) equal to or greater than 6.0). Of all patients studied, 351 developed an INR above 6.0, and 51 of this group (15%) had used a laxative on the index date. Among 5 types of laxatives used by the high INR group, concomitant use of lactulose with either phenprocoumon or acenocoumarol was most strongly associated with a state of over-anticoagulation. The adjusted relative risk (A/RR) for over-anticoagulation associated with lactulose-phenprocoumon or lactulose-acenocoumarol co-therapy was 3.4 (95% confidence interval (CI): 2.2, 5.3). There was no clear lactulose dose-effect relationship. When stratified by duration of laxative exposure, the use of lactulose initially conferred a protective effect against over-anticoagulation when used for less than 27 days (RR=0.5, 95% CI: 0.3, 0.8). However, this effect was reversed for lactulose-phenprocoumon/acenocoumarol cotreatment in excess of 27 days duration; for days 28 through 97, over-anticoagulation RR was 1.7 (95% CI: 0.9, 3.0) and for greater than 98 days duration, RR was 2.1 (95% CI: 1.2, 3.7) 1.

Common questions

Can I take Lactulose and Phenprocoumon together?

Elevated International Normalized Ratio serum values with potentiation of anticoagulation effects Always confirm with your pharmacist or prescriber before making any change.

How serious is the Lactulose and Phenprocoumon interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Lactulose or Phenprocoumon need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there anything you'd monitor while I'm on both?

References (1)

  1. Visser LE, Penning-van Beest FJA, Wilson JHP, et al: Overanticoagulation associated with combined use of lactulose and acenocoumarol or phenprocoumon. Br J Clin Pharmacol 2003; 57(4):522-524. PubMed
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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.