Lactulose
Regulatory sources consulted
- openfda-label-bda4ccaa-fa33-4911-b3bd-12391c365f47
- aemps-cima-ft-60189
- ansm-bdpm-rcp-69429411
- PubMed PMID:37159031 ↗
- PubMed PMID:35739133 ↗
- PubMed PMID:37211380 ↗
- PubMed PMID:40314389 ↗
- PubMed PMID:37751393 ↗
- OpenFDA · A06AD11
- RxNorm rxcui 6218 ↗
Approved indications
- For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.
- Symptomatic treatment of constipation.
- Pharmacological management of chronic idiopathic constipation (CIC).
Contraindications
Absolute
- Patients who require a low galactose diet (lactulose contains galactose).
- Gastrointestinal obstruction or subocclusive syndromes.
Relative
- Phenylketonuria (for formulations containing aspartame).
Clinical warnings
- Major warning · Theoretical hazard of explosion from hydrogen (H2) gas accumulation during electrocautery procedures (e.g., colonoscopy). Thorough bowel cleansing with a non-fermentable solution is recommended before such procedures. — FDA
- Lactulose-induced diarrhea can cause electrolyte imbalance (hypokalemia, hypernatremia) and dehydration. Monitor in at-risk patients. — EMA SPC
Drug interactions
- ModerateNon-absorbable antacidsA02A
Mechanism: May inhibit the lactulose-induced drop in colonic pH, reducing its effectiveness in treating hepatic encephalopathy.
Recommendation: Consider the potential lack of effect. Monitor clinical efficacy (mental status, ammonia levels) if given concomitantly.
FDA label
- ModerateNeomycin and other oral anti-infectivesA07AA01
Mechanism: Theoretically, elimination of colonic bacteria that metabolize lactulose may interfere with its degradation and acidification of the colon, decreasing its effect.
Recommendation: Closely monitor the patient's status. Evidence is conflicting, but a potential reduction in lactulose efficacy should be watched for.
FDA label
- ModerateOther laxativesA06A
Mechanism: Loose stools induced by other laxatives may mask the need for lactulose dose titration, leading to suboptimal dosing for hepatic encephalopathy.
Recommendation: Avoid concomitant use of other laxatives, especially during the initial phase of therapy for portal-systemic encephalopathy.
FDA label
Adverse events
Common (≥1%)
abdominal distension · flatulence · belching · abdominal cramps · diarrhea (dose-dependent)
Rare but serious
severe diarrhea with dehydration · hypernatremia · hypokalemia
Pregnancy and lactation
FDA category: B
Animal studies have not revealed evidence of fetal harm. However, there are no adequate and well-controlled studies in pregnant women. Since systemic absorption is minimal, risk to the fetus is considered low. Use during pregnancy only if clearly needed. Compatible with breastfeeding.
Recent literature (PubMed)
Revisión exhaustiva sobre cirrosis. Destaca que, en metaanálisis de ensayos aleatorizados, la lactulosa se asoció con una reducción de la mortalidad en comparación con placebo (8.5% vs 14%) en pacientes con encefalopatía hepática.
Revisión primaria sobre encefalopatía hepática (EH). Describe la fisiopatología (amonio, inflamación, edema cerebral de bajo grado) y posiciona a la lactulosa y la rifaximina como los pilares del tratamiento médico actual para la EH.
Guía de práctica clínica conjunta de AGA/ACG para el estreñimiento idiopático crónico (EIC). Otorga una recomendación condicional para el uso de lactulosa en el tratamiento del EIC en adultos, basándose en la evidencia disponible.
Guía clínica del ACG sobre nutrición en enfermedad hepática. Señala que los aminoácidos de cadena ramificada (BCAA) aumentan la eficacia de la lactulosa y la rifaximina en el tratamiento de la encefalopatía hepática.
Revisión sobre el sobrecrecimiento bacteriano del intestino delgado (SIBO). Menciona el test de aliento con lactulosa como una herramienta diagnóstica común, no invasiva y accesible para el SIBO.