ENULOSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENULOSE (ENULOSE).
Lactulose is a synthetic disaccharide that is not absorbed from the gastrointestinal tract. It is metabolized by colonic bacteria to form low molecular weight organic acids, which lower the colonic pH and increase osmotic pressure, resulting in increased stool volume and laxative effect. In hepatic encephalopathy, the acidification of the colon inhibits the growth of ammonia-producing bacteria and promotes the conversion of ammonia to ammonium ion, which is trapped in the colon and excreted, thereby reducing systemic ammonia levels.
| Metabolism | Lactulose is not metabolized in the human small intestine due to the absence of appropriate enzymes. It reaches the colon unchanged and is fermented by colonic bacteria (e.g., Lactobacillus, Bacteroides) into short-chain fatty acids (lactic acid, acetic acid, and formic acid) and gases (hydrogen, carbon dioxide). |
| Excretion | Primarily renal (95% unchanged by glomerular filtration); biliary/fecal less than 5%. |
| Half-life | Terminal elimination half-life is 2.1 hours in normal renal function; prolonged to up to 6 hours in renal impairment. |
| Protein binding | Negligible (<1%), not bound to plasma proteins. |
| Volume of Distribution | Vd approximately 0.25 L/kg, primarily confined to extracellular fluid. |
| Bioavailability | Oral: very low (<3%) as minimally absorbed; rectal: negligible systemic absorption. |
| Onset of Action | Oral: within 24–48 hours; rectal: within 2–24 hours. |
| Duration of Action | Oral: onset of laxative effect within 24–48 hours, duration variable; used for hepatic encephalopathy, duration of effect is sustained with continued dosing. |
15-45 mL orally once daily, titrated to produce 2-3 soft stools per day. Maximum 60 mL per day.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment; use with caution in severe renal impairment due to electrolyte disturbances. |
| Liver impairment | No specific adjustment recommended; monitor for electrolyte imbalances in severe hepatic impairment. |
| Pediatric use | Infants and children: 2.5-10 mL orally once daily, adjusted to produce 2-3 soft stools per day. Maximum 40 mL per day. |
| Geriatric use | Start at lower end of dosing range (15-30 mL daily) due to increased risk of electrolyte disturbances and dehydration. Monitor serum electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENULOSE (ENULOSE).
| Breastfeeding | Excreted in breast milk in small amounts; M/P ratio not established. Considered compatible with breastfeeding, but monitor infant for gastrointestinal effects. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human data in first trimester. Second and third trimester: No known fetal risks associated with therapeutic doses. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Patients with galactosemia (since lactulose contains galactose and may increase galactose levels), intestinal obstruction, or a history of hypersensitivity to lactulose or any component of the formulation.
| Precautions | Diabetic patients should use with caution due to the sugar content. Prolonged use may lead to electrolyte disturbances (e.g., hypernatremia, hypokalemia). Use with caution in patients with galactosemia or lactose intolerance, as lactulose may contain trace amounts of lactose. Excessive dosing may cause diarrhea and fluid loss. |
Loading safety data…
| No specific monitoring required beyond routine pregnancy care. Monitor maternal glucose levels if used for constipation in diabetic patients. |
| Fertility Effects | No known effects on human fertility. Animal studies show no impairment of fertility. |