CHOLAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHOLAC (CHOLAC).
Lactulose is a synthetic disaccharide that is not absorbed in the small intestine. It is metabolized by colonic bacteria to short-chain fatty acids, primarily lactic acid and acetic acid, which lower the colonic pH. This acidification traps ammonia (NH3) as ammonium (NH4+) in the gut lumen, reducing serum ammonia levels. Additionally, the osmotic effect of lactulose draws water into the colon, producing a laxative effect.
| Metabolism | Not absorbed systemically. Metabolized by colonic bacteria (e.g., Lactobacillus, Bacteroides) to lactic acid, acetic acid, and other short-chain fatty acids. |
| Excretion | Primarily fecal (biliary excretion of unchanged drug and metabolites); minimal renal excretion (<5%). |
| Half-life | 0.5-1.5 hours for lactulose; active metabolites (e.g., acetic acid) have negligible systemic half-life due to rapid local metabolism. |
| Protein binding | Negligible (<1%); not significantly bound to plasma proteins. |
| Volume of Distribution | Approximately 0.2 L/kg; indicates distribution primarily in extracellular fluid. |
| Bioavailability | Oral: <2% systemic bioavailability due to extensive first-pass metabolism and local gut action; rectal: minimal systemic absorption. |
| Onset of Action | Oral: 24-48 hours for laxative effect; 30 minutes to 2 hours for ammonia reduction via rectal administration. |
| Duration of Action | Laxative effect persists 24-48 hours after single dose; ammonia-lowering effect sustained during therapy. |
15-30 mL (10-20 g lactulose) orally once daily, titrated to produce 2-3 soft stools per day; maximum dose 60 mL/day. For hepatic encephalopathy: 30-45 mL (20-30 g) orally 3-4 times daily, titrated to 2-3 soft stools per day.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No specific Child-Pugh based adjustments. Use with caution in severe hepatic impairment due to risk of electrolyte disturbances; monitor serum electrolytes. |
| Pediatric use | Infants: 2.5-10 mL/day in divided doses. Children: 40-90 mg/kg/day (as lactulose) divided 1-2 times daily, titrated to produce soft stools. For hepatic encephalopathy: 2.5-10 mL (1.7-6.7 g) orally 3-4 times daily, titrated to 2-3 soft stools per day. |
| Geriatric use | Initiate at lower end of dosing range (15 mL once daily) and titrate slowly to avoid diarrhea and electrolyte imbalance; monitor renal function and electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CHOLAC (CHOLAC).
| Breastfeeding | Excretion into breast milk is negligible due to minimal systemic absorption. M/P ratio not determined. Considered compatible with breastfeeding. |
| Teratogenic Risk | Lactulose is not absorbed systemically; no teratogenic effects reported in animal studies or human case reports. FDA Pregnancy Category B. Trimester-specific risks: no known fetal harm in any trimester. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Patients with galactosemia (due to galactose content)","Gastrointestinal obstruction (including ileus)","Hypersensitivity to lactulose or any component of the formulation"]
| Precautions | ["Electrolyte disturbances (e.g., hypernatremia) may occur, especially with prolonged use or in patients with renal impairment","Diarrhea can lead to fluid and electrolyte loss; dosage should be adjusted to produce 2-3 soft stools per day","Galactose content: lactulose contains galactose and lactose; use with caution in patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption","Risk of colonic perforation in patients with severe colonic ulceration, toxic megacolon, or gastrointestinal obstruction"] |
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| Monitor maternal electrolyte levels (especially potassium, chloride) with prolonged use due to potential diarrhea-induced losses. Fetal monitoring not required. |
| Fertility Effects | No known effects on fertility in animal or human studies. |