CEPHULAC
Clinical safety rating
cautionComprehensive clinical and safety monograph for CEPHULAC (CEPHULAC).
Lactulose, a synthetic disaccharide, is not absorbed from the gastrointestinal tract. It is metabolized by colonic bacteria to form short-chain fatty acids (e.g., lactic, acetic, formic acids), which acidify the colonic contents. In hepatic encephalopathy, the acidic environment converts ammonia (NH3) to ammonium (NH4+), which is poorly absorbed and excreted in feces. Additionally, the osmotic effect of lactulose draws water into the colon, softening stools and increasing bowel movements.
| Metabolism | Not absorbed; metabolized by colonic bacteria (e.g., Lactobacillus, Bacteroides) to low molecular weight organic acids. |
| Excretion | Primarily renal (20-30% as unchanged drug) and fecal (up to 70% as unmetabolized drug via biliary elimination; following gastric acid-mediated degradation, only 5-10% reaches urine as intact lactulose; hepatic metabolism is negligible). |
| Half-life | Terminal elimination half-life is 7-10 hours (renal impairment: prolonged); systemic absorption is minimal (<3%) after oral administration, so half-life reflects clearance of absorbed fraction. |
| Protein binding | Negligible (<5%): lactulose does not bind significantly to albumin or other plasma proteins due to its hydrophilic nature. |
| Volume of Distribution | 0.5-1.0 L/kg (estimated from systemic absorption studies; limited data due to minimal absorption; reflects distribution largely into extracellular water). |
| Bioavailability | Oral: <3% (due to poor absorption and extensive metabolism by colonic bacteria; most of the drug remains in the gut lumen). Rectal: similar to oral, as systemic absorption is minimal. |
| Onset of Action | Oral: 24-48 hours for laxative effect (dependent on gut flora metabolism; delayed if flora disturbed). Rectal: 15-60 minutes for laxative effect (for retention enema). |
| Duration of Action | Oral: 24-48 hours after a single dose (effects persist until bowel evacuation). Chronic use: 1-2 days after discontinuation for normalization of bowel function. |
| Molecular Weight | 342.3 |
30-45 mL (6.67-10 g lactulose) orally 3-4 times daily for constipation; for hepatic encephalopathy, 30-45 mL orally 3-4 times daily titrated to produce 2-3 soft stools per day, or 300 mL in 700 mL of water or saline as retention enema for 30-60 min every 4-6 hours.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment as lactulose is minimally absorbed and primarily acts locally in the colon. |
| Liver impairment | Not specifically adjusted based on Child-Pugh score; dose is titrated to achieve desired stool frequency; caution in severe hepatic impairment due to risk of electrolyte disturbances. |
| Pediatric use | Infants: 2.5-10 mL/day in divided doses; older children: 10-25 mL/day; adolescents: 15-30 mL/day; all for constipation; for hepatic encephalopathy, doses as low as 5-10 mL 3-4 times daily with dose adjusted to produce 2-3 soft stools per day. |
| Geriatric use | Initiate at lower end of dosing range (15-30 mL/day) due to increased risk of dehydration and electrolyte imbalance; monitor for diarrhea and adjust accordingly. |
| 1st trimester | No evidence of fetal harm in animal studies; use with caution if benefit outweighs risk. Limited human data. |
| 2nd trimester | No evidence of fetal harm in animal studies; use with caution if benefit outweighs risk. Limited human data. |
| 3rd trimester | No evidence of fetal harm in animal studies; use with caution if benefit outweighs risk. Limited human data. |
Clinical note
Comprehensive clinical and safety monograph for CEPHULAC (CEPHULAC).
| Placental transfer | Minimal to no systemic absorption; negligible placental transfer expected. |
| Breastfeeding | Not absorbed systemically after oral administration; therefore, no expected effect on breastfed infant. Use is considered compatible with breastfeeding. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | Lactulose (CEPHULAC) is not absorbed systemically; therefore, fetal exposure is negligible. Animal studies have not shown teratogenic effects. In clinical practice, no fetal risks have been identified in any trimester. |
| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal serum electrolytes if prolonged therapy, due to risk of diarrhea and electrolyte imbalance. |
| Fertility Effects | No known effects on fertility. Lactulose does not interfere with reproductive hormones or gamete function. |
■ FDA Black Box Warning
None
| Serious Effects |
GalactosemiaIntestinal obstructionLactose intolerance
| Precautions | Electrolyte imbalance with prolonged use, especially in debilitated patients, Diarrhea may cause fluid and electrolyte loss, Galactose intolerance (contraindicated in patients requiring low galactose diet due to lactose content in some preparations), Monitor serum electrolytes in patients receiving high doses for hepatic encephalopathy |
| Food/Dietary | No specific food interactions. Avoid concurrent use with other laxatives unless directed. High-fiber foods may enhance effect; ensure adequate fluid intake. |
| Clinical Pearls | Cephulac (lactulose) is a non-absorbable disaccharide used for constipation and hepatic encephalopathy. In hepatic encephalopathy, titrate to produce 2-3 soft stools per day. Monitor serum electrolytes, especially in elderly or renal impairment. Onset of action for constipation may be 24-48 hours. Do not confuse with other lactose-containing products. |
| Patient Advice | Take exactly as prescribed; may take 24-48 hours to produce a bowel movement. · For hepatic encephalopathy, maintain 2-3 soft stools daily; do not skip doses. · May cause bloating, gas, or cramping initially; usually resolves. · Do not take other laxatives without consulting your doctor. · Report severe diarrhea, vomiting, or muscle cramps to your healthcare provider. |
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