Dose:   0.02 to 0.04 mcg/kg/dose IV, IM           

Frequency:     Q 8 to 12 hours

Comments:  Sincalide is a synthetic octapeptide fragment of cholecystokinin which increases bile flow, promotes biliary tract motility and gallbladder emptying, and inhibits con- traction of the sphincter of Oddi. These actions occur within 15 minutes of dosing. Although used in GI function tests, Sitzmann (Surg Gynecol Obstet 1990; 170:25) reported using sincalide in adults receiving parenteral nutrition to prevent formation of biliary sludge. Rintala (J Pediatr Surg 1995; 30:827) used porcine cholecystokinin (CCK) in eight infants with TPN associated cholestasis. The infants had received TPN from 20 to 150 days following surgery for NEC (3), midgut volvulus (1), gastroschisis (1), gastric necrosis (1), diaphragmatic hernia (1), and a cardiac anomaly (1). Seven of the infants had been weaned from TPN and were on full feeds for 20 to 55 days before starting therapy. All of the infants had acholic stools, conjugated hyperbilirubinemia, and on Technetium scan showed an absence of secretion to the biliary tree or duodenum. The CCK was administered three times a day for 3 to 5 days. If there was no effect, the dose was doubled for a second course. In seven of eight patients the bile flow was restored. Stool color returned to normal within one to three days in most of the infants. Four infants had abdominal cramps or restlessness during the infusions. Following the course of CCK, Actigall was administered (10 mg/kg/day) for 4 to 6 weeks. Teitelbaum (J Pediatr Surg 1995; 30:1082) used sincalide in a low dose (0.02 mcg/kg) and in a high dose (0.32 mcg/kg) to treat 11 infants with TPN associated cholestasis. Treatment was effective in both doses (except for 3 infants with irreversible liver failure). Teitelbaum (JPEN 1997; 21:100) then administered sincalide (0.02 mcg/kg/dose, BID) to 21 infants receiving TPN for at least 2 weeks. The incidence of severe cholestasis (conjugated bilirubin >5.0 mg/dl) was 9.5% in the treatment group compared to 38.5% in historical controls.

Toxicity: Gastrointestinal symptoms including abdominal cramps and an urge to defecate have been reported in adults. The symptoms are due to spasm of the pyloric sphincter which delays gastric emptying and an overall increase in intestinal motility. Cardiovascular symptoms are much more infrequent and include dizziness (hypotension) and flushing (Facts and Comparisons, Inc. Drug Facts and Comparisons. Olin, B.R. ed. St. Louis, MO:Facts and Comparisons, Inc; 1997, page 749b). In the pediatric reports above (Rintala, 1995; Teitelbaum, 1995; and Teitelbaum, 1997), noted adverse reactions were not common and included feeding problems and abdominal discomfort during administration.

Preparation: Sincalide (Kinevac) is available in 5 mcg vial. Add 5 ml of Sterile Water for Injection to the vial to produce 5 ml of solution with a concentration of 1 mcg/ml. Further dilution will be required for IV infusions, use 1 ml of the 1 mcg/ml concentration and mix with 9 ml normal saline for a final concentration of 0.1 mcg/ml.. Administer over 30 to 60 seconds. Stable at room temperature for 8 hours after reconstitution.

Compatibility: No information available about compatibility with TPN or filter.  Do not mix with other medications.