sincalide injection, powder, lyophilized, for solution Bracco Diagnostics Inc.
KINEVAC® Sincalide for Injection
Kinevac (Sincalide for Injection) is a cholecystopancreatic-gastrointestinal hormone peptide for
parenteral administration. The agent is a synthetically-prepared C-terminal octapeptide of
cholecystokinin. Each vial of sincalide provides a sterile nonpyrogenic lyophillized white powder
consisting of 5 mcg sincalide with 170 mg mannitol, 30 mg arginine hydrochloride, 15 mg
lysine hydrochloride, 9 mg potassium phosphate dibasic, 4 mg methionine, 2 mg pentetic acid,
0.04 mg sodium metabisulfite, and 0.005 mcg polysorbate 20. The pH is adjusted to 6.0 - 8.0
with hydrochloric acid and/or sodium hydroxide prior to lyophilization. Sincalide is designated
chemically as L-α-aspartyl-O-sulfo-L-tyrosyl-L-methionylglycyl-L-tryptophyl-L-methionyl-
L-α-aspartyl-L-phenylalaninamide. Graphic formula:
When injected intravenously, sincalide produces a substantial reduction in gallbladder size by
causing this organ to contract. The evacuation of bile that results is similar to that which
occurs physiologically in response to endogenous cholecystokinin. The intravenous (bolus)
administration of sincalide causes a prompt contraction of the gallbladder that becomes maximal
in 5 to 15 minutes, as compared with the stimulus of a fatty meal which causes a progressive
contraction that becomes maximal after approximately 40 minutes. Generally, a 40
percent reduction in radiographic area of the gallbladder is considered satisfactory contraction,
although some patients will show area reduction of 60 to 70 percent.
Like cholecystokinin, sincalide stimulates pancreatic secretion; concurrent administration
with secretin increases both the volume of pancreatic secretion and the out-put of bicarbonate and protein (enzymes) by the gland. This combined effect of secretin and sincalide permits the
assessment of specific pancreatic function through measurement and analysis of the duodenal
aspirate. The parameters usually determined are: volume of the secretion; bicarbonate concentration;
and amylase content (which parallels the content of trypsin and total protein).
Both cholecystokinin and sincalide stimulate intestinal motility, and may cause pyloric contraction
which retards gastric emptying.
INDICATIONS AND USAGE
Kinevac (Sincalide for Injection) may be used: (1) to stimulate gallbladder contraction, as
may be assessed by various methods of diagnostic imaging, or to obtain by duodenal aspiration
a sample of concentrated bile for analysis of cholesterol, bile salts, phospholipids, and
crystals; (2) to stimulate pancreatic secretion (especially in conjunction with secretin) prior
to obtaining a duodenal aspirate for analysis of enzyme activity, composition, and cytology;
(3) to accelerate the transit of a barium meal through the small bowel, thereby decreasing
the time and extent of radiation associated with fluoroscopy and x-ray examination of the
The preparation is contraindicated in patients hypersensitive to sincalide and in patients with
Because of Kinevac’s effect on smooth muscle, pregnant patients should be advised that spontaneous
abortion or premature induction of labor may occur (see Pregnancy Category B).
The possibility exists that stimulation of gallbladder contraction in patients with small gallbladder
stones could lead to the evacuation of the stones from the gallbladder, resulting in their
lodging in the cystic duct or in the common bile duct. The risk of such an event is considered
to be minimal because sincalide, when given as directed, does not ordinarily cause complete
contraction of the gallbladder.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic
potential, or possible impairment of fertility in males or females.
Pregnancy Category B
Reproduction studies in rats in which sincalide was administered subcutaneously at doses up
to 12.5 times the maximum recommended human dose revealed no evidence of harm to the
fetus due to sincalide. There are, however, no adequate and well-controlled studies in pregnant
women. Because animal reproduction studies are not always predictive of human response,
this drug should be used during pregnancy only if clearly needed (see WARNINGS).
Labor and Delivery
Sincalide should not be administered to pregnant women near term because of its effect on
smooth muscle; the possibility of inducing labor prematurely exists. The effects of sincalide on
labor, delivery and lactation in animals has not been determined (see WARNINGS).
It is not known whether this drug is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when sincalide is administered to a
Safety and effectiveness in children have not been established.
Reactions to sincalide are generally mild and of short duration. The most frequent adverse
reactions were abdominal discomfort or pain, and nausea; rapid intravenous injection of 0.04
mcg sincalide per kg expectably causes transient abdominal cramping. These phenomena are
usually manifestations of the physiologic action of the drug, including delayed gastric emptying
and increased intestinal motility. These reactions occurred in approximately 20 percent of
patients; they are not to be construed as necessarily indicating an abnormality of the billiary
tract unless there is other clinical or radiologic evidence of disease.
The incidence of other adverse reactions, including vomiting, flushing, sweating, rash,
hypotension, hypertension, shortness of breath, urge to defecate, headache, diarrhea, sneezing,
and numbness was less than 1 percent; dizziness was reported in approximately 2 percent
of patients. These manifestations are usually lessened by slower injection rate.
Although no overdosage reports have been received, gastrointestinal symptoms (abdominal
cramps, nausea, vomiting and diarrhea) would be expected. Hypotension with dizziness or
fainting might also occur. Overdosage symptoms should be treated symptomatically and
should be of short duration. Starting with single bolus i.v. injection comparable to the human
does of 0.4 mg/kg, sincalide caused hypotension and bradycardia in dogs. Higher doses
injected once or repeatedly in dogs caused syncope and ECG changes in addition. These
effects were attributed to sincalide-induced vagal stimulation in that all were prevented by pretreatment
with atropine or bilateral vagotomy.
DOSAGE AND ADMINISTRATION
Reconstitution and Storage
Sincalide for Injection may be stored at room temperature prior to reconstitution.
To reconstitute, aseptically add 5 mL of Sterile Water for Injection USP to the vial. This
solution may be kept at room temperature and should be used within 8 hours of reconstitution,
after which time any unused portion should be discarded.
Parenteral drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit.
For prompt contraction of the gallbladder, a dose of 0.02 mcg sincalide per kg (1.4 mcg/70
kg) is injected intravenously over a 30- to 60-second interval; if satisfactory contraction of the gallbladder does not occur in 15 minutes, a second dose, 0.04 mcg sincalide per kg, may be
administered. To reduce the intestinal side effects (see ADVERSE REACTIONS), an intravenous
infusion may be prepared at a dose of 0.12 mcg/kg in 100 mL of Sodium Chloride Injection
USP and given at a rate of 2 mL per minute; alternatively, an intramuscular dose of 0.1 mcg/kg
may be given. When Kinevac (Sincalide for Injection) is used in cholecystography,
roentgenograms are usually taken at five-minute intervals after the injection. For visualization
of the cystic duct, it may be necessary to take roentgenograms at one-minute intervals during
the first five minutes after the injection.
For the Secretin-Kinevac test of pancreatic function, the patient receives a dose of 0.25 units
secretin per kg by intravenous infusion over a 60-minute period. Thirty minutes after the initiation
of the secretin infusion, a separate IV infusion of Kinevac at a total dose of 0.02 mcg per
kg is administered over a 30-minute interval. For example, the total dose for a 70 kg patient is
1.4 mcg of sincalide; therefore, dilute 1.4 mL of reconstituted Kinevac solution to 30 mL with
Sodium Chloride Injection USP and administer at a rate of 1 mL per minute.
To accelerate the transit time of a barium meal through the small bowel, administer Kinevac
after the barium meal is beyond the proximal jejunum. (Sincalide, like cholecystokinin, may
cause pyloric contraction.) The recommended dose is 0.04 mcg sincalide per kg (2.8 mcg/70
kg) injected intravenously over a 30- to 60- second interval; if satisfactory transit of the barium
meal has not occurred in 30 minutes, a second dose of 0.04 mcg sincalide per kg may be
administered. For reduction of side effects, a 30-minute IV infusion of sincalide [0.12 mcg per
kg (8.4 mcg/70 kg) diluted to approximately 100 mL with Sodium Chloride Injection USP] may
Sodium Chloride Injection dilutions may be kept at room temperature and should be used
within one hour of dilution.
Kinevac (Sincalide for Injection) is supplied in packages of 10 vials containing 5 mcg of sincalide
per vial (NDC 0270-0556-15).
Store at 25° C (77° F); excursions permitted to 15-30° C (59-86° F) [See USP Controlled
U.S. Patent 6,803,046
Manufactured for Bracco Diagnostics Inc. Princeton, NJ 08543 by Hollister-Stier Laboratories LLC Spokane, WA 99207
Printed in USA Revised May 2007 875016-H01
sincalide injection, powder, lyophilized, for solution
HUMAN PRESCRIPTION DRUG
Item Code (Source)
Route of Administration
Name (Active Moiety)
5 MICROGRAM In 5 MILLILITER
170 MILLIGRAM In 5 MILLILITER
30 MILLIGRAM In 5 MILLILITER
15 MILLIGRAM In 5 MILLILITER
potassium phosphate diabasic
9 MILLIGRAM In 5 MILLILITER
4 MILLIGRAM In 5 MILLILITER
2 MILLIGRAM In 5 MILLILITER
0.04 MILLIGRAM In 5 MILLILITER
0.005 MICROGRAM In 5 MILLILITER
contains a VIAL
This package is contained within the PACKAGE (0270-0556-15)