BRACCO DIAGNOSTICS™
`
`J3-398J
`
`CAUTION: Federal law prohibits dispensing without prescription.
`
`KINEVAC®
`Sincalide for Injection
`
`DESCRIPTION
`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
`via] of sincalide provides a sterile nonpyrogenic lyophilized white powder consisting of 5 mcg sincalide
`with 45 mg sodium chloride to provide tonicity; sodium hydroxide or hydrochloric acid may have been
`added prior to lyophilization for pH adjustment (5.5 to 6.5). At the time of manufacture, the air in the vial
`is replaced with nitrogen. Sincalide is designated chemically as L-aspartyl-L-tyrosyl-L-methionylglycyl-L-
`tryptophyl-L-methionyl-L-aspartylphenyK-alaninamide hydrogen sulfate (ester). Graphic formula:
`
`SO3H
`
`Asp
`1
`
`Tyr
`2
`
`Met
`3
`
`Gly
`4
`
`Trp
`5
`
`Met
`6
`
`Asp
`7
`
`Phe
`8
`
`NH2
`
`C49H62N10O16S3
`
`MW 1143.27
`
`CAS-25126-32-3
`
`CLINICAL PHARMACOLOGY
`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 output 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 contrast agent cholecystography or ultrasonography, 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 intestinal tract.
`
`CONTRAINDICATIONS
`The preparation is contraindicated in patients hypersensitive to sincalide and in patients with intestinal
`obstruction.
`
`-1-
`
`
`
`
`MAIA Exhibit 1029
`MAIA V. BRACCO
`IPR PETITION
`
`

`

`WARNINGS
`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).
`
`PRECAUTIONS
`
`General
`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.
`Teratogenic Effects
`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).
`Nursing Mothers
`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 nursing woman.
`Pediatric Use
`Safety and effectiveness in children have not been established.
`
`ADVERSE REACTIONS
`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 biliary 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.
`
`OVERDOSAGE
`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 dose 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.
`
`-2-
`
`
`
`
`

`

`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; any additional dilution
`should be made with Sodium Chloride Injection USP, 0.9%. The solution may be kept at room
`temperature and should be used within 24 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 sincallde 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-mlnute 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 be administered.
`
`HOW SUPPLIED
`Kinevac (Sincalide for Injection) is supplied in packages of 10 vials containing 5 mcg of sincalide per via]
`(NDC 0270-0556-15).
`Storage
`Store at room temperature, 15°-30° C (59°-86° F).
`
`Manufactured for
`Bracco Diagnostics Inc.
`Princeton, N.J. 08543
`by E.R. Squibb & Sons Inc. New Brunswick, N.J. 08903
`
`J3-398J Printed in USA Revised November-1994
`
`J3-398J
`
`-3-
`
`
`
`
`