DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. For injection: mcg of sincalideas lyophilized white powder for reconstitution in single-dosevial.. For injection: mcg of sincalideas lyophilized powder in single-dose vial for reconstitution (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Drugs that AffectGallbladder Motility or Contractile Response: May interferewith response to sincalide. Consider discontinuing these drugs priorto administration of Kinevac, when used to stimulate contraction ofthe gallbladder. (7.1). 7.1 Drugsthat Affect Gallbladder Motility or Contractile Response. Drugs that may stimulate or inhibitgallbladder motility or contractile response may interfere with theresponse to sincalide. Consider discontinuing these drugs prior toadministration of Kinevac, when used to simulate contraction of thegallbladder.

GERIATRIC USE SECTION.

8.5 GeriatricUse. Clinicalstudies of Kinevac did not include sufficient numbers of subjectsaged 65 and over to determine whether they respond differently fromyounger subjects.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING Kinevac (sincalide for injection) is suppliedas mcg of sincalide as lyophilized white powder for reconstitutionin single-dose vial; in packages of 10 vials (NDC 0270-0556-15).Store at 25 (77 F); excursionspermitted to 15-30 (59-86 F) [See USP Controlled Room Temperature].

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Kinevac is indicated in adults to:to stimulate gallbladder contraction, as may be assessedby various methods of diagnostic imaging, or to obtain by duodenalaspiration sample of concentrated bile for analysis of cholesterol,bile salts, phospholipids, and crystals; to stimulate pancreatic secretion in combination with secretinprior to obtaining duodenal aspirate for analysis of enzyme activity,composition, and cytology; to accelerate the transit of barium meal through the smallbowel, thereby decreasing the time and extent of radiation associatedwith fluoroscopy and x-ray examination of the intestinal tract.. to stimulate gallbladder contraction, as may be assessedby various methods of diagnostic imaging, or to obtain by duodenalaspiration sample of concentrated bile for analysis of cholesterol,bile salts, phospholipids, and crystals; to stimulate pancreatic secretion in combination with secretinprior to obtaining duodenal aspirate for analysis of enzyme activity,composition, and cytology; to accelerate the transit of barium meal through the smallbowel, thereby decreasing the time and extent of radiation associatedwith fluoroscopy and x-ray examination of the intestinal tract.. Kinevac is cholecystokinin(CCK) analog indicated in adults to:stimulate gallbladder contraction, as may be assessed byvarious methods of diagnostic imaging, or to obtain by duodenal aspirationa sample of concentrated bile for analysis of cholesterol, bile salts,phospholipids, and crystals. (1)stimulate pancreatic secretion in combination with secretinprior to obtaining duodenal aspirate for analysis of enzyme activity,composition, and cytology. (1)accelerate the transit of barium meal through the smallbowel, thereby decreasing the time and extent of radiation associatedwith fluoroscopy and x-ray examination of the intestinal tract. (1). stimulate gallbladder contraction, as may be assessed byvarious methods of diagnostic imaging, or to obtain by duodenal aspirationa sample of concentrated bile for analysis of cholesterol, bile salts,phospholipids, and crystals. (1). stimulate pancreatic secretion in combination with secretinprior to obtaining duodenal aspirate for analysis of enzyme activity,composition, and cytology. (1). accelerate the transit of barium meal through the smallbowel, thereby decreasing the time and extent of radiation associatedwith fluoroscopy and x-ray examination of the intestinal tract. (1).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactionsassociated with the use of Kinevac were identified in clinical trialsor postmarketing reports. Because these reactions were reported voluntarilyfrom population of uncertain size, it is not always possible toestimate their frequency, reliably, or to establish causal relationshipto drug exposure.Themost frequent adverse reactions (20% or greater) are gastrointestinal:abdominal discomfort or pain, and nausea; these may not necessarilyindicate an abnormality of the biliary tract unless there is otherclinical or radiologic evidence of disease.Less common adverse reactions include:Hypersensitivity reactions: anaphylaxis and anaphylactic shock, hypotension, throat tightness,bradycardia, shortness of breath, nausea, abdominal cramping, diaphoresis,hives, rash, itching; and numbness of face, lips and eyes [see Contraindications (4), (5.1)].Neurological reactions: seizures,headache.Vasovagalreactions: dizziness, loss of consciousness, nausea, diaphoresis,syncope and hypotension (generally self-limiting).Other: nausea, vomiting,flushing, hypertension, urge to defecate, diarrhea, sneezing.. Most common adverse reactions(>=20%) are: abdominal discomfort or pain, and nausea. (6)To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc. at 1-800-257-5181 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term studies in animals havenot been performed to evaluate carcinogenic or mutagenic potential,or possible impairment of fertility in males or females.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. When injected intravenously, sincalide stimulatesgallbladder contraction and reduction in size. The evacuation of bilethat results is similar to that which occurs physiologically in responseto endogenous cholecystokinin. Sincalide also stimulates pancreaticsecretion and intestinal motility causing pyloric contraction andslows gastric emptying.Concurrent administration of sincalide with secretin increases boththe volume of pancreatic secretion and the out-put of bicarbonateand enzymes. This combined effect of secretin and sincalide permitsthe assessment of specific pancreatic function through measurementand analysis of the duodenal aspirate.. 12.2 Pharmacodynamics. Following an intravenous (bolus) injectionof 0.02 mcg/kg of sincalide, maximal contraction of the gallbladderoccurred in to 15 minutes. Sincalide reduced gallbladder radiographicsize by at least 40%, which is generally considered satisfactory contraction.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. KINEVAC iscontraindicated in patients with:a history of hypersensitivity to sincalide.Serious hypersensitivity reactions have included anaphylaxis and anaphylacticshock [see Warnings and Precautions (5.1), Adverse Reactions (6)].intestinal obstruction.. history of hypersensitivity to sincalide.Serious hypersensitivity reactions have included anaphylaxis and anaphylacticshock [see Warnings and Precautions (5.1), Adverse Reactions (6)].. intestinal obstruction.. History of hypersensitivity to sincalide. (4, 5.1)Intestinal obstruction. (4). History of hypersensitivity to sincalide. (4, 5.1). Intestinal obstruction. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Kinevac (sincalide for injection)is cholecystopancreatic-gastrointestinal hormone for parenteraladministration. The agent is synthetically-prepared C-terminal octapeptideof cholecystokinin.Each single-dose vial of sincalide provides sterile nonpyrogeniclyophilized white powder consisting of mcg sincalide with 30 mgarginine hydrochloride, 15 mg lysine hydrochloride, 170 mg mannitol,4 mg methionine, mg pentetic acid, 0.005 mcg polysorbate 20, mgpotassium phosphate dibasic, and 0.04 mg sodium metabisulfite.The pH is adjusted to 6.0 to 8.0with hydrochloric acid and/or sodium hydroxide prior to lyophilization.Sincalide is designated chemically as L--aspartyl-O-sulfo-L-tyrosyl-L-methionylglycyl-L-tryptophyl-L-methionyl-L--aspartyl-L-phenylalaninamide. Graphic formula:. kinevac-struct.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Recommended Adult Dosage andAdministration by Indication: To Stimulate Contractionof the Gallbladder 0.02 mcg/kg as single dose over 30 to 60 seconds via intravenousinjection. If satisfactory contraction does not occur in 15 minutes,administer dose of 0.04 mcg/kg over 30 to 60 seconds. (2.1)Alternatively consider an intravenous infusion toreduce gastrointestinal adverse reactions: 0.12 mcg/kg dilutedin 100 mL of 0.9% Sodium Chloride Injection USP and infused over 50minutes at rate of mL per minute. (2.1, 2.2, 5.3)To Stimulate PancreaticSecretion in Combination with Secretin30 minutes after initiation of secretin for injection, administer0.02 mcg/kg diluted in 30 mL of 0.9% Sodium Chloride Injection USPand infused over 30 minutes at rate of mL per minute. (2.1, 2.2)To Accelerate Transitof Barium Meal Through the Small IntestineAfter the barium meal is beyond the proximal jejunum, administer0.04 mcg/kg over 30 to 60 seconds via intravenous injection. (2.1)If satisfactory transit of the barium meal has not occurredin 30 minutes, administer second dose of 0.04 mcg/kg over 30 to60 seconds. (2.1)Alternatively consider an intravenous infusion toreduce gastrointestinal adverse reactions: 0.12 mcg/kg dilutedin 100 mL 0.9% Sodium Chloride Injection USP and infused over 30 minutes.(2.1, 2.2, 5.3). 0.02 mcg/kg as single dose over 30 to 60 seconds via intravenousinjection. If satisfactory contraction does not occur in 15 minutes,administer dose of 0.04 mcg/kg over 30 to 60 seconds. (2.1). Alternatively consider an intravenous infusion toreduce gastrointestinal adverse reactions: 0.12 mcg/kg dilutedin 100 mL of 0.9% Sodium Chloride Injection USP and infused over 50minutes at rate of mL per minute. (2.1, 2.2, 5.3). 30 minutes after initiation of secretin for injection, administer0.02 mcg/kg diluted in 30 mL of 0.9% Sodium Chloride Injection USPand infused over 30 minutes at rate of mL per minute. (2.1, 2.2). After the barium meal is beyond the proximal jejunum, administer0.04 mcg/kg over 30 to 60 seconds via intravenous injection. (2.1). If satisfactory transit of the barium meal has not occurredin 30 minutes, administer second dose of 0.04 mcg/kg over 30 to60 seconds. (2.1). Alternatively consider an intravenous infusion toreduce gastrointestinal adverse reactions: 0.12 mcg/kg dilutedin 100 mL 0.9% Sodium Chloride Injection USP and infused over 30 minutes.(2.1, 2.2, 5.3). 2.1 Recommended Dosage and Administration Instructions. The recommended dosage and administrationof Kinevac by indication is shown in Table 1. For preparation instructionssee Dosage and Administration (2.2).Table 1: Recommended Adult Dosage and Administration of Kinevacby Treatment IndicationIndicationRecommended Adult Dosageand Administration of KINEVACTo stimulate contraction ofthe gallbladderKinevac 0.02 mcg/kg as single dose over 30 to 60 seconds via intravenousinjection. If satisfactory contraction does not occur in 15 minutes,administer dose of 0.04 mcg/kg over 30 to 60 seconds.Alternatively, Consideran Intravenous Infusion to Reduce Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.3)]: 0.12 mcg/kg diluted in 100 mL of 0.9% Sodium Chloride Injection USPand infused over 50 minutes at rate of mL per minute.To stimulate pancreatic secretionin combination with secretin for injectionSecretin for Injection: 0.25 units/kg as intravenous infusion over60 minutesKinevac:30 minutes after initiation of secretin infusion, administer Kinevac0.02 mcg/kg diluted in 30 mL of 0.9% Sodium Chloride Injection USPand infused over 30 minutes at rate of mL per minute.To accelerate the transit ofa barium meal through the small intestineAfter the barium meal is beyond the proximal jejunum, administerKinevac 0.04 mcg/kg over 30 to 60 seconds via intravenous injection.If satisfactory transit of thebarium meal has not occurred in 30 minutes, administer second doseof 0.04 mcg/kg over 30 to 60 seconds.Alternatively, Consider an IntravenousInfusion to Reduce Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.3)]: 0.12 mcg/kg diluted in 100 mL 0.9% Sodium Chloride Injection USPand infused over 30 minutes.. 2.2 PreparationInstructions. For Intravenous InjectionReconstitute Kinevac aseptically by adding mL of SterileWater for Injection USP to the vial.Inspect the reconstituted solution visually for particulatematter and discoloration after reconstitution and prior to administration.Withdraw the prescribed dose of the reconstituted solutionfrom the vial and administer as an intravenous injection over 30 to60 seconds, as shown in Table 1. Discard the unused portion.Store the reconstituted solution at room temperature. Discard after hours. For single use only; discard unused portion.For IntravenousInfusion Reconstitute Kinevac aseptically by adding mL of SterileWater for Injection USP to the vial.After reconstitution, withdraw the prescribed dose of thesolution from the vial. Discard unused portion.Dilute the reconstituted solution in 30 mL or 100 mL of0.9% Sodium Chloride Injection USP, depending on the indication, asdescribed in Table 1.Inspect the Kinevac solutions visually for particulate matterand discoloration after reconstitution, dilution and prior to administration.Store the diluted solution at room temperature. Discard after hour.. Reconstitute Kinevac aseptically by adding mL of SterileWater for Injection USP to the vial.. Inspect the reconstituted solution visually for particulatematter and discoloration after reconstitution and prior to administration.. Withdraw the prescribed dose of the reconstituted solutionfrom the vial and administer as an intravenous injection over 30 to60 seconds, as shown in Table 1. Discard the unused portion.. Store the reconstituted solution at room temperature. Discard after hours. For single use only; discard unused portion.. Reconstitute Kinevac aseptically by adding mL of SterileWater for Injection USP to the vial.. After reconstitution, withdraw the prescribed dose of thesolution from the vial. Discard unused portion.. Dilute the reconstituted solution in 30 mL or 100 mL of0.9% Sodium Chloride Injection USP, depending on the indication, asdescribed in Table 1.. Inspect the Kinevac solutions visually for particulate matterand discoloration after reconstitution, dilution and prior to administration.. Store the diluted solution at room temperature. Discard after hour.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Anaphylaxis, Anaphylactic Shockand Other Hypersensitivity ReactionsInform patients that hypersensitivity reactions,including anaphylaxis and anaphylactic shock have been reported duringor following administration of Kinevac. Advise patients to reportimmediately to healthcare provider if they experience symptoms ofa hypersensitivity reaction [see Warnings and Precautions(5.1)]. Gastrointestinal Adverse ReactionsAdvise patients thatKinevac may cause transient gastrointestinal symptoms [seeWarnings and Precautions (5.3)].PregnancyAdvise pregnant womenof the potential risk for preterm labor and spontaneous abortion [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)]. U.S. Patent6,803,046Rx onlyManufactured forBracco Diagnostics Inc.Monroe Township, NJ 08831By Jubilant HollisterStier LLCSpokane, WA 99207.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data regarding the presence ofsincalide in human or animal milk, the effects on the breastfed infant,or the effects on milk production. The developmental and health benefitsof breastfeeding should be considered along with the mothers clinicalneed for Kinevac and any potential adverse effect on the breastfedinfant from Kinevac or from the underlying condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. When injected intravenously, sincalide stimulatesgallbladder contraction and reduction in size. The evacuation of bilethat results is similar to that which occurs physiologically in responseto endogenous cholecystokinin. Sincalide also stimulates pancreaticsecretion and intestinal motility causing pyloric contraction andslows gastric emptying.Concurrent administration of sincalide with secretin increases boththe volume of pancreatic secretion and the out-put of bicarbonateand enzymes. This combined effect of secretin and sincalide permitsthe assessment of specific pancreatic function through measurementand analysis of the duodenal aspirate.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term studies in animals havenot been performed to evaluate carcinogenic or mutagenic potential,or possible impairment of fertility in males or females.

OVERDOSAGE SECTION.

10 OVERDOSAGE. In the event of an overdose, symptoms related to vagal stimulation,such as gastrointestinal symptoms (abdominal cramps, nausea, vomitingand diarrhea), hypotension with dizziness or fainting may occur. Overdosagesymptoms should be treated symptomatically and should be of shortduration.A single bolusintravenous injection of 0.05 mcg/kg (approximately to times thehuman dose of 0.02 mcg/kg), sincalide caused hypotension and bradycardiain dogs. In addition, higher doses injected intravenously once orrepeatedly in dogs caused syncope and ECG changes (approximately 5times the human dose of 0.02 mcg/kg). These effects were attributedto sincalide-induced vagal stimulation in that all were preventedby pretreatment with atropine or bilateral vagotomy.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Kinevac5 mcg LabelNDC: 0270-0556-15. Carton.

PEDIATRIC USE SECTION.

8.4 PediatricUse. The safetyand effectiveness in pediatric patients have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Following an intravenous (bolus) injectionof 0.02 mcg/kg of sincalide, maximal contraction of the gallbladderoccurred in to 15 minutes. Sincalide reduced gallbladder radiographicsize by at least 40%, which is generally considered satisfactory contraction.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryBased on limited human data and mechanismof action, sincalide may cause preterm labor or spontaneous abortion [see Warnings and Precautions (5.4)]. Available data with sincalide for injection are insufficientto establish drug-associated risk of major birth defects, miscarriageor adverse maternal or fetal outcomes. In animal embryo-fetal developmentstudies in which sincalide was administered to hamsters and rats duringthe period of organogenesis, no effects were seen at doses comparableto the maximum recommended clinical dose on mg/kg basis. However,in prenatal development study in which rats were administered sincalideduring organogenesis through parturition, decreased weight gain anddevelopmental delays were observed at dose 122 times higher thanthe maximum recommended human dose based on body surface area.The estimated background riskof major birth defects and miscarriage for the indicated populationis unknown. All pregnancies have background risk of birth defect,loss, or other adverse outcomes. In the U.S. general population, theestimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is to 4% and 15 to 20%, respectively. DataAnimal DataThere were no effects on embryo-fetaldevelopment in hamsters when sincalide was administered subcutaneouslyat 250 or 750 ng/kg during organogenesis (Gestation Days to 13)at doses up to 0.8 times the maximum recommended dose of 120 ng/kgon body surface area basis. No effects on embryo-fetal developmentwere observed in Sprague-Dawley rats at subcutaneous doses of 250,450, or 750 ng/kg from Gestation Days to16, representing 1.0 timethe maximum recommended human dose on body surface area basis. Ina separate study at higher dose of 90 mcg/kg administered subcutaneouslyto CFY rats from Gestation Day 10 through parturition (representing122 times the maximum recommended human dose on body surface areabasis), offspring showed decreased growth, behavioral changes, anddevelopmental delays.

RECENT MAJOR CHANGES SECTION.

Contraindications (4)03/2018Warnings and Precautions (5.1)03/2018.

SPL UNCLASSIFIED SECTION.

2.1 Recommended Dosage and Administration Instructions. The recommended dosage and administrationof Kinevac by indication is shown in Table 1. For preparation instructionssee Dosage and Administration (2.2).Table 1: Recommended Adult Dosage and Administration of Kinevacby Treatment IndicationIndicationRecommended Adult Dosageand Administration of KINEVACTo stimulate contraction ofthe gallbladderKinevac 0.02 mcg/kg as single dose over 30 to 60 seconds via intravenousinjection. If satisfactory contraction does not occur in 15 minutes,administer dose of 0.04 mcg/kg over 30 to 60 seconds.Alternatively, Consideran Intravenous Infusion to Reduce Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.3)]: 0.12 mcg/kg diluted in 100 mL of 0.9% Sodium Chloride Injection USPand infused over 50 minutes at rate of mL per minute.To stimulate pancreatic secretionin combination with secretin for injectionSecretin for Injection: 0.25 units/kg as intravenous infusion over60 minutesKinevac:30 minutes after initiation of secretin infusion, administer Kinevac0.02 mcg/kg diluted in 30 mL of 0.9% Sodium Chloride Injection USPand infused over 30 minutes at rate of mL per minute.To accelerate the transit ofa barium meal through the small intestineAfter the barium meal is beyond the proximal jejunum, administerKinevac 0.04 mcg/kg over 30 to 60 seconds via intravenous injection.If satisfactory transit of thebarium meal has not occurred in 30 minutes, administer second doseof 0.04 mcg/kg over 30 to 60 seconds.Alternatively, Consider an IntravenousInfusion to Reduce Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.3)]: 0.12 mcg/kg diluted in 100 mL 0.9% Sodium Chloride Injection USPand infused over 30 minutes.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryBased on limited human data and mechanismof action, sincalide may cause preterm labor or spontaneous abortion [see Warnings and Precautions (5.4)]. Available data with sincalide for injection are insufficientto establish drug-associated risk of major birth defects, miscarriageor adverse maternal or fetal outcomes. In animal embryo-fetal developmentstudies in which sincalide was administered to hamsters and rats duringthe period of organogenesis, no effects were seen at doses comparableto the maximum recommended clinical dose on mg/kg basis. However,in prenatal development study in which rats were administered sincalideduring organogenesis through parturition, decreased weight gain anddevelopmental delays were observed at dose 122 times higher thanthe maximum recommended human dose based on body surface area.The estimated background riskof major birth defects and miscarriage for the indicated populationis unknown. All pregnancies have background risk of birth defect,loss, or other adverse outcomes. In the U.S. general population, theestimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is to 4% and 15 to 20%, respectively. DataAnimal DataThere were no effects on embryo-fetaldevelopment in hamsters when sincalide was administered subcutaneouslyat 250 or 750 ng/kg during organogenesis (Gestation Days to 13)at doses up to 0.8 times the maximum recommended dose of 120 ng/kgon body surface area basis. No effects on embryo-fetal developmentwere observed in Sprague-Dawley rats at subcutaneous doses of 250,450, or 750 ng/kg from Gestation Days to16, representing 1.0 timethe maximum recommended human dose on body surface area basis. Ina separate study at higher dose of 90 mcg/kg administered subcutaneouslyto CFY rats from Gestation Day 10 through parturition (representing122 times the maximum recommended human dose on body surface areabasis), offspring showed decreased growth, behavioral changes, anddevelopmental delays.. 8.2 Lactation. Risk SummaryThere are no data regarding the presence ofsincalide in human or animal milk, the effects on the breastfed infant,or the effects on milk production. The developmental and health benefitsof breastfeeding should be considered along with the mothers clinicalneed for Kinevac and any potential adverse effect on the breastfedinfant from Kinevac or from the underlying condition.. 8.4 PediatricUse. The safetyand effectiveness in pediatric patients have not been established.. 8.5 GeriatricUse. Clinicalstudies of Kinevac did not include sufficient numbers of subjectsaged 65 and over to determine whether they respond differently fromyounger subjects.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Anaphylaxis, Anaphylactic Shock and Other HypersensitivityReactions: May occur during or soon after administration. If symptoms occur, discontinue the drug. (4, 5.1)Evacuation of Gallstones: Stimulationof gallbladder contraction in patients with small gallbladder stonescould lead to the evacuation of the stones from the gallbladder, resultingin their lodging in the cystic duct or in the common bile duct. (5.2)Gastrointestinal Adverse Reactions with IntravenousInjection: Administration as an intravenous injectionmay cause transient nausea, vomiting, abdominal pain or cramping,dizziness or flushing. To reduce the risk of adverse reactions whenused to simulate contraction of the gallbladder or accelerate transitof barium meal through the small intestine, administer as an intravenousinfusion over 50 or 30 minutes, respectively. (2.1, 5.3)Preterm Labor or Spontaneous Abortion: Advise pregnant women of the potential risk for preterm laborand spontaneous abortion. (5.4, 8.1). Anaphylaxis, Anaphylactic Shock and Other HypersensitivityReactions: May occur during or soon after administration. If symptoms occur, discontinue the drug. (4, 5.1). Evacuation of Gallstones: Stimulationof gallbladder contraction in patients with small gallbladder stonescould lead to the evacuation of the stones from the gallbladder, resultingin their lodging in the cystic duct or in the common bile duct. (5.2). Gastrointestinal Adverse Reactions with IntravenousInjection: Administration as an intravenous injectionmay cause transient nausea, vomiting, abdominal pain or cramping,dizziness or flushing. To reduce the risk of adverse reactions whenused to simulate contraction of the gallbladder or accelerate transitof barium meal through the small intestine, administer as an intravenousinfusion over 50 or 30 minutes, respectively. (2.1, 5.3). Preterm Labor or Spontaneous Abortion: Advise pregnant women of the potential risk for preterm laborand spontaneous abortion. (5.4, 8.1). 5.1 Anaphylaxis, Anaphylactic Shock and Other Hypersensitivity Reactions In postmarketingexperience, anaphylaxis, anaphylactic shock and other serious hypersensitivityreactions have been reported during and within one hour followingadministration of Kinevac [see Adverse Reactions (6)].Due to thepotential for anaphylaxis, appropriate medical support should be readilyavailable when Kinevac is administered. If anaphylaxis or other hypersensitivityreactions occur, immediately discontinue the infusion and initiateappropriate medical treatment. Observe patients closely during andafter the infusion. Do not reinitiate Kinevac in patients who haveexperienced symptoms of hypersensitivity [see Contraindications(4)].. 5.2 Evacuationof Gallstones. Stimulation of gallbladder contraction in patients with small gallbladderstones could lead to the evacuation of the stones from the gallbladder,resulting in their lodging in the cystic duct or in the common bileduct. 5.3 Gastrointestinal Adverse Reactions with Intravenous Injection. Administration of Kinevac as anintravenous injection may cause adverse reactions such as nausea,vomiting, abdominal pain or cramping, dizziness, and flushing [see Adverse Reactions (6)]. These reactions are generally transient. To reduce the risk ofadverse reactions with intravenous injection when used to simulatecontraction of the gallbladder or accelerate transit of barium mealthrough the small intestine, administer Kinevac as an intravenousinfusion over 50 or 30 minutes, respectively [see Dosage andAdministration (2.1)].. 5.4 PretermLabor or Spontaneous Abortion. Because of Kinevacs effect on smooth muscle,pregnant patients should be advised that spontaneous abortion or prematureinduction of labor may occur [see Use in Specific Populations(8.1)].