KINEVAC- sincalide injection, powder, lyophilized, for solution
Bracco Diagnostics Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use KINEVAC safely and effectively. See full prescribing information for KINEVAC
KINEVAC (sincalide for injection), for intravenous use Initial U.S. Approval: 1976
INDICATIONS AND USAGE
Kinevac is a cholecystokinin (CCK) analog indicated in adults to:
DOSAGE AND ADMINISTRATION
Recommended Adult Dosage and
Administration by Indication:
To Stimulate Pancreatic Secretion in Combination with Secretin
To Accelerate Transit of a Barium Meal Through the Small Intestine
DOSAGE FORMS AND STRENGTHS
For injection: 5 mcg of sincalide as a lyophilized powder in a single-dose vial for reconstitution (3)
WARNINGS AND PRECAUTIONS
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.
Drugs that Affect Gallbladder Motility or Contractile Response: May interfere with response to sincalide. Consider discontinuing these drugs prior to administration of Kinevac, when used to stimulate contraction of the gallbladder. (7.1)
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
The recommended dosage and administration of Kinevac by indication is shown in Table 1. For preparation instructions see Dosage and Administration (2.2).
|Indication||Recommended Adult Dosage and Administration of KINEVAC|
|To stimulate contraction of the gallbladder||
Alternatively, Consider an 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 USP and infused over 50 minutes at a rate of 2 mL per minute.
|To stimulate pancreatic secretion in combination with secretin for injection||
Kinevac: 30 minutes after initiation of secretin infusion, administer Kinevac 0.02 mcg/kg diluted in 30 mL of 0.9% Sodium Chloride Injection USP and infused over 30 minutes at a rate of 1 mL per minute.
|To accelerate the transit of a barium meal through the small intestine||
Alternatively, Consider an Intravenous Infusion to Reduce Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.3)]: 0.12 mcg/kg diluted in 100 mL 0.9% Sodium Chloride Injection USP and infused over 30 minutes.
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.
Administration of Kinevac as an intravenous 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 of adverse reactions with intravenous injection when used to simulate contraction of the gallbladder or accelerate transit of a barium meal through the small intestine, administer Kinevac as an intravenous infusion over 50 or 30 minutes, respectively [see Dosage and Administration (2.1)].
Because of Kinevac’s effect on smooth muscle, pregnant patients should be advised that spontaneous abortion or premature induction of labor may occur [see Use in Specific Populations (8.1)].
The following adverse reactions associated with the use of Kinevac were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure.
The most frequent adverse reactions (20% or greater) are gastrointestinal: abdominal discomfort or pain, and nausea; these may not necessarily indicate an abnormality of the biliary tract unless there is other clinical or radiologic evidence of disease.
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)].
Drugs that may stimulate or inhibit gallbladder motility or contractile response may interfere with the response to sincalide. Consider discontinuing these drugs prior to administration of Kinevac, when used to simulate contraction of the gallbladder.
Based on limited human data and mechanism of action, sincalide may cause preterm labor or spontaneous abortion [see Warnings and Precautions (5.4)]. Available data with sincalide for injection are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal embryo-fetal development studies in which sincalide was administered to hamsters and rats during the period of organogenesis, no effects were seen at doses comparable to the maximum recommended clinical dose on a mg/kg basis. However, in a prenatal development study in which rats were administered sincalide during organogenesis through parturition, decreased weight gain and developmental delays were observed at a dose 122 times higher than the maximum recommended human dose based on body surface area.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
There were no effects on embryo-fetal development in hamsters when sincalide was administered subcutaneously at 250 or 750 ng/kg during organogenesis (Gestation Days 7 to 13) at doses up to 0.8 times the maximum recommended dose of 120 ng/kg on a body surface area basis. No effects on embryo-fetal development were observed in Sprague-Dawley rats at subcutaneous doses of 250, 450, or 750 ng/kg from Gestation Days 6 to16, representing 1.0 time the maximum recommended human dose on a body surface area basis. In a separate study at a higher dose of 90 mcg/kg administered subcutaneously to CFY rats from Gestation Day 10 through parturition (representing 122 times the maximum recommended human dose on a body surface area basis), offspring showed decreased growth, behavioral changes, and developmental delays.
There are no data regarding the presence of sincalide in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Kinevac and any potential adverse effect on the breastfed infant from Kinevac or from the underlying condition.
In the event of an overdose, symptoms related to vagal stimulation, such as gastrointestinal symptoms (abdominal cramps, nausea, vomiting and diarrhea), hypotension with dizziness or fainting may occur. Overdosage symptoms should be treated symptomatically and should be of short duration.
A single bolus intravenous injection of 0.05 mcg/kg (approximately 2 to 3 times the human dose of 0.02 mcg/kg), sincalide caused hypotension and bradycardia in dogs. In addition, higher doses injected intravenously once or repeatedly in dogs caused syncope and ECG changes (approximately 5 times the human dose of 0.02 mcg/kg). These effects were attributed to sincalide-induced vagal stimulation in that all were prevented by pretreatment with atropine or bilateral vagotomy.
Each single-dose vial of sincalide provides a sterile nonpyrogenic lyophilized white powder consisting of 5 mcg sincalide with 30 mg arginine hydrochloride, 15 mg lysine hydrochloride, 170 mg mannitol, 4 mg methionine, 2 mg pentetic acid, 0.005 mcg polysorbate 20, 9 mg potassium phosphate dibasic, and 0.04 mg sodium metabisulfite.
The pH is adjusted to 6.0 to 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 stimulates gallbladder contraction and reduction in size. The evacuation of bile that results is similar to that which occurs physiologically in response to endogenous cholecystokinin. Sincalide also stimulates pancreatic secretion and intestinal motility causing pyloric contraction and slows gastric emptying.
Concurrent administration of sincalide with secretin increases both the volume of pancreatic secretion and the out-put of bicarbonate and enzymes. This combined effect of secretin and sincalide permits the assessment of specific pancreatic function through measurement and analysis of the duodenal aspirate.
Inform patients that hypersensitivity reactions, including anaphylaxis and anaphylactic shock have been reported during or following administration of Kinevac. Advise patients to report immediately to a healthcare provider if they experience symptoms of a hypersensitivity reaction [see Warnings and Precautions (5.1)].
Advise patients that Kinevac may cause transient gastrointestinal symptoms [see Warnings and Precautions (5.3)].
sincalide injection, powder, lyophilized, for solution
|Labeler - Bracco Diagnostics Inc. (849234661)|
|Registrant - Bracco Diagnostics Inc. (849234661)|
|Jubilant HollisterStier LLC||069263643||ANALYSIS(0270-0556) , MANUFACTURE(0270-0556)|
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