Document
DailyMed Label: KINEVAC
Title
DailyMed Label: KINEVAC
Date
2023
Document type
DailyMed Prescription
Name
KINEVAC
Generic name
sincalide
Manufacturer
Bracco Diagnostics Inc.
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Product information
NDC: 0270-0556
Description
Kinevac (sincalide for injection)
is a cholecystopancreatic-gastrointestinal hormone for parenteral
administration. The agent is a synthetically-prepared C-terminal octapeptide
of cholecystokinin.
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:
kinevac-struct
Indications
Kinevac is indicated in adults to:
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;
to stimulate pancreatic secretion in combination with secretin
prior to obtaining a duodenal aspirate for analysis of enzyme activity,
composition, and cytology;
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.
Kinevac is a cholecystokinin (CCK) analog indicated in adults 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. ( 1 )
stimulate pancreatic secretion in combination with secretin prior to obtaining a duodenal aspirate for analysis of enzyme activity, composition, and cytology. ( 1 )
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. ( 1 )
Dosage
Recommended Adult Dosage and
Administration by Indication:
To Stimulate Contraction
of the Gallbladder
0.02 mcg/kg as a single dose over 30 to 60 seconds via intravenous
injection. If satisfactory contraction does not occur in 15 minutes,
administer a dose of 0.04 mcg/kg over 30 to 60 seconds. ( 2.1 )
Alternatively consider an intravenous infusion to
reduce gastrointestinal adverse reactions : 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. ( 2.1 , 2.2 , 5.3 )
To Stimulate Pancreatic
Secretion in Combination with Secretin
30 minutes after initiation of secretin for injection, administer
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. ( 2.1 , 2.2 )
To Accelerate Transit
of a Barium Meal Through the Small Intestine
After the barium meal is beyond the proximal jejunum, administer
0.04 mcg/kg over 30 to 60 seconds via intravenous injection. ( 2.1 )
If satisfactory transit of the barium meal has not occurred
in 30 minutes, administer a second dose of 0.04 mcg/kg over 30 to
60 seconds. ( 2.1 )
Alternatively consider an intravenous infusion to
reduce gastrointestinal adverse reactions : 0.12 mcg/kg diluted
in 100 mL 0.9% Sodium Chloride Injection USP and infused over 30 minutes.
( 2.1 , 2.2 , 5.3 )
The recommended dosage and administration
of Kinevac by indication is shown in Table 1. For preparation instructions
see Dosage and Administration ( 2.2 ) .
Table 1: Recommended Adult Dosage and Administration of Kinevac by
Treatment Indication
Indication
Recommended Adult Dosage
and Administration of KINEVAC
To stimulate contraction of
the gallbladder
Kinevac 0.02 mcg/kg as a single dose over 30 to 60 seconds via intravenous
injection. If satisfactory contraction does not occur in 15 minutes,
administer a dose of 0.04 mcg/kg over 30 to 60 seconds.
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
Secretin for Injection: 0.25 units/kg as intravenous infusion over
60 minutes
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
After the barium meal is beyond the proximal jejunum, administer
Kinevac 0.04 mcg/kg over 30 to 60 seconds via intravenous injection.
If satisfactory transit of the
barium meal has not occurred in 30 minutes, administer a second dose
of 0.04 mcg/kg over 30 to 60 seconds.
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.
For Intravenous Injection
Reconstitute Kinevac aseptically by adding 5 mL of Sterile Water for Injection USP to the vial.
Inspect the reconstituted solution visually for particulate matter and discoloration after reconstitution and prior to administration.
Withdraw the prescribed dose of the reconstituted solution from the vial and administer as an intravenous injection over 30 to 60 seconds, as shown in Table 1. Discard the unused portion.
Store the reconstituted solution at room temperature.
Discard after 8 hours.
For single use only; discard unused portion.
For Intravenous Infusion
Reconstitute Kinevac aseptically by adding 5 mL of Sterile Water for Injection USP to the vial.
After reconstitution, withdraw the prescribed dose of the solution from the vial. Discard unused portion.
Dilute the reconstituted solution in 30 mL or 100 mL of 0.9% Sodium Chloride Injection USP, depending on the indication, as described in Table 1.
Inspect the Kinevac solutions visually for particulate matter and discoloration after reconstitution, dilution and prior to administration.
Store the diluted solution at room temperature.
Discard after 1 hour
.
Dosage forms
For injection: 5 mcg of sincalide
as a lyophilized white powder for reconstitution in a single-dose
vial.
For injection: 5 mcg of sincalide
as a lyophilized powder in a single-dose vial for reconstitution ( 3 )
Contraindications
KINEVAC is contraindicated
in patients with:
a history of hypersensitivity to sulfites
or sincalide. Serious hypersensitivity reactions have included anaphylaxis
and anaphylactic shock [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6 )] .
intestinal obstruction.
History of hypersensitivity to sulfites or sincalide. ( 4 , 5.1 )
Intestinal obstruction. ( 4 )
Warnings
Anaphylaxis, Anaphylactic Shock and Other Serious Hypersensitivity
Reactions : Contains sodium metabisulfite. Serious reactions
may occur during or soon after administration. If symptoms occur,
discontinue the drug. ( 4 , 5.1 )
Evacuation of Gallstones : 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. ( 5.2 )
Gastrointestinal Adverse Reactions with Intravenous
Injection : Administration as an intravenous injection
may cause transient nausea, vomiting, abdominal pain or cramping,
dizziness or flushing. To reduce the risk of adverse reactions when
used to stimulate contraction of the gallbladder or accelerate transit
of a barium meal through the small intestine, administer as an intravenous
infusion over 50 or 30 minutes, respectively. ( 2.1 , 5.3 )
Preterm Labor or Spontaneous Abortion : Advise pregnant women of the potential risk for preterm labor and
spontaneous abortion. ( 5.4 , 8.1 )
Contains sodium
metabisulfite [see Description ( 11 )] , a sulfite that may cause allergic-type reactions including
anaphylactic symptoms and life-threatening or less severe asthmatic
episodes in certain susceptible people. The overall prevalence of
sulfite sensitivity in the general population is unknown and probably
low. Sulfite sensitivity is seen more frequently in asthmatic than
in non-asthmatic people.
In postmarketing experience,
anaphylaxis, anaphylactic shock and other serious hypersensitivity
reactions have been reported during and within one hour following
administration of Kinevac [see Adverse Reactions ( 6 )] .
Kinevac is
contraindicated in patients with a history of hypersensitivity to
sulfites. Due to the potential for anaphylaxis, appropriate medical
support should be readily available when Kinevac is administered.
If anaphylaxis or other hypersensitivity reactions occur, immediately
discontinue the infusion and initiate appropriate medical treatment.
Observe patients closely during and after the infusion. Do not reinitiate
Kinevac in patients who have experienced symptoms of hypersensitivity [see Contraindications ( 4 )] .
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 stimulate 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 ) ].
Adverse reactions
The following clinically significant adverse
reactions are described elsewhere in labeling:
Drug interactions
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 )
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 stimulate contraction of the gallbladder.
Use in_specific_populations
Risk Summary
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.
Data
Animal Data
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.
Risk Summary
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.
The safety
and effectiveness in pediatric patients have not been established.
Clinical
studies of Kinevac did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from
younger subjects.
How supplied
Kinevac (sincalide for injection) is supplied
as 5 mcg of sincalide as a lyophilized white powder for reconstitution
in a single-dose vial; in packages of 10 vials (NDC 0270-0556-15).
Store at 25° C (77° F); excursions
permitted to 15-30° C (59-86° F) [See USP Controlled Room Temperature].
Clinical pharmacology
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.
Following an intravenous (bolus) injection
of 0.02 mcg/kg of sincalide, maximal contraction of the gallbladder
occurred in 5 to 15 minutes. Sincalide reduced gallbladder radiographic
size by at least 40%, which is generally considered satisfactory contraction.
Nonclinical toxicology
Long-term studies in animals have
not been performed to evaluate carcinogenic or mutagenic potential,
or possible impairment of fertility in males or females.
Package label
Kinevac
5 mcg Vial Label NDC: 0270-0556-15
kinevac vial label-fk-403895
1 organization
1 product
Product
sincalideOrganization
Bracco Diagnostics Inc.