Professional Drug Information > Sincalide

Sincalide (Systemic)

VA CLASSIFICATION
Primary: HS900
Secondary: DX900

Commonly used brand name(s): Kinevac.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Cholecystokinetic—

Diagnostic aid (gallbladder function; pancreatic function)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Gallbladder disorders (diagnosis) or
Pancreas disorders (diagnosis)—Sincalide is indicated as a diagnostic aid for evaluation of gallbladder and pancreatic disorders. It is used to stimulate gallbladder contraction and emptying prior to or during cholecystography with contrast media or hepatobiliary scintigraphy (e.g., using technetium Tc 99m–labeled iminodiacetic acid derivatives) to aid in visualization of the cystic duct and gallbladder. Also, gallbladder contraction provides a sample of bile that may be aspirated from the duodenum for analysis of its composition (for example, to determine the degree of cholesterol saturation). ^{{01} {02} {04} {05} {06} {07} {08} {09} {10} {12}}
—In conjuction with secretin, sincalide is used to stimulate pancreatic secretion for analysis of its composition and cytological examination, such as in suspected cancer of the pancreas. ^{{01} {04}}
—Sincalide is used to accelerate small bowel transit time of contrast media, such as barium sulfate, thus decreasing the time and extent of radiation associated with fluoroscopy and x-ray examination of the intestinal tract. ^{{01} {02} {04}}

[Ileus, postoperative (treatment)]—Sincalide is used to restore normal bowel activity in patients with postoperative ileus uncomplicated by inflammatory processes such as pancreatitis and peritonitis, or by the presence of tumors or other obstructions in the lower digestive tract. ^{04}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Sincalide, a synthetically-prepared C-terminal octapeptide of the natural hormone cholecystokinin, induces contraction of the gallbladder muscle, resulting in reduction of gallbladder size and evacuation of bile. Also, sincalide, like cholecystokinin, stimulates secretion of pancreatic enzymes. ^{{02} {03} {04} {09} {10} {11}}

Other actions

Sincalide decreases intestinal transit time; delays gastric emptying; decreases esophageal sphincter tone; inhibits gastric secretions; and stimulates intestinal muscle. ^{{02} {03} {11}}

Time to peak effect:

Maximum contraction (³ 40% reduction in size) of gallbladder occurs 5 to 15 minutes after injection. ^{{03} {04} {09}}

Duration of action:

Gallbladder returns to basal size within 1 hour. ^{03}


Precautions to Consider

Pregnancy/Reproduction
Fertility—
Although adequate studies in humans have not been done, studies in animals have not shown that sincalide causes impairment of fertility. ^{01}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. ^{01}

Studies in rats given doses up to 12.5 times the maximum recommended human dose have not shown that sincalide causes adverse effects in the fetus. ^{01}

FDA Pregnancy Category B. ^{01}

Labor—

Although adequate studies in humans have not been done, sincalide should not be administered to pregnant women near term since sincalide, a smooth muscle stimulant, may induce spontaneous abortion or premature labor. ^{01}

Breast-feeding

It is not known whether sincalide is distributed into breast milk. However, problems in humans have not been documented. ^{01}

Pediatrics

Appropriate studies on the relationship of age to the effects of sincalide have not been performed in the pediatric population. Safety and efficacy have not been established. ^{01}


Geriatrics


No information is available on the relationship of age to the effects of sincalide in geriatric patients.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Intestinal obstruction    (condition may be aggravated ^{{01} {02}})


Risk-benefit should be considered when the following medical problems exist
Gallbladder stones    (stimulation of gallbladder contraction in patients with small gallbladder stones may lead to the evacuation of the stones from the gallbladder resulting in their lodging in the cystic duct or in the common bile duct; however, this is unlikely with usual doses of sincalide since complete contraction of the gallbladder is not induced ^{{01} {09}})


Sensitivity to sincalide^{01}{03}{04}




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Allergic reaction (shortness of breath, skin rash)
    
hypotension (dizziness, lightheadedness, or fainting)
    
increase in blood pressure^{01}{04}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Gastrointestinal effects (nausea, abdominal or stomach pain, cramps, or discomfort)—20%^{01}{04}

Incidence less frequent
    
Diarrhea
    
dizziness
    
flushing or redness of skin
    
headache
    
increased sweating
    
numbness
    
sneezing
    
urge to have bowel movement
    
vomiting^{01}


Note: The less frequent side effects listed occur in less than 1% of patients, except for diarrhea, which occurs in about 2% of patients.
The above side effects are generally mild and of short duration; they are usually lessened by a slower injection rate. ^{01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sincalide (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Procedure for sincalide test: Dose of sincalide is based on body weight and must be determined by doctor; sincalide is injected intravenously

Before having this test
»   Conditions affecting use, especially:
Sensitivity to sincalide
Other medical problems, especially gallbladder stones and intestinal obstruction

Preparation for this test
Special preparatory instructions may be given; patient should inquire in advance


Side/adverse effects
Signs of potential side effects, especially allergic reaction, hypertension, and hypotension


General Dosing Information

For use in hepatobiliary imaging
During hepatobiliary imaging with technetium Tc 99m–labeled iminodiacetic acid (IDA) derivatives, prolonged fasting (e.g., more than 24 hours) may result in a false-positive hepatobiliary scan (i.e., nonvisualization of the gallbladder despite a patent cystic duct) due to the development of increased intraluminal gallbladder pressure (biliary stasis or sludge), which reduces radiotracer flow to the gallbladder. To avoid this, prior administration of sincalide (0.02 to 0.04 mcg per kg of body weight [mcg/kg]), to induce contraction of the gallbladder, is recommended for pre-emptying the gallbladder before the injection of the radiotracer. Whenever there is doubt about the dietary history of the patient, especially in emergency situations, a cholecystokinetic agent should be administered. ^{{05} {07} {12}}

In patients receiving parenteral alimentation, the relative inactivity of the gallbladder results in bile stasis and the formation of thick viscous bile (sludge), which reduces the flow of the radiotracer into the gallbladder. Pretreatment with intravenous sincalide (0.02 to 0.04 mcg/kg administered slowly over a thirty- to sixty-second interval) may be useful to empty stored bile from the gallbladder, and thus may prevent a false-positive hepatobiliary scan. ^{{05} {06} {07} {12}}

In patients demonstrating radiotracer localization in the gallbladder, intravenous sincalide (0.02 to 0.04 mcg/kg) may be useful to stimulate gallbladder contraction, and thereby, evaluate the contractile function of the gallbladder. Quantitation of gallbladder emptying yields the ejection fraction (³ 35% is usually considered normal). ^{{07} {08}}


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

SINCALIDE FOR INJECTION

Usual adult and adolescent dose
Gallbladder function diagnosis


For prompt contraction of gallbladder:
Intravenous, 0.02 mcg per kg of body weight, administered over a thirty- to sixty-second period. ^{{01} {04}}

Note: If satisfactory gallbladder contraction does not occur in fifteen minutes, a second dose of 0.04 mcg per kg of body weight may be administered. ^{02}
When used in cholecystography, radiographs are usually taken at five-minute intervals after the injection. However, for visualization of the cystic duct, it is recommended that radiographs be taken at one-minute intervals during the first five minutes after the injection. ^{01}
For reduction of side effects, an intravenous infusion of sincalide (0.12 mcg per kg of body weight diluted with 0.9% Sodium Chloride Injection USP to approximately 100 mL) may be administered at a rate of 2 mL per minute; alternatively, 0.1 mcg per kg of body weight may be used intramuscularly. ^{01}



Pancreatic function diagnosis
Intravenous infusion, 0.02 mcg per kg of body weight, administered over a thirty-minute period. ^{01}

Note: Sincalide is administered, as a separate intravenous infusion, thirty minutes after the patient has started receiving secretin (0.25 units per kg of body weight) by intravenous infusion over a sixty-minute period. ^{01}


To accelerate small bowel transit time of barium sulfate
Intravenous, 0.04 mcg per kg of body weight, administered over a thirty- to sixty-second period after the barium meal is beyond the proximal jejunum. ^{01}

[Treatment of postoperative ileus]
Intravenous, 0.04 mcg per kg of body weight, administered over a thirty- to sixty-second period. ^{04}

Note: Dose may be repeated or increased to 0.08 mcg per kg of body weight at 4-hour intervals, up to a maximum of five doses of sincalide. ^{04}



Usual pediatric dose
Safety and efficacy have not been established. ^{01}

Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


5 mcg (0.005 mg) (Rx) [Kinevac]^{01}

Canada—


5 mcg (0.005 mg) (Rx) [Kinevac^{04}]

Packaging and storage:
Store between 15 and 30 °C (59 to 86 °F), unless otherwise specified by manufacturer. ^{01}

Preparation of dosage form:
To prepare injection, 5 mL of Sterile Water for Injection USP is added to the vial containing sincalide. Additional dilutions should be made with 0.9% Sodium Chloride Injection USP. ^{01}

Stability:


Following reconstitution of:
U.S. product: Sincalide injection is stable for 24 hours at room temperature. ^{03}

Canadian product: Sincalide injection may be stored under refrigeration for up to 24 hours. ^{01}

Developed: 02/27/1995

References

1. Kinevac package insert (Squibb—US), Rev 3/92, Rec 10/7/94.
   

2. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 30th ed. London: The Pharmaceutical Press, 1993: 778.
   

3. McEvoy GK, editor. AHFS Drug information 94. Bethesda, MD: American Society of Hospital Pharmacists, 1994: 1555-6.
   

4. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 663.
   

5. Fink-Bennett D. Augmented cholescintigraphy: its role in detecting acute and chronic disorders of the hepatobiliary tree. Semin Nucl Med 1991; 21(2): 128-39.
   

6. Krishnamurthy GT, Turner FE. Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med 1990; 20(2): 130-49.
   

7. Reviewers' comments per technetium Tc 99m disofenin monograph revision of 11/03/92.
   

8. Hepatobiliary imaging protocol as of 03/91 sent by USP Radiopharmaceuticals Advisory panelist.
   

9. Sargent EN, Meyers HI, Hubsher J. Cholecystokinetic cholecystography: efficacy and tolerance study of sincalide. Am J Roentgenol 1976; 127: 267-71.
   

10. Pickleman J, Peiss RL, Henkin R, et al. The role of sincalide cholescintigraphy in the evaluation of patients with acalculous gallbladder disease. Arch Surg 1985; 120: 693-7.
    

11. Guyton AC. Textbook of medical physiology. 7th ed. Philadelphia: W.B. Saunders, 1986: 778-82.
    

12. Reviewers' responses to monograph draft of 10/10/94.