Cholecystokinin (Systemic)


BAN:
Pancreozymin {04}

VA CLASSIFICATION
Primary: HS900
Secondary: DX900

Other commonly used names are:
CCK and pancreozymin .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.



Category:


Cholecystokinetic—

diagnostic aid (gallbladder disorders; pancreatic disorders)—

peristaltic stimulant—

Indications

Accepted

Cholecystography, oral, adjunct or
Cholangiography adjunct—Cholecystokinin is indicated as a diagnostic aid for evaluation of gallbladder disorders. It is used to stimulate gallbladder contraction and emptying prior to, or during, cholecystography with contrast media to aid in visualization of the cystic duct and gallbladder. As part of oral cholecystography or preoperative cholangiography, cholecystokinin facilitates the evaluation of the contractile patterns of the gallbladder, filling of the bile ducts, flow of contrast medium into the duodenum, and localization of gallstones in the lower common bile duct. {02} {03} {09} {13} {14} {17} {20} {21} {24}
—Although cholangiography is an acceptable procedure for visualizing the biliary ducts, it has generally been replaced by cholescintigraphy, in which a radioisotope-labeled substance that is rapidly excreted into the bile (e.g., a technetium Tc 99m–labeled iminodiacetic acid derivative) is used. Cholescintigraphy is the preferred method rather than cholangiography, especially in patients in whom acute cholecystitis is suspected. {05} {06} {07} {08} {10} {11} {12} {13} {14} {17} {18}

Small intestine studies—Cholecystokinin is indicated to accelerate small bowel transit time of contrast media, such as barium sulfate, thus decreasing transit time and flocculation of the barium meal. {03} {09} {19} {23}

Pancreatic insufficiency (diagnosis adjunct)—In conjunction with secretin, cholecystokinin is indicated in the diagnosis of pancreatic insufficiency. {01} {02} {03} {09}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Cholecystokinetic and

Diagnostic aid (gallbladder disorders)—Cholecystokinin, a natural polypeptide formed in the amine precursor uptake and decarboxylation (APUD) cells of the proximal mucosa of the small intestine, induces contraction of the gallbladder muscle, resulting in reduction of gallbladder size and evacuation of bile. {01} {02} {03} {11} {14} {16}

Diagnostic aid (pancreatic disorders)—Cholecystokinin stimulates secretion of pancreatic digestive enzymes and secretion from the glands of Brunner. {01} {02} {03} {09}

Peristaltic stimulant—Cholecystokinin increases muscle contractions of the stomach and small intestine. {01} {03} {09} {11} {19} {23} {24}


Other actions/effects:

Cholecystokinin inhibits contraction of the lower esophageal sphincter and the sphincter of Oddi. {01} {03} {09} {11}

Onset of action:

Contraction of the gallbladder—Within 1 to 3 minutes. {01} {03} {24}

Peristaltic stimulant—1 to 2 minutes. {19} {23}

Time to peak effect

Contraction of gallbladder—5 to 15 minutes after injection. {11} {15} {22}

Duration of action:

Contraction of gallbladder—Approximately 2 hours or more. {03}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Although adequate studies in humans have not been done, cholecystokinin should not be administered to pregnant women near term because it is a smooth muscle stimulant and may induce spontaneous abortion or premature labor. {15} {24}

Breast-feeding

It is not known whether cholecystokinin is distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of cholecystokinin have not been performed in the pediatric population.


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of cholecystokinin in the elderly. {10} {11} {17} {20}

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    (stimulation of gastrointestinal motility may aggravate condition {15} {19} {24})


Risk-benefit should be considered when the following medical problem exists
Sensitivity to the cholecystokinin preparation{02}{15}


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 only if they continue or are bothersome
Incidence more frequent
    
Flushing or redness of skin{01}{02}{03} —with rapid administration
    
gastrointestinal effects (abdominal or stomach pain, cramps, or discomfort)





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

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

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

Before having this test
»   Conditions affecting use, especially:
Sensitivity to the cholecystokinin preparation

Pregnancy—Use not recommended; may induce spontaneous abortion or premature labor {15} {24}
Other medical problems, especially intestinal obstruction

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


Parenteral Dosage Forms

CHOLECYSTOKININ FOR INJECTION

Usual adult and adolescent dose
Cholecystokinetic or
Diagnostic aid (gallbladder disorders)


Cholecystography:


For prompt contraction of gallbladder—
Intravenous, 1 Ivy dog unit (IDU) (0.1 mL) per kg of body weight, administered slowly over 30 to 60 seconds. {03} {09} {11}

Note: For oral cholecystography, the patient should be given the contrast medium on the evening before the examination. Fluoroscopy is recommended before the x-ray examination. If the gallbladder is visible, cholecystokinin may be injected. {01} {03}
For cholescintigraphy, prior administration of cholecystokinin is recommended for pre-emptying the gallbladder before the injection of the radiotracer (e.g., a technetium Tc 99m–labeled iminodiacetic acid derivative). {05} {06} {07} {08} {10} {11} {12} {13} {14} {17} {18} {21}





Cholangiography:
Preoperative—Intravenous, 40 Ivy dog units (IDU) (4 mL) administered approximately one minute prior to administration of contrast medium. {01} {03}

Secondary—Intravenous, 75 IDU administered daily for one week, if a concretion remains after surgery. Concurrent with the last injection, cholangiography may be performed. {01} {03}


Diagnostic aid (pancreatic disorders)
Intravenous, 0.5 to 1 Ivy dog unit (IDU) per kg of body weight, administered slowly. {03}

Peristaltic stimulant
To accelerate small bowel transit time of barium sulfate: Intravenous, 0.5 to 1 Ivy dog unit (IDU) per kg of body weight, administered slowly after the barium meal has passed into the first part of the jejunum. {03}

Note: After ingestion of 200 to 300 mL of barium mixture, patients should lie on their right side for 10 to 15 minutes; if fluoroscopy shows that most of the contrast medium has passed into the first part of the jejunum, cholecystokinin is injected. {03}



Usual pediatric dose
Dosage has not been established.

Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—
Not commercially available. However, sincalide (CCK-8), a synthetically prepared C-terminal octapeptide of cholecystokinin, is commercially available in the U.S. {15}

Canada—


75 Ivy dog units (IDU) (Rx)[Generic](0.4 mg L-cysteine, 0.1 mg L-cysteine hydrochloride, 20 mg mannitol){01}

Packaging and storage:
Store at -20 °C (-4 °F), unless otherwise specified by manufacturer. {01} {03}

Preparation of dosage form:
To prepare injection, 7.5 mL of an isotonic sodium chloride solution is added to the vial containing 75 Ivy dog units (IDU) of cholecystokinin, giving a final concentration of 10 IDU per mL. {01} {03}

Stability:
Following reconstitution, cholecystokinin injection must be used immediately. {03}

Any unused portion remaining in the container should be discarded. {03}



Developed: 05/27/1996



References
  1. Product monograph (Ferring—Canada), Rev 5/91, Rec 1/10/95.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 30th ed. London: The Pharmaceutical Press, 1993: 778.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 242.
  1. Fleeger CA, editor. USAN 1995. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 502.
  1. 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.
  1. Krishnamurthy GT, Turner FE. Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med 1990; 20(2): 130-49.
  1. Reviewers' comments per technetium Tc 99m disofenin monograph revision of 11/03/92.
  1. Hepatobiliary imaging protocol as of 03/91 sent by USP Radiopharmaceuticals Advisory panelist.
  1. Jorpes JE, Mutt V. The gastrointestinal hormones, secretin and cholecystokinin—pancreozymin. Ann Intern Med 1961; 55: 395-405.
  1. Fink-Bennett D, DeRidder P, Kolozsi W, et al. Cholecystokinin cholescintigraphic findings in the cystic duct syndrome. J Nucl Med 1985; 26(10): 1123-8.
  1. Freeman LM, Sugarman LA, Weissmann HS. Role of cholecystokinetic agents in Tc 99m-IDA cholescintigraphy. Semin Nucl Med 1981; 11(3): 186-93.
  1. Reviewers' responses to Sincalide (Systemic) monograph draft of 10/10/94.
  1. Topper TE, Ryerson TW, Nora PF. Quantitative gallbladder imaging following cholecystokinin. J Nucl Med 1980; 21: 694-6.
  1. Davis GB, Berk RN, Scheible FW, et al. Cholecystokinin cholecystography, sonography, and scintigraphy: detection of chronic acalculous cholecystitis. Am J Radiol 1982 Dec; 139: 1117-21.
  1. Sincalide package insert (Kinevac, Squibb—US), Rev 3/92, Rec 10/7/94.
  1. Tokunaga Y, Kenneth LC, Coleman R, et al. Characterization of cholecystokinin receptors on the human gallbladder. Surgery 1993 Feb; 113(2): 155-62.
  1. Halverson JD, Garner BA, Siegel BA, et al. The use of hepatobiliary scintigraphy in patients with acalculous biliary colic. Arch Intern Med 1992 Jun; 152(6): 1305-7.
  1. Marton K, Doubilet P. How to image the gallbladder in suspected cholecystitis. Ann Intern Med 1988; 109: 722-9.
  1. Parker JG, Beneventano TC. Acceleration of small bowel contrast study by cholecystokinin. Gastroenterol 1970 May; 58(5): 679-84.
  1. Griffen WO, Bivins BA, Rogers EL, et al. Cholecystokinin cholecystography in the diagnosis of gallbladder disease. Ann Surg 1980 May; 191(5): 636-40.
  1. Iocetamic acid package insert (Cholebrine, Mallinckrodt—US), Rev 4/84.
  1. Maton PN, Selden AC, Fitzpatrick ML, et al. Infusion of cholecystokinin octapeptide in man: relation between plasma cholecystokinin concentrations and gallbladder emptying rates. Eur J Clin Invest 1984 Feb; 14(1): 37-41.
  1. Fleckenstein P, Oigaard A. Effects of cholecystokinin on the motility of the distal duodenum and the proximal jejunum in man. Scand J Gastroenterol 1977; 12(3): 375-8.
  1. Reviewers' comments per monograph revision of 9/11/95.
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