Chirhostim Drug Information

ChiRhoStim ® is indicated for the stimulation of: pancreatic secretions, including bicarbonate, to aid in the diagnosis of pancreatic exocrine dysfunction. gastrin secretion to aid in the diagnosis of gastrinoma, and pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP).

2.2 Preparation and Dosage Regimen The recommended dosage regimen of ChiRhoStim® by indication is shown below in Table 1. TABLE 1: Dosage by Preparation of Recommended Dosage ChiRhoStim ® is a lyophilized powder, which requires reconstitution prior to intravenous administration. Determine the number of vials needed for the prescribed dosage based on the patient’s weight and recommended dosage.

Follow these steps to determine the patient dose: Total dose (mcg) = patient’s weight (kg) x prescribed dose (mcg/kg). Total injection volume (mL) = total dose (mcg) divided by the concentration of the reconstituted solution (2 mcg/mL). Round the total injection volume to the nearest tenth of a mL.

Total number of vials = total injection volume divided by the vial volume (8 mL). Shake vigorously to ensure dissolution. Inspect the reconstituted solution visually for particulate matter and discoloration prior to administration.

If particulate matter or discoloration is seen, discard the reconstituted solution. Repeat steps above to reconstitute additional vials, as needed, to administer the total dose. Use immediately after reconstitution and discard any unused portion. 2.3 Administration and Test Methods Stimulation testing with ChiRhoStim ® should only be performed by physicians with sufficient expertise.

Ensure that the institution has established normative ranges for pancreatic exocrine response. Stimulation of Pancreatic Secretions, including Bicarbonate, to Aid in the Diagnosis of Exocrine Pancreas Dysfunction: Preparation: Instruct patients to fast for at least 12 to 15 hours prior to beginning the test. Sample Collection: Gastroduodenal (Dreiling) Tube Collection Method Pass a radiopaque, double-lumen gastroduodenal tube through the mouth using a guidewire.

Under fluoroscopic guidance, place the opening of the proximal lumen in the gastric antrum and the opening of the distal lumen beyond the ampulla of Vater. Confirm the tube positioning and secure the tube. Connect both the proximal (gastric) and distal (duodenal) lumens to low intermittent suction, and apply negative pressure of 25 to 40 mmHg to both lumens.

Collect a sample of the duodenal contents and check the pH of the aspirate to verify tube position. Proceed to next step if the duodenal aspirate has a pH of 6 or higher. If the pH is less than 6, reposition the tube.

Collect a baseline sample of duodenal fluid for a 15-minute period. Administer ChiRhoStim ® at a dose of 0.2 mcg/kg body weight intravenously over 1 minute. For the 60-minute period following the injection, collect four consecutive 15-minute samples of duodenal fluid.

Clear the duodenal lumen of the tube with an injection of air after each 15-minute sample collection. Note that wide variation in aspirate volumes is indicative of incomplete aspiration between samples. Endoscopic Collection Method: Endoscopic Pancreatic Function Test (ePFT) Administer a topical anesthetic spray to the posterior pharynx and place a bite block in the mouth.

Perform a standard upper endoscopy by passing the endoscope into the stomach with the patient in the left lateral decubitus position. After gastric insufflation, aspirate all gastric fluid through the endoscope and discard. Pass the endoscope through the pylorus into small intestine and position the tip of the endoscope at the junction of the second and third portion of the duodenum.

Aspirate duodenal fluid for several seconds to clear the residual gastric acid from the tube. Collect a baseline aspirate of duodenal fluid (3 to 5 mL) from the post-bulbar duodenum. Keep the patient in the left lateral decubitus position throughout the procedure.

Sample Handling and Interpretation: Place fluid specimens on ice for immediate measurement of bicarbonate concentration. If samples will not be analyzed immediately, store fluid at –80°C. Peak bicarbonate concentrations of 80 to 130 mEq/L after administration indicate normal pancreatic exocrine function.

Stimulation of Gastrin Secretion to Aid in the Diagnosis of Gastrinoma: Preparation: Instruct patients to fast for at least 12 hours prior to beginning the test. Sample Collection: Before administering ChiRhoStim ®, draw two blood samples for determination of fasting serum gastrin levels (baseline values). Collect post-injection blood samples after minutes for determination of serum gastrin concentrations.

Sample Interpretation: Gastrinoma is strongly suspected in patients who show an increase in serum gastrin concentration of more than 110 picograms (pg) per mL over baseline levels on any of the post injection samples. Visible excretion of pancreatic fluid from the orifices of these papillae will enable their identification and facilitate cannulation. To avoid an incorrect stimulation test result, discontinue the following drugs for the recommended amount of time prior to administration of ChiRhoStim®: anticholinergic drugs: at least 5 half-lives.

H2-receptor antagonists: at least 2 days. proton pump inhibitors (PPIs): consult the prescribing information for specific PPIs.

6.1 Clinical Trials Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials of a drug cannot always be directly compared to the rates observed during the clinical trials of another drug and may not reflect the adverse reaction rates observed in practice. The data described below reflect exposure to ChiRhoStim® in 531 patients from an open-label clinical trial. Most patients received a single dose of ChiRhoStim® in a dose range of 0.2 mcg/kg to 0.4 mcg/kg.

The most common adverse reactions (reported in at least 2 patients in the trial) are listed in Table 2. To report SUSPECTED ADVERSE REACTIONS, contact ChiRhoClin, Inc. at 1-877-272-4888 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION.

Revised: 07/2017

7.1 Hyporesponse with Anticholinergics The concomitant use anticholinergic drugs may cause a hyporesponse to stimulation testing with ChiRhoStim ®. Discontinue anticholinergic drugs at least 5 half-lives before administering ChiRhoStim ®. 7.2 Hyperresponse of Gastrin Secretion with H 2 -Receptor Antagonists and PPIs The concomitant use of H 2 -receptor antagonists or PPIs may cause a hyperresponse in gastrin secretion in response to stimulation testing with ChiRhoStim ®, falsely suggesting gastrinoma. Discontinue H 2 -receptor antagonists at least 2 days before administering ChiRhoStim ® to aid in the diagnosis of gastrinoma.

The time it takes for serum gastrin concentrations to return to baseline following discontinuation of PPIs is specific to the individual drug. Consult the prescribing information of each specific PPI before administering ChiRhoStim ® to aid in the diagnosis of gastrinoma.

Pregnancy Risk Summary There are no available data (either clinical studies or postmarketing reports) of use of synthetic human secretin in pregnant women. Animal reproduction studies have not been conducted with synthetic human secretin. The estimated background risk of major birth defects and miscarriage for the indicated populations are 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 respectively.

Pediatric Use The safety and effectiveness of ChiRhoStim ® in pediatric patients have not been established.