PORCINE SECRETIN

Porcine Secretin for Injection 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).

For injection: 16 mcg of porcine secretin, lyophilized sterile powder in a single-dose vial for reconstitution; NDC # 67066-004-01. Store at -20°C (freezer). Protect from light.

2.1 Preparation Prior to Secretin Stimulation Testing, Including Administration of a Test Dose Discontinue Interacting Drugs To avoid an incorrect stimulation test result, discontinue the following drugs prior to administration of Porcine Secretin for Injection: • anticholinergic drugs: at least 5 half -lives prior to testing [see Warnings and Precautions (5. 2), Drug Interactions (7.1)] • H2-receptor antagonists: at least 2 days prior to testing [see Warnings and Precautions (5. 3), Drug Interactions (7.2)]. • proton pump inhibitors (PPIs): Consult the prescribing information for specific PPIs [see Warnings and Precautions (5.3), Drug Interactions (7.2)]. Test Dose Preparation and Administration • Because of a potential hypersensitivity reaction to Porcine S ecretin for Injection , administer an intravenous test dose of 0.2 mcg to all patients . A test dose is especially important in patients with a history of atopy [see Warnings and Precautions (5.1)]. • Porcine Secretin for Injection is a lyophilized powder, which requires reconstitution prior to intravenous administration. Prepare the test dose as follows: o Dissolve the contents of the Porcine Secretin for Injection 16 mcg vial in 8 mL of 0.9% Sodium Chloride Injection, USP, to yield a concentration of 2 mcg/mL. o Shake vigorously to ensure dissolution. o Inspect the reconstituted solution visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is seen, discard the reconstituted solution. o Withdraw 0.1 mL of the reconstituted solution for administration as the test dose. o Use immediately after reconstitution and discard any unused portion. • Appropriate measures for the treatment of acute hypersensitivity reactions should be immediately available. • If no hypersensitivity reaction is noted after one minute, administer intravenously the recommended dosage shown in Table 1 for the specific indication [see Dosage and Administration (2.2)] slowly over 1 minute. 2.2 Preparation and Dosage Regimen The recommended dosage regimen of Porcine Secretin for Injection by indication is shown below in Table 1. Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda TABLE 1: Dosage by Indication Indication Recommended Dosage Regimen Stimulation of pancreatic secretions, including bicarbonate, to aid in the diagnosis of exocrine pancreas dysfunction 0.2 mcg/kg by intravenous injection over 1 minute Stimulation of gastrin secretion to aid in the diagnosis of gastrinoma 0.4 mcg/kg by intravenous injection over 1 minute Stimulation of pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP) 0.2 mcg/kg by intravenous injection over 1 minute Preparation of Recommended Dosage • Porcine Secretin for Injection 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: o Total dose (mcg) = patient’s weight (kg) x prescribed dose (mcg/kg). o Total injection volume (mL) = total dose (mc g) divided by the concentration of the reconstituted solution (2 mcg/mL). o Round the total injection volume to the nearest tenth of a mL o Total number of vials = total injection volume divided by the vial volume (8 mL). • To reconstitute one vial: o Dissolve the contents of the Porcine Secretin for Injection 16 mcg vial i n 8 mL of 0.9% Sodium Chloride Injection, USP, to yield a concentration of 2 mcg/mL. o Shake vigorously to ensure dissolution. o 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 Porcine Secretin for Injection 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: [performed using either the gastroduodenal/Dreiling tube (fluoroscopic) or endoscopic collection method] Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda • Gastroduodenal (Dreiling) Tube Collection Method o Pass a radiopaque, double-lumen gastroduodenal tube through the mouth using a guidewire. o 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. o 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. o 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. o Collect a baseline sample of duodenal fluid for a 15-minute period. o Administer an intravenous test dose of 0.2 mcg of Porcine Secretin for Injection and monitor the patient for an acute hypersensitivity reaction for at least 1 minute [see Dosage and Administration (2.1)]. o If no hypersensitivity reaction occurs, administer Porcine Secretin for Injection at a dose of 0.2 mcg/kg body weight intravenously over 1 minute [see Dosage and Administration (2.2)]. 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) o Administer a topical anesthetic spray to the posterior pharynx and place a bite block in the mouth. o Perform a standard upper endoscopy by passing the endoscope into the stomach with the patient in the left lateral decubitus position. o After gastric insufflation, aspirate all gastric fluid through the endoscope and discard. o 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. o Aspirate duodenal fluid for several seconds to clear the residual gastric acid from the tube. o Collect a baseline aspirate of duodenal fluid (3 to 5 mL) from the post-bulbar duodenum. o Administer an intravenous test dose of 0.2 mcg of Porcine Secretin for Injection and monitor the patient for an acute hypersensitivity reaction [see Dosage and Administration (2.1)]. o If no hypersensitivity reaction occurs, administer Porcine Secretin for Injection at a dose of 0.2 mcg/kg of body weight intravenously over 1 minute [see Dosage and Administration (2.2)]. o Starting 15 minutes after administration of Porcine Secretin for Injection, collect 4 timed duodenal fluid aspirates (each 3 to 5 mL) at 15-minute intervals. 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. Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda 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 Porcine Secretin for Injection , draw two blood samples for determination of fasting serum gastrin levels (baseline values). • Administer a n intravenous test dose of 0.2 mcg of Porcine Secretin for Injection and monitor the patient for an acute hypersensitivity reaction [see Dosage and Administration (2.1)]. • After one minute, if there are no hypersensitivity react ions, administer Porcine Secretin for Injection at a dose of 0.4 mcg/kg of body weight intravenously over 1 minute [see Dosage and Administration (2.2)]. • Collect p ost-injection blood samples after 1, 2, 5, 10, and 30 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. Stimulation of Pancreatic Secretions to Facilitate the Identification of the Ampulla of Vater and Accessory Papilla During Endoscopic Retrograde Cholangiopancreatography (ERCP): When difficulty is encountered by the endoscopist in identifying the ampulla of Vater or in identifying the accessory papilla in patients with pancreas divisum: • Administer a test dose of Porcine Secretin for Injection 0.2 mcg intravenously to test for possible acute hypersensitivity reactions [see Dosage and Administration (2.1)]. • After one minute, if there are no hypersensitivity reactions, administer Porcine Secretin for Injection at a dose of 0.2 mcg/kg of body weight intravenously over 1 minute [see Dosage and Administration (2.2)]. • Visible excretion of pancreatic fluid from the orifices of these papillae will enable their identification and facilitate cannulation.

Porcine Secretin for Injection is contraindicated in patients who: • develop an acute hypersensitivity reaction in response to a test dose[see Warnings and Precautions (5.1)], or • have a documented hypersensitivity reaction to porcine products. Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda

Advise patients of the potential for hypersensitivity reactions [see Warnings and Precautions (5.1)]. Manufactured for: ChiRhoClin, Inc Burtonsville, MD 20866-6129 004PI01 Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda

7.1 Hyporesponse with Anticholinergics The concomitant use anticholinergic drugs may cause a hyporesponse to stimulation testing with Porcine Secretin for Injection. Discontinue anticholinergic drugs at least 5 half -lives before administering Porcine Secretin for Injection [see Dosage and Administration (2.1)]. 7.2 Hyperresponse of Gastrin Secretion with H2-Receptor Antagonists and PPIs The concomitant use of H2-receptor antagonists or PPIs may cause a hyperresponse in gastrin secretion in response to stimulation testing with Porcine Secretin for Injection, falsely suggesting gastrinoma. Discontinue H2-receptor antagonists at least 2 days before administering the Porcine Secretin for Injection 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 Porcine Secretin for Injection to aid in the diagnosis of gastrinoma.

Risk Summary There are no available data on porcine secretin use in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with porcine secretin. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda

The safety and effectiveness of Porcine Secretin for Injection in pediatric patients have not been established.

Among the 957 subjects who have received Porcine Secretin for Injection in clinical trials , 16% were 65 years of age or older and 10% were 75 years of age or older. No overall differences in safety, pharmacological response, or diagnostic effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and the younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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 a single dose of Porcine Secretin for Injection in 957 patients in placebo and active controlled trials. The population consisted of patients ages 1 to 93, 379 males, 574 females, and 4 unspecified ; 816 Caucasians, 106 Blacks, 10 Hispanics, 10 American Indians, 8 Asians, 1 Indian, 1 Native Alaskan, and 5 unspecified, with known or suspected diseases of the exocrine pancreas including chronic pancreatitis and pancreatic cancer. Most patients received a single dose of Porcine Secretin for Injection of 0.2 mcg/kg to 0.4 mcg/kg. The most common adverse reactions reported in at least 2% of patients in clinical trials are shown in Table 2. Reference ID: 4004155 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda TABLE 2 Adverse Reactions in at Least 2% of Patients Treated with a Single-Dose of Porcine Secretin for Injection in Clinical Trials Adverse Reaction Porcine Secretin for Injection Percent Incidence (Number of Patients) N = 957 Abdominal discomfort 7 (7) Nausea 7 (7) Flushing 4 (4) Burning in stomach 3 (2) Diaphoresis 3 (2) Bradycardia 2 (2) Decreased blood pressure 2 (2)