ADVERSE REACTIONS SECTION.

Adverse Reactions. No adverse reactions were reported in clinical trials.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, mutagenesis, impairment of fertility. No studies have been conducted with 14C-urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.

CLINICAL PHARMACOLOGY SECTION.

Clinical Pharmacology. The urease enzyme is not present in mammalian cells, so the presence of urease in the stomach is evidence that bacteria are present. The presence of urease is not specific for H.pylori, but other bacteria are not usually found in the stomach. The principle of the breath test is shown in Figure 1.Figure 1: Principle of Breath TestTo detect H.pylori, urea labeled with 14C is swallowed by the patient. If gastric urease from H.pylori is present, urea is split to form CO2 and NH3 at the interface between the gastric epithelium and lumen and14CO2 is absorbed into the blood and exhaled in the breath.Following ingestion of the capsule by patient with H.pylori, 14CO2excretion in the breath peaks between 10 and 15 minutes and declines thereafter with biological half-life of about 15 minutes. 14C-urea that is not hydrolyzed by H.pylori is excreted in the urine with half-life of approximately 12 hours. About 10% of the 14C remains in the body at 72 hours and is gradually excreted with biological half-life of 40 days.

CLINICAL STUDIES SECTION.

Clinical Studies. Two studies were performed. In both studies, patients with gastrointestinal symptoms underwent the breath test and an endoscopy. During the endoscopy, biopsy samples were taken from the antral gastric mucosa for histological analysis (2 samples, Giemsa stain) and rapid urease test (1 sample, CLOtest). Breath samples were mailed to the TRI-MED lab where they were read in liquid scintillation counter.Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. breath sample DPM <50 was defined as negative result. DPM >=200 was defined as positive result. DPM in the range of 50 -199 was classified as indeterminate.. STUDY 1. Of 186 patients who had histopathology and CLOtest (80 men, 106 women), 53 were infected with H.pylori as determined by agreement between histology and CLOtest. The study results are summarized below:Table 1: Study (n=186, Indeterminate results included)Histology and CLOtest H.pyloriPositiveNegativeTotalNotes: PYtest at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.ppv positive predictive value (true positive divided by total PYtest positive)npv negative predictive value (true negative divided by total PYtest negative)PYtest Positive518 59 ppv. 86%(DPMIndeterminate1 9 10m.)Negative1 117118npv. 99%Total53133186sensitivity96%specificity88%. STUDY 2. Breath tests were performed on 436 outpatients attending gastroenterology practices at sites in the United States. Seventy-six patients (40 men, 36 women) who had histology and CLOtest were evaluated. The results are summarized below:Table 2: Study (n=76, Indeterminate results included)Histology and CLOtest H.pyloriPositiveNegativeTotalNotes: PYtest at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.ppv positive predictive value (true positive divided by total PYtest positive)npv negative predictive value (true negative divided by total PYtest negative)PYtest Positive220 22ppv. 100%(DPMIndeterminate4 6 10m.)Negative1 4748npv. 98%Total274976sensitivity82%specificity96%.

CONTRAINDICATIONS SECTION.

Contraindications. None.

DESCRIPTION SECTION.

Description. PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (14C-Urea Breath Test) is qualitative and non-invasive method for the diagnosis of Helicobacter pylori (H.pylori). To detect H.pylori, 14C-urea supplied in capsule is swallowed by the patient. If gastric urease from H.pylori is present, Urea is split to form CO2 and NH3. Ten minutes after the patient ingests the capsule, breath sample is collected into balloon. The breath sample is later transferred to collection fluid to trap the labeled CO2. The liquid sample is then analyzed in liquid scintillation counter.The PYtest Kit (14C-Urea Breath Test) is designed for use with the PYtest capsule, gelatin capsule for oral administration containing uCi of 14C labeled urea. The urea is adsorbed on sugar spheres and colored yellow with fluorescein.. Data on 14C-urea. Structural Formula (14C-urea): NH2 14CONH2 Radiation emission: beta-emission, 49 keVmean, 156 keVmax, no other emissionsExternal emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.Radiological Half-life: 5730 yearsMaximum effective dose equivalent (EDE) 0.3 mrem/uCi. Figure 1. Figure 2. Figure 3.

DOSAGE & ADMINISTRATION SECTION.

Dosage and Administration. Materials provided. As shown in Figure 2, the PYtest Kit contains:PYtest capsuleTwo 30 mL disposable cupsOne drinking strawOne mylar collection balloonOne report formOne mailing box with labelsThe kit includes analysis by Kimberly-Clark of one balloon from one patient at one time point. Figure 2: PYtest Kit. PYtest capsule. Two 30 mL disposable cups. One drinking straw. One mylar collection balloon. One report form. One mailing box with labelsThe kit includes analysis by Kimberly-Clark of one balloon from one patient at one time point. Materials Needed but not Provided. Stopwatch/Timer capable of timing an interval up to 10 minutes.Water (40mL). Stopwatch/Timer capable of timing an interval up to 10 minutes.. Water (40mL). Dosage. One PYtest capsule.. Procedural Notes. Inform the patient to fast for hours prior to the test.The patient should be off antibiotics and bismuth for month, and proton pump inhibitors and sucralfate for weeks prior to the test.Have patient sitting at rest while doing the test.The capsule should not be handled directly as this may interfere with the test result.To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.. Inform the patient to fast for hours prior to the test.. The patient should be off antibiotics and bismuth for month, and proton pump inhibitors and sucralfate for weeks prior to the test.. Have patient sitting at rest while doing the test.. The capsule should not be handled directly as this may interfere with the test result.. To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.. Step by Step Procedure for Balloon. Table 3: Breath Sample Collection by BalloonBefore the testLabel balloon and fill in breath test report form.Check that all materials are present.Minus 1Open the package containing the 14C-urea capsule minute and tip the capsule into the empty 30 mL cup. Do not handle the capsule directly.Hand the cup to the patient.Fill the second cup with 20 mL lukewarm water.0 minuteAsk the patient to tip the capsule directly into his/her mouth, then swallow it with the 20 mL of lukewarm water.Start the stopwatch when the patient swallows the capsule.Discard waste (e.g., capsule packaging, used straws) according to your facilitys regulations.3 minutesAsk the patient to drink another 20 mL of lukewarm water (in case the capsule may have lodged in the esophagus and not yet reached the gastric mucosa). 10 minutesPush drinking straw into the neck of the balloon.Ask the patient to hold his/her breath for 5-10 seconds, then blow up balloon with slow breath through the straw, filling the balloon completely.Tie the neck of the balloon into tight knot.Check that the balloon label and the breath test report form are completed correctly.After the testPlace the filled balloon and breath test report in the box and forward to Kimberly-Clark for analysis. Label balloon and fill in breath test report form.. Check that all materials are present.. Open the package containing the 14C-urea capsule minute and tip the capsule into the empty 30 mL cup. Do not handle the capsule directly.. Hand the cup to the patient.. Fill the second cup with 20 mL lukewarm water.. Ask the patient to tip the capsule directly into his/her mouth, then swallow it with the 20 mL of lukewarm water.. Start the stopwatch when the patient swallows the capsule.. Discard waste (e.g., capsule packaging, used straws) according to your facilitys regulations.. Push drinking straw into the neck of the balloon.. Ask the patient to hold his/her breath for 5-10 seconds, then blow up balloon with slow breath through the straw, filling the balloon completely.. Tie the neck of the balloon into tight knot.. Check that the balloon label and the breath test report form are completed correctly.. Quality Control. minimum of mM of CO2 is required to perform analysis of breath sample. The amount of breath required to provide mM of CO2varies depending on the amount of CO2 the patient is producing. Since full balloon typically contains at least mM of CO2, the balloon should be completely filled.. Results. Interpretation of results (10 minute sample) <50 DPMNegative for H.pylori 50-199 DPMIndeterminate for H.pylori >=200 DPMPositive for H.pylori The indeterminate result should be evaluated by repeating the PYtestor using an alternative diagnostic method. If repeat breath testing is undertaken, careful history to exclude confounding factors should be obtained. If confounding factors are present, wait an appropriate time (refer to Table 4) before repeating the PYtest.The cutoff point of 50 DPM was determined to be the mean 3SD of results obtained in patients who did not have H.pylori.DPM Disintegrations per minuteTable 4: Factors which might cause sub-optimal breath test resultsFactorResultCommentRecent antibiotic or bismuth (Pepto-Bismol, etc.)false neg.Relapse of partially treated Hp may take 1-4 weeks.Omeprazole (or other proton pump inhibitors)false neg.These agents suppress Hp in 40% of patients. Discontinue for at least weeks before performing the PYtest.Resective gastric surgeryfalse neg.Isotope may empty rapidly from the stomach.Resective gastric surgeryfalse pos.Patient may be achlorhydric and have bacterial overgrowth (non-Hp urease).Food in stomach (also bezoar, gastroparesis)unknownIsotope may not come into contact with gastric mucosa. Patient may be achlorhydric and/or have bacterial overgrowth (non-Hp urease).. Expected Values. As shown in Figure approximately 30% of patients tested will be positive for H.pylori.Figure 3: Histogram showing DPM distribution for the PYtest.Note: DPM groupings were calculated on logarithmic scale. Empty DPM groupings were not included. Chart includes all patients from Studies and 2.Frequency of DPM group includes samples with DPM Group Name. DPM Disintegrations per minute Gold Standard Agreement between histology and CLOtest If the capsule is damaged or appears abnormal in any way, it may give inaccurate results.

DRUG INTERACTIONS SECTION.

Drug Interactions. Antibiotics, proton pump inhibitors, sucralfate, and bismuth preparations are known to suppress H.pylori. Ingestion of antibiotics or bismuth within weeks and proton pump inhibitors or sucralfate within weeks prior to performing the test may give false negative results.

GENERAL PRECAUTIONS SECTION.

General. After the patient ingests the 14C-urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.A false positive test could occur in patients who have achlorhydria. Very rarely, false positive test may occur due to urease associated with Helicobacters other than H.pylori (i.e. Helicobacter heilmanni).

HOW SUPPLIED SECTION.

How Supplied. PYtest Kit (14C-Urea Breath Test) is supplied as kit containing PYtest Capsule, clear gelatin capsule containing 1uCi of 14C-urea and breath collection equipment.PYtest Capsules are also supplied separately in unit dose packages of 1,10 and 100.The PYtest Capsule has shelf life of two years. The expiration date is printed on the capsule label.. PYtest Capsules and Kit should be stored at 15-30C (59-86F) in an area designated by each individual institutions regulations.Rx Only.

INDICATIONS & USAGE SECTION.

Indications and Usage. PYtest (14C-Urea Breath Test) is indicated for use in the detection of gastric urease as an aid in the diagnosis of H.pylori infection in the human stomach. The test utilizes liquid scintillation counter for the measurement of 14CO2 in breath samples.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. It is necessary for the patient to fast for hours before the test. The patient should also be off antibiotics and bismuth for month, and proton pump inhibitors and sucralfate for weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.

NURSING MOTHERS SECTION.

Nursing mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest is administered to nursing woman.

OVERDOSAGE SECTION.

Overdosage. Risk from radiation is negligible even with 1000 capsule overdose (0.3 rem). If overdose occurs, the patient may drink one glass of water (150 mL) every hour to hasten excretion of the isotope. Maximum excretion of Urea is achieved at urine output of >=2.0 mL/min.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 1 Capsule Blister Pack Kit Label. AVANOSPYtest KIT 14C-UREA BREATH TEST FOR THE DETECTION OF HELICOBACTER PYLORIContents 1 PYtest Capsule each containing uCi 14C-UreaPYtest Breath Collection Accessories 14C-Urea (5730 years1/2, 156 keV[max.] -emission)For dosage information, please see package insertThis package conforms to the conditions andlimitations specified in 49 CFR 173.421 forradioactive material, excepted package-limitedquantity of material, UN 2910.For In Vitro Diagnostic UseRx OnlyStore at 15-30C (59- 86F)Distributed in the USA by Avanos Medical Sales, LLC, 5405 Windward Parkway, Alpharetta, GA 30004 USA. In USA, 1-844-428-2667. www.avanos.com Avanos Medical, Inc., 5405 Windward Parkway, Alpharetta, GA 30004 USA. ECREP Avanos Medical Belgium BVBA, Leonardo Da Vincilaan 1, 1930 Zaventem, Belgium. Sponsored in Australia by TRI-MED Distributors Pty Ltd, 11 Southport Street, West Leederville, WA 6007, Australia. (+61 1793 3012). Registered Trademark or Trademark of Avanos Medical, Inc., or its affiliates. (C) 2018 AVNS. All rights reserved. 20-M1-025-01 70211178SHELL is shown for placement onlyLOT 000000000000000Use By YYYY-MM-DD(01)00000000000000 (240)000000000 (17)YYMMDD (10)000000000000000REF 60461109269502NDC 42536-6046-1. PRINCIPAL DISPLAY PANEL 1 Capsule Blister Pack Kit Label.

PEDIATRIC USE SECTION.

Pediatric Use. Clinical studies in children have not been conducted. However, PYtest is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into straw.

PRECAUTIONS SECTION.

Precautions. General. After the patient ingests the 14C-urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.A false positive test could occur in patients who have achlorhydria. Very rarely, false positive test may occur due to urease associated with Helicobacters other than H.pylori (i.e. Helicobacter heilmanni).. Limitations of the Test. The test has been evaluated in outpatients before elective endoscopy.Test results should be evaluated with clinical signs and patient history when diagnosing H.pylori infection.The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H.pylori infection.A negative result does not completely rule out the possibility ofH.pylori infection. If clinical signs and patient history suggest H.pyloriinfection, repeat the PYtest or use an alternative diagnostic method.The integrity of samples in balloons sent by air transport has not been adequately determined. In studies simulating the effects of air transport for two to seven days at temperatures of -40C, 20C and 55C, no balloon failures were observed. However, the data could not provide statistical determination that no changes in 14CO2concentration took place.For ground transport, integrity of samples in balloons has not been determined beyond days. During this time frame, concentration of labeled CO2 can decrease as much as 0.36% per day.. The test has been evaluated in outpatients before elective endoscopy.. Test results should be evaluated with clinical signs and patient history when diagnosing H.pylori infection.. The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H.pylori infection.. negative result does not completely rule out the possibility ofH.pylori infection. If clinical signs and patient history suggest H.pyloriinfection, repeat the PYtest or use an alternative diagnostic method.. The integrity of samples in balloons sent by air transport has not been adequately determined. In studies simulating the effects of air transport for two to seven days at temperatures of -40C, 20C and 55C, no balloon failures were observed. However, the data could not provide statistical determination that no changes in 14CO2concentration took place.. For ground transport, integrity of samples in balloons has not been determined beyond days. During this time frame, concentration of labeled CO2 can decrease as much as 0.36% per day.. Radioactivity. Persons concerned about very low doses of radioactivity may postpone the test or may decide to use an alternative means of diagnosis. The test produces radiation exposure equal to 24 hours of normal background. In animal experiments, such low doses of radiation do not carry measurable risk.Preclinical studies were not conducted on 14C-urea. The estimated dose equivalent received from single administration of PYtest (1uCi 14C) is about 0.3 mrem.. Information for Patients. It is necessary for the patient to fast for hours before the test. The patient should also be off antibiotics and bismuth for month, and proton pump inhibitors and sucralfate for weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.. Carcinogenesis, mutagenesis, impairment of fertility. No studies have been conducted with 14C-urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.. Drug Interactions. Antibiotics, proton pump inhibitors, sucralfate, and bismuth preparations are known to suppress H.pylori. Ingestion of antibiotics or bismuth within weeks and proton pump inhibitors or sucralfate within weeks prior to performing the test may give false negative results.. Pregnancy. Pregnancy category C. Animal reproduction studies have not been conducted with PYtest (14C-urea). It is also not known whether PYtest can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. PYtest should be given to pregnant woman only if clearly needed.. Nursing mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest is administered to nursing woman.. Pediatric Use. Clinical studies in children have not been conducted. However, PYtest is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into straw.

PREGNANCY SECTION.

Pregnancy. Pregnancy category C. Animal reproduction studies have not been conducted with PYtest (14C-urea). It is also not known whether PYtest can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. PYtest should be given to pregnant woman only if clearly needed.

SPL UNCLASSIFIED SECTION.

Data on 14C-urea. Structural Formula (14C-urea): NH2 14CONH2 Radiation emission: beta-emission, 49 keVmean, 156 keVmax, no other emissionsExternal emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.Radiological Half-life: 5730 yearsMaximum effective dose equivalent (EDE) 0.3 mrem/uCi.

STORAGE AND HANDLING SECTION.

PYtest Capsules and Kit should be stored at 15-30C (59-86F) in an area designated by each individual institutions regulations.Rx Only.

TERATOGENIC EFFECTS SECTION.

Pregnancy category C. Animal reproduction studies have not been conducted with PYtest (14C-urea). It is also not known whether PYtest can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. PYtest should be given to pregnant woman only if clearly needed.

WARNINGS SECTION.

Warnings. None.