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.

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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 10 Capsule Package Label. AVANOSPYtest 14C-UREA BREATH TEST CAPSULES FOR THE DETECTION OF HELICOBACTER PYLORIContents 10 PYtest Capsules each containing uCi 14C-UreaFor dosage information, please see package insert14C-Urea (5730 years1/2, 156 keV[max.] -emission)NDC 42536-6044-2For In Vitro Diagnostic UseRx OnlyStore at 15-30C (59-86F)REF 60442. PRINCIPAL DISPLAY PANEL 10 Capsule Package 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.

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 and 14CO2 is absorbed into the blood and exhaled in the breath.Following ingestion of the capsule by patient with H. pylori, 14CO2 excretion 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.. Figure 1: Principle of Breath Test. 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 Positive51859ppv.86%(DPMIndeterminate18910 min.)Negative1117118npv.99%Total53133186sensitivityspecificity96%88%. 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 Positive22022ppv.100%(DPMIndeterminate42610 min.)Negative14748npv.98%Total274976sensitivityspecificity82%96%.

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.

CONTRAINDICATIONS SECTION.

Contraindications. None.

DESCRIPTION SECTION.

Description. PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (14C-urea capsules) is intended for use in the detection of gastric urease as an aid in the diagnosis of Helicobacter pylori (H. pylori) infection in the human stomach. The test utilizes liquid scintillation counter for the measurement of 14CO2 in breath samples. The capsules are to be used when analysis is planned at the site where the sample is taken.PYtest capsule is 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.

DOSAGE & ADMINISTRATION SECTION.

Dosage and Administration. Materials Needed but not Provided. FOR ANALYSIS AT TEST SITE BREATH SAMPLE COLLECTED INTO BALLOON (RECOMMENDED METHOD; SEE FIGURE 2)Breath test report formStopwatch/Timer capable of timing an interval up to 10 minutesMarking pen1 20 ml scintillation vialBreath transfer pumpPipette (10 ml) for measuring fluidsCollection fluid (2.5 ml/vial)Scintillation fluid (10 ml/vial)1 Mylar collection balloon1 Straw2 Needles2 30 ml medicine cupsWater (40 ml)Any gas pump that is airtight and has flow rate between .5 and liter per minute may be used.Figure 2: Other Components. Breath test report form. Stopwatch/Timer capable of timing an interval up to 10 minutes. Marking pen. - 20 ml scintillation vial. Breath transfer pump. Pipette (10 ml) for measuring fluids. Collection fluid (2.5 ml/vial). Scintillation fluid (10 ml/vial). - Mylar collection balloon. - Straw. - Needles. - 30 ml medicine cups. Water (40 ml). Any gas pump that is airtight and has flow rate between .5 and liter per minute may be used.. Figure 2: Other Components. FOR ANALYSIS ON SITE BREATH SAMPLE COLLECTED INTO VIALCAUTION: Kimberly-Clark does not endorse breath sample collection by this method because patients might come into direct contact with the hyamine.Breath test report formStopwatch/Timer capable of timing an interval up to 10 minutesSafety trap (Figure 3)1 Straw1 20 ml scintillation vialMarking penPipette (10 ml) for measuring fluidsCollection fluid (2.5 ml/vial)Scintillation fluid (10 ml/vial)Figure 3: Typical Safety Trap. Breath test report form. Stopwatch/Timer capable of timing an interval up to 10 minutes. Safety trap (Figure 3). - Straw. - 20 ml scintillation vial. Marking pen. Pipette (10 ml) for measuring fluids. Collection fluid (2.5 ml/vial). Scintillation fluid (10 ml/vial). Figure 3: Typical Safety Trap.

DOSAGE FORMS & STRENGTHS SECTION.

Dosage. One PYtest capsule.

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).. 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 of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest or use an alternative diagnostic method.. 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 of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest or use an alternative diagnostic method.. 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 (1 uCi 14C) is about 0.3 mrem.

HOW SUPPLIED SECTION.

HOW SUPPLIED. PYtest Capsules, clear gelatin capsules each containing uCi of 14C-urea in unit dose packages of 1, 10 and 100.PYtest Kit (14C-urea breath test) is also supplied as kit containing PYtest Capsule and breath collection equipment.. 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 15-30 (59-86 F) in an area designated by each individual institutions regulations.

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 of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest or use an alternative diagnostic method.. 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 of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest or use an alternative diagnostic method.. 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 (1 uCi 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.

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 15-30 (59-86 F) in an area designated by each individual institutions regulations.

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.