Consumer medicine information

PYtest

Urea (14C)

BRAND INFORMATION

Brand name

PYtest

Active ingredient

Urea (14C)

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using PYtest.

1. What is the PYtest capsule?

PYtest capsule is a gelatin capsule for oral use containing one microgram of 14C labelled urea which is adsorbed onto the sugar spheres made of maize-starch, sugar and coloured yellow with a dye called fluorescein sodium.

2. What is the PYtest used for?

PYtest (Urea [14C] capsule) is used as a single dose test in the diagnosis of Helicobacter pylori (H.pylori) infection in the human stomach. The presence of H.pylori infection of the stomach has been linked with inflammation of the stomach, which can give rise to stomach ulcers, and even cancer of the stomach. PYtest is available in a capsule or kit form. PYtest may be performed by the patient unsupervised and returned to TRI-MED or an affiliated laboratory for anlaysis, or performed under supervision when the patient is referred to a laboratory.

3. How does the PYtest work?

The PYtest capsule contains sugar beads coated with small amounts of a chemical called urea. Urea is naturally found in the human body, and the amount in a capsule is much smaller than the head of a pin. The urea in the PYtest has been “labelled” with carbon 14 (14C), so it can be detected after it is taken into the body.

After the patient swallows the capsule, it takes about three minutes to dissolve in the patient’s stomach. If the patient has H.pylori in his or her stomach, when the 14C-urea (which is released from the capsule) comes into contact with H. pylori in the patient’s stomach, it is immediately broken down into 14C-carbon dioxide and ammonia. The carbon dioxide is carried to the patient’s lungs through the bloodstream and is breathed out. 10 minutes after the patient takes the capsule, a breath sample is collected in a balloon. The breath sample is then analysed to measure the amount of the 14C-carbon dioxide breathed out by the patient.

If 14C is present in the breath, the patient has H. pylori. If H. pylori is not present in the patient’s stomach, the 14C-urea simply washes through the stomach and is passed in the urine.

4. What instructions must I follow before taking the PYtest?

You must not eat or drink (including water) for at least six hours before your test. If you have taken any antibiotics in the past 4 weeks please tell your doctor before taking the test. The test will need to be post-poned until you have been off antibiotics for four weeks.

If you have been taking Sucralfate tell your doctor at least 2 weeks before you go for the breath test.

If you are taking a proton pump inhibitor such as Losec (Omeprzaole), Somac (Pantaprazole) or Zoton (Lansoprazole) you will need to stop taking it for 1 week before the test.

During the test, avoid handling the capsule for an extended period of time and swallow the capsule whole, to ensure optimal performance of the test.

5. What you need to tell your doctor.

Before you have your breath test it is important that you give your doctor information on the following:

Antibiotics: Tell your doctor if you are taking or have taken antibiotics or bismuth containing medicines in the past 4 weeks. (Please read Point 4 of this leaflet carefully).

Other medications you may be taking: Tell your doctor if you are taking any other medication including any bought over the counter from a pharmacy, health food shop or supermarket. It is especially important to tell your doctor if you have taken any medication for stomach problems or reflux in the past 1 week.

Allergies: Tell your doctor if you are allergic to any of the ingredients listed in this leaflet.

Pregnancy: If you are pregnant, or think you could be pregnant tell your doctor or specialist before you have the test.

Nursing mothers: Tell your doctor if you are breast-feeding before you have the test.

Paediatrics: PYtest has not been studied in children.

6. What are the unwanted effects of PYtest?

There have been no reported adverse reactions to the PYtest capsule. Tell your doctor if you do not feel well after taking the PYtest.

7. How safe is the PYtest?

Natural 14C is found in every living thing on earth, including our own bodies. This is what gives rise to “natural environmental radiation”. A single PYtest gives a tiny amount of 14C that is equal to 3 microsieverts, which is half the environmental dose of radiation that we receive in a normal day. Compared to the PYtest, a mammogram gives a radiation dose of 940 microsieverts and a chest X-ray gives 32 microsieverts. So, the PYtest is 10 times safer than a chest X-ray and 300 times safer than a mammogram.

Every person living anywhere in the world is subject to a small inevitable dose of unavoidable (environmental) radiation. Just like we measure the length of an object in centimeters or millimeters , radiation doses are measured in microseieverts. Every person living in Australia gets a daily dose of 6 microsieverts natural (background) environmental radiation during 24hrs.

Although the PYtest contains a tiny amount of radiation it is less than the unavoidable radiation an average person receives every day from natural environmental (or “background”) radiation.

8. Can one overdose with the PYtest capsule?

When the test is performed according to the set instructions, an overdose is not likely.

9. How should the PYtest capsule be stored?

The Pytest capsule should be stored below 30°C in a secure location. The PYtest capsule has a shelf life of three years from the date of manufacture. The expiry date is printed on the capsule label. The PYtest capsule should not be used after the expiry date.

10. How do I get further information?

A prescription is not required for the PYtest. Ask your doctor if you want to know more information about the PYtest or contact TRI-MED.

The PYtest is distributed in Australia by TRI-MED Distributors Pty Ltd.

This Information Leaflet was first prepared as approved by the TGA on 26th October 2000.

Phone: +61 (08) 9388 1444
Email: [email protected]
http://www.trimed.com.au

Corporate Office: Unit 6, 15 Walters Drive, Osborne Park, WA 6017

23rd November, 2020

CMI 1.7

Published by MIMS February 2021

BRAND INFORMATION

Brand name

PYtest

Active ingredient

Urea (14C)

Schedule

Unscheduled

 

1 Name of Medicine

Urea [14C].

2 Qualitative and Quantitative Composition

Each clear gelatin capsule contains 1 microgram yellow beads equivalent to 37 kBq (± 20%) 14C.
Each PYtest Kit (C14-Urea Breath Test) contains one capsule.

Excipients.

Starch, sucrose, fluorescein sodium and gelatin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clear, hard, unprinted gelatin capsules.

4 Clinical Particulars

4.1 Therapeutic Indications

PYtest (C14-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.

4.2 Dose and Method of Administration

PYtest (C14-Urea breath test) is a qualitative and non-invasive method for the diagnosis of Helicobacter pylori (H. pylori).

Dosage.

Adults.

One PYtest capsule.

Children.

Clinical studies in children have not been conducted.

Method of administration.

For oral administration.

Procedural notes.

Inform the patient to fast for 4 hours prior to the test.
The patient should not have taken antibiotics and bismuth containing products for 1 month, proton pump inhibitors for 1 week and sucralfate for 2 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.
Also see Section 4.4. Special Warnings and Precautions for Use.

Step by step procedure for balloon.

Materials needed but not provided.

1. Stopwatch/timer capable of timing an interval up to 10 minutes.
2. Water (40 mL).

Materials provided.

As shown in Figure 1, the PYtest kit contains: PYtest capsule, two 30 mL disposable cups, one drinking straw, one Pioneer brand Biax balloon, one report form, and one mailing box with labels**.
The PYtest Kit (C14-Urea breath test) is designed for use with the PYtest capsule, a gelatin capsule for oral administration containing 37 kBq (± 20%) of 14C labelled urea. The urea is absorbed on sugar spheres and coloured yellow with fluorescein.
** The kit includes analysis by Tri-Med Distributors Pty Ltd, of one balloon from one patient at one time point.
See Table 1.

Sample preparation.

The breath sample is later transferred to collection fluid to trap the labelled CO2. The liquid sample is then analysed in a liquid scintillation counter.

Quality control.

A minimum of 1 mmol of CO2 is required to perform analysis of a breath sample. The amount of breath required to provide 1 mmol of CO2 varies depending on the amount of CO2 the patient is producing. Since a full balloon typically contains at least 1 mmol of CO2, the balloon should be completely filled.

Post treatment evaluation.

A negative PYtest 28 days after completing antibiotic treatment is evidence that the infection has been eradicated.

Results.

Interpretation of results (10 minute sample).

< 50 DPM Negative for H. pylori.
50-199 DPM Borderline positive for H. pylori.
≥ 200 DPM Positive for H. pylori.
Borderline positive results should be evaluated by repeating the PYtest or 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 (see Table 2) before repeating the PYtest. The cut-off point of 50 DPM was determined to be the mean +3SD of results obtained in-patients who did not have H. pylori.

Expected values.

As shown in Figure 2, approximately 30% of patients tested will be positive for H. pylori.

4.3 Contraindications

Hypersensitivity to the active substance, or any of the excipients.

4.4 Special Warnings and Precautions for Use

After the patient ingests the urea[14C] 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, a false positive test may occur due to urease associated with Helicobacters other than H. pylori (e.g. Helicobacter heilmanii).

Information for patients.

It is necessary for the patient to fast for 4 hours before the test. The patient should not have taken antibiotics or bismuth containing products for 1 month, sucralfate for 2 weeks and proton pump inhibitors for 1 week 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. The capsule should not be chewed.

Limitations of the test.

The test has been evaluated in outpatients before elective endoscopy.
Test results should be considered together with clinical signs and patient history when diagnosing 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.

Use in renal and hepatic impairment.

No data available.

Use in the elderly.

No data available.

Paediatric use.

Clinical studies in children have not been conducted. No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Antibiotics, proton pump inhibitors, sucralfate, and bismuth containing drug preparations are known to suppress H. pylori. Ingestion of antibiotics or bismuth within 4 weeks, sucralfate within 2 weeks or proton pump inhibitors within 1 week prior to performing the test may give false negative results.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal reproduction studies have not been conducted with PYtest (Urea[14C]). It is also not known whether PYtest can affect reproduction capacity.
Animal reproduction studies have not been conducted with PYtest (urea[14C]). It is also not known whether PYtest can cause foetal harm when administered to a pregnant woman.
When administration of PYtest to a woman of child-bearing potential is considered, information should always be sought about pregnancy.
 It is not known whether this drug is excreted in human milk.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of this registration.

4.8 Adverse Effects (Undesirable Effects)

There were no adverse reactions reported in clinical trials at a rate > 1%. All adverse reactions reported were felt by the investigators to be unrelated to the PYtest.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

In the event of overdose, the patient should drink one glass of water (150 mL) every hour to hasten excretion of the radioisotope. Maximum excretion of urea is achieved at a urine output of > 2.0 mL/min.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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 3.

Clinical trials.

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 a laboratory where they were read in a liquid scintillation counter. Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. A breath sample DPM < 50 was defined as a negative result. DPM ≥ 200 was defined as a positive result. DPM in the range of 50-199 was classified as indeterminate.

Study 1.

Of 186 patients who had histopathology and Campylobacter Like Organism [(CLO)test] (80 men, 106 women), 53 were infected with H. pylori as determined by agreement between histology and CLOtest. The study results are summarized in Table 3.

Study 2.

Breath tests were performed on seventy-six patients (40 men, 36 women) who had histology and CLOtest performed also. The results are summarized in Table 4.
See Table 5.

5.2 Pharmacokinetic Properties

Metabolism.

To detect H. pylori, urea labelled 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.

Excretion.

14CO2 is absorbed into the blood and exhaled in the breath.
Following ingestion of the capsule by a patient with H. pylori, 14CO2 excretion in the breath peaks between 10 and 15 minutes and declines thereafter with a biological half-life of about 15 minutes. 14C-urea that is not hydrolysed by H. pylori is excreted in the urine with a half-life of approximately 12 hours. About 10% of the 14C remains in the body at 72 hours and is gradually excreted with a biological half-life of 40 days.

5.3 Preclinical Safety Data

Radiation safety.

To allow radiation sources to be effectively compared emissions of various origins are expressed in terms of "effective dose" (ED). The ED of 14C takes into account the fraction of isotope sequestered in each organ tissue (as recommended by the International Commission for Radiological Protection 60 [ICRP-60] which is adopted in Australia), the biological half life of the isotope in that tissue, the effective energy of the beta particles compared with standard ionising radiation (200kV x-ray source) and the administered dose. ED is expressed in Sieverts (1 Sievert [Sv]; 10-6 Sv = 1 microSv). The maximum estimated ED received from a single administration of PYtest capsule (37 kBq of [14C]-urea) is 3 microSv; Figure 4 summarizes radiation exposure from the PYtest in comparison with other common sources of radiation exposure.
The Australian population is subjected to an annual radiation dose of about 1800 microSv to 2400 microSv per caput as a result of natural environmental radiation and the in vivo presence of radionuclides such as natural 14C and 40K in the body. 2400 microSv is equivalent to the radiation dose afforded by the ingestion of 800 PYtest capsules. A single PYtest procedure is the equivalent of about 11 hours of normal and essentially inevitable radiation exposure from the environment.

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

Radiation dosimetry.

Maximum effective dose (ED) (H. pylori positive): 3 microSv/37 kBq.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sugar spheres containing sucrose and starch 0.2 g (± 20%), fluorescein sodium 7.0 microgram (± 20%), gelatin.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

PYtest capsules and kit have a shelf life of three years.

6.4 Special Precautions for Storage

Store below 30°C in an area designated by each individual institution's regulations.

6.5 Nature and Contents of Container

PYtest capsules are supplied in unit dose packages of 1, 10 and 100.
PYtest kit (C14-Urea breath test) is supplied as a kit containing a PYtest capsule and breath collection accessories.
The PYtest kit contains:
One PYtest capsule.
Two 30 mL disposable cups.
One drinking straw.
One Pioneer brand Biax balloon.
One report form.
One mailing box with labels**.
** The kit includes analysis by Tri-Med Distributors Pty Ltd, of one balloon from one patient at one time point.

6.6 Special Precautions for Disposal

Because of the very low radioactivity of individual PYtest capsules, no special precautions are needed for the disposal of small numbers of capsules. Where it is necessary to dispose of large quantities of capsules, the disposal of waste should be carried out in accordance with the NHMRC Code of Practice for Disposal of Radioactive Waste by Users, (1985).

6.7 Physicochemical Properties

Chemical structure.

Molecular formula: NH214CONH2.

CAS number.

594-05-8.

Physical characteristics of 14C.

Radiation emission: Beta-emission, 49 keV mean, 156 keVmax, no other emissions.
External emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.
Physical half-life: 5730 years.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Summary Table of Changes