Diabact
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Diabact (Diabact)
Composition:
Active substance: 13C-urea;
One tablet contains 13C-urea 50 mg;
Excipients: anhydrous citric acid, sodium croscarmellose, microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate, talc.
Pharmaceutical form. Tablets.
Main physico-chemical characteristics: white, round, convex tablets, 12 mm in diameter.
Pharmacotherapeutic group.
Other diagnostic agents. 13C-urea. ATC code V04CX05.
Pharmacological properties.
Pharmacodynamics.
Mechanism of action
After oral administration, tablets containing 13C-labelled urea rapidly disintegrate upon entering the stomach. In the case of H. pylori infection, 13C-urea is metabolized by H. pylori urease.
The enzyme urease
H2N(13CO)NH2 + H2O → 2NH3 + 13CO2
The carbon dioxide produced diffuses into blood vessels and is transported as bicarbonate to the lungs, where it is subsequently exhaled as 13CO2 in breath. H. pylori infection significantly alters the ratio of carbon isotopes 13C/12C.
The proportion of 13CO2 in breath samples is determined by isotope ratio mass spectrometry (IRMS) or another appropriate validated method performed by any qualified laboratory and defined as the absolute quantitative difference (excess) between breath samples collected before and after urea administration (see section "Directions for use and dosage").
The cut-off value for differentiating H. pylori-positive and H. pylori-negative patients was established in a study involving 885 patients. Values below 1.5 ‰, i.e., ≤ 1.5 ‰, are considered negative, while values above, i.e., > 1.5 ‰, are considered positive.
To determine test performance and compensate for the lack of direct comparison with the standard of truth (SoT) for the registered dose, a simulation analysis was conducted based on two comparative studies: sensitivity was 94.3% (95% CI = [85.1–98.5%]), specificity was 97.1% (95% CI = [92.4–99.2%]). Accuracy was 96.2% (95% CI = [92.2–98.5%]), PPV (positive predictive value) was 94.0% (95% CI = [84.6–98.3%]), and NPV (negative predictive value) was 97.3% (95% CI = [92.7–99.3%]).
Pharmacokinetics.
Absorption
Urea is rapidly absorbed from the gastrointestinal tract.
Distribution
Urea distributes into extracellular and intracellular fluids, including lymph, bile, cerebrospinal fluid, and blood. It has been reported to cross the placenta and penetrate into the eye.
Elimination
Urea is excreted unchanged in urine.
Clinical characteristics.
Indications.
This medicinal product is intended for diagnostic use only.
For the in vivo diagnosis of primary or residual gastritis and duodenal infection with Helicobacter pylori.
Contraindications.
This test must not be performed in patients with documented or suspected gastric infection that could interfere with the urea breath test.
Hypersensitivity to the active substance or to any of the excipients.
Interaction with other medicinal products and other forms of interaction.
The reliability of the test results may be compromised if the patient is currently being treated with antibiotics or proton pump inhibitors, or has recently completed therapy with these medicinal products. Results may generally be affected by any treatment influencing the H. pylori status or urease activity.
Suppression of H. pylori may lead to false-negative results. Therefore, the test should not be performed within at least four weeks after systemic antibacterial therapy and at least two weeks after the last dose of acid secretion-inhibiting agents. This is particularly important following eradication therapy.
Special precautions for use.
A single positive urea breath test result is not a clinical confirmation for prescribing eradication therapy. Alternative diagnostics using invasive endoscopic methods may be indicated to determine the presence of any other complications, such as gastric ulcer, autoimmune gastritis, or malignant diseases.
There are insufficient data to recommend the use of Diabact in patients with partial gastrectomy.
Use during pregnancy or breastfeeding.
Endogenous urea production amounts to 25–35 g/day. Therefore, it is unlikely that a 50 mg dose of urea could cause any adverse effects in pregnant women or women who are breastfeeding.
No harmful effect of the medicinal product Diabact is expected on the fetus/newborn when the test is performed during pregnancy or breastfeeding. Diabact can be used during pregnancy and breastfeeding.
Ability to influence the reaction rate while driving or operating machinery.
The medicinal product Diabact has no effect or has a negligible effect on the reaction rate while driving or operating machinery.
Method of Administration and Dosage
Dosage
One tablet as a single dose for one test procedure.
Method of Administration
The medicinal product Diabact in tablet form is intended for oral administration. The patient should not eat for at least six hours prior to the test. An initial exhaled air sample is collected, after which the patient must swallow the whole tablet with a glass of water. Ten minutes later, a second exhaled air sample is collected.
If the patient chews the tablet, the test must be repeated, as the risk of false-positive results increases. A new test may be performed the following day.
The test should be conducted in the presence of a qualified healthcare professional.
If the test is performed in the morning, the patient should not eat during the night and should not have breakfast. If the test is performed later in the day, or if fasting is problematic for the patient, only a light breakfast (e.g., tea and toast) is recommended. If the patient has consumed a substantial meal, no further food should be taken for six hours before the test.
Collection of exhaled air samples can be carried out using sample tubes or air bags. Air bags are supplied separately.
Care should be taken when handling sample tubes and air bags to avoid any damage that could lead to leakage.
Step-by-step description of the test procedure using sample tubes (see Fig. 1)
For the test, 4 sample tubes with caps and 1 straw are used.
One additional barcode label should be retained as a reference label for the patient's medical records.
- The patient begins the procedure by exhaling into two baseline (00-minute) sample tubes with blue caps.
- Unscrew the cap and place the straw to the bottom of the tube.
- Take a deep breath and gently exhale into the tube.
- Remove the straw from the tube and close the tube with the cap. Ensure the cap is properly sealed.
- Repeat the procedure with the second 00-minute tube.
- Swallow the tablet with a glass of water. Wait 10 minutes in an upright position (sitting or standing).
- Exhale into two 10-minute sample tubes with red caps in the same manner as described above.
Fig. 1. Performing the test using sample tubes.
After completing the test, the 4 tubes should be labeled as shown below, with one barcode label applied lengthwise on each tube (see Fig. 2).
Fig. 2. Applying the barcode label.
The 4 labeled sample tubes should be sent to the local diagnostic laboratory for analysis.
Step-by-step description of the test procedure using exhaled air bags (see Fig. 3)
For the test, 1 double air bag or 2 single air bags and 1 mouthpiece are used.
- The patient begins the procedure by exhaling through the mouthpiece into the baseline (00-minute) air bag.
- Remove the cap from the air bag tubing and attach the mouthpiece to the tubing.
- Take a deep breath and exhale through the mouthpiece connected to the air bag.
- Remove the mouthpiece from the air bag and seal the bag with the cap.
- Swallow the tablet with a glass of water. Wait 10 minutes in an upright position (sitting or standing).
- Exhale into the unused half of the double air bag or into another single air bag to obtain the 10-minute sample, as described above.
Label the air bags to identify the different samples (e.g., “00-minute” and “10-minute”).
Fig. 3. Performing the test using air bags.
Analysis of Exhaled Air Samples
Ensure that the analysis is performed by an approved and certified/accredited laboratory. Laboratories and analytical equipment used must comply with the requirements of the Technical Regulation on Medical Devices and the Technical Regulation on in vitro Diagnostic Medical Devices. These technical regulations require that analytical equipment must bear the conformity marking and be approved for the analysis of breath test samples.
Interpretation of Test Results
Δ δ-value: the difference in parts per thousand (‰) between the 00-minute value and the 10-minute value.
H. pylori status:
≤ 1.5 ‰ Δ δ-value = negative H. pylori status.
1.5 ‰ Δ δ-value = positive H. pylori status.
Any unused medicinal product or waste material must be disposed of in accordance with local requirements.
Children
There are insufficient data to recommend the use of Diabact in patients under 18 years of age.
Overdose
Overdose is unlikely under conditions of clinical use as prescribed. No cases of overdose have been reported.
Side effects.
In one clinical study, isolated reports of stomach pain, fatigue, and smell disorders (parosmia) were recorded.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after a medicinal product has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.
Shelf life. 4 years.
Storage conditions. Store at a temperature not exceeding 25 °C. Keep in the original packaging to protect from light. Store out of reach of children.
Packaging.
- 1 tablet in a blister; 1 blister together with 2 glass vials with blue caps for the 00-minute breath sample, 2 glass vials with red caps for the 10-minute breath sample, 1 single-use straw, 4 barcode labels for the 4 vials for samples, and 2 additional barcode labels, all in a polyethylene bag, placed in a cardboard box.
- 1 tablet in a blister; 10 blisters in a cardboard box.
Prescription category. Prescription only.
Manufacturer.
Laboratoires Mayoly Spindler.
Manufacturer's location and address of its site of operation.
6, Avenue de l’Europe, 78400 Chatou, France.