Helicobacter Test INFAI: Uses, Dosage & Side Effects

What Is Helicobacter Test INFAI and What Is It Used For?

Helicobacter Test INFAI contains 75 mg of 13C-urea as the active substance. 13C-urea is urea in which the carbon atom has been replaced with the stable isotope carbon-13 (13C), a naturally occurring, non-radioactive form of carbon that makes up approximately 1.1% of all carbon in nature. Unlike the radioactive carbon-14 (14C) used in older breath tests, 13C is entirely safe and does not expose the patient to any ionizing radiation, making it suitable for repeated testing and use in children and pregnant women when clinically indicated.

Helicobacter pylori is a gram-negative, spiral-shaped bacterium that colonizes the gastric mucosa of approximately half of the world's population. First identified by Barry Marshall and Robin Warren in 1982 (a discovery that earned them the 2005 Nobel Prize in Physiology or Medicine), H. pylori is now recognized as the primary cause of chronic gastritis, the dominant risk factor for peptic ulcer disease (responsible for approximately 80–90% of duodenal ulcers and 60–70% of gastric ulcers), and a WHO Class I carcinogen associated with gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Accurate detection of this organism is therefore of critical importance in clinical gastroenterology.

The principle underlying the 13C-urea breath test is elegantly simple. H. pylori produces exceptionally large quantities of the enzyme urease, which catalyses the hydrolysis of urea into carbon dioxide (CO₂) and ammonia (NH₃). The ammonia serves to neutralize gastric acid in the bacterium's immediate environment, creating a protective alkaline microenvironment that allows H. pylori to survive in the otherwise hostile acidic conditions of the stomach. When a patient ingests 13C-labelled urea, the bacterial urease cleaves the labelled urea, releasing 13CO₂. This 13CO₂ is rapidly absorbed across the gastric and intestinal epithelium into the bloodstream, transported to the lungs, and exhaled in the breath. By comparing the ratio of 13CO₂ to 12CO₂ in exhaled breath before and 30 minutes after ingestion of the labelled urea, the test can determine whether active urease-producing H. pylori organisms are present in the stomach.

The analytical measurement of the 13CO₂/12CO₂ ratio is performed using either isotope ratio mass spectrometry (IRMS) or non-dispersive infrared spectroscopy (NDIRS). The result is expressed as a delta over baseline (DOB) value, representing the change in the 13CO₂/12CO₂ ratio compared to the baseline breath sample. A DOB value exceeding a defined cut-off (typically 4.0‰ for the Helicobacter Test INFAI) indicates the presence of active H. pylori infection, while a value below this threshold indicates the absence of infection or successful eradication.

Helicobacter Test INFAI is indicated for two primary clinical scenarios. First, it is used for the initial diagnosis of H. pylori infection in patients presenting with symptoms suggestive of peptic ulcer disease, dyspepsia, or other H. pylori-related conditions where non-invasive testing is appropriate according to the “test and treat” strategy recommended by international guidelines. Second, and equally importantly, it is used for confirmation of eradication after completion of H. pylori eradication therapy. Verification of successful eradication is critical because treatment failure occurs in 10–30% of patients depending on the regimen used and local antibiotic resistance patterns. Current guidelines recommend performing the breath test at least 4 weeks after completing eradication therapy to avoid false-negative results.

What Should You Know Before Taking Helicobacter Test INFAI?

Contraindications

There are no absolute contraindications to the use of Helicobacter Test INFAI in terms of patient safety, as 13C-urea is a naturally occurring substance and the dose used (75 mg) is physiologically insignificant. However, the test should not be used as a substitute for endoscopy with biopsy when there is clinical suspicion of gastric malignancy or when alarm symptoms are present, including unintended weight loss, dysphagia, persistent vomiting, gastrointestinal bleeding, iron deficiency anaemia, or an abdominal mass. In patients over 60 years with new-onset dyspepsia, guidelines generally recommend endoscopy rather than non-invasive testing to exclude malignancy.

The test is also not recommended in patients who have undergone partial gastrectomy, as the altered gastric anatomy may affect the reliability of results. Similarly, patients with achlorhydria (absence of gastric acid secretion) may have altered test dynamics, although the clinical significance of this is debated.

Warnings and Precautions

The accuracy of the 13C-urea breath test depends critically on appropriate patient preparation. The following medications can suppress H. pylori urease activity or reduce bacterial load without achieving complete eradication, potentially leading to false-negative results:

• Proton pump inhibitors (PPIs): Omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, and all other PPIs must be discontinued for at least 14 days before testing. PPIs have direct bacteriostatic effects on H. pylori and can redistribute the organism from the antrum to the corpus, reducing urease activity in the stomach.
• Antibiotics: All antibiotics, regardless of the reason for prescription, must be stopped at least 4 weeks (28 days) before the breath test. Even antibiotics prescribed for conditions unrelated to H. pylori (such as respiratory or urinary tract infections) can temporarily suppress the gastric bacterial population.
• Bismuth-containing preparations: Bismuth subsalicylate (Pepto-Bismol), bismuth subcitrate, and other bismuth compounds have direct antimicrobial activity against H. pylori and must be discontinued for at least 4 weeks before testing.
• H2-receptor antagonists: Ranitidine, famotidine, and other H2 blockers should ideally be stopped at least 24 hours before the test, although their impact on test accuracy is less pronounced than that of PPIs.

Additionally, patients should fast for a minimum of 6 hours before the test. Overnight fasting is recommended as the optimal preparation. Food in the stomach can interfere with the test by diluting the 13C-urea solution, delaying gastric emptying, and potentially affecting the baseline 13CO₂ measurement. Patients should not smoke, chew gum, or engage in vigorous physical exercise on the morning of the test, as these activities can alter the 13CO₂/12CO₂ ratio in exhaled breath.

Pregnancy and Breastfeeding

13C-urea is a stable, non-radioactive isotope that occurs naturally in the body. The 75 mg dose used in the test is negligible compared to the approximately 12–20 grams of urea that the body produces daily through normal protein metabolism. There are no known risks associated with the use of Helicobacter Test INFAI during pregnancy or breastfeeding. However, as with all diagnostic procedures during pregnancy, the test should only be performed when the clinical benefit of diagnosing or excluding H. pylori infection outweighs any theoretical concerns. In practice, the test is considered safe for use in pregnant and breastfeeding women, and no special precautions are required. No adverse reproductive outcomes have been reported in either animal studies or post-marketing surveillance.

Children and Adolescents

Helicobacter Test INFAI is approved for use in children aged 3 years and older. For children aged 3 to 11 years, the same 75 mg dose of 13C-urea is used, but the volume of the test meal (orange juice) is reduced to 100 mL instead of the standard 200 mL used in adults and adolescents aged 12 and older. The test is performed in an identical manner to adult testing, and diagnostic accuracy in children is comparable to that observed in adults. Children under 3 years of age should not undergo this test because there are insufficient data on the reliability and cut-off values in this very young age group. In paediatric populations, international guidelines (ESPGHAN/NASPGHAN) generally recommend invasive testing with endoscopy and biopsy as the primary diagnostic approach rather than the “test and treat” strategy used in adults, reserving the breath test primarily for confirming eradication after treatment.

How Does Helicobacter Test INFAI Interact with Other Drugs?

Since Helicobacter Test INFAI is a diagnostic agent rather than a therapeutic drug, it does not interact with other medications through pharmacokinetic or pharmacodynamic mechanisms. The 13C-urea is not metabolized by cytochrome P450 enzymes, does not bind to plasma proteins, and does not affect any physiological processes at the diagnostic dose of 75 mg. However, the diagnostic accuracy of the test can be significantly affected by concomitant or recent use of certain medications that interfere with H. pylori colonization, urease activity, or gastric physiology.

The following table summarizes the medications that can affect the results of the Helicobacter Test INFAI and the required washout periods before testing:

Major Interactions (False-Negative Risk)

The most clinically significant interactions are with PPIs and antibiotics. Proton pump inhibitors do not merely raise gastric pH; they have direct antibacterial effects on H. pylori by inhibiting bacterial urease and ATPase enzymes. This dual mechanism means that even short courses of PPI therapy can substantially reduce H. pylori urease activity and bacterial density, particularly in the gastric antrum where the highest density of organisms is typically found. Studies have demonstrated that the false-negative rate of the 13C-urea breath test can increase to 20–30% in patients who have taken PPIs within the preceding 2 weeks.

Antibiotics represent an even greater concern for false-negative results. Even a single dose of an antibiotic with activity against H. pylori (such as amoxicillin or clarithromycin) can transiently suppress the bacterial population below the detection threshold of the breath test. This is why a 4-week washout period is mandatory, allowing sufficient time for any surviving bacteria to repopulate to detectable levels if eradication was not achieved.

Minor Interactions

H2-receptor antagonists have a relatively minor effect on test accuracy compared to PPIs. Their mechanism of action (competitive inhibition of histamine H2 receptors on parietal cells) reduces gastric acid secretion without directly affecting H. pylori urease activity. A 24-hour washout period is generally sufficient. Antacids (such as aluminium hydroxide, magnesium hydroxide, and calcium carbonate) do not significantly affect the accuracy of the breath test and do not require discontinuation, although it is advisable not to take them on the morning of the test.

Potassium-competitive acid blockers (P-CABs), such as vonoprazan, are newer acid-suppressive agents that are increasingly used in H. pylori eradication regimens. Like PPIs, P-CABs may affect breath test accuracy and should be discontinued for at least 2 weeks before testing, although specific data on the optimal washout period for P-CABs are still emerging.

What Is the Correct Dosage of Helicobacter Test INFAI?

Adults and Adolescents (12 Years and Older)

The complete test procedure is performed as follows. The patient must have fasted for at least 6 hours (overnight fasting is recommended). The patient is seated comfortably and begins by providing a baseline breath sample by blowing into the first breath collection tube or bag. This baseline sample establishes the patient's natural 13CO₂/12CO₂ ratio before the test substance is administered.

Next, the patient drinks 200 mL of 100% orange juice. The orange juice serves as a “test meal” with two important functions: it delays gastric emptying to ensure adequate contact time between the 13C-urea and any H. pylori organisms in the stomach, and its citric acid content stimulates the closure of the pyloric sphincter, retaining the urea solution in the stomach for an optimal duration. In patients who cannot tolerate orange juice (for example, due to citrus allergy), an alternative test meal of 1 g of citric acid dissolved in 200 mL of water may be used.

Immediately after finishing the test meal, the patient dissolves the contents of the container (75 mg 13C-urea) in approximately 50 mL of water and drinks the solution. The patient then remains seated and at rest for exactly 30 minutes, during which time no food, drink, smoking, or physical exertion is permitted. After 30 minutes, the patient provides a second breath sample by blowing into the second collection tube or bag. Both breath samples are sealed, labelled, and sent to a qualified laboratory for analysis.

Children (3–11 Years)

The test procedure for children aged 3 to 11 years is identical to the adult procedure except that the volume of the test meal is reduced from 200 mL to 100 mL of orange juice. The dose of 13C-urea remains the same at 75 mg. Children should be accompanied by a parent or guardian during the test. It is important that children understand the need to remain still and not eat, drink, or engage in physical activity during the 30-minute waiting period. For very young children who may have difficulty blowing into breath collection tubes, special paediatric collection bags with face masks are available. The diagnostic cut-off value (DOB threshold) for children is the same as for adults.

Elderly Patients

No dose adjustment is required for elderly patients. The standard 75 mg dose and the standard test procedure apply regardless of the patient's age. The diagnostic performance of the 13C-urea breath test is not significantly affected by age, and the test is well tolerated in elderly populations. However, particular attention should be paid to the medication washout requirements in elderly patients, who are more likely to be taking PPIs, antibiotics, or other medications that can affect test results. Healthcare providers should carefully review the medication list of elderly patients before scheduling the test and plan appropriate washout periods.

Missed Dose

The concept of a missed dose does not apply to Helicobacter Test INFAI, as it is a single-administration diagnostic test rather than a regularly scheduled medication. If the test is not completed (for example, if the patient vomits the urea solution before the 30-minute collection period, or if a breath sample is not properly collected), the test should be rescheduled and repeated in its entirety on another day. There is no risk associated with repeating the test, as the 13C-urea is completely non-toxic at the diagnostic dose.

Overdose

Overdose with Helicobacter Test INFAI is not a clinical concern. The 75 mg dose of 13C-urea represents a negligible fraction of the body's daily urea turnover. The human body produces approximately 12–20 grams of urea per day through normal hepatic metabolism of amino acids, and circulating blood urea levels are typically in the range of 2.5–7.8 mmol/L (15–47 mg/dL). Even if the entire contents of several test containers were ingested simultaneously, the additional urea load would be insignificant in physiological terms. No cases of overdose or adverse effects from excessive dosing have been reported in clinical trials or post-marketing surveillance. No specific antidote is required, and no treatment measures would be necessary.

What Are the Side Effects of Helicobacter Test INFAI?

Helicobacter Test INFAI has an exceptional safety profile. Since its initial approval by the European Medicines Agency, the test has been used in millions of patients worldwide, and no adverse drug reactions attributable to the 13C-urea have been identified. This outstanding safety record reflects the nature of the test substance: 13C-urea is a naturally occurring molecule. The carbon-13 isotope is a stable, non-radioactive isotope that constitutes approximately 1.1% of all carbon atoms in nature and is already present in every cell, tissue, and organ in the human body.

The 75 mg dose of urea administered during the test is physiologically insignificant when compared to the body's endogenous urea production. The human liver produces approximately 12–20 grams of urea per day as the end product of protein catabolism via the urea cycle. The test dose of 75 mg (0.075 grams) represents less than 0.6% of the daily urea production, an amount that has no measurable effect on blood urea nitrogen levels, kidney function, or any metabolic parameter.

The following frequency grid reflects the adverse event profile of Helicobacter Test INFAI as reported in the Summary of Product Characteristics (SmPC) and based on over 20 years of clinical use and pharmacovigilance data:

While the 13C-urea itself causes no side effects, it is worth noting that some patients may experience mild discomfort related to the test procedure rather than the test substance. These procedure-related effects are not adverse drug reactions but may include:

• Mild nausea: Rarely, patients may feel slightly nauseous after drinking the orange juice test meal on an empty stomach, particularly patients who are prone to gastric sensitivity. This is related to the test meal, not the 13C-urea.
• Bloating or fullness: The combination of 200 mL of orange juice and 50 mL of urea solution on an empty stomach may cause a transient feeling of fullness in some patients.
• Discomfort from fasting: Some patients, particularly those with diabetes or other metabolic conditions, may experience discomfort from the required 6-hour fast before the test.

These mild, transient effects are self-limiting and resolve spontaneously after the test is completed. They do not constitute adverse reactions to the medicinal product and are not reported in the product's SmPC.

How Should You Store Helicobacter Test INFAI?

Helicobacter Test INFAI should be stored at a temperature not exceeding 25°C (77°F). The product does not require refrigeration, and no special storage conditions such as protection from light or moisture are necessary. The 13C-urea powder is a stable, crystalline substance that maintains its chemical integrity under normal room temperature conditions for the duration of its shelf life.

The product should be kept in its original packaging until the time of use to protect the powder from accidental spillage and to ensure that the labelling information, including the batch number and expiry date, remains accessible. Each test kit contains individual containers of 13C-urea powder, breath collection materials, and a patient record form. The kit should not be opened until the test is to be performed.

As with all medicinal products, Helicobacter Test INFAI should be kept out of the reach and sight of children. While accidental ingestion of the 13C-urea powder by a child would not be harmful (given the negligible amount and non-toxic nature of the substance), the product is a prescription medical device intended for use under professional supervision.

Do not use Helicobacter Test INFAI after the expiry date stated on the outer packaging and the container label. The expiry date refers to the last day of that month. Once the 13C-urea powder has been dissolved in water, the solution should be consumed immediately. The dissolved solution should not be stored for later use, as the stability of the solution after reconstitution has not been validated.

Unused product and waste materials should be disposed of in accordance with local regulations for pharmaceutical waste. The 13C-urea is not classified as hazardous waste and can be disposed of through standard pharmaceutical waste collection systems.

What Does Helicobacter Test INFAI Contain?

Helicobacter Test INFAI has an exceptionally simple composition. Each sealed glass container holds 75 mg of 13C-urea (carbon-13 labelled urea) as a white, crystalline powder. The 13C-urea is the only active ingredient and the only substance present in the container. Unlike most pharmaceutical products, Helicobacter Test INFAI contains no excipients, binders, fillers, preservatives, colourings, flavourings, or coating agents whatsoever. This simplicity minimizes the risk of allergic reactions or intolerances and makes the product suitable for patients with multiple drug sensitivities or specific dietary restrictions.

The 13C-urea used in the test is produced by chemical synthesis using carbon dioxide enriched with the stable isotope carbon-13. The 13C enrichment of the urea is greater than 99 atom percent, meaning that virtually all of the carbon atoms in the urea molecules are the 13C isotope rather than the more common 12C isotope. This high level of enrichment is essential for the diagnostic sensitivity of the test, as it ensures that a measurable change in the 13CO₂/12CO₂ ratio can be detected in exhaled breath even with the small 75 mg dose.

The molecular formula of urea is CO(NH₂)₂, and the molecular weight of 13C-urea is 61.06 g/mol (compared to 60.06 g/mol for ordinary 12C-urea). Urea is a colourless, odourless, highly water-soluble organic compound that is the primary end product of nitrogen metabolism in mammals. It is produced by the liver through the urea cycle and excreted by the kidneys. In the body, urea is present in blood, urine, sweat, and all body fluids at concentrations of 2.5–7.8 mmol/L in plasma under normal physiological conditions.

The complete Helicobacter Test INFAI kit typically includes:

• One sealed container with 75 mg 13C-urea powder
• Two breath collection tubes or bags (for baseline and post-dose samples)
• A straw or mouthpiece for breath collection
• A patient record form with pre-printed labels
• A package insert with instructions for use
• A padded return envelope for mailing samples to the analysis laboratory

The breath collection tubes or bags are inert, sealed containers designed to preserve the 13CO₂/12CO₂ ratio of the exhaled breath sample during transport to the laboratory. They are typically stable for several weeks at room temperature, allowing samples to be collected at remote locations and shipped to centralized analytical laboratories without loss of accuracy.