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Update - contamination with N-nitrosodimethylamine
The below information (originally published 17 September 2019) has been updated with new information, including:
- publication of the TGA laboratory testing results, and
- an update on what steps the TGA is taking to ensure ranitidine products are safe for Australian consumers.
The TGA is advising consumers and health professionals that several ranitidine-containing products have been removed from the Australian market due to contamination with an impurity called N‑nitrosodimethylamine (NDMA).
Ranitidine tablets and oral liquids are now in short supply as a number of commonly-used brands have been recalled from pharmacies, hospitals, wholesalers, and other retail outlets, such as supermarkets and online stores. Additional brands may be recalled as TGA continues testing and discussions with companies that supply ranitidine.
Ranitidine, which is marketed in Australia under the brand name Zantac and various generic brands, is used to reduce stomach acid and is commonly used to treat heartburn. It may also be prescribed by a doctor to treat and prevent heartburn, reflux and ulcers.
Ranitidine is available in Australia as a prescription medicine and can also be purchased without a prescription from pharmacies, supermarkets and other retailers.
What is NDMA?
NDMA is a type of N-nitroso compound. N-nitroso compounds are commonly found in low levels in a variety of foods, particularly smoked and cured meats, as well as in some drinking water and in air pollution. Long-term exposure, over years, can increase an individual's risk of developing cancer.
The additional risk posed by NDMA from ranitidine, at the levels identified to date, is considered to be very low. However, such contamination is considered unacceptable for a medicine. The actual health risks depend on dose and will vary from person to person. The risks from short-term use of ranitidine are expected to be extremely low.
The TGA has been investigating NDMA and other N-nitroso compounds that have been found in 'sartan' blood pressure medicines since 2018.
What should consumers do?
There is no immediate health risk associated with this medication as the risks are associated with long-term use.
People who use ranitidine may need to switch to alternative therapies because there is a shortage of ranitidine tablets and oral liquids due to the recalls. There are other medicines available to treat heartburn, ulcers and reflux, including prescription medicines and products that can be purchased without a prescription from pharmacies, supermarkets and other retailers.
People who are taking ranitidine without a prescription should speak to their pharmacist about their treatment options. NPS Medicinewise has also published information about managing reflux and heartburn for consumers.
For people who have been prescribed ranitidine, the risks of not treating their condition may pose a greater risk to health than the potential contamination with NDMA. These people should speak to their doctor about an alternative treatment.
What should health professionals do?
Doctors who are treating patients with ranitidine may need to consider alternative management, as oral dose forms of ranitidine are in short supply.
Alternative management may include another H2 receptor antagonist, proton pump inhibitors, and/or diet and lifestyle modification. Guidance on the management of gastro-oesophageal reflux disease can be found on the NPS MedicineWise website.
The NPS MedicineWise website also provides advice about the treatment of acid reflux and bloating as part of the overall management of nausea and vomiting in pregnancy. The risks to the foetus associated with use in pregnancy of ranitidine contaminated with NDMA, at the levels observed to date, are expected to be very low. However, consideration should be given to alternative treatments while the issue is being investigated.
Pharmacists who are providing advice to patients accessing ranitidine over the counter should discuss treatment options and review whether ongoing pharmacotherapy is appropriate.
Health professionals can reassure patients that the additional risk posed by NDMA from ranitidine at the levels identified to date is very low. However, for patients who are currently taking ranitidine these risks may outweigh the clinical benefits.
Acceptable levels of nitrosamines are set in nanograms (ng). They are based on what is considered safe if a patient continues to take the affected medicine every day over a lifetime of 70 years. The levels of NDMA contamination detected in ranitidine to date, if taken over decades, may modestly increase an individual's risk of developing cancer. While acceptable levels have been derived from animal carcinogenicity studies and incorporate a wide margin of safety, it is not possible to provide an accurate number estimate of the magnitude of carcinogenic risk associated with NDMA contamination based on currently available safety data.
What is the TGA doing?
The TGA is working with international regulators and medicine sponsors to investigate this issue. The TGA has undertaken laboratory testing of Australian ranitidine medications to determine if these batches are affected. The TGA has published a detailed testing report.
A number of recalls are being undertaken in relation to this issue. The TGA continues to work with sponsors to determine suitable actions on a case-by-case basis.
The TGA is also introducing new requirements for ranitidine products to ensure that they do not contain unacceptable levels of NDMA. The internationally agreed limits for NDMA are set so that an individual who takes a product over their life-time (70 years) will not increase their risk of cancer by more than 1 in 100,000, based on animal studies. Additionally, the TGA is considering suspending the registration for products which cannot demonstrate adequate safety and quality.
Notifications of shortages of prescription ranitidine products and alternative prescription medicines used to treat the same conditions will be published via the TGA's Medicines Shortage Information Initiative.
Retail level recalls relating to this issue are being undertaken for various strengths, pack sizes and dosage forms for:
- Sandoz ranitidine (marketed under the brand names "Sandoz Ranitidine" and "Mylanta Ranitidine")
- Aspen ranitidine (marketed under the brand name "Zantac")
- Alphapharm ranitidine (marketed under the brand name "RANI 2")
- Apotex ranitidine (marketed under the brand names "APO", "CHEMMART", "TERRY WHITE CHEMISTS" and "APOHEALTH")
- Symbion ranitidine (marketed under the brand names "Pharmacy Choice Acid and Heartburn Relief" / "Extra Strength")
- Cipla Australia ranitidine (marketed under the brand names "AMCAL" and "Pharmacy Care" and "Priceline Reflux Relief Extra Strength Ranitidine")
- Generic Health ranitidine (marketed under the brand name "Pharmacy Action").
- Nova Pharmaceuticals Australasia ranitidine (marketed under the brand names "Coles (and) Medix Heartburn & Acid Indigestion").
- Australian Pharmaceutical Industries Ltd t/a Soul Pattinson Manufacturing ranitidine (marketed under the brand names "Pharmacy Health (and) Priceline Pharmacy Reflux Relief Extra Strength Ranitidine" and "Terrywhite Chemmart Heartburn Relief Extra Strength Ranitidine")
- Arrow Pharma ranitidine (marketed under the brand names "AUSRAN Ranitidine", "CHEMIST'S OWN RANITIDINE FORTE" and "CHEMIST'S OWN RANITIDINE").
- Note: while ALL batches of the previous nine sponsor's products are being recalled, following TGA testing, only some batches of Arrow Pharma ranitidine are being recalled. Refer to the System for Australian Recall Actions (SARA) database for specific, affected batch numbers and expiry dates.
Details of these recall actions will appear in the TGA's SARA database. Search for 'ranitidine' in the field under '2. Select products' and tick the brand names of any products you would like to view.
The recall actions being undertaken in Australia are consistent with actions being taken in other countries globally.
Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.
The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.