The Therapeutic Goods Administration (TGA) is investigating potential contamination of quinapril medicines with very low levels of the nitrosamine impurity N-nitroso-quinapril and in quinapril medicines with hydrochlorothiazide.
Quinapril, marketed in Australia under multiple trade names, is an angiotensin converting enzyme (ACE) inhibitor prescription medicine used to treat high blood pressure (also known as hypertension).
Hydrochlorothiazide, also marketed under multiple trade names, is a diuretic prescription medicine often used in combination with blood pressure medicines to reduce fluid retention.
The TGA has been advised that very low levels of the N-nitroso-quinapril have been detected in all quinapril products supplied in Australia, including when quinapril has been combined with hydrochlorothiazide. This issue also affects quinapril products and quinapril with hydrochlorothiazide supplied internationally.
As a precautionary measure, the sponsors of all marketed quinapril tablet products and quinapril with hydrochlorothiazide products have paused supply of these medicines while this issue is investigated. In addition, all batches of quinapril tablets and quinapril with hydrochlorothiazide tablets that were identified as containing unacceptable levels of N-nitroso-quinapril have been recalled from pharmacies. Details of the recalls can be found in the TGA's System for Australian Recall Actions database.
Pfizer Australia has notified the TGA of the shortage of their quinapril tablet and quinapril with hydrochlorothiazide tablet products. Generic Health and Arrotex Pharmaceuticals have also notified the TGA of shortages for their quinapril tablet products. Information about the shortages is published on the Medicine Shortage Reports Database.
Consumers are advised to continue to take their quinapril medicines as prescribed. Quinapril products will not be available while there is a shortage due to recalls. Patients should speak to their doctor regarding alternative treatment options. Patients should not stop taking their quinapril medicines unless instructed to by their doctor.
What is N-nitroso-quinapril?
N-Nitroso-quinapril is a type of nitrosamine that is present as an impurity. Nitrosamines are a group of compounds which can damage DNA. They are commonly found in low levels in a variety of foods, including smoked and cured meats, dairy products, vegetables, 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 that would be posed by the trace levels of N-nitroso-quinapril being detected in quinapril products is likely to be very low. However, the presence of nitrosamine impurities is generally considered unacceptable for a medicine. The actual health risk depends on the medicine and dose taken and will vary from person to person.
Nitrosamine impurities have also been found in other medicines. They were first identified in 'sartan' medicines in 2018. Medicines affected by nitrosamine impurities in Australia include 'sartan' blood pressure medicines in 2018, metformin and ranitidine products in 2019, varenicline products and rifampicin products in 2021, and sitagliptin products in 2022.
What should consumers do?
There is no immediate health risk from this issue as the risks are associated with long-term use.
Consumers who have been prescribed quinapril should speak to their doctor as soon as possible about an alternative treatment plan. There is a range of medicines available to effectively treat hypertension, and your doctor will be able to advise you about the most appropriate treatment options.
If you take quinapril medicines including quinapril with hydrochlorothiazide, contact your doctor to review your treatment. Do not stop your treatment before consulting your doctor. Suddenly stopping blood pressure medicines can pose a greater and more immediate risk to health than potential contamination with N-nitroso-quinapril.
Not all 'ACE inhibitor' medications are affected. People who use quinapril medicines, including quinapril with hydrochlorothiazide, may need to switch to alternative therapies because there is a shortage of quinapril products due to the recalls. There are other prescription medicines available to treat hypertension.
If you have any other questions or concerns about this issue, you should speak to your health professional.
What should health professionals do?
Please advise patients of this potential issue. It has been confirmed that N-nitroso-quinapril is present at very low levels in quinapril products supplied in Australia including in quinapril combined with hydrochlorothiazide products.
There will be limited availability of quinapril and quinapril with hydrochlorothiazide products due to the current shortage. Alternative treatment options should be considered while quinapril medicines are unavailable. Alternative management may include one of the multiple other single ingredient ACE inhibitor medicines supplied in Australia. There are also other treatments available for hypertension.
You may wish to reassure patients that that the risks posed by N-nitroso-quinapril at the trace levels observed are considered very low.
You may wish to advise patients to continue taking quinapril medicines as normal, until they have an alternative treatment in place.
What is the TGA doing?
The TGA is working with quinapril medicine sponsors to further investigate this issue and determine what actions may be required.
The TGA has reviewed results reported by sponsors of quinapril and quinapril with hydrochlorothiazide medicines on the ARTG.
Sponsors of affected medicines are taking corrective action to introduce impurity control measures to ensure that only batches of quinapril that comply with internationally acceptable intake limits are released.
The TGA and other international regulators will continue to monitor medicines to ensure that they meet appropriate quality standards.
Reporting problems
Consumers and health professionals can report problems with medicines or vaccines. The reports will contribute to the TGA's product monitoring.
The TGA cannot give advice about an individual's medical condition. Consumers are strongly encouraged to talk with a health professional if they are concerned about a possible adverse event associated with a medicine or vaccine.