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 Australian quinapril products 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 sponsor of Accupril and Accuretic/Aquinaretic, Pfizer Australia has paused supply of their quinapril products while this issue is investigated. In addition, all batches of Accupril and Accuretic/Aquinaretic tablets have been recalled from pharmacies that were identified as containing unacceptable levels of N-nitroso-quinapril. Details of this recall 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. Information about the shortages is published on the Medicine Shortage Reports Database.
Consumers are advised to continue to take their quinapril medicines as prescribed. Patients should not stop taking their quinapril medicines unless instructed to by their health professional.
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.
What should consumers do?
There is no immediate health risk from this issue as the risks are associated with long-term use.
If you take quinapril medicines including quinapril with hydrochlorothiazide, do not stop your treatment without first consulting a doctor or pharmacist.
Consumers should be aware that not all 'ACE inhibitor' medications are affected. Suddenly stopping blood pressure medicines can pose a greater and more immediate risk to health than potential contamination with N-nitroso-quinapril.
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. Consumers who have been prescribed quinapril should speak to their doctor about an alternative treatment.
If you have any other questions or concerns about this issue, you should speak to your health professional.
What should health professionals do?
Please be aware of this potential issue and advise patients accordingly. 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.
Health professionals should be aware that there may be limited availability of quinapril and quinapril with hydrochlorothiazide products due to the current shortage . Alternative treatment options should be considered while Accupril and Accuretic/Acquinapril 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 remind patients to keep taking their medicines as normal, in line with the instructions in the Product Information and reassure them that that the risks posed by N-nitroso-quinapril at the trace levels observed overseas are considered very low.
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.