Transitioning people off Accuretic
5 minutes to Read
Contributor
Dr Noni Richards
4 July 2022
Quinapril image

The antihypertensive medicine Accuretic (quinapril with hydrochlorothiazide) is being withdrawn and prescribers are advised to change patients from Accuretic to alternative medicine(s) with some urgency.

Pfizer pulled stock from distribution on 31 October 2022.

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Accuretic is being withdrawn

Accuretic (quinapril 10mg + hydrochlorothiazide 12.5mg and quinapril 20mg + hydrochlorothiazide 12.5mg) is indicated in New Zealand for the treatment of hypertension in patients not adequately controlled with monotherapy.

Pfizer test results have identified the levels of N-nitroso-quinapril exceed the acceptable daily intake (ADI) level in their Accuretic products. This is a global issue, with voluntary recalls happening in other countries, including in Australia, Europe, the US, and Canada. Medsafe has issued a safety alert and Pharmac has advised prescribers to stop prescribing Accuretic and to urgently switch patients currently taking Accuretic to alternative options.

At the time of publishing, in New Zealand 35,077 people were taking Accuretic: 23,825 patients were taking Accuretic (20mg + 12.5mg) and 11,252 were taking Accuretic (10mg + 12.5mg). Almost all practices in New Zealand (98 per cent) had at least one enrolled patient taking Accuretic.

N-Nitroso-quinapril is a nitrosamine. Nitrosamines can be found in water and foods, including cured and grilled meats, dairy products and vegetables and are classified as probable human carcinogens (substances that could cause cancer). Nitrosamine impurities may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time.

For this reason, Pharmac is advising prescribers to:

  • Not start any new patients on Accuretic.
  • Urgently switch patients currently taking Accuretic to an alternative ACE inhibitor/angiotensin II receptor blocker (ACEI/ARB) or an alternative blood pressure-lowering medicine.

Current supplies of Accuretic will begin to be disrupted from August 2022, therefore this switch is required as soon as possible. Once supplies of Accuretic are exhausted, it is unlikely to be available again for at least 12 months. People currently taking Accuretic must continue taking it until an alternative has been prescribed, as the risk of suddenly stopping medication for blood pressure is higher than the potential risk presented by the impurity.

Switching advice

A straight switch from Accuretic to another brand of quinapril + hydrochlorothiazide is not possible as no other combined tablet is available in New Zealand. Although the single agent quinapril tablet remains available, and has not been affected by the Accuretic impurity, hydrochlorothiazide is not available here as a single agent to use alongside it.

Therefore, alternative fully funded options to Accuretic include a combination ARB + hydrochlorothiazide, OR quinapril (single agent) or another ACEI/ARB used in combination with a different thiazide or thiazide-like diuretic. Current options for switching from Accuretic to other agent(s) are:

  • losartan + hydrochlorothiazide – this is the only alternative funded ACEI/ARB + thiazide diuretic combination available
  • quinapril (single agent) or another ACEI/ARB, in combination with a thiazide or thiazide-like diuretic such as bendroflumethiazide
  • alternative blood-pressure-lowering medicine(s).

It is possible to discontinue an ACEI one day and start another ACEI or ARB the following day.2 This is also true for changing a thiazide diuretic.

Examples of each of these three options are given in the coloured panels below.

Changing from Accuretic to losartan + hydrochlorothiazide

This may be the easiest option for the patient as it enables the continuation of treatment with a single tablet.

In this combination product the dose of hydrochlorothiazide is the same as in the Accuretic formulations, but only one strength of losartan is currently available (ie, losartan 50mg + hydrochlorothiazide 12.5mg). Refer to Table 1, below, for dose equivalence of losartan to quinapril.

Example: For a patient taking once daily Accuretic (quinapril 10mg or 20mg + hydrochlorothiazide 12.5mg) change to once daily losartan + hydrochlorothiazide (50mg + 12.5mg). Monitor blood pressure after two to four weeks; the dose may need increasing if blood pressure is elevated beyond baseline after four weeks.

Changing from Accuretic to quinapril (single agent) or another ACEI/ARB in combination with a thiazide or thiazide-like diuretic

This gives the option of enabling the patient to continue to use quinapril but will require adding a thiazide or thiazide-like diuretic as a separate tablet. Alternatively, another ACEI/ARB may be used instead of quinapril, with a thiazide or thiazide-like diuretic added as a separate tablet. These options increase the pill burden for patients and may be problematic for people who are already experiencing polypharmacy. The steps for this change are:

  • prescribe the same dose of quinapril that the patient had on Accuretic; or prescribe an equivalent dose of another ACEI or ARB, using Table 1 (below) as a guide, and
  • prescribe an equivalent dose of a thiazide or thiazide-like diuretic to the hydrochlorothiazide dose the patient had on Accuretic, using Table 2 (below) as a guide.

Example: For a patient taking Accuretic (quinapril 20mg + hydrochlorothiazide 12.5mg), change to quinapril 20mg tablets and indapamide 2.5mg tablets. Another option would be ramipril 5mg capsules and bendroflumethiazide 2.5mg tablets.

Tables 1 and 2, below, are approximate dose equivalence guides for ACEI/ARBs and thiazide/thiazide-like diuretics. Doses will need adjustment in some cases, such as for people with renal impairment. Each patient may respond differently, so it is recommended that they are followed up two to four weeks after changing. Assess blood pressure, creatinine and electrolytes, and ask about any adverse effects such as signs of hypotension, or cough.

Table 1: Approximate dose equivalence guide for ACE inhibitors and ARBs (adapted from1–3)

Quinapril Enalapril Lisinopril Perindopril Ramipril* Candesartan Losartan
10mg 5-10mg 10mg 2-4mg 2.5mg 8mg 50mg
20-40mg 20mg 20-40mg 8mg 5–10mg 16mg 50-100mg


Note that clinical trials show variations in approximate equivalent dosages for ACEi/ARBs.
Only funded options are included in this table. *Ramipril is funded from 1 December 2022.

Table 2: Approximate dose equivalence guide for thiazide and thiazide-like diuretics (adapted from4)

Hydrochlorothiazide Bendroflumethiazide Chlortalidone Indapamide
12.5mg 2.5mg 12.5mg 2.5mg


Note that clinical trials show variations in approximate equivalent dosages for thiazide diuretics.
Lower doses may be necessary for elderly people – refer to NZ Formulary.

Changing to a single antihypertensive or adding an alternative antihypertensive medicine

While most patient's transition off Accuretic will be covered by the first two options above, there may be some who would benefit from, or prefer to:

  • Use an alternative blood-pressure-lowering medicine – calcium channel blockers are also considered a first-line option for hypertension.5 They could be used as a single agent or added to quinapril (or an alternative ACEI). The ACCOMPLISH trial found that the combination of an ACEI with a dihydropyridine calcium channel blocker eg, amlodipine or felodipine, was more effective at reducing cardiovascular events in patients with a high CVD risk, compared with an ACEI-thiazide diuretic combination.6
  • Transition to quinapril alone – this may be a possible option for older adults or for those with very well-controlled hypertension.

See the 2018 “Cardiovascular Disease Risk Assessment and Management for Primary Care” guidelines for advice about managing hypertension.

Patient considerations

When changing from Accuretic to an ACEI or ARB:

  • Choose once-a-day treatment wherever possible – simpler treatment regimens improve adherence.
  • Where appropriate (see table below) consider an ARB because there is less risk of adverse effects, particularly the dry irritating cough associated with ACE inhibitors.7

ACE inhibitor or ARB?

Table 3: Guide for choosing between an ACEI and ARB1

Conditions where either an ACEI or an ARB are appropriate as a first-line choice: Conditions where an ACEI is the first-line choice:
Hypertension, including people with type 2 diabetes Heart failure
(However, the combination of sacubitril + valsartan can be considered first-line for heart failure)
Chronic kidney disease Following a myocardial infarction
Diabetic nephropathy*

* Unapproved indication for ARB

Some patients may be concerned about possible increased cancer risk from nitrosamines in the Accuretic they’ve been taking long-term. Some key points to provide to patients when discussing the required transition off Accuretic include:

  • Most people have a low-level exposure to nitrosamines in the food and water they consume.
  • Although a potential excess lifetime cancer risk from N-nitroso-quinapril may exist, it is low based on currently available data.
  • There is no immediate risk to patients who have been taking this medication, based on the available data.

Other considerations include:

  • The risks of suddenly stopping medication for blood pressure is higher than the potential risk presented by the impurity.
  • Patients will need follow-up to ensure blood pressure is controlled and any side effects are tolerable.

A resource for patients is available at Health Navigator.

Funding of consultation and prescription copayments(s)

Patients making the change from Accuretic to alternative treatment(s) will not have to pay for the initial consultation with their primary-care prescriber, or for the prescription copayment(s) for the first dispensing.

Extra funding is being added to support primary care with this change. This includes:

  • a GP payment for the waived patient consultation fee
  • a one-off bulk payment to community pharmacies, which will include a prescription copayment for the first dispensing of the alternative medicine(s) and a payment for work in supporting the patient in the transition.

Additionally, Pharmac is exploring the listing of further treatment options.

Check the Pharmac website for the latest information regarding the Accuretic supply issue, including funding arrangements for prescribers and dispensers.

Acknowledgments

Written by: Dr Noni Richards (BPharm, PhD)
Reviewed by: Dr Sam Whittaker (MBChB FRNZCGP)

Content updates

24 August 2022: Removed mention of ARB from the ACCOMPLISH trial summary from the section Transitioning to a single blood pressure-lowering medicine or adding an alternative blood-pressure-lowering medicine.

8 November 2022: Updated wording in second example in Switching advice section to clarify quinapril use. Updated dose equivalence table to include ramipril (funded from 1 December 2022).

References

  1. bpacnz. Prescribing ACE inhibitors: time to reconsider old habits. BPJ Published Online First: March 2021. https://bpac.org.nz
  2. Coca A, Kreutz R, Manolis AJ, et al. A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension. J Hypertens 2020;38:1890–8. doi:10.1097/HJH.0000000000002464
  3. London New Drugs Group. ACE Inhibitors and Angiotensin II Receptor-Antagonists for hypertension. APC/DTC Briefing Document 2008.
  4. Jentzer JC, DeWald TA, Hernandez AF. Combination of Loop Diuretics with Thiazide-Type Diuretics in Heart Failure. J Am Coll Cardiol 2010;56:1527–34. doi:10.1016/j.jacc.2010.06.034
  5. Ministry of Health. Cardiovascular Disease Risk Assessment and Management for Primary Care 2018. Wellington. Ministry of Health.
  6. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients. N Engl J Med 2008;359:2417–28. doi:10.1056/NEJMoa0806182
  7. Messerli FH, Bangalore S, Bavishi C, et al. Angiotensin-Converting Enzyme Inhibitors in Hypertension. J Am Coll Cardiol 2018;71:1474–82. doi:10.1016/j.jacc.2018.01.058

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