Switching blood pressure medications – it’s time to break the cilazapril habit

3 minutes to Read
Contributor
Chris Ellis
2 August 2021
ECG

Last year, cilazapril with hydrochlorothiazide was discontinued, and now cilazapril alone is no longer funded for new patients. Consultant cardiologist Chris Ellis discusses what to do when patients with hypertension run out of their supply of these medications.


This article was originally published in New Zealand Doctor Rata Aotearoa on 3 June 2021. It is reproduced here with permission from the author.


Key points

  • With recent changes to the funding of cilazapril, now is the time to consider other medicines for the treatment of hypertension.
  • Angiotensin II receptor blockers offer equal efficacy to ACE inhibitors in the treatment of hypertension, but with fewer adverse effects.
  • Candesartan 32mg plus either chlortalidone 12.5mg or indapamide 2.5mg is a stronger combination than losartan 50mg/hydrochlorothiazide 12.5mg

A 69-year-old electrician with hypertension has been managed with medication for 19 years. He currently takes three tablets each morning and attends for a repeat prescription. He has heard that “his medicine” may no longer be available.

In 2002, he had been started on cilazapril at a dose of 0.5mg. This was gradually up-titrated to 5mg each morning. In 2010, he was changed to cilazapril 5mg with hydrochlorothiazide 12.5mg (Inhibace Plus). In 2015, amlodipine 2.5mg was added, along with atorvastatin 20mg daily to lower his overall cardiovascular risk.

He has also been encouraged to maintain the recognised lifestyle methods to lower his blood pressure: exercise more, lose weight, eat less salt, drink less alcohol and stop smoking (he has never smoked).

His blood pressure is 145/85mmHg. You arrange for an electrocardiogram and discuss the current situation.

Discussion

Details of this case study have been changed to protect patient confidentiality.

1. What does the ECG show?

The ECG shows sinus rhythm, a normal axis and a rate of 60 beats per minute. It is normal, as for most patients with hypertension.

2. Which ACE inhibitors and angiotensin II receptor blockers (ARBs) are now funded in New Zealand?

Currently, enalapril, lisinopril, perindopril and quinapril are funded ACE inhibitors for adult patients with hypertension. Cilazapril is subsidised for patients who were taking it prior to 1 May 2021 and the prescription is endorsed accordingly. Pharmacists may annotate the prescription as endorsed where there exists a record of prior dispensing of cilazapril.1 Losartan and candesartan are funded ARBs.

3. Why is prescribing of cilazapril being discouraged by Pharmac and cilazapril/hydrochlorothiazide already discontinued?

Most countries use ACE inhibitors other than cilazapril. In New Zealand, slightly more than half of the 500,000 annual ACE inhibitor prescriptions are for cilazapril. However, as most other countries do not use cilazapril, there is now only one manufacturer left that still makes it. Further, the combined cilazapril 5mg/hydrochlorothiazide 12.5mg tablet is no longer being manufactured.

4. What are the options for changing the combined cilazapril/hydrochlorothiazide tablet to an alternative combined ACE inhibitor or ARB plus diuretic hypertension tablet?

The option is to simply swap cilazapril/hydrochlorothiazide to a combined diuretic with an ACE inhibitor or ARB. At approximately the equivalent strength, the funded tablets are quinapril 20mg/hydrochlorothiazide 12.5mg or losartan 50mg/hydrochlorothiazide 12.5mg. However, your patient’s blood pressure is a little high for a direct swap.

a. If your patient had been taking only cilazapril 5mg daily, could he continue taking it?

Yes, but as of 1 May, the prescription needs to note that this medication was being taken by the patient prior to 1 May. No new patients will be funded for cilazapril alone.

5. What unique opportunity is currently present for treating hypertension?

It is perfectly reasonable to simply change a patient from cilazapril to another funded ACE inhibitor. However, the limited supply of cilazapril, and the end of the supply of cilazapril/ hydrochlorothiazide, could be an opportunity to move to the equally efficacious but better tolerated ARB medications for hypertension.

a. What are the benefits of ARBs over ACE inhibitors for hypertension management?

A 2018 comprehensive review of ACE inhibitors and ARBs used in hypertension management, published in the Journal of the American College of Cardiology, concluded that ARB medicines are a better, safer option than ACE inhibitor medicines. The review states: “Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension.”2

6. What changes do you now make with your patient’s medication regimen?

You elect to change the combined cilazapril 5mg/hydrochlorothiazide 12.5mg tablet to candesartan 16mg for two weeks, then 32mg long term. You ask your patient to return at two and six weeks to have his blood pressure reassessed. If his blood pressure remains high, you will add either chlortalidone 12.5mg daily or indapamide 2.5mg each morning. This will be a stronger combination. Hence, he would then be taking four tablets each morning.

a. What safety follow-up plans do you have for his blood pressure management?

You plan to check creatinine and electrolyte levels at your two-week blood pressure review, and also two weeks after adding the diuretic, then every three to six months in the first year. You then plan to check them on an annual basis. You are aware that some patients have a significant fall in the serum sodium level or significant renal impairment with ACE inhibitors, ARBs or diuretic medicines.

b. What is the treated blood pressure target in 2021?

You appreciate that your patient’s amlodipine dose could also be up-titrated in the medium term, as required for blood pressure control. For optimal blood pressure management, you are aiming for an average blood pressure of 130/80mmHg or below.

Chris Ellis is a consultant cardiologist at Auckland City Hospital, and at The Heart Group and Mercy Hospital, Auckland

Professional college endorsements

This activity has been endorsed by The Royal New Zealand College of General Practitioners (RNZCGP) and has been approved for 0.25 CME credits for the General Practice Educational Programme (GPEP) and Continuing Professional Development (CPD) purposes. To claim your credits, log in to your RNZCGP dashboard to record this activity in the CME component of your CPD programme.

endorsements

References

  1. Pharmac. Pharmaceutical Schedule. https://schedule.pharmac.govt.nz/ScheduleOnline.php?osq=Cilazapril. Accessed July 2021.
  2. Messerli FH, Bangalore S, Bavishi C, et al. Angiotensin converting enzyme inhibitors in hypertension: To use or not to use? J Am Coll Cardiol 2018;71(13):1474–82.