Amlodipine is one of the most commonly prescribed drugs in the UK and the most prescribed high blood pressure (BP) medication. When patients are diagnosed with high blood pressure and a drug is recommended, amlodipine may be the first choice, but not always. Taking any drugs comes with a risk of side effects, with amlodipine associated with few common side effects. Ultimately, patients may be prescribed amlodipine alternative drug. Today, I will discuss amlodipine alternative drugs according to recommended treatment guidelines. Perhaps the most important message to take in is that the choice of amlodipine alternative drug(s) will be driven by the national guidance on blood pressure, which clearly states recommended treatment for different groups of patients.
What is high blood pressure? (video)
Doctor Mike give an excellent overview of what high blood pressure is. I encourage everyone to view this 10 minutes video.
Amlodipine is classified as a calcium channel blocker (CCB). As the name suggests, amlodipine stops calcium movement into cells in blood vessels, the heart and pancreas. Calcium is responsible for smooth muscle contractions. Consequently, amlodipine causes the dilation of a blood vessel, which helps to decrease blood pressure.
Is amlodipine a beta-blocker?
Many patients ask if amlodipine is a beta-blocker. The answer is: no. Calcium channel blockers have a distinct mechanism of action to beta-blockers.
Why amlodipine is the most popular blood pressure drug in the UK?
High blood pressure is managed in the UK in a stepwise manner. Three main patient factors that determine the choice of blood pressure medication are:
- the age
- diabetes status
Calcium channel blockers like amlodipine are the first-line treatment in no-diabetic patients over 55 years of age or patients of the Caribbean or African origin (any age).
The prevalence of high blood pressure increases with age, for example in England, 58% of men and women aged 65 to 74 have high blood pressure (GOV.UK, 2017), which partly explains amlodipine’s popularity.
High blood pressure medication is changed, or an additional drug is prescribed if treatment does not produce satisfactory results or patients experience side effects.
Amlodipine & ankle swelling (oedema) and other side effects
The use of amlodipine and other calcium channel blockers is associated with many common side effect, including (BNF, 2021):
- tachycardia (fast heart rate)
- oedema (swellings)
- muscle cramps
Ankle swelling (oedema) is one of the common side effects associated with amlodipine use. Ankle swelling caused by amlodipine is probably the most troublesome side effect and usually requires changing amlodipine to alternative treatment.
Do all calcium channel blockers cause ankle swelling (oedema)?
Sometimes in practice, patients get switched from amlodipine to an alternative calcium channel blocker. It would be reasonable to ask whether all calcium channel blockers have the potential to cause ankle swelling. The simple answer is: yes.
Available information suggests that lercanidipine may be associated with a lower frequency of oedema when compared to first-generation calcium channel blockers (for example, nifedipine, verapamil, and diltiazem) as confirmed by meta-analysis (review of a large number of clinical studies), but not when compared to a second-generation CCB (amlodipine).
In the UK, verapamil and diltiazem are mainly used to manage angina rather than high blood pressure. Other side effects (headache and flushing) were found to be of a similar frequency between calcium channel blockers.
The same review concluded that investigated calcium channel blockers are equally effective in terms of blood pressure reduction.
Can you replace amlodipine with lifestyle changes?
This post mainly focuses on drugs alternative to amlodipine. Patients are usually advised by their doctor about lifestyle, which may contribute to high blood pressure. The area of lifestyle and its impact on blood pressure deserves a separate discussion. However, the importance of the topic should not be ignored.
Lifestyle changes, diet and exercise, have a significant impact on blood pressure. The critical aspect of lifestyle changes is physical exercise. There is an overwhelming amount of evidence to show the beneficial effects of exercise on the prevention and treatment of hypertension. Exercise reduces both systolic and diastolic blood pressure. Additionally, reduction of blood pressure due to exercise is immediate, with a lowering effect lasting for more than 24 hours. Regular exercise contributes to a sustained decrease in blood pressure (Hegde et al., 2015).
Amlodipine alternative drugs: diuretics
Diuretics (thiazide-type) are offered to patients over 55 or patients of the Caribbean or African origin (no diabetes), when amlodipine is not tolerated, for example, due to oedema.
Diuretics, commonly known as ‘water tablets’, increase the amount of urine output. Increased excretion of water from the body reduces the blood volume, consequently reducing the blood pressure.
Diuretics common side effects (NICE, 2021)
- dry mouth;
- erectile dysfunction;
- hyperglycaemia (increased sugar level);
- hyperuricaemia; nausea;
- postural hypotension (drop in blood pressure when standing up);
- skin reactions (rashes)
Indapamide is second-most prescribed thiazide-type diuretics. According to the guide on the management of high blood pressure, indapamide is the prehferred diuretic in the treatment of hypertension.
Also classified as a diuretic, chlortalidone is not commonly prescribed in the UK to manage high blood pressure.
Bendroflumethiazide is the most commonly prescribed diuretic in the UK. However, bendroflumethiazide is no longer recommended diuretic in the UK for the treatment of high blood pressure. Indapamide and chlorthalidone are preferred diuretics in the management of BP.
Amlodipine alternative drugs: ACE inhibitors
ACE inhibitors are another popular class of antihypertensive drugs. ACE inhibitors would be offered as first-line treatment of high BP to all diabetic patients (regardless of ethnicity) and patients under 55 years of age without diabetes.
The whole list of ACE inhibitors includes over ten drugs that are licensed for high blood pressure treatment.
How does ACE-inhibitors reduce blood pressure?
Cause widening of the blood vessels and consequently reduction of blood pressure.
What are the common side effects associated with ACE inhibitors?
Common side effect associated with ACE inhibitors include:
- Headaches, dizziness
- Tickling, dry cough which does not go away
- Abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting
- ACE inhibitors are usually started at a low dose and titrated up according to the response, hence the availability of different tablets and capsules strengths.
Ramipril is the most popular ACE inhibitor prescribed for blood pressure in the UK and the second most popular high blood pressure medication. There are no specific recommendations to prescribe ramipril as a first-line treatment in BP. Ramipril, lisinopril and perindopril may be preferred for people who had a heart attack or patients with heart failure (NICE, 2020).
Ramipril comes in the form of capsules and tablets. The strength of ramipril varies from 1.25mg of ramipril to 10mg.
Lisinopril is the second most prescribed ACE inhibitor in the UK for the treatment of blood pressure. Lisinopril comes only in the form of tablets, ranging from 2.5mg to 20mg of lisinopril per tablet.
There is a significant gap in the numbers of prescriptions issued for enalapril and the second most popular ACE inhibitor, lisinopril. With over 1.5 mln prescriptions issued in the last 12 months (OpenPrescribing.net, 2021), enalapril is still a popular drug for managing high BP.
Enalapril’s strength ranges from 2.5mg to 20mg per tablet.
Angiotensin II receptor antagonists as amlodipine alternatives
Angiotensin II receptor antagonists (blockers) are used to treat the same conditions as ACE inhibitors, including high blood pressure.
The mechanism of action of angiotensin II receptor blockers differs from calcium channel blockers (amlodipine) or ACE inhibitors. As the name suggests, angiotensin II receptor antagonists block angiotensin II (a ‘compound’) and consequently relax the smooth muscle and decrease the blood pressure.
Unlike ACE inhibitors, angiotensin II receptor blockers do not cause cough or oedema.
Most common angiotensin II receptor blockers used in the UK are:
Angiotensin II receptor blockers: common side effects
- Hyperkalaemia (low level of potassium)
- Abdominal pain, nausea, and vomiting
- Postural hypotension (drop in blood pressure when standing up)
Can angiotensin II receptor antagonists be alternative for amlodipine?
Looking at the guidelines for the management of high blood pressure, angiotensin II receptor antagonists can be offered instead of ACE inhibitors (ramipril) when initiating the treatment, in particular to patients who:
- Have diabetes of any age or family origin.
- They are under 55 years of age but not of black African or African–Caribbean family origin.
Losartan is the most commonly prescribed angiotensin II receptor blockers, with over ten mln prescriptions issued in the last 12 months (OpenPrescribing.net, 2021).
The second most prescribed angiotensin II receptor blockers do not differ in terms of effectiveness from losartan.
Current evidence is insufficient to show that one particular angiotensin II receptor blocker is more effective than others in reducing blood pressure (Tsoi et al., 2018).
The above list was completed based on STAGE 1 on blood pressure management (initiating the treatment).
Further treatment of blood pressure combines the use of two, three or even four drugs. For example, at STAGE 2 one could be treated with:
Calcium channel blocker (amlodipine) and ACE inhibitor (ramipril) or angiotensin II receptor blocker (losartan) or diuretic.
At STAGE 3, patients are treated with three different drugs and stage 4 with four antihypertensive drugs.
I listed the most popular antihypertensive drugs used in the UK, which are considered the first-line treatment of high blood pressure. Although this post aimed to list amlodipine alternative drugs, it is clear that selecting amlodipine alternative medicines is based on individual patients and any other underlying conditions they may have.
BNF (2021). Amlodipine: side effects (For all calcium channel blockers). Available at: https://bnf.nice.org.uk/drug/amlodipine.html Accessed on 30/03/2021
Gov.UK (2017). Health matters: combating high blood pressure. Available at: https://www.gov.uk/government/publications/health-matters-combating-high-blood-pressure/health-matters-combating-high-blood-pressure#:~:text=In%20terms%20of%20prevalence%2C%20in,aged%2065%20to%2074%20years. Accessed on 30/03/2021
Hegde SM, Solomon SD (2015). Influence of Physical Activity on Hypertension and Cardiac Structure and Function. Curr Hypertens Rep. 2015;17(10):77. doi:10.1007/s11906-015-0588-3 Available at: https://dx.doi.org/10.1007%2Fs11906-015-0588-3 Accessed on 31/03/2021
NICE (2020). Angiotensin-converting enzyme inhibitors. Available at: https://cks.nice.org.uk/topics/hypertension-not-diabetic/prescribing-information/angiotensin-converting-enzyme-inhibitors/ Accessed on 30/03/2021
NICE (2021). Side-effects: For all THIAZIDES AND RELATED DIURETICS. Available at https://bnf.nice.org.uk/drug/bendroflumethiazide.html#sideEffects Accessed on 26/03/2021
OpenPrescribing.net (2021). The period included – last 12 months (Feb ’20—Jan ’21). Available at: https://openprescribing.net/analyse/ Accessed on 30/03/2021
Tsoi B, Akioyamen LE, Bonner A, Frankfurter C, Levine M, Pullenayegum E, Goeree R, O’Reilly D (2018). Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. Heart Lung Circ. 2018 Jun;27(6):666-682. doi: 10.1016/j.hlc.2017.06.721. Epub 2017 Jul 14. PMID: 28807582. Available at: https://doi.org/10.1016/j.hlc.2017.06.721 Accessed on 31/03/2021