Amlodipine – solving the swelling

Deepa has swollen ankles. “I didn’t sign up for this! Sort it out, doc!”

You initiated amlodipine four weeks ago after she was diagnosed with hypertension. We all know leg oedema is a potential side effect, we hope it doesn’t happen, but it frequently does. 

How are we going to help Deepa? 

The Specialist Pharmacy Service, a branch of the NHS, recently updated its advice on how clinicians can approach this common problem. With amlodipine being the second most prescribed medication in the UK, this guidance provides some highly useful recommendations for general practice clinicians.

How common is calcium channel blocker (CCB)-induced peripheral oedema? The Summary of Product Characteristics for amlodipine 10mg reports oedema as a ‘very common’ side effect, meaning it affects more than 1 in 10 people. While exact figures are difficult, a 2019 meta-analysis in the Journal of Hypertension reports the rate of oedema as 16.6% vs 6.2% with placebo. The risk is further increased in women, older people, heart failure, and, relevant at the moment, warm environments.

CCB oedema affecting the ankles and feet often starts very soon after initiation or a change in dose, within weeks to months. It usually worsens throughout the day, and improves overnight when lying down. While described as “usually not clinically serious” it can impact medicine adherence and I’ve had patients where the swelling is highly symptomatic or where the fluid increases the weight of the legs to such an extent that it affects mobility and stability. 

This is a persisting problem – it does not improve while the person continues on the CCB – and prolonged exposure can lead to permanent changes and long-term oedema.

The good news is there are a range of options that may help.

• Non-pharmacological
  • Leg elevation and/or compression stockings may be sufficient if mild oedema
• Optimising the calcium channel blocker
  • Adjust the dose – could it be reduced? 
    • Risk of oedema is dose-dependent in most patients (but not all!) so reducing the dose could help. Although rarely used in the UK, even 2.5mg amlodipine has data supporting its efficacy 
  • Switching CCBs – careful with your choice…
    • Felopidine and nifedipine are both dihydropyridine (DHP) CCB like amlodipine, and as likely to cause oedema, so not a good alternative.
    • Lercanidipine and lacidipine - newer lipophilic DHP CCBs, have a lower incidence of oedema, so may be a more suitable alternative. 
    • Non-DHP CCBs, verapamil and diltiazem, are not commonly used for hypertension management but may be less likely to cause oedema. However, other aspects need to be considered, particularly the effect on the heart and contractility, so are not appropriate in patients with heart failure, those on beta blockers, caution if conduction disorder, etc.
  • Switching to an alternative anti-hypertensive
    • With persisting oedema despite the above, discontinuation is appropriate and trial of alternative anti-hypertensive.

What if continuation of the CCB is important despite peripheral oedema? 

One option would be to cautiously consider an additional drug to counteract the side effects. 

What isn’t recommended is thiazide or loop diuretics. Apparently these have little to no effect on this type of oedema because of the underlying mechanism. CCBs cause fluid to leak into dependent soft tissue due to precapillary arteriolar dilatation driving increased intracapillary pressure. This is not fluid overload, and so diuretics fail to treat it. 

The best option would be an ACEi or ARB. While it isn’t completely clear how – they may reduce that intracapillary pressure – these classes have been shown to reduce the chance of CCB-linked oedema.

Back to Deepa. In an ideal world she wouldn’t need anti-hypertensives at all. Have non-drug options been explored? In the real world, she might still need some assistance to control her blood pressure. Combination therapy is known to be more effective than monotherapy, and according to Scottish hypertensive guidelines only 25% of patients achieve control on a single agent - adding a ACEi or ARB could be a good option. If she prefers to stick to monotherapy, a completely different class would be an alternative, but it would be a shame to right off a whole group of anti-hypertensives as she may need treatment escalation in the future. Switching to lercanidipine and trialling that would be a very reasonable choice.

As with so much of general practice, there isn’t one perfect solution, but hopefully with this range of options we can find a solution for our patients.