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GPs warned over muscle risk with simvastatin-amlodipine combination

GPs should switch all patients taking simvastatin 40mg and amlodipine to a lower dose of statin, or another statin altogether, because of the risk of muscle damage, recommends the medicines regulator.

The warning from the Medicines and Healthcare products Regulatory Agency - issued in its August drug safety update - changes the dosage recommendations for simvastatin, with those patients taking the cholesterol-lowering drug in conjunction with diltiazem or amlodipine to only be given the maximum dose of 20mg a day.

The latest update from the agency also warns that simvastin is now also contraindicated with ciclosporin, danazol and gemfibrozil.

The dosage change and additional contraindications are due to recent analysis of clinical trial data which found that‘theseinteractions may increase plasma concentrations of simvastatin which is associated with an increased risk of myopathy and/or rhabdomyolysis', according to the MHRA.

The changes come after the MHRA issued a warning in May 2010 about the increased risk of myopathy which was associated with the use of high-dose simvastatin of 80mg a day.

The dosage change is expected to have a big impact on GPs and their prescribing, with NICE currently recommending generic simvastatin 40 mg daily as the first-choice drug for primary prevention of cardiovascular disease.

Dr John Allingham, a GP in Dover and medical secretary at Kent LMC,said that 40mg was the ‘standard dose' for primary prevention and the move would affect many of his patients being treated for hypertension.

‘Practices will have to identify their patients, write to them and then change them over,' he said.  ‘I think most GPs will change them over to atorvastatin instead.

Dr Terry McCormack, a GP in Whitby, North Yorkshire, said he was surprised at the recommendations: 'I would have thought that it is very commonly used with that dose and I am not aware of a large upsurge in cases of rhabdomyolysis.

'Amlodipine is such an excellent antihypertensive that it will continue to be commonly prescribed. We will just need to use different statins with it. Now that atorvastatin is off patent it will undoubtedly become the most commonly used statin.'

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Readers' comments (34)

  • good reminder to check on simvastatin doses in our hypertensive patients.

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  • I contacted my Dr. with regards, to this problem around six weeks ago, he just said lots of people take both medications and they're fine. Yesterday on returning from holiday I find a letter from the practice with a prescription and message inside saying I must change my Simvastatin to atorvastatin. My dose was 40mg plus Amlodipine at 5mg. I have a lot of muscle pain as I have Fibromyalgia. I am 63 years of age, anything detrimental to my body is going to have a bigger impact on myself and elderly patients.

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  • I haven't met any pts with such a significant Interaction. I suppose I will change it to Atorvastatin,

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  • I would have thought switching such a patient to a water soluble statin e.g.rosuvastatin 5mg.

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  • We are in the process of changing all our patients on this combination to atorvastatin. Once warned it simply isnt worth risking adverse effects! Statins do give muscle problems and a feeling of being non specifially unwell even with a normal CK. Happy to be given advice which may prevent problems in our patients.

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  • As a locum GP I will ask practices if they have checked patients with this combination of drugs especially Asian patients and Diabetics who do c/o of generalized pain.?Cultural ?symptomatic
    Once an interaction for these 2 commonly used drugs is highlighted again,we must do our bit

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  • Very interesting debate - it makes one wonder about so many aspects of therapy - how long before the whole statin family becomes "dangerous" and we loose the widespread benefit of statin therapy on CVS Morbidity/mortality

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  • This comment has been deleted by the moderator

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  • already given up hope NI GP

    Is this now an area for general rants/concerns?

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  • I have to say I'm a bit sceptical that the interaction is specific to Simvastatin.

    Why would Atorvastatin not cause similar interactions?? Simvastatin is widely prescribed and hence there is a lot more data around this...

    I'll watch with interest in the future for similar warnings around other Statins.

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  • The evidence is that patients on Simvastatin alone have a 0.36% risk of muscle problems. On Simvastatin and Amlodpipne their risk rises to - wait for it - 1%.
    So yes its an increase, from almost no risk to just a bit more than almost no risk.
    Changing patients on stable medication on the basis of this evidence (rather than the rhetoric) is stupid.
    Paul Cundy

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  • What dose of atorvastatin is equivalent to simva 40mg?

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  • Whilst I broadly agree with switching to lower doses of simvastatin or switching to atorvastatin I would point out that cases of myopathy and rhabdomyolysis occurred with very high simvastatin doses rather than a moderate dose of 40mg. Amlodipine is not exactly a clean drug as swollen ankles nasal congestion and facial flushing are common side effects. An alternative plan would be to change to a sartan (which I did when I suffered from these side effects).

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  • Simvastatin caused severe pins & needles cramps & it was only me deciding to come off the medication that found this out. As once off right as rain??!! I only did that because of paperwork attatched.

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  • I was a bit surprised with the recommendations
    There are few question I would ask myself
    1. which age group the interaction is common in
    2. Is it both for amlodipine 5mg and 10mg with simvastatin 40mg and above
    3. What do we do to patients who are absolutely stable on the combinations for years - is it worth disturbing it
    4. does CKD play a role in interaction
    5. What about other CCB like Lercanidipine / Felodipine etc

    likely atorvastatin is generic now and hence cheaper
    as one of the comments rightly pointed out what if Atorvastatin goes as the same way once data becomes available and also possible effect on lipid profile / QOF targets etc
    time to think about QALY

    I presume the MHRA has given a blanket advice as looking thro individual patients may be onerous and time consuming ??

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  • I mean luckily atorvastatin is generic and hence much cheaper

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  • Why not simply switch to Simvastatin 20mg/day as advised. It will still do the job in most patients, you are following advice & it is cheaper.
    There is no doubt in my mind that though statins are safe drugs & of benefit in reducing risk in vascular disease their nuisance side effects have been under recognised by the medical profession and played down by the drug companies.

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  • I think the answer is to stop the amlodipine. It is an appalling but presumably chosen as a cheap agent.

    For the over 65s, ....week 1 start amlodipine,
    week 12 pt develops swelling of the ankles... stop amlodipine..

    ... and how many agree that diuretics have no place in the treatment of hypertension ?

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  • I have been taking Atrovastatin 40mg for a number of years and Amlodipine 5 mg for a couple of years. For the past 6 months I have been have joint pains and pains in my thighs sometimes severe. I also have been having oedema. GP says these are the result of the medication I am taking, but no changes made.
    however reading the enclosed leaflet with Atorvastatin (A) says " there are some medicines that might change the effect of A or their effect may be changed by A. This type of interaction could make one or both less effective. Or it could increase the risk or severity of side effects incl the important muscle- wasting condition rhabdomyolysis which could be life threatning. Amlodipine is the medicine listed which could cause problems. So why are we still being prescribed this combination? On the days I donot take Amlodipine the result is immediate.

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  • How many GP’s and patients have taken the trouble to find out why this new edict has been handed down from on high? Like many others on here and elsewhere I have been taking simvastatin and amplodipine in the recommended way i.e. amlodipine first thing in the morning and simvastatin last thing at night for some time now with no symptoms of myopathy or anything else but have just been instructed by my GP to halve the simvastatin from 40mg to 20mg whilst continuing with the 5mg amlodipine.
    It now appears that the ‘scare’ over any interaction between the 2 drugs resulted from the publication of two peer reviewed papers that looked at this. Their findings are somewhat suspicious in that in their trials they administered the doses of the two drugs together. Regardless of whether one has a medical/scientific training or not this is clearly bad science and the papers should have been rejected on these grounds alone as irrelevant. Blood concentrations of the two drugs at any one time would be very different on the ‘two together regime’ as opposed to the two apart regime’. It’s easy to see why the researchers may have taken the ‘wrong’ approach i.e. difficult to be sure patients were taking drugs several hours apart or simply that the researchers were unaware that patients took them separately. Either way the research is flawed and should have been rejected by reviewers. It wasn’t and now the flawed advice is no doubt costing the NHS millions in wasted time and drug switching.

    You can read about the problem papers with possible explanations on the web at
    HeartMeds by Steve Dunn 28 June 2012 edition

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  • MHRA should have or give us an Idea about the incidence of myopathy rather than explaining a theorotical risk

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  • already switched .Is there an explanation why simva and not all statins/?-good timing now that atorva is off patent .Is that just a coincidence?

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  • I will audit that once back from holiday

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  • How fortuitous that atorvastatin is now off patent and pennies more expensive than simva. We as a practice have completed the switch to atorvastatin for all those on simva 40 and above. I blame it all on cytochrome p450 but why oh why did it wait until Atorva came off patent before it reared its ugly head or is that just the old cynic in me??

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  • A rare complication BUT a very dangerous complication is Rhabdomyolisis..... I had the un-fortunate experience of looking after one of my patients.. .. However, life style e.g. Alcohol Consumption, Smoking ,Obesity & Junk Foods DO NOT DO any body any favours

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  • I may not be the Simvastatin - Amlodipine combo.

    Has anyone asked the pateint((s) about their grapefruit (fruit or juice) intake? (or possibly other citrous fruits).

    Via inhibition of the P450 3A4 (CYP3A4) enzyme, there is a significant simvastatin-grapefruit (via contained furanocoumarins) interaction with a dose related adverse event of rhabdomyolysis.

    Atorvastatin and Lovastatin pose the same interaction risk, whereas pravastatin, rosuvastatin, and fluvastatin do not (different metabolism). So if the statin is to be changed it should be one of the later 3.

    Amlodione does not have the grapefruit interaction but Felodipine does.

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  • I hope that GPs are starting to realise that statins are not wise drugs to prescribe as they interfere with so many physiological mechanisms, and don't improve health outcomes, in fact they worsen them. We should all watch Beatrice Golomb here: http://www.youtube.com/watch?v=3_Oc2xElvL4
    where she demonstrates the deceptions we have all had perpetrated on us. Get wise now, and we may yet be able to look ourselves in the face with a bit of self respect. But let's not be tricked by the great tricksters any longer!

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  • Jeanne Fortnight

    I am convinced that not all pharmaceutical drugs are of benefit to patients, but instead designed to worsen their health, thereby leading to further prescribing and further profits for Big Pharma.

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  • I have long thought this is a knee jerk reaction to flawed research and that the MHRA have over-reacted to what is actually still quite a small risk; what about patients who are on SIMVASTATIN 80mg alone - aren't their blood levels higher? No advice received about that.
    The way we have been "forced" to amend patients prescriptions by the PCT(CCG)'s attached practice pharmacists is another example of the erosion of our own professional judgement by diktat.

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  • I was admitted to cardiology AFTER this information was released. I was on amlodipine when admitted and then PUT ON simvastatin40 mg by cardiologist. I took it the first night, but never again - dreadful reaction.

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  • I took simvastatin 40 for a while. It took me 3 months to realise that my general malaise and insomnia weren't due to the job, and I felt better within days of stopping it. Since then I have been more sympathetic to my patients, regardless of my QOF targets. And as for amlodipine, you'd have to pay me to take it. We need to wake up to the side effects of the these drugs and be more careful and empathic with our poor patients, many of whom follow our every instruction by the book, regardless of whether they feel crap or not.

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  • I was changed from simvastatin 40mg by my gp to atorvastatin 20mg this was because I was taking diltizem and of the possible interaction, I had the occasional leg ache on simva but nothing I couldn't cope with and my cholesterol was 5.5. I started on the atorva in January 2013 in 20mg, about a month later I started getting very bad thigh pain so bad I could hardly walk and I felt 10 years older (im 52) I went to my gp who did my routine bloods and they came back fine, however noticed my cholesterol had gone up to 6.5 on the atorva, my gp said she would double the dose because I have coronary spasm and need to aim for under 5. I have now decided to stop them for a month to see what happens...already after 5 days I have no more pain in my thighs and feeling a lot better as the aching was getting me down. I hope I can get an alternative as I know the importance of high cholesterol, at the moment I am trying a low cholesterol die, hope that does some good. will be going back for bloods in 6 weeks.

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  • I suffered much muscle pain and general weakness when taking these. two together. I thought that I was coming to the end of my life. 12 years later my muscles have not fully recovered. But I am very elderly I did tell my GP and practice nurse who lowered statin dosage but there was no change in symptoms until I stopped intake voluntarily.

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  • I am concerned as i already take Amlodipine and simvastatin, Ramipril, levothyroxine and anti-depressants. I sweat profusely, especially at night. My weight has ballooned and my mood seems to be worsening. I am only 53 but feel that I am falling apart.

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