If You Stop Plavix

SoS: Anti-clotting drugs – Fiona's story

May viii, 2013 | 93 Comments

Editorial note: Fiona's story (FB) was the outset RxISK story filed. Information technology is reproduced here. Information from FDA'due south MedWatch system noting withdrawal problems on clopidogrel and Plavix are laid out in the Table at the bottom.

Fiona's story

I had a eye attack two years agone and was prescribed Clopidogrel and low dose Aspirin equally my after care. Several months ago it was decided that I should come off the Clopidogrel. I was peachy to practise and then as I had begun to get tinnitus and my research suggested that aspirin-similar drugs could cause this. As I was told I would have no side effects, I stopped it dead. Three times that week I was admitted by ambulance to hospital with numbness down my left side and headaches. I had an emergency brain scan – all normal. I asked if it could be withdrawal from the Clopidogrel. They said no.

I went dorsum on information technology. I then started to wean myself slower. Equally I did the tinnitus stopped. But then I was admitted to infirmary once more. Worse I had acute anxiety, suicidal thoughts and hallucinations. My dr. told me to go back on Clopidogrel and when I did the symptoms stopped but the tinnitus came dorsum. I then tried an fifty-fifty slower withdrawal. Again I was admitted to hospital – this time with sweats, agitation, anxiety, pain, and headaches. I was told this is in my head and is anxiety in instance I have another heart set on – absolute rubbish. This is following a design. I know it's this drug.

The combination of Clopidogrel and aspirin I was told could cause gut problems and has acquired me gut bug. But every time I try lansoprazole or omeprazole I get anxiety, hallucinations and numbness.

Can you offer me whatsoever advice or where to get help? I know I am chemically dependent on this drug. I don't want to be on this for the balance of my life equally was suggested by the cardiologist. You don't have a problem on it so keep taking it, he said. What happens if the drug manufacture changes or I become tolerant and need more? What happens if I need surgery and accept to cease it in instance I accept a drain? I know my body would not take the shock of it stopping suddenly.

I was addicted to the benzodiazepines in the 1980s. Information technology took me 3 years of hell to come off them so I know what withdrawal feels like and this is it. Please can you assist? I don't know who else to ask that will believe me.

RxISK response

The kickoff point to make is that the options are to agree that this is a withdrawal syndrome or else to disbelieve FB. For FB, the stakes are loftier, including death and significant disability. For the doctors there are no bad consequences of disbelieving her. Indeed ane of the consequences of believing her might be to kickoff doubting the standard line about Clopidogrel and other drugs.

2nd, FB presents a compelling case for a withdrawal syndrome from clopidogrel. The problems emerge on stopping a drug she had no reason to think could cause a trouble, clear up on going dorsum on the drug and reappear on reducing again, and this happens more than in one case. This is as compelling as information technology gets.

The offset defense for those who don't desire to believe is to say that nosotros cannot run across how information technology could be happening and therefore the problems are not what they might appear to be. Taking this approach requires an alternate explanation – and in this case there is a temptation to selection on the feet symptoms and possibly even the prior history of dependence on benzodiazepines. Someone with less inner confidence than FB may even be persuadable that this is all in her mind.

Merely there are means to explain what is happening. Amongst the types of withdrawal is one that is sometimes termed rebound (Medicine Induced Stress Syndromes, Dependence and Withdrawal). This tin can lead to rebound middle rate increases in drugs like beta-blockers that slow center rate and rebound clotting in drugs that reduce clotting. And in fact rebound clotting is well recognized on drugs like aspirin. Another that might fit the pecker here is a legacy effect – an enduring consequence after a drug is stopped.

Searching in RxISK nether Clopidogrel shows that a withdrawal syndrome has been reported on a number of occasions (7 – in FDA'due south database these reports come from Europe). European regulators may have many more reports. This frequency is so low that its proportional reporting ratio is close to 0. There is in other words no signal. On the basis of this we are faced with a pick between a compelling description of a withdrawal trouble and the data which says no betoken. I'1000 inclined to go with the compelling description. Part of the reason we likely accept no signal is that the people affected past issues similar this are not doing the reporting; information technology is doctors who find something like this close to inconceivable who are still the primary reporters of adverse events.

Farther supporting inquiry

My inclination on reading FB's report was to believe her. But more than inquiry on RxISK throws up further reasons to become with FB. There is a condition that is usually thought of as rare called thrombotic thrombocytopenic purpura (TTP). In TTP, platelets in the blood form micro-clots (thrombosis) which tin cause bug. But the micro-clots also remove platelets from blood which leads to haemorrhage (purpura). There are 169 reports of TTP on clopidogrel to FDA. This is a whopping signal – PRR = 22.2. (if the PRR is over 2.0, this is taken every bit evidence of a signal). Nosotros don't know whether these have happened on withdrawal or non – FDA reporting systems don't brand these distinctions. Only at that place is every hazard that a meaning number have happened on withdrawal. If recoded as part of a withdrawal syndrome, the signal for withdrawal would be much more than salient. At that place is in fact a keen deal of bear witness that stopping clopidogrel is linked to problems. Michael Ho and colleagues in JAMA (2008), 299: 532-539 have shown a doubling of bloodshed and in particular heart attacks in the xc days subsequently stopping clopidogrel.

TTP or related issues could readily give rise to merely the clinical features FB reports, including anxiety, numbness down her arm, hallucinations and the rest.

RxISK too shows 108 reports of hemorrhagic stroke on clopidogrel. Again the signal for this (PRR = 13.6) suggests strongly that clopidogrel may be causing the problem. These strokes may exist TTP related cases. The problem may be happening on the drug or on withdrawal – we merely don't know from the fashion the data is collected at the moment.

Finally some other characteristic of FB'southward example is her reaction to lansoprazole and omeprazole. European regulators accept advised confronting combining clopidogrel with proton pump inhibiting drugs like these. Eliminating acrid from the gut likely interferes with a range of different drugs, but in this case PPIs and clopidogrel too interact in the liver, causing FB to sideslip into withdrawal. If you are a doctor you can put FB'due south difficulties downwards to problems on the drug and not withdrawal but if you do this, so yous cannot likewise say to FB that staying on clopidogrel is take chances-gratuitous. Who moreover should make the option every bit to whether she dies of a heart attack or stroke? FB or her doctor? For many suffering a stroke is close to the ultimate horror.

Staying on the drug is not an piece of cake way-out for other reasons. The risks FB outlines are very real – needing surgery, having the drug discontinued, or accidentally ending upward without a supply. But in improver, staying on the drug itself cannot be assumed to exist without consequences. We think of drugs like aspirin or the statins as acting just on platelets or cholesterol levels and as a event wonder where the trouble might exist in staying on them.

But in fact just as the SSRIs do not work solely or even primarily on encephalon serotonin levels simply fifty-fifty more then on blood system serotonin where just similar aspirin they reduce platelet adhesiveness, leading to rebound clotting when stopped and cases of TTP and stroke, so also aspirin and statins can lead to extensive changes through the body that touch the brain and other organs. This tin include alter of personality, or might lead to other conditions improving or getting worse. We know a smashing bargain well-nigh what happens before long afterwards we start taking many drugs but know piddling almost what the longer term effects are, and FB is right to be concerned.

Solutions

Information technology will need keen skill to come up an answer. FB may need input from a haematologist rather than a cardiologist. In other cases of withdrawal, I advocate using liquid forms of a drug to wean off very slowly, but Clopidogrel permanently blocks some receptors and so this approach is of no apply. She would likely to better stopping Clopidogrel while taking warfarin or a heparin analogue, until her entire supply of platelets accept turned over.

FB's case challenges us to recognize that problems like this may be a manifestation of dependence and withdrawal, and that for case many aspects of SSRI withdrawal may be intensely physical in origin rather than mental as people sometimes assume. We exercise not in this example know for instance if the permanent changes Clopidogrel causes in platelets might also happen in encephalon.

This is a case where patients need a doctor to piece of work closely with them every bit a team. FB has filled a RxISK report and has taken a re-create of this to her doc.

Since then

Since this post was fabricated Fiona has been to a haematologist. A range of screening tests have been done. But no-one has been able to pinpoint what is going wrong.

In the Tabular array below, we reproduce the figures from FDA's adverse event database specifically linked to Symptoms on Stopping rather than for example stroke or TTP. What this brings out is in that location are far more things happening on drugs like clopidogrel that are probable linked to withdrawal than are ever reported equally withdrawal problems. These are events that are not captured by current systems, and as a result our image of withdrawal is seriously skewed.

One final point to note that in addition to Clopidogrel (Plavix), there are other grels – Prasugrel, and Ticagrelor. Nosotros have non included these here notwithstanding, just will update the table in due course.

Drug	Symptoms on stopping	Corruption	Addiction	Dependence	Intoxication
Aspirin	91	125	149	104	173
Clopidogrel	20	xviii	12	8	72
enoxaparin	6	eight	4	3	29
heparin	16	eleven	11	6	42
warfarin	34	12	fifteen	11	134

Symptoms on Stopping: Any problems that appear on withdrawal or stopping including firsthand rebound effects linked to the drug or illness, and prolonged reactions that endure after a drug has been stopped.

Corruption: Whatsoever use of a drug in ways other than the orthodox. This may include recreational use or delivery of the drug in ways or in combinations that are not standard medical exercise.

Addiction: This covers drug seeking behaviors such as stealing supplies or criminal activity to secure supplies of the drug. Information technology too includes craving for the drug.

Dependence: Dependence leads to difficulties on lowering a dose or stopping a drug. It may exist accompanied by tolerance where the taker needs to increase the dose of their drug to accomplish the same effect. If you are dependent on a drug, y'all are hooked or in lay terms addicted, fifty-fifty if you are not behaving like an aficionado or a junkie.

Intoxication: Whatsoever drunken, dislocated, or other matted or disinhibited state on the drug.

As well see the blog post, Heartattack and Vine – and Plavix.

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Source: https://rxisk.org/sos-anti-clotting-drugs-fionas-story/

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