How Do You Warn Patients for Your Prescriptions

[jmj11]

There’s a question at the end of this.

I came to work this morning to learn of terrible medication adverse event with one of my patients and I feel really bad about it. To make a long story short, this is a 60 year old lady with severe, daily intractable migraine. She has been seen at numerous headache clinics. She has a very complex medical history, including a lot of mental health issues and is on a long list of drugs. I’ve been working with her for several months. She was suicidal when I first met her. On the last visit, she was four weeks headache free. That’s the good news.

One (of many) medications that I had prescribed along the way was mirtazapine. It appears (from a discharge summary) that she became acutely ill about three weeks ago, was taken to the ER. She was admitted for severe pancytopenia with associated lower GI bleed and encephalitis and transferred to a larger hospital in Seattle.

Her hospital course was unfortunately eventful as she developed a DVT, and then was put on heparin and a PICC line. Then her PICC line became infected with MRSA. She was just discharged and seems like she will recover.

The hematologist concluded that the whole problem (pancytopenia) was caused by the mirtazapine.

In my reading, pancytopenia is extremely rare with mirtazapine (as it is with many drugs). When I write a new prescription, I verbally discuss the top 4-5 side effects of the drug and then tell the patient to read the handout that all our pharmacist give them.

I work in an office that is electronically challenged. The owners are not computer savvy. Before coming here I had access to my own digital handouts and gave one for each drug I wrote. But he pharmacist has great (and too detailed) handouts and I rely on them. However, I looked up the hand out for mirtazapine and pancytopenia is not mentioned.

I regret this happening. The patient’s family is pissed. But I had never seen anything like this before with mirtazapine and I’ve written hundreds of prescriptions for it. I had even taken it myself for insomnia back in the 90s.

So how far do we go? Some days I fell like becoming acupuncturists.

So, what kind of warnings do you give your patients when you prescribe? How do you cover every conceivable bad event? Like I said, even the standard handout didn’t mention pancytopenia with mirtazapine.

[andersenpa]

I'm glad you bring this up, Mike. I was having a discussion with an intensivist at my place re: informed consent, which is what this is really about, and the lengths to which we go to cover all the bases.

 

We explain the risk of the biggies- death, MI, stroke, bleeding, dialysis, infections. But do we discuss the less common things- a severe protamine reaction? Line sepsis if they're on inotropes for a week? Heparin induced thrombocytopenia? No....while all those things may happen (at a rate exceeding that of mirtazapine induced cytopenia,I'm guessing), it's not part of the consent. You could go on for an hour listing all the potential complications, but that would make you ineffecient.

 

Ethics purists might say this is paternalism, and frankly I don't know the right answer, but it seems like we need to weigh the risks and benefits in how we provide informed consent in every way- including which information is relevant. If you handed this patient a adverse drug event list with this complication on it, with it's low incidence, it's safe to say most patients would assume that risk given the severity of the HAs. Most patients behave this way- most txs have some risk, yet we're all working every day and seeing patients take on the risks.

 

Again, this is like paternalism by some standards, but I don't think we are witholding information in order to get the patient to consent- we are consenting in a way that is apporpriate in almost every single case.

[coloradopa]

There’s a question at the end of this.

 

I came to work this morning to learn of terrible medication adverse event with one of my patients and I feel really bad about it. To make a long story short, this is a 60 year old lady with severe, daily intractable migraine. She has been seen at numerous headache clinics. She has a very complex medical history, including a lot of mental health issues and is on a long list of drugs. I’ve been working with her for several months. She was suicidal when I first met her. On the last visit, she was four weeks headache free. That’s the good news.

 

One (of many) medications that I had prescribed along the way was mirtazapine. It appears (from a discharge summary) that she became acutely ill about three weeks ago, was taken to the ER. She was admitted for severe pancytopenia with associated lower GI bleed and encephalitis and transferred to a larger hospital in Seattle.

 

Her hospital course was unfortunately eventful as she developed a DVT, and then was put on heparin and a PICC line. Then her PICC line became infected with MRSA. She was just discharged and seems like she will recover.

 

The hematologist concluded that the whole problem (pancytopenia) was caused by the mirtazapine.

 

In my reading, pancytopenia is extremely rare with mirtazapine (as it is with many drugs). When I write a new prescription, I verbally discuss the top 4-5 side effects of the drug and then tell the patient to read the handout that all our pharmacist give them.

 

I work in an office that is electronically challenged. The owners are not computer savvy. Before coming here I had access to my own digital handouts and gave one for each drug I wrote. But he pharmacist has great (and too detailed) handouts and I rely on them. However, I looked up the hand out for mirtazapine and pancytopenia is not mentioned.

 

I regret this happening. The patient’s family is pissed. But I had never seen anything like this before with mirtazapine and I’ve written hundreds of prescriptions for it. I had even taken it myself for insomnia back in the 90s.

 

So how far do we go? Some days I fell like becoming acupuncturists.

 

So, what kind of warnings do you give your patients when you prescribe? How do you cover every conceivable bad event? Like I said, even the standard handout didn’t mention pancytopenia with mirtazapine.

We had this same discussion concerning Levaquin last week. We have patients that are on it for six months or longer. We traditionally haven't warned people but with a new black box warning do we have to.

 

Part of the discussion is the alternatives. The alternative is to not use it and risk a life threatening infection. The only other drugs that are as effective are in the same class and carry the same risk. The risk for not taking the drug is higher than the risk for taking the drug. We will tell the patient about the risk but thats the only change.

 

The informed consent issue is a real one and hard to differentiate. I once had an anesthesiologist tell me that his insurance said they don't have to tell the patient about risks that are >1:10,000. However they discuss death and paralysis which are much lower than that. It is not conceivable to go through the whole adverse reaction list for every med. I usually highlight the main ones. While pancytopenia is not mentioned, agranulocytosis is.

 

If you look at the evidence while there are isolated reports of pancytopenia with Mirtazapine they are very rare. Probably less than 1:100,000. To have it only the only drug causing it (not polypharmacy) is even rarer. You did nothing wrong here. For the hematologist to name it as the only drug is probably a stretch also.

 

If you want to look at the real culprits I would point at the hospital. She had not one but two of what CMS refers to as never events.

http://www.cms.hhs.gov/apps/media/press/release.asp?Counter=3041&intNumPerPage=10&checkDate=&checkKey=&srchType=1&numDays=3500&srchOpt=0&srchData=&srchOpt=0&srchData=&keywordType=All&chkNewsType=1%2C+2%2C+3%2C+4%2C+5&intPage=&showAll=&pYear=&year=&desc=&cboOrder=date

Not one to point fingers but they took what should have been a relatively routine problem and magnified it. Would the patients family be mad if they had a one or two day hospital stay and then went home?

 

When you sit at the pointy part of the pyramid its tough. You did what the patient wanted, got her HA free which a number of others were unable to. The fact that this led to a highly improbable reaction shouldn't deter you for doing this again. You'll probably order more bloodwork for a little while. Apologize to the patient while stressing the rarity of the event and move on.

 

Yes you may get gored by the occasional zebra but thats better than being run over by horses every day.

 

David Carpenter, PA-C

[jmj11]

I have her chart on my desk and I plan on calling her. She was just discharged last night so I want to give her a few days.

[d2305]

I've only written for it once, and he was already on it. I didn't know about that complication, and I won't use it again.

[coloradopa]

I've only written for it once, and he was already on it. I didn't know about that complication, and I won't use it again.

You can find some obscure side effect for any medication. Almost any medication has the possibility of causing Stevens-Johnson's which can be fatal and has roughly the same incidence that Remeron has of causing Pancytopenia or more. Are you going to stop using all medications?

 

Like Jim I work in a setting where every single patient is polypharmacy. I go over all of our discharge prescriptions with our transplant pharmacist who is also on rounds where we discuss the medications. Despite this adverse reactions still occur. Some of them life threatening. Every medication is a risk benefit analysis just like procedures. If this went to court it is unlikely that there would be any payout.

 

If you make a mistake you correct it. But reacting to unlikely events is bad medical practice. I would continure to counsel patients on the listed warnings and common side effects. For what its worth I prescribe and will continue to prescribe Remeron for a number of issues including sleep.

 

David Carpenter, PA-C

[jmj11]

You can find some obscure side effect for any medication. Almost any medication has the possibility of causing Stevens-Johnson's which can be fatal and has roughly the same incidence that Remeron has of causing Pancytopenia or more. Are you going to stop using all medications?

 

Like Jim I work in a setting where every single patient is polypharmacy. I go over all of our discharge prescriptions with our transplant pharmacist who is also on rounds where we discuss the medications. Despite this adverse reactions still occur. Some of them life threatening. Every medication is a risk benefit analysis just like procedures. If this went to court it is unlikely that there would be any payout.

 

If you make a mistake you correct it. But reacting to unlikely events is bad medical practice. I would continure to counsel patients on the listed warnings and common side effects. For what its worth I prescribe and will continue to prescribe Remeron for a number of issues including sleep.

 

David Carpenter, PA-C

 

I agree. I prescribe carbmazepine often, and I'm sure it has been associated with bone marrow depression far more often than mirtazapine. I prescribe lamotrigene almost every day, and I've know two patient (neither under my watch at the time) have a Steven-Johnson reaction, one almost died. But the risk is still low, especially with a slow titration. So, pay your money and take your risk. Leaving trigeminal neuraliga or seizures untreated also has its risk (in quality of life at least).

[coloradopa]

I agree. I prescribe carbmazepine often, and I'm sure it has been associated with bone marrow depression far more often than mirtazapine. I prescribe lamotrigene almost every day, and I've know two patient (neither under my watch at the time) have a Steven-Johnson reaction, one almost died. But the risk is still low, especially with a slow titration. So, pay your money and take your risk. Leaving trigeminal neuraliga or seizures untreated also has its risk (in quality of life at least).

Almost every one of my patients goes home from the hospital on Prograf, Cellcept, Prednisone, Acyclovir and Levaquin. A lot of them also go home on Insulin and Metoprolol. Thats just the start. The consequennces of not taking these meds is generally death. Pretty easy decision.

 

David Carpenter, PA-C

[d2305]

There are enough antidepressants that don't supress the bone marrow. I didn't know it was a headache med.

[jmj11]

There's some good news to this story. This patient returned to see me today. I listened to her entire horror story of having mirtazapine-induced aplastic anemia . . . followed by a DVT and other complications. I told her how sorry I was that this happened. But she still wants me to take care of her headaches and she is not going to sue me.:)

[primadonna22274]

I think that's a bit reactionary...it's a darn good drug for a lot of folks and Mike's patient had an exceedingly rare, although unfortunate, adverse reaction.

 

Mike, I'm sorry this happened, but I agree with David's interpretation that two of her bad events were hospital-driven (DVT and MRSA infection). You don't have any extraordinary blame here. Bad things happen; that's medicine. All drugs are poison; we try to pick our poison based on our best estimate of benefit vs. risk while individualizing for the patient (cost, compliance, other meds etc.)

 

If anything I guess we will think to check a CBC periodically if someone's on mirtazapine long-term. All the time I see people on chronic meds without appropriate monitoring (how many folks do you know on Dilantin or Depakote without a level, CBC or LFTs in the past year? two years? unfortunately way too many that I see in the practice I'm in.) Stevens-Johnson with lamotrigine? (rare but everybody worries about it). People on long-term nitrofurantoin for chronic UTI never warned of the possibility of pulmonary fibrosis?

 

I appreciate you sharing this vignette. Good luck to your lady.

 

I've only written for it once, and he was already on it. I didn't know about that complication, and I won't use it again.

[foreveryoung]

I would suggest if this really is a concern to you, you can encourage patients to be knowledgable about their own health care. There are many great websites available that can give the patient warnings and precautions. The pharmacy gives information. Pharmacists are available to answer questions. Unless you have given a patient a med that you know (or should know) they are at heightened risk for complications, naming the most common side effects and letting a patient know to contact you if they have any concerns or don't feel things are going well, etc should be sufficent.

[ortho_tim]

"Yes you may get gored by the occasional zebra but thats better than being run over by horses every day. " - David Carpenter PA-C

 

This sounds like an issue that comes up a lot in practice. Take it in stride.

This is true wisdom> as a PA student I may use this quote in some papers, but I will always cite your name. Haha

[d2305]

A zebra does not have horns. Glad your pt is still happy with you.

[Contrarian]

The Remeron (mirtazapine) discussion is on target since most/many insurance companies won't pay for rozerem, lunesta, or sonota... and therefore I find myself using quite a bit of it for my Psych and "Substance Use Disordered" patients for their sleep disorders trying to avoid benzos.

 

Insomnia and Bipolar Disorder is a BAD Mix...!!!!!

 

As for the "zebra/horses" exchange...

Try:

 

"Yes you may get gored by the occasional "Gazelle" but thats better than being run over by common "mule deer" every day."

 

Mule Deer:

 

 

Gazelle:

 

[physasst]

This is a great discussion Mike. And it's something we are grappling in both practice and research as shared decision making models become ever more prominent. How much do you share? How do you do so efficiently? You can scare pretty much anyone about any medication, but then you have an additional anxiety issue. Paternalistic care as Andersen mentioned isn't as effective (thinking of all outcome measures). I think we as providers have an obligation to discuss the main or prominent side effects, but I don't think it's realistic to discuss ALL possible adverse outcomes.

 

We are going to be confronted with these issues on an ever increasing basis as we move towards an inclusionary, shared model of medical decision making. For example, in one of the papers we published last year, we did a study looking at chest pain in the ED....standard models of care would indicate admission to observation, serial enzymes, and then a functional study. But we wound up doing so many negative functional exams that we wondered how cost effective and clinically necessary that was. We developed the North American Chest Pain Rule and then validated it, and subsequently developed a visual aid tool to use with patients in discussion about their chest pain. It would have 100 small blue humans on it, and anywhere from 1-10 of them might be red....based on the Chest Pain Rule which factored in history, pain, ECG findings, and enzymes, we would then show the patient this chart and discuss THEIR individual risk of a serious coronary event in the next 48 hours. We would then give the patient the option of being admitted to the Observation Unit and undergoing usual care, OR, having a next day (within 48 hours) follow up with Cardiology and a pre-scheduled functional study on an outpatient basis....It was simply amazing how many would read the visual aid tool....look at their risk, and then decide to wait for an outpatient appointment...some didn't, but they had the choice.

 

Personally, I discuss the major side effects, and pre-cautions (TCN's stay out of the sun, etc.) but I always end with the phrase "and those are the main side effects or possible adverse effects, but there can always be other rare adverse reactions with almost any medication". Some patients ask for more information, in which case we go down that path (and I've even pulled up Micromedex in the room with the patient to show them the list).....but the overwhelming majority do not. I feel it covers the bases.....sort of the "risks of the procedure were discussed in advance with the patient including BUT NOT LIMITED TO infection, nerve damage, adverse reaction, or a need for hospitalization" that we all dictate into our procedure notes....

 

I dunno...that's what I do.....

[d2305]

I haven't written for Remeron in the last 4 years, unless it was a refill. You had to dig deep to find this post.

[Contrarian]

Interesting...

 

How can we expect patients to be educated and reasonable about prescription meds when it is becoming increasingly obvious that some folks with Rx privileges have little more knowledge about meds than the typical patient does.

 

For example...

 

While Remeron like trazodone is a poor choice for antidepressent treatment... they're GREAT alternatives to addictive substances for patients with sleep disturbance... and especially so for patients with extensive substance use/addiction histories.

 

We often use Remeron in dosages of 15mgs or less and trazodone in dosages of 150mgs or less in Mental Health/Psychiatry with GREAT results and I've yet to have any episodes of pancytopenia.

 

Why...???? Because MOST patients in Community Mental Health are state pay which doesn't pay for novel sleep aids, and about 70% have co-occuring substance use/addiction issues... which demands we try to avoid benzodiazepines if at all possible and only use them as a last result.

 

So if we have providers refusing to prescribe due to rare occurances... then they should also quit recommending tylenol, ibuprophen, asprin, docusate sodium, and hydrocortisone cream....

[CAdamsPAC]

You can find some obscure side effect for any medication. Almost any medication has the possibility of causing Stevens-Johnson's which can be fatal and has roughly the same incidence that Remeron has of causing Pancytopenia or more. Are you going to stop using all medications?

 

Like Jim I work in a setting where every single patient is polypharmacy. I go over all of our discharge prescriptions with our transplant pharmacist who is also on rounds where we discuss the medications. Despite this adverse reactions still occur. Some of them life threatening. Every medication is a risk benefit analysis just like procedures. If this went to court it is unlikely that there would be any payout.

 

If you make a mistake you correct it. But reacting to unlikely events is bad medical practice. I would continure to counsel patients on the listed warnings and common side effects. For what its worth I prescribe and will continue to prescribe Remeron for a number of issues including sleep.

 

David Carpenter, PA-C

 

Absolutely, take a look at the reported ill effects of Bactrim, which we all know is used so frequently by many providers.

[d2305]

Trimethropirm was developed as an oncology drug.