Clozapine patient goes awol?

[meow1985]

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Let's say you have a stable clozapine patient. One month they do not get their labs. The clozapine still gets filled but you get a message from the pharmacy that the ANC is not current. You try to get a hold of the patient and their caregiver repeatedly, to no avail. There are clozapine refills on file. Let's say the clozapine is pretty darn necessary. After all, people don't just end up on clozapine for no reason. At what point do you stop the med?

I guess this doesn't often happen because many clozapine patients are in a facility or have some sort of service through the pharmacy that does the blood draws, but there is the odd person who lives independently or have family/a guardian who manages their care.

 

[wolfvgang22]

I'd send a certified letter if they miss their next appointment and labs. I would not discontinue Clozaril, nor would I renew it. Same as any other patient.

 

[NickNaylor]

I wouldn’t be refilling it, and frankly the pharmacy shouldn’t be filling it either if there isn‘t an up-to-date ANC in REMS.

 

[Ironspy]

I wouldn’t be refilling it, and frankly the pharmacy shouldn’t be filling it either if there isn‘t an up-to-date ANC in REMS.

In many places ANC requirements are suspended during covid. Regular bloodwork is still recommend but if a patient can’t get bloodwork right now pharmacists will still fill the prescription in my state.

 

[meow1985]

I wouldn’t be refilling it, and frankly the pharmacy shouldn’t be filling it either if there isn‘t an up-to-date ANC in REMS.

The REMS rules state that a lack of ANC does not prevent a fill, it just requires the pharmacy to call the MD and inform them that there are no up to date labs.

 

[robellis]

The REMS rules state that a lack of ANC does not prevent a fill, it just requires the pharmacy to call the MD and inform them that there are no up to date labs.

Then you tell him they shouldn’t fill it because patient hasn’t been following up

 

[Stagg737]

Then you tell him they shouldn’t fill it because patient hasn’t been following up

Realistically though, if they’ve been on it for several months the odds of them developing agranulocytosis is nearly negligible if they keep taking it appropriately. I agree with Wolfgang. Do not refill, send a certified letter telling them this and make sure it reiterates risks and monitoring requirements. I would not tell the pharmacy to stop dispensing it, I just wouldn’t refill it until the patient followed up.

 

[kopftonmd]

Realistically though, if they’ve been on it for several months the odds of them developing agranulocytosis is nearly negligible if they keep taking it appropriately. I agree with Wolfgang. Do not refill, send a certified letter telling them this and make sure it reiterates risks and monitoring requirements. I would not tell the pharmacy to stop dispensing it, I just wouldn’t refill it until the patient followed up.

I'm confused though... at some point they will end up out of refills if you stop renewing it. At that point, isn't it the same as discontinuing?

 

[wolfvgang22]

I'm confused though... at some point they will end up out of refills if you stop renewing it. At that point, isn't it the same as discontinuing?

Ethically, no. In this situation OP has tried to call the patient multiple times at different times. There are a couple of refills available in case the patient can't afford phone minutes, or got hospitalized somewhere, or went on vacation, or had a flat tire, etc, etc. So the patient has quite a bit of time to call or show up. You also send a certified letter expressing concern and desire to help, and importance of labs and follow up. You aren't abandoning the patient.

In this situation you are waiting for the patient to uphold their minimal responsibility in the doctor patient relationship, which is the responsibility to simply show up or call you. Are you firing a patient if you don't drive to their home and start a search and rescue effort when they no-show appointments? Of course not. Same thing.

 

[robellis]

Ethically, no. In this situation OP has tried to call the patient multiple times at different times. There are a couple of refills available in case the patient can't afford phone minutes, or got hospitalized somewhere, or went on vacation, or had a flat tire, etc, etc. So the patient has quite a bit of time to call or show up. You also send a certified letter expressing concern and desire to help, and importance of labs and follow up. You aren't abandoning the patient.

In this situation you are waiting for the patient to uphold their minimal responsibility in the doctor patient relationship, which is the responsibility to simply show up or call you. Are you firing a patient if you don't drive to their home and start a search and rescue effort when they no-show appointments? Of course not. Same thing.

If pharmacist calls you and asks whether or not they should refill his clozapine, what do you say? The refills are there and are contingent on getting labs

 

[Stagg737]

Continue the prescription. If you’re not comfortable with a certain number of refills, don’t prescribe that many.

Again, unless Clozapine is a new prescription or they have a history of agranulocytosis, the risk is very minimal. The monitoring guidelines in the US are more of a historical remnant of big pharma’s influence on drug choice than the actual clinical need for such stringent monitoring.

 

[wolfvgang22]

I never put refills on clozapine for this reason.

 

[deleted1012620]

I wouldn't even know what to do if the white count dropped on one of my patients on clozapine. It hasn't come up yet in my resident clinic somehow. I guess you'd want to stop the med and maybe rechallenge if the white count recovered? But it seems like coming off clozapine might be worse than whatever risk there is for infection.

 

[kopftonmd]

Ethically, no. In this situation OP has tried to call the patient multiple times at different times. There are a couple of refills available in case the patient can't afford phone minutes, or got hospitalized somewhere, or went on vacation, or had a flat tire, etc, etc. So the patient has quite a bit of time to call or show up. You also send a certified letter expressing concern and desire to help, and importance of labs and follow up. You aren't abandoning the patient.

In this situation you are waiting for the patient to uphold their minimal responsibility in the doctor patient relationship, which is the responsibility to simply show up or call you. Are you firing a patient if you don't drive to their home and start a search and rescue effort when they no-show appointments? Of course not. Same thing.

That makes a lot of sense. Thank you!

 

[meow1985]

I took over care from another MD and there are still refills from that MD on file. Interestingly, the REMS website states that not having a timely CBC on file does not prevent the pharmacy dispensing. All they are required to do is let the prescribing MD know.

Do you get in trouble for not following REMS rules, though?

This is one of those cases where rules are one thing but clinical common sense are another.

Clinically, I think it would be disastrous to just stop clozapine generally. After all, people don't end up on it because they are doing well. I also had a mentor who also argued that the monthly monitoring is unnecessary and just monitoring for fevers is a better indication of any harm.

 

[wolfvgang22]

Paralytic ileus is in my experience a much more frequent concern with clozapine than agranulocytosis. I've had maybe one or two patients ever have agranulocytosis with clozapine but many more who have problems with chronic constipation on clozapine that can and has progressed to a bowel obstruction. I've found miralax and lubriprostone to be helpful for these patients.

 

[calvnandhobbs68]

I wouldn't even know what to do if the white count dropped on one of my patients on clozapine. It hasn't come up yet in my resident clinic somehow. I guess you'd want to stop the med and maybe rechallenge if the white count recovered? But it seems like coming off clozapine might be worse than whatever risk there is for infection.

Dude this is literally part of REMS. You were required to do this as a requirement of being able to prescribe Clozapine....

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

 

[calvnandhobbs68]

I took over care from another MD and there are still refills from that MD on file. Interestingly, the REMS website states that not having a timely CBC on file does not prevent the pharmacy dispensing. All they are required to do is let the prescribing MD know.

Do you get in trouble for not following REMS rules, though?

This is one of those cases where rules are one thing but clinical common sense are another.

Clinically, I think it would be disastrous to just stop clozapine generally. After all, people don't end up on it because they are doing well. I also had a mentor who also argued that the monthly monitoring is unnecessary and just monitoring for fevers is a better indication of any harm.

It says this in REMS as well. Page 14. Doesn't seem very ambiguous.

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

"Prescribers must ensure that their patients are on the appropriate monitoring frequency and adhere to the corresponding blood draw dates in order for their patients to receive clozapine"

LOL literally the motto of the Clozapine REMS Website: "No blood, No drug"

 

[wolfvgang22]

Dude this is literally part of REMS. You were required to do this as a requirement of being able to prescribe Clozapine....

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

neverdone is a resident and may have not done a lot with REMS. Thank you for the educational link, we all have things we can learn.

 

[Stagg737]

Clinically, I think it would be disastrous to just stop clozapine generally. After all, people don't end up on it because they are doing well. I also had a mentor who also argued that the monthly monitoring is unnecessary and just monitoring for fevers is a better indication of any harm.

Exactly, I'm not discontinuing Clozapine on someone who has been stable on it for 12 months+ and has never had a dip in their WBC with titration because I can't contact them for a few weeks. I don't generally give refills, but imo the risks of becoming psychotic often outweigh the risk of sudden neutropenia.

The part about the fever is interesting though. I'm not advocating for no monitoring, but just using fever as a monitoring tool (especially in psychotic patients) seems like a bad idea...

Paralytic ileus is in my experience a much more frequent concern with clozapine than agranulocytosis. I've had maybe one or two patients ever have agranulocytosis with clozapine but many more who have problems with chronic constipation on clozapine that can and has progressed to a bowel obstruction. I've found miralax and lubriprostone to be helpful for these patients.

100% agree. Every patient I start on Clozapine also gets a bowel regimen. If they want to stop after a few weeks at therapeutic dose that's up to them, but given the risk of death from this along with a few experiences where patients went nearly a week without a BM has made this part of my regular protocol.

It says this in REMS as well. Page 14. Doesn't seem very ambiguous.

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

"Prescribers must ensure that their patients are on the appropriate monitoring frequency and adhere to the corresponding blood draw dates in order for their patients to receive clozapine"

LOL literally the motto of the Clozapine REMS Website: "No blood, No drug"

This is where I have problems with REMS. The evidence for this practice is pretty poor and I feel like it's essentially there to discourage the prescription of Clozapine. When you also include aplastic anemia and thrombocytopenia the rates of incidence are actually higher for meds like Carbamazepine and Oxcarb (depending on study) yet we don't have REMS systems for those meds. As I've said above, depending on the patient I may be much more concerned about them becoming psychotic than developing hematologic problems. This is a perfect example of the problems with cook-book medicine and algorithms being used over good clinical decision making.

 

[deleted1012620]

Dude this is literally part of REMS. You were required to do this as a requirement of being able to prescribe Clozapine....

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

Yea that's gonna be it for me. I'm done w/ SDN. I'm actually doing just fine in my residency but somehow coming here makes me consistently makes me feel like ****.

 

[Stagg737]

Yea that's gonna be it for me. I'm done w/ SDN. I'm actually doing just fine in my residency but somehow coming here makes me consistently makes me feel like ****.

I don't think anyone is trying to make you feel bad and seems like people are trying to help by providing links and educational tools. Some people here can be blunt, but the psych sub-forum is very academic compared to some of the other sub-forums (and the dumpster fire forums of pre-med and med students). I've found this particular forum to be a really great resource for difficult cases as well as just knowing where to find information. It's also a great place to learn about all the things residency doesn't teach well (billing, business models, various sub-specialty info, etc).

You do you, but I think the community on this sub-forum is pretty great and I feel pretty lucky that we've got a resource/forum like this available.

 

[calvnandhobbs68]

Yea that's gonna be it for me. I'm done w/ SDN. I'm actually doing just fine in my residency but somehow coming here makes me consistently makes me feel like ****.

Uh if that made you feel like **** how exactly did you make it through your surgery rotation?

It was direct but you were actually required to review that document and the table of what to do about different ANCs as part of REMS. If a resident came and told me they had no idea what to do when a patients neutrophils dropped on clozapine I would do the exact same thing...refer you back to the document which tells you exactly what to do in that instance.

 

[birchswing]

It's hard to tell when you've been in a forum long enough how it's changed you. It's like when you can't smell what your house smells like until you go on vacation and come back. The Internet rewards a bit of snark in general, it seems. No different here; although, vastly better than the day-trading forum that masquerades under the title of anesthesiology (see, I just did snark).

 

[calvnandhobbs68]

Exactly, I'm not discontinuing Clozapine on someone who has been stable on it for 12 months+ and has never had a dip in their WBC with titration because I can't contact them for a few weeks. I don't generally give refills, but imo the risks of becoming psychotic often outweigh the risk of sudden neutropenia.

The part about the fever is interesting though. I'm not advocating for no monitoring, but just using fever as a monitoring tool (especially in psychotic patients) seems like a bad idea...



100% agree. Every patient I start on Clozapine also gets a bowel regimen. If they want to stop after a few weeks at therapeutic dose that's up to them, but given the risk of death from this along with a few experiences where patients went nearly a week without a BM has made this part of my regular protocol.



This is where I have problems with REMS. The evidence for this practice is pretty poor and I feel like it's essentially there to discourage the prescription of Clozapine. When you also include aplastic anemia and thrombocytopenia the rates of incidence are actually higher for meds like Carbamazepine and Oxcarb (depending on study) yet we don't have REMS systems for those meds. As I've said above, depending on the patient I may be much more concerned about them becoming psychotic than developing hematologic problems. This is a perfect example of the problems with cook-book medicine and algorithms being used over good clinical decision making.

i actually agree with you about that but the REMS guidelines are what they are. I tend not to be a person who cares much about getting sued in general but I think you’re going to have a hard time defending yourself if there’s an adverse event if not following guidelines put in place by the FDA as a “Risk Evaluation and Mitigation Strategy” specifically designed to ensure that benefits outweigh risks of certain medications. Gotta play by the rules sometimes...that’s why the home ANC checker thing is getting pushed so hard right now.

 

[Stagg737]

i actually agree with you about that but the REMS guidelines are what they are. I tend not to be a person who cares much about getting sued in general but I think you’re going to have a hard time defending yourself if there’s an adverse event if not following guidelines put in place by the FDA as a “Risk Evaluation and Mitigation Strategy” specifically designed to ensure that benefits outweigh risks of certain medications. Gotta play by the rules sometimes...that’s why the home ANC checker thing is getting pushed so hard right now.

True, but I'd still look at it on a case-by-case basis. If I have a patient who gets psychotic and makes a legitimate suicide attempt every time they go off Clozapine, that risk is still greater than taking them off because they don't get labs if they've never had issues with neutrophilia/agranulocytosis. I'd rather argue why I continued the med against FDA recommendations in court than explain why I didn't continue a med that we know saves the patient's life. Though I do agree that outside of the extreme cases (which if they're on Clozapine, they're much more likely to qualify as "extreme") I would also follow the unnecessarily strict guidelines.

 

[clausewitz2]

Uh if that made you feel like **** how exactly did you make it through your surgery rotation?

For real. Actual exchange related to me by a friend from his surg onc rotation:

Attending: "Tim, are you an idiot?"
Med Student: "Uhh... no, sir."
Attending: "Tim, can you read?"
Med Student: "Uhh, yes sir."
Attending: "Then I have no idea how you could have possibly thought what you just said was an answer to my question."

 

[wolfvgang22]

For real. Actual exchange related to me by a friend from his surg onc rotation:

Attending: "Tim, are you an idiot?"
Med Student: "Uhh... no, sir."
Attending: "Tim, can you read?"
Med Student: "Uhh, yes sir."
Attending: "Then I have no idea how you could have possibly thought what you just said was an answer to my question."

These are the sort of abusive interactions that have no place in training and should be reported and eliminated. They never helped me learn, but did help make me jaded.

 

[Mass Effect]

In many places ANC requirements are suspended during covid. Regular bloodwork is still recommend but if a patient can’t get bloodwork right now pharmacists will still fill the prescription in my state.

This right here. I don't know how many states are still suspending them, but it was definitely the wild west over much of 2020. Drug monitoring wasn't done in patients at risk, including clozapine.

 

[Mass Effect]

It says this in REMS as well. Page 14. Doesn't seem very ambiguous.

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

"Prescribers must ensure that their patients are on the appropriate monitoring frequency and adhere to the corresponding blood draw dates in order for their patients to receive clozapine"

LOL literally the motto of the Clozapine REMS Website: "No blood, No drug"

The person you were talking to in your other post was a resident. Not all residents are well-versed in REMS until they need to be (for most that's 3rd yr).

As for the REMS guidelines, I call BS on "no blood, no drug." Like everything else patient related you make a risk/benefit analysis and document carefully. Obviously you want the patients to have blood drawn, but if a patient misses one draw, are we going to just take away the med? Of course not, most of us would document that patient has been compliant with blood draws up til now, they've been normal, and outline the risks of discontinuing for one missed draw, then make a clinical judgment.

There's a reason pharmacists will still dispense even without an ANC.

 

[Mass Effect]

Yea that's gonna be it for me. I'm done w/ SDN. I'm actually doing just fine in my residency but somehow coming here makes me consistently makes me feel lik

I hope you don't leave. Stick around. It's a great place usually and can be educational, even for us attendings.

 

[clausewitz2]

The person you were talking to in your other post was a resident. Not all residents are well-versed in REMS until they need to be (for most that's 3rd yr).

As for the REMS guidelines, I call BS on "no blood, no drug." Like everything else patient related you make a risk/benefit analysis and document carefully. Obviously you want the patients to have blood drawn, but if a patient misses one draw, are we going to just take away the med? Of course not, most of us would document that patient has been compliant with blood draws up til now, they've been normal, and outline the risks of discontinuing for one missed draw, then make a clinical judgment.

There's a reason pharmacists will still dispense even without an ANC.

I wish more pharmacists in my neck of the woods thought like this. I am much more likely to get a blanket refusal to fill without up to date REMS, or even refusal if they just can't access it because of technical issues on their end temporarily.

 

[pisekar]

Let's say you have a stable clozapine patient. One month they do not get their labs. The clozapine still gets filled but you get a message from the pharmacy that the ANC is not current. You try to get a hold of the patient and their caregiver repeatedly, to no avail. There are clozapine refills on file. Let's say the clozapine is pretty darn necessary. After all, people don't just end up on clozapine for no reason. At what point do you stop the med?

I guess this doesn't often happen because many clozapine patients are in a facility or have some sort of service through the pharmacy that does the blood draws, but there is the odd person who lives independently or have family/a guardian who manages their care.

Don't overthink this. Even if you prescribe/refill clozapine, pharmacy is not going to give the medication without a blood test. It is patient's responsibility to follow recommendations. Write your prescription, order your lab test, call patient and leave a voice message if you can't reach them. After you document this, it is up to patient to follow up or not.

 

[calvnandhobbs68]

The person you were talking to in your other post was a resident. Not all residents are well-versed in REMS until they need to be (for most that's 3rd yr).

As for the REMS guidelines, I call BS on "no blood, no drug." Like everything else patient related you make a risk/benefit analysis and document carefully. Obviously you want the patients to have blood drawn, but if a patient misses one draw, are we going to just take away the med? Of course not, most of us would document that patient has been compliant with blood draws up til now, they've been normal, and outline the risks of discontinuing for one missed draw, then make a clinical judgment.

There's a reason pharmacists will still dispense even without an ANC.

Sure but there’s quite a difference between a patient missing one blood draw and a patient going AWOL on you but then someone still randomly showing up to pick up clozapine scripts at the pharmacy. If a patient isn’t having blood draws done and isn’t maintaining their regular followup appointments, it’s hard to justify continuing to prescribe this for months at a time. This is what basically everyone else is saying to do above, sure give them one miss but if they miss again or don’t make it to their followup appointment unfortunately would need to cut them off.

 

[Mass Effect]

Sure but there’s quite a difference between a patient missing one blood draw and a patient going AWOL on you but then someone still randomly showing up to pick up clozapine scripts at the pharmacy. If a patient isn’t having blood draws done and isn’t maintaining their regular followup appointments, it’s hard to justify continuing to prescribe this for months at a time. This is what basically everyone else is saying to do above, sure give them one miss but if they miss again or don’t make it to their followup appointment unfortunately would need to cut them off.

But the OP is referring to only one missed draw. I think it's too early to recommend discontinuing treatment.

 

[Evidence Based]

Agree that this absolutely depends on the patient/situation- a patient who goes AWOL during week 6 of titration when risk of agranulocytosis and myocarditis are highest is much different than someone who has been stable on clozapine for like 3 years and misses one appointment or blood draw. The clozapine clinic at my institution vey much individualizes treatment, and given the huge benefits in folks who need it we would ever have a policy like "no refills for clozapine ever" and "cut off refills if you miss one ANC."
Clozapine certainly has risks, but as others have mentioned above it's things like bowel obstruction that worry me much more than blood dycrasias. I think there's a case to be made that the ridiculously tight monitoring requirements on a life saving medication that other meds w/ similar or higher risks (ex. AEDs) don't have results in overall harm to the population w/ a small number of people protected from rare SEs compared to a much larger number or people who don't get appropriate treatment for their psychosis.

 

[clozareal]

Let's say you have a stable clozapine patient. One month they do not get their labs. The clozapine still gets filled but you get a message from the pharmacy that the ANC is not current. You try to get a hold of the patient and their caregiver repeatedly, to no avail. There are clozapine refills on file. Let's say the clozapine is pretty darn necessary. After all, people don't just end up on clozapine for no reason. At what point do you stop the med?

I guess this doesn't often happen because many clozapine patients are in a facility or have some sort of service through the pharmacy that does the blood draws, but there is the odd person who lives independently or have family/a guardian who manages their care.

I would not discontinue the medication after one missed lab draw or being unable to reach the patient or their caregiver. There's lots of reasons for this–being in the hospital, going out of town, becoming more psychotic and disconnecting all the phone lines, losing their phone, etc. Since they've been stable for >1 year, the risk of severe neutropenia is much lower than someone starting out with it and I would argue the benefits > risks.

Also, if they're still going to the pharmacy to pick up their meds, they're either 1) physically well enough which makes me less concerned for anything severe or 2) if their caregiver is picking up the meds, then they should know if a patient is not doing well. I worry more about the patients that stop getting labs and stop picking up refills and aren't picking up their phone.

My first step would be to try to figure out why they aren't getting the lab, which may be the same reason as why they aren't picking up their phone. If you're really worried, you can always call a welfare check on the patient.

 

[meow1985]

It says this in REMS as well. Page 14. Doesn't seem very ambiguous.

https://www.clozapinerems.com/CpmgClozapineUI/rems/pdf/resources/Clozapine_REMS_A_Guide_for_Healthcare_Providers.pdf

"Prescribers must ensure that their patients are on the appropriate monitoring frequency and adhere to the corresponding blood draw dates in order for their patients to receive clozapine"

LOL literally the motto of the Clozapine REMS Website: "No blood, No drug"

Ensure. Ok. But short of coming to the patient's house and doing the blood draw myself, lol, the question is what is a reasonable effort. I believe that question has been answered.

The refills on file were from another doc. I was asked if I wanted to cancel them.

And if it was truly no blood, no drug, then pharmacies wouldn't dispense, but they totally do. All they need to do per REMS is notify the prescribing MD.

In the end, the patient did turn up. They have home delivery, so that's how they got the med without doing the blood draw.