Clozapine REMS still plagued by problems

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.