Clozapine FDA Alerts

The FDA Alerts below may be specifically about clozapine or relate to a group or class of drugs which include clozapine.

MedWatch Safety Alerts are distributed by the FDA and published by Drugs.com. Following is a list of possible medication recalls, market withdrawals, alerts and warnings.

Recent FDA Alerts for clozapine

FDA Removes Risk Evaluation and Mitigation Strategy (REMS) Program for the Antipsychotic Drug Clozapine

Aug 27, 2025 | Audience: Patient, Pharmacy, Health Care Professional

August 27, 2025 -- FDA Removes Risk Evaluation and Mitigation Strategies (REMS) Program for the Antipsychotic Drug Clozapine Neutropenia Risk Remains, but REMS No Longer Necessary and REMS May Prevent Treatment Access

What Is FDA Announcing?

The U.S. Food and Drug Administration (FDA) removed the risk evaluation and mitigation strategy (REMS) for clozapine (currently marketed as Clozaril, Versacloz, and generics), effective June 13, 2025. Clozapine, an antipsychotic medicine, can cause severe neutropenia (a low level of certain white blood cells), which can lead to serious and fatal infections. The removed REMS required enrollment of prescribers, pharmacies, and patients in a restricted distribution program and reporting of the level of certain white blood cells (i.e., the absolute neutrophil count (ANC)) to mitigate the risk of severe neutropenia.

Based on FDA’s re-evaluation of the Clozapine REMS and on the November 19, 2024 Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Psychopharmacologic Drugs Advisory Committee, the Agency determined that the REMS was no longer necessary to ensure the benefits of clozapine outweigh the risk of severe neutropenia. Although there remains a risk of severe neutropenia with clozapine use, clozapine labeling (including a new Medication Guide) is sufficient to mitigate this risk and maintain a positive benefit/risk profile. ANC monitoring can help identify neutropenia early to allow for timely intervention. Therefore, prescribers should continue to monitor patients’ ANC according to the monitoring frequencies described in the prescribing information. Eliminating the REMS is expected to improve access to clozapine and decrease the burden on the health care delivery system.

What Is FDA Doing?

FDA has removed the REMS for clozapine. As a result, prescribers, pharmacies, and patients are no longer required to participate in the REMS program and report patients’ ANC results to the REMS in order for clozapine to be dispensed to the patient.

Information about severe neutropenia is in the prescribing information for all clozapine medicines, including in a Boxed Warning and a new Medication Guide.

Severe neutropenia remains a serious, potentially fatal risk that is greatest in the first several months of clozapine treatment. ANC monitoring can help identify neutropenia early to allow for timely intervention. Therefore, FDA recommends that prescribers monitor patients’ ANC according to the monitoring frequencies described in the prescribing information.

What Is Clozapine, and How Can It Help Me?

Clozapine is an atypical antipsychotic medicine used to treat people who are severely ill with schizophrenia who remain symptomatic on other schizophrenia medicines. Clozapine is thought to work by balancing the brain’s levels of dopamine and serotonin, two neurotransmitters involved in brain function. Clozapine is also approved to treat people with schizophrenia or schizoaffective disorder who have been suicidal and may be at risk for recurrent suicidal behavior.

Schizophrenia is a chronic and severe mental health disorder characterized by psychosis—including hallucinations and delusions—disorganized thinking, and abnormal motor behavior. Schizoaffective disorder includes symptoms of schizophrenia and mood disorders, such as bipolar disorder or depression.

Clozapine is an oral tablet that patients take either once or twice a day. Its most common side effects are sleepiness or drowsiness, headache, dizziness, shaking movements (tremors), heart and blood vessel problems, low blood pressure, fast heartbeat, a lot of saliva in your mouth, passing out (syncope), dry mouth, increased sweating, constipation and nausea, vision problems, and fever.

The most serious side effects are severe neutropenia (very low white blood cell counts) that can lead to serious infection and death; decreased blood pressure, slow heart rate, or syncope that can lead to death; seizures; serious heart problems; and increased risk of death in people with dementia. Regarding severe neutropenia, the risk appears to be greatest in the first several months of clozapine treatment, but the risk never goes away. Frequent absolute neutrophil count (ANC) monitoring is necessary to identify neutropenia early so that health care professionals can intervene.

What Should Patients and Caregivers Do?

Patients should be aware that they no longer need to be enrolled in the REMS to receive clozapine. That means that pharmacies no longer need to verify patients’ enrollment in the REMS and patients’ absolute neutrophil count (ANC) before dispensing clozapine.

However, patients should talk with their health care professional about the need for monitoring ANC before starting clozapine and during treatment, including the frequency of lab testing. Patients should be aware that they may need to modify, pause, or stop clozapine treatment based on results of ANC monitoring. Patients should contact their health care professional if they notice symptoms of neutropenia such as:

Flu-like symptoms
Wounds that take a long time to heal
Fever or chills
Skin, throat, vaginal, urinary tract, or lung infection
Extreme fatigue or weakness
Pain or burning while urinating
Sores or ulcers inside the mouth or gums
Unusual vaginal discharge or itching skin
Sores or pain in the rectal area
Abdominal pain or bloating

What Should Health Care Professionals Do?

Prescribers of clozapine no longer have to be enrolled in the REMS or to enroll their patients in it. They also do not have to submit absolute neutrophil count (ANC) results to the REMS program. Prescribers should continue to monitor their patients’ ANC before starting clozapine and during treatment according to the prescribing information and to counsel patients about the risk of severe neutropenia. Pharmacies do not need to be enrolled in the REMS to order clozapine from wholesaler distributors. Pharmacists do not need to verify patient eligibility, including ANC monitoring, before dispensing clozapine to patients.

Health care professionals should be advised that the risk of neutropenia is generally greatest in the first several months of clozapine treatment and persists at a lower level thereafter. In addition, they should tell their patients to seek medical care if they experience symptoms that may indicate neutropenia.

What Did FDA Find?

FDA used a systematic, structured approach to re-evaluate the Clozapine REMS, which included collaborating on several studies to assess clozapine use and participants’ adherence to monitoring, as well as neutropenia outcomes. This evaluation included a literature review, a review of the FDA Adverse Event Reporting System, and additional studies designed and analyzed in collaboration with Brigham and Women’s Hospital, the U.S. Department of Veterans Affairs, and through the FDA Sentinel System.

This re-evaluation aimed to determine:

If the risk of severe neutropenia has changed since the initial approval of clozapine in 1989;
If health care professionals’ knowledge of the risk of and need for monitoring has changed since 1989; and
The extent that health care professionals monitor patients’ absolute neutrophil count (ANC) results.

Regarding the risk of severe neutropenia with clozapine use, FDA concluded that the risk appears to be greatest in the first several months of clozapine treatment but never reaches zero. This is consistent with the currently approved clozapine prescribing information, which states that the risk is greatest in the first 18 weeks of clozapine initiation. FDA’s assessment confirmed that frequent ANC monitoring is necessary to identify neutropenia early so that health care professionals can intervene.

The re-evaluation found that prescribers appear to more broadly understand the risk of severe neutropenia and the need for ANC monitoring, and that medical training and health care systems have more widely incorporated information and training on clozapine and its safe use today compared to 1989. In addition, guidelines and resources available to prescribers about clozapine have greatly expanded since 1989.

In addition to FDA’s evaluation, the Agency considered the advice of the November 19, 2024, Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Psychopharmacologic Drugs Advisory Committee. In general, the committee members agreed with the continued need to monitor ANCs; however, they concluded that ANC documentation and training for health care 4 professionals through the REMS are no longer necessary to ensure safe use of clozapine. During the Advisory Committee’s open public hearing, the Agency also heard from patients and caregivers that the REMS can sometimes impede access to clozapine.

Data Summary

Data to support the removal of the Clozapine REMS included a literature review, a review of the FDA Adverse Event Reporting System, and additional studies designed and analyzed in collaboration with Brigham and Women’s Hospital, the U.S. Department of Veterans Affairs, and through the FDA Sentinel System. Together these studies capture 20 years of data from different types of health care delivery systems and insurance coverage. These data were presented and discussed during the November 19, 2024 Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Psychopharmacologic Drugs Advisory Committee.

What Is My Risk?

All medicines may have side effects—even when used correctly as prescribed. People respond differently to medicines depending on their health, genetic factors, other medicines they are taking, and many other factors. As a result, it is difficult to determine how likely it is that someone will develop neutropenia after taking clozapine. Talk to your health care professional(s) if you have questions or concerns about the risks of taking clozapine.

How Do I Report Side Effects of Clozapine?

To help FDA track safety issues with medicines, we urge patients and health care professionals to report side effects involving clozapine or other medicines to the FDA MedWatch program using the information in the “Contact FDA” box at the bottom of this page.

How Can I Get New safety Information on Medicines I’m Prescribing or Taking?

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Source: FDA

Drug Safety Communication: Clozapine (Clozaril, Fazaclo ODT, Versacloz) - FDA Strengthens Warning That Untreated Constipation Can Lead to Serious Bowel Problems

Jan 28, 2020 | Audience: Patient, Health Professional

ISSUE: FDA is strengthening an existing warning that constipation caused by the schizophrenia medicine clozapine (Clozaril, Fazaclo ODT, Versacloz, generics) can, uncommonly, progress to serious bowel complications. This can lead to hospitalization or even death if constipation is not diagnosed and treated quickly.

BACKGROUND: Clozapine affects how the intestines (bowels) function in the majority of patients. It produces effects ranging from constipation (trouble having a bowel movement), which is a common occurrence, to serious but uncommon bowel problems, including complete blockage of the bowel.

RECOMMENDATION: Patients should contact your health care professional if:

their bowel movements are less frequent than normal.
they do not have a bowel movement at least three times a week.
they have hard or dry stools.
they have difficulty passing gas.

Patients should contact your health care professional right away if you have symptoms which can be associated with serious bowel problems such as:

nausea
vomiting
bloating or belly swelling, or belly pain.

Health care professionals should:

Evaluate bowel function before starting a patient on clozapine.
Avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility.
Advise patients frequently of the significant risk of constipation and life-threatening bowel issues and the need to stay hydrated to prevent constipation.
Question patients about the frequency and quality of their bowel movements throughout treatment.
Advise patients to contact a health care professional right away if they have difficulty having a bowel movement or passing stools, do not have a bowel movement at least three times a week or less than their normal frequency, or are unable to pass gas.
Monitor patients for symptoms of potential complications associated with gastrointestinal hypomotility such as nausea, abdominal distension or pain, and vomiting.
Consider prophylactic laxative treatment when starting clozapine in patients with a history of constipation or bowel obstruction.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report online
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form or submit by fax to 1-800-FDA-0178

[01/28/2020 - Drug Safety Communication - FDA]

Source: FDA

Clozapine: Drug Safety Communication - FDA Modifies Monitoring for Neutropenia; Approves New Shared REMS Program

Sep 15, 2015 | Audience: Psychiatry, Pharmacy, Hematology

ISSUE: FDA is making changes to the requirements for monitoring, prescribing, dispensing, and receiving the schizophrenia medicine clozapine, to address continuing safety concerns and current knowledge about a serious blood condition called severe neutropenia. Severe neutropenia is a dangerously low number of neutrophils, white blood cells that help fight infections. Severe neutropenia can be life-threatening.

There are two parts to the changes in the requirements for treating patients with clozapine. First, FDA clarified and enhanced the prescribing information for clozapine that explains how to monitor patients for neutropenia and manage clozapine treatment. Second, FDA approved a new, shared risk evaluation and mitigation strategy (REMS) called the Clozapine REMS Program. The revised prescribing information and the Clozapine REMS Program will improve monitoring and management of patients with severe neutropenia. The shared REMS is also expected to reduce the burden and possible confusion related to having separate registries for individual clozapine medicines. The requirements to monitor, prescribe, dispense, and receive all clozapine medicines are now incorporated into the Clozapine REMS Program.

BACKGROUND: Clozapine is an antipsychotic medicine used to treat schizophrenia in patients whose symptoms are not controlled with standard antipsychotic treatment. It is also used to treat recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder.

RECOMMENDATION: Patients who are currently treated with clozapine will be automatically transferred to the Clozapine REMS Program. In order to prescribe and dispense clozapine, prescribers and pharmacies will be required to be certified in the Clozapine REMS Program according to a specific transition schedule starting October 12, 2015 (see Additional Information for Prescribers, Additional Information for Pharmacies, and Additional Information for Patients and Caregivers sections of the Drug Safety Communication for more details).

Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[09/15/2015 - Drug Safety Communication - FDA]

Antipsychotic drugs: Class Labeling Change - Treatment During Pregnancy and Potential Risk to Newborns

Feb 22, 2011 | Audience: Psychiatry, OBGYN

Drugs include: Haldol, FazaClo, Fanapt, Clozaril, Risperdal, Zyprexa, Seroquel, Abilify, Geodon, Invega, Loxitane, Moban, Navane, Orap, Saphris, Stelazine, Thorazine, Symbyax

ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment.

Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[02/22/2011 - Drug Safety Communication - FDA]

Antipsychotics, Conventional and Atypical

Jun 16, 2008 | Audience: Neuropsychiatric and geriatrics healthcare professionals[Posted 06/16/2008] FDA notified healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics. Antipsychotics are not indicated for the treatment of dementia-related psychosis. The prescribing information for all antipsychotic drugs will now include the same information about this risk in a BOXED WARNING and the WARNINGS section.

[June 16, 2008 - Information for Healthcare Professionals - FDA]

Clozaril (clozapine) - Jan 13, 2006

Jan 13, 2006 | Audience: Neuropsychiatric healthcare professionals and patients[Posted 01/13/2006] Novartis and FDA notified healthcare professionals of revisions to the BOXED WARNING, WARNINGS, CONTRAINDICATIONS, PRECAUTIONS (Information for Patients and Pharmacokinetic-Related Interactions subsections), and ADVERSE REACTIONS (Postmarketing Clinical Experience subsection) sections of the prescribing information for Clozaril (clozapine) tablets. Recommendations from the FDA's Psychopharmacological Drugs Advisory Committee regarding the white blood cell monitoring schedule, required for all clozapine users, has resulted in modification in the monitoring schedule. Additional labeling changes address safety issues related to dementia-related psychosis, parlytic ileus, hypercholesterolemia and pharmacokinetic interaction with citalopram.

[December, 2005 - Letter with attachments - Novartis]

Atypical Antipsychotic Drugs

Apr 11, 2005 | Audience: Neuropsychiatric healthcare professionals, patients and caregiversThe Food and Drug Administration has issued a public health advisory to alert health care providers, patients, and patient caregivers to new safety information concerning an unapproved, “off-label” use of certain antipsychotic drugs approved for the treatment of schizophrenia and mania. FDA has determined that the treatment of behavioral disorders in elderly patients with dementia with atypical (second generation) antipsychotic medications is associated with increased mortality. Clinical studies of these drugs in this population have shown a higher death rate associated with their use compared to patients receiving a placebo.

[April 11, 2005 - Public Health Advisory - FDA]
[April 11, 2005 - Drug Information Page - FDA]

Clozaril (clozapine tablets)

Apr 7, 2004 | Audience: Neuropsychiatric healthcare professionalsFDA and Novartis notified healthcare professionals of revision to the WARNINGS section of labeling, describing the increased risk of hyperglycemia and diabetes in patients taking Clozaril. FDA has asked all manufacturers of atypical antipsychotic medications, including Novartis, to add this Warning statement to labeling.

[April 1, 2004 Letter - Novartis]
[December 2003 Revised Label - Novartis]

Clozaril (clozapine) - Feb 20, 2002

Feb 20, 2002 | Audience: Psychiatrists, PharmacistsFDA and Novartis have strengthened the BOXED WARNING and WARNINGS sections of the prescribing information (PI) for Clozaril (clozapine) as follows: (1) The previously existing BOXED WARNING has been relocated to the beginning of the PI and revised to advise health care providers of the association of myocarditis with clozapine therapy; (2) A subsection has been added to the WARNINGS section entitled "Myocarditis" to provide data and clozapine treatment guidelines related to this issue.

[Feb 20, 2002 Letter - Novartis] PDF Format
[Feb 20, 2002 Revised Package Insert - Novartis] 112 kb PDF Format