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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 Following is a list of possible medication recalls, market withdrawals, alerts and warnings.

Recent FDA Alerts for clozapine

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

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

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).

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:

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

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

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.

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:

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

Antipsychotics, Conventional and Atypical

[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

[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

The 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)

FDA 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

FDA 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

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