Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

CAPLYTA (NDA-209500)

(LUMATEPERONE TOSYLATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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11/05/2025 (SUPPL-16)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

CAPLYTA is contraindicated in patients with history of hypersensitivity reaction to lumateperone or any components of CAPYLTA. Reactions have included pruritus, rash (e.g. allergic dermatitis, papular rash, and generalized rash), and urticaria.

5 Warnings and Precautions

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Additions and/or revisions underlined:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. In an analysis of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, the risk of death in antipsychotic drug-treated patients was 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the incidence of death in antipsychotic-treated patients was about 4.5%, compared to an incidence of about 2.6% in placebo-treated patients. Although the causes of death varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia).

CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage (1)].

5.2 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients

Subsection title revised

Additions and/or revisions underlined:

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated pediatric and young adult patients was greater than in placebo-treated patients. There were differences in absolute risk of suicidal thoughts and behaviors across the different uses, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.

Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo- Controlled Trials of Antidepressants in Pediatric* and Adult Patients

…

It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer- term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients, especially during the initial few months of anti-depressant drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the health care provider. Consider changing the therapeutic regimen, including possibly discontinuing CAPLYTA, in patients whose depression is persistently worse, or who experience suicidal thoughts or behaviors.

5.5 Tardive Dyskinesia

Additions and/or revisions underlined:

Tardive dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including CAPLYTA. TD can develop after a relatively brief treatment period at low dosages and may also occur after discontinuation of treatment. If antipsychotic treatment is discontinued, TD may partially or completely remit. Antipsychotic treatment, however, may suppress or partially suppress the signs and symptoms of TD, and may mask the underlying process. The effect that symptomatic suppression has upon the long-term course of TD is unknown.

The TD risk appears to be highest among the elderly, especially elderly women, but it is not possible to predict which patients are likely to develop TD. The TD risk and the likelihood that TD will become irreversible increase with the duration of antipsychotic drug treatment and the cumulative dosage.

Periodically reassess the need for continued treatment. If signs and symptoms of TD appear in CAPLYTA-treated patients, consider drug discontinuation. However, some patients may require CAPLYTA treatment despite the presence of TD.

5.6 Metabolic Changes

Additions and/or revisions underlined:

Antipsychotic drugs have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain.

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. There have been reports of hyperglycemia in patients treated with CAPLYTA. Assess fasting plasma glucose before or soon after initiation of CAPLYTA and monitor periodically during long-term treatment.

In pooled data from short-term (4- to 6-week), placebo-controlled trials of adult patients with schizophrenia, mean changes from baseline and the proportion of patients with shifts from normal to greater than normal levels of fasting glucose were similar in CAPLYTA-treated and placebo-treated patients. In an uncontrolled open-label trial of CAPLYTA for up to 1 year in adult patients with stable schizophrenia, the percentages of patients with shifts in fasting glucose and insulin values from normal to high were 8% and 12%, respectively. In this trial, 5% of CAPLYTA-treated patients with normal hemoglobin A1c (<6.5%) at baseline developed elevated levels (?6.5%) post-baseline.
In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with shifts from normal to greater than normal levels of fasting glucose and insulin were similar in CAPLYTA-treated and placebo-treated patients.
In pooled data from short-term (6-week), placebo-controlled adjunctive therapy MDD trials, mean changes from baseline and the proportion of patients with shifts from normal to greater than normal levels of fasting glucose in were similar in CAPLYTA-treated and placebo-treated patients.

Dyslipidemia

Antipsychotics have caused adverse alterations in lipids. Before or soon after initiation of antipsychotic medications, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

…

In pooled data from short-term (6-week), placebo-controlled adjunctive therapy MDD trials, mean changes from baseline and the proportion of patients with shifts to higher levels of fasting total cholesterol and triglycerides were similar in CAPLYTA-treated and placebo-treated patients.

Weight Gain

Weight gain has been observed with use of antipsychotics. Monitor weight at baseline and frequently thereafter.

…

In pooled data from short-term (6-week), placebo-controlled adjunctive therapy MDD trials, mean changes from baseline and the proportion of patients with an increase in weight greater than or equal to 7% from baseline to end of study were similar in CAPLYTA-treated and placebo-treated patients.
In a long-term open-label adjunctive therapy MDD trial of CAPLYTA for up to 6 months, the mean change in body weight was -0.16 kg (SD 3.7) at Week 26.

5.7 Leukopenia, Neutropenia, and Agranulocytosis

Additions and/or revisions underlined:

Leukopenia and neutropenia have been reported during treatment with antipsychotic drugs, including CAPLYTA. Agranulocytosis (including fatal cases) has been reported other with other antipsychotic drugs.

Possible risk factors for antipsychotic drug-leukopenia and neutropenia include pre-existing low white blood cell count (WBC) or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia.

In patients with a pre-existing low WBC or ANC or a history of drug-induced leukopenia or neutropenia, perform complete blood count (CBC) monitoring during the first few months of CAPLYTA therapy. Consider discontinuing CAPLYTA in patients who have a clinically significant decline in WBC in the absence of other causative factors.

Discontinue CAPLYTA in patients with clinically significant neutropenia or ANC < 1000/mm3 and monitor closely until the neutropenia resolves.

5.8 Orthostatic Hypotension and Syncope

Additions and/or revisions underlined:

Atypical antipsychotics cause orthostatic hypotension and syncope. Generally, the risk is greatest during initial dose administration.

…

In pooled data from short-term (6-week), placebo-controlled adjunctive therapy MDD trials, the frequencies of orthostatic hypotension for CAPLYTA-treated and placebo-treated patients were 6.6% and 6.2%, respectively. The incidence of syncope for CAPLYTA-treated and placebo-treated patients were 0.2% and 0%, respectively.

5.9 Falls

Additions and/or revisions underlined:

Antipsychotics, including CAPLYTA, may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures and other injuries.

If patients have a condition (or take concomitant drugs) that could exacerbate these effects, complete fall risk assessments when initiating CAPLYTA treatment and periodically during long-term treatment.

5.11 Potential for Cognitive and Motor Impairment

Additions and/or revisions underlined:

…

In short term (6-week), placebo-controlled adjunctive therapy MDD trials, somnolence and sedation were reported in 12% of CAPLYTA-treated patients, compared to 2% of placebo-treated patients.

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

7 Drug Interactions

7.1 Drugs Having Clinically Important Interactions with CAPLYTA

Extensive changes; please refer to label for complete information

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including CAPLYTA, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/.

…

8.5 Geriatric Use

Additions and/or revisions underlined:

Controlled clinical studies of CAPLYTA for the treatment of schizophrenia and as adjunctive therapy with antidepressants for the treatment of MDD did not include any patients aged 65 or older to determine whether or not they respond differently from younger adult patients.

Among the CAPLYTA-treated patients in clinical studies for the treatment of depressive episodes associated with bipolar depression, 20 (6%) were 65 to 74 years of age, and none were 75 years of age or older [see Clinical Studies (14.2)].

These clinical studies did not include sufficient numbers of patients aged 65 years of age or older to determine whether or not they respond differently from younger adult patients.

Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning, Warnings and Precautions (5.1) and (5.3)].

Elderly patients with dementia-related psychosis treated with antipsychotics have an increased risk of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) including fatalities, compared to those treated with placebo [see Warnings and Precautions (5.1)].

Antipsychotic drugs increase the risk of tardive dyskinesia and this risk appears to be highest among the elderly, particularly elderly women [see Warnings and Precautions (5.5)].

The use of serotonin reuptake inhibitors (SRIs) has been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction. The concomitant use of CAPLYTA with an SRI may increase this risk [see Drug Interactions 7.1].

8.6 Hepatic Impairment

Additions and/or revisions underlined:

Patients with moderate hepatic impairment (HI) (Child-Pugh class B) and severe HI (Child-Pugh class C) generally had higher exposure to lumateperone than patients with normal hepatic function; therefore, the recommended CAPLYTA dosage in patients with moderate or severe HI is lower than those with normal hepatic function [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

The recommended dosage in patients with mild HI (Child-Pugh class A) is the same as those with normal hepatic function.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about CAPLYTA? CAPLYTA may cause serious side effects, including:

…

Increased risk of suicidal thoughts and actions. CAPLYTA and antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed.

…

See “What are the possible side effects of CAPLYTA?” for more information about side effects.

…

What is CAPLYTA?

CAPLYTA is a prescription medicine used in adults:

to treat schizophrenia
alone or along with the medicine lithium or valproate to treat depressive episodes that happen with bipolar I or bipolar II disorder (bipolar depression) along with antidepressant medicines to treat major depressive disorder (MDD) It is not known if CAPLYTA is safe and effective in children.

…

The most common side effects of CAPLYTA include sleepiness, dizziness, nausea, dry mouth, feeling tired, and diarrhea.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behavior

Advise patients and caregivers to look for the emergence of suicidal thoughts and behaviors, especially early during CAPLYTA treatment and instruct them to report such symptoms to their healthcare provider [see Boxed Warning, Warnings and Precautions (5.2)].

…

Effects on Driving and Operating Heavy Machinery

Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that CAPLYTA therapy does not affect them adversely [see Warnings and Precautions (5.11)].

…

Concomitant Drugs

Advise patients to inform their health care providers of any changes to their current prescription or over-the-counter drugs because there is a potential for clinically significant interactions [see Drug Interactions (7.1)].

…

06/28/2023 (SUPPL-11)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

New subsection added:

The following adverse reaction has been identified during post-approval use of CAPLYTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Central and Peripheral Nervous System Disorders: burning sensation, including skin burning sensation

8 Use in Specific Populations

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

Lumateperone and its metabolites are present in human breast milk in low amounts. In a clinical lactation study, lumateperone was detected in human milk at an estimated daily infant dose 0.0004 mg/kg, with a relative infant dose (RID) of 0.06% the maternal weight-adjusted dosage. Several major circulating metabolites were similarly detected in breast milk in low amounts; however, aniline metabolites were not present in milk or maternal plasma at quantifiable levels (see Data). There are no data on the effects of lumateperone on the breastfed infant or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAPLYTA and any potential adverse effects on the breastfed child from CAPLYTA or from the underlying maternal condition.

Data

A lactation study in 17 lactating women evaluated the concentrations of lumateperone and its metabolites in plasma and mature breast milk following a single dose of 42 mg CAPLYTA. The estimated daily infant dose of lumateperone in human milk was 0.0004 mg/kg/day (with assumed average milk consumption of 200 ml/kg/day). The mean relative infant dose (RID) (with assumed mean milk consumption of 200 mL/kg/day and average maternal weight of 71 kg) was 0.06% of the maternal weight-adjusted dosage. Several major circulating metabolites were also present in breastmilk at estimated daily infant dose of 0.0004 mg/kg/day. Aniline metabolites were not present in milk or maternal plasma at quantifiable levels.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Before taking CAPLYTA, tell your healthcare provider about all of your medical conditions, including if you:

…

are breastfeeding or plan to breastfeed. CAPLYTA passes into your breastmilk. Talk to your healthcare provider about the risks and benefits of breastfeeding and the best way to feed your baby during treatment with CAPLYTA.
…

12/17/2021 (SUPPL-5)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1)].

Suicidal Thoughts and Behaviors

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short- term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.2)]. The safety and effectiveness of CAPLYTA have not been established in pediatric patients [see Use in Specific Populations (8.4)].

5 Warnings and Precautions

5.11 Potential for Cognitive and Motor Impairment

Additions underlined

…

Bipolar Depression

In short term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression clinical trials, somnolence and sedation were reported in 13% of CAPLYTA-treated patients, compared to 3% of placebo-treated patients.

5.2 Suicidal Thoughts and Behaviors in Children, Adolescents in Children and Young Adults

New subsection added

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1.

Please refer to label to view Table 1

It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing CAPLYTA, in patients whose depression is persistently worse, or who are experiencing suicidal thoughts or behaviors.

5.6 Metabolic Changes

Additions underlined

…

Hyperglycemia and Diabetes Mellitus

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with shifts from normal to greater than normal levels of fasting glucose and insulin in patients treated with CAPLYTA were similar to those in patients treated with placebo.

…

Dyslipidemia

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with shifts to higher levels of fasting total cholesterol and triglycerides were similar in patients treated with CAPLYTA and placebo.

In an uncontrolled open-label trial of CAPLYTA for up to 6 months in patients with bipolar depression, the proportion of patients with a shift from normal to high were 10%, 5%, and 2% for total cholesterol, triglycerides, and LDL cholesterol, respectively.

…

Weight Gain

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with an increase in weight greater than or equal to7% from baseline to end of study were similar in patients treated with CAPLYTA and placebo.

In an uncontrolled open-label trial of CAPLYTA for up to 6 months in patients with bipolar depression, the mean change in body weight was -0.01 kg (SD 3.1) at Day 175.

Additions underlined

…

Hyperglycemia and Diabetes Mellitus

…

Bipolar Depression

…

Dyslipidemia

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with shifts to higher levels of fasting total cholesterol and triglycerides were similar in patients treated with CAPLYTA and placebo.

…

Weight Gain

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with an increase in weight greater than or equal to7% from baseline to end of study were similar in patients treated with CAPLYTA and placebo.

In an uncontrolled open-label trial of CAPLYTA for up to 6 months in patients with bipolar depression, the mean change in body weight was -0.01 kg (SD 3.1) at Day 175.

5.8 Orthostatic Hypotension and Syncope

Additions underlined

…

Schizophrenia

In pooled data from short-term (4- to 6-week), placebo-controlled schizophrenia trials, the frequencies of orthostatic hypotension for CAPLYTA and placebo were 0.7% and 0%, respectively. The rates of syncope for CAPLYTA and placebo were 0.2% and 0.2%.

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, the frequencies of orthostatic hypotension for CAPLYTA and placebo were both 0%. The rates of syncope for CAPLYTA and placebo were 0.3% and 0.5%, respectively in the monotherapy trials, and there were no reports for CAPLYTA or placebo in the adjunctive therapy trial.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Suicidal Thoughts and Behaviors [see Boxed Warning, Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Extensive additions and/or revision; please refer to label for complete information.

8 Use in Specific Populations

8.4 Pediatric Use

Additions underlined

Safety and effectiveness of CAPLYTA have not been established in pediatric patients.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions (5.2)].

8.5 Geriatric Use

Additions underlined

Controlled clinical studies of CAPLYTA in the treatment of schizophrenia did not include any patients aged 65 or older to determine whether or not they respond differently from younger patients. Controlled clinical studies of CAPLYTA in the treatment of bipolar depression included patients aged 65 or older; the number of patients was not sufficient to determine whether or not they respond differently from younger patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions underlined

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behavior

Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and instruct them to report such symptoms to their healthcare provider [see Boxed Warning, Warnings and Precautions (5.2)].

MEDICATION GUIDE

New section added; please refer to label for complete information.

12/17/2021 (SUPPL-6)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Suicidal Thoughts and Behaviors

5 Warnings and Precautions

5.11 Potential for Cognitive and Motor Impairment

Additions underlined

…

Bipolar Depression

5.2 Suicidal Thoughts and Behaviors in Children, Adolescents in Children and Young Adults

New subsection added

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1.

Please refer to label to view Table 1

5.6 Metabolic Changes

Additions underlined

…

Hyperglycemia and Diabetes Mellitus

…

Bipolar Depression

…

Dyslipidemia

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with shifts to higher levels of fasting total cholesterol and triglycerides were similar in patients treated with CAPLYTA and placebo.

…

Weight Gain

…

Bipolar Depression

In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with an increase in weight greater than or equal to7% from baseline to end of study were similar in patients treated with CAPLYTA and placebo.

In an uncontrolled open-label trial of CAPLYTA for up to 6 months in patients with bipolar depression, the mean change in body weight was -0.01 kg (SD 3.1) at Day 175.

5.8 Orthostatic Hypotension and Syncope

Additions underlined

…

Schizophrenia

Bipolar Depression

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Suicidal Thoughts and Behaviors [see Boxed Warning, Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Extensive additions and/or revision; please refer to label for complete information.

8 Use in Specific Populations

8.4 Pediatric Use

Additions underlined

Safety and effectiveness of CAPLYTA have not been established in pediatric patients.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions (5.2)].

8.5 Geriatric Use

Additions underlined

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions underlined

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behavior

MEDICATION GUIDE

New section added; please refer to label for complete information.