Applies to lumateperone: oral capsule.

Serious side effects of Lumateperone

Along with its needed effects, lumateperone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking lumateperone:

Incidence not known

• Black, tarry stools
• blurred vision
• chest pain
• confusion
• cough or hoarseness
• double vision
• dry mouth
• fast heartbeat
• fever with or without chills
• flushed, dry skin
• fruit-like breath odor
• general feeling of tiredness or weakness
• headache
• high fever
• inability to move the arms, legs, or facial muscles
• inability to move the eyes
• inability to speak
• increased blinking or spasms of the eyelid
• increased hunger
• increased sweating
• increased thirst
• increased urination
• lip smacking or puckering
• loss of bladder control
• lower back or side pain
• nausea
• numbness or tingling in the face, arms, or legs
• painful or difficult urination
• puffing of the cheeks
• rapid or worm-like movements of the tongue
• seizures
• severe muscle stiffness
• slow speech
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sticking out of the tongue
• stomach pain
• sweating
• swollen glands
• tiredness
• trouble in breathing, speaking, or swallowing
• trouble thinking or walking
• uncontrolled chewing movements
• uncontrolled movements of the arms and legs
• uncontrolled twisting movements of the neck, trunk, arms, or legs
• unexplained weight loss
• unusual bleeding or bruising
• unusual facial expressions
• unusual tiredness or weakness
• unusually pale skin
• vomiting

Other side effects of Lumateperone

Some side effects of lumateperone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Dizziness
• dry mouth
• sleepiness or unusual drowsiness
• weight gain

Incidence not known

• Burning feeling

For Healthcare Professionals

Applies to lumateperone: oral capsule.

General

The most commonly reported side effects included sedation/somnolence, nausea, dry mouth, and dizziness.^[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Orthostatic hypotension^[Ref]

Endocrine

Common (1% to 10%): Increased blood prolactin^[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, dry mouth, vomiting, diarrhea, abdominal pain (includes abdominal discomfort, abdominal pain, upper abdominal pain, lower abdominal pain)

Antipsychotic drugs:

-Frequency not reported: Esophageal dysmotility, dysphagia^[Ref]

Hematologic

Frequency not reported: Leukopenia, neutropenia

Antipsychotic drugs:

-Frequency not reported: Agranulocytosis^[Ref]

Hepatic

Common (1% to 10%): Increased hepatic transaminases (includes increased ALT, increased AST, increased hepatic enzymes, abnormal liver function test)^[Ref]

Metabolic

Very common (10% or more): Shifts in insulin values from normal to high (up to 12%)

Common (1% to 10%): Decreased appetite, shifts in fasting glucose from normal to high

Frequency not reported: Hyperglycemia, increased hemoglobin A1c levels

Antipsychotic drugs:

-Frequency not reported: Metabolic changes (including hyperglycemia [some cases extreme and associated with ketoacidosis, hyperosmolar coma, death], diabetes mellitus, dyslipidemia, weight gain)^[Ref]

In pooled data from short-term (4- to 6-week) 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 in patients treated with this drug were similar to those in patients treated with placebo. In an uncontrolled trial of this drug for up to 1 year in 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; 4.7% of patients with normal hemoglobin A1c (less than 6.5%) at baseline developed elevated levels (at least 6.5%) postbaseline.

In data from short-term (6-week) 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 this drug were similar to those in patients treated with placebo.^[Ref]

Musculoskeletal

Common (1% to 10%): Increased creatine phosphokinase^[Ref]

Nervous system

In the 4- to 6-week schizophrenia trials, the frequency of reported events related to EPS (including akathisia, extrapyramidal disorder, muscle spasms, restlessness, musculoskeletal stiffness, dyskinesia, dystonia, muscle twitching, tardive dyskinesia, tremor, drooling, involuntary muscle contractions) was 6.7% for this drug and 6.3% for placebo.

In the 6-week monotherapy bipolar depression trials, the frequency of reported reactions related to EPS (including muscle spasms, dyskinesia, extrapyramidal disorder, movement disorder, tremor, restlessness, akathisia) was 1.3% for this drug and 1.1% for placebo. In the 6-week adjunctive therapy bipolar depression trial, the frequency of reported reactions related to EPS (including tremor, muscle spasms, akathisia, extrapyramidal disorder, gait disturbance, restlessness) was 4% for this drug and 2.3% for placebo.

In placebo-controlled trials in older patients with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke.^[Ref]

Very common (10% or more): Somnolence/sedation (up to 24%), headache (up to 14%), dizziness (includes dizziness, postural dizziness; up to 11%)

Common (1% to 10%): Extrapyramidal symptoms (EPS; including akathisia, extrapyramidal disorder, muscle spasms, restlessness, musculoskeletal stiffness, dyskinesia, dystonia, muscle twitching, tardive dyskinesia, tremor, drooling, involuntary muscle contractions, movement disorder, gait disturbance)

Uncommon (0.1% to 1%): Syncope

Antipsychotic drugs:

-Frequency not reported: Cerebrovascular adverse reactions, stroke, transient ischemic attack, neuroleptic malignant syndrome, tardive dyskinesia^[Ref]

Ocular

Common (1% to 10%): Blurred vision^[Ref]

Other

Common (1% to 10%): Fatigue, increased total cholesterol, increased triglycerides, increased low-density lipoprotein (LDL) cholesterol

Frequency not reported: Weight gain, weight loss

Antipsychotic drugs:

-Frequency not reported: Increased mortality (in older patients with dementia-related psychosis), adverse alterations in lipids, weight gain^[Ref]

In pooled data from short-term (4- to 6-week) trials of adult patients with schizophrenia, 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 this drug and placebo. In an uncontrolled trial of this drug for up to 1 year in patients with stable schizophrenia, the percentages of patients with a shift from normal to high were 8%, 5%, and 4% for total cholesterol, triglycerides, and LDL cholesterol, respectively.

In data from short-term (6-week) 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 this drug and placebo. In an uncontrolled trial of this drug 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.

In pooled data from trials of adult patients with schizophrenia, mean changes from baseline and the proportion of patients with an increase in weight at least 7% from baseline to end of study was similar in patients treated with this drug and placebo. In an uncontrolled trial of this drug for up to 1 year in patients with stable schizophrenia, the mean change in body weight was about -2 kg at Day 175 and about -3.2 kg at Day 350.

In data from short-term (6-week) monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with an increase in weight at least 7% from baseline to end of study were similar in patients treated with this drug and placebo. In an uncontrolled trial of this drug for up to 6 months in patients with bipolar depression, the mean change in body weight was -0.01 kg at Day 175.

Analyses of 17 placebo-controlled trials (modal duration: 10 weeks), mainly in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that in placebo-treated patients. Over the course of a typical 10-week trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in placebo-treated patients. Although the causes were varied, most deaths were either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.^[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection

Frequency not reported: Difficulty breathing

Antipsychotic drugs:

-Frequency not reported: Aspiration^[Ref]