Safety & Tolerability

Adverse Reactions in 6-Week Clinical Trials

Pooled safety: adverse reactions with LATUDA

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Note: Figures rounded to the nearest integer
*Extrapyramidal symptoms includes adverse event terms: bradykinesia, cogwheel rigidity, drooling, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, oculogyric crisis, oromandibular dystonia, parkinsonism, psychomotor retardation, tongue spasm, torticollis, tremor, and trismus
**Somnolence includes adverse event terms: hypersomnia, hypersomnolence, sedation, and somnolence

Dose-Related Adverse Reactions in the Schizophrenia Studies
Akathisia and extrapyramidal symptoms were dose-related. The frequency of akathisia increased with dose up to
120 mg/day (5.6% for LATUDA 20 mg, 10.7% for LATUDA 40 mg, 12.3% for LATUDA 80 mg, and 22.0% for LATUDA 120 mg). Akathisia was reported by 7.4% (9/121) of patients receiving 160 mg/day. Akathisia occurred in 3.0% of subjects receiving placebo. The frequency of extrapyramidal symptoms increased with dose up to 120 mg/day (5.6% for LATUDA 20 mg, 11.5% for LATUDA 40 mg, 11.9% for LATUDA 80 mg, and 22.0% for LATUDA 120 mg).1

Pooled Safety: Metabolic Changes by Dose with LATUDA

Mean change in weight—pooled 6-week trials

3.9_Weight_Change_Chart

Mean change in lipids—pooled 6-week trials

3.9_Lipids_Chart

Mean change in glucose—pooled 6-week trials

3.9_Glucose_Chart

Metabolic changes at Year 1 in primarily open-label extension studies

3.9_1-Year_Chart
  • In the uncontrolled longer-term studies (primarily open-label extension studies), LATUDA was associated with a median change in prolactin of –2.2 ng/mL at week 52 (n=307).


References:
1.
 Latuda® (lurasidone HCl) prescribing information. Sunovion Pharmaceuticals Inc. July 2013.
2. Data on file. Sunovion Pharmaceuticals Inc.

Important Safety Information & Indications

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

 

CONTRAINDICATIONS
LATUDA is contraindicated in the following:

WARNINGS AND PRECAUTIONS
Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with administration of antipsychotic drugs, including LATUDA. NMS can cause hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems.

Tardive Dyskinesia (TD): TD is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements that can develop in patients with antipsychotic drugs. There is no known treatment for established cases of TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Given these considerations, LATUDA should be prescribed in a manner that is most likely to minimize the occurrence of TD. If signs and symptoms appear in a patient on LATUDA, drug discontinuation should be considered.

Metabolic Changes

Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing.  In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, LATUDA elevates prolactin levels.  Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Adult patients with bipolar depression:

In the short-term, placebo-controlled monotherapy study, the median change from baseline to endpoint in prolactin levels for LATUDA-treated females was 3.1 ng/mL and was 1.5 ng/mL for males.  The proportion of female patients with prolactin elevations ≥5x ULN was 0.6% for LATUDA-treated patients versus 0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥5x ULN was 0% for LATUDA-treated patients versus 0% for placebo-treated male patients.In the short-term, placebo-controlled adjunctive therapy with lithium or valproate study, the median change from baseline to endpoint in prolactin levels for LATUDA-treated females was 3.2 ng/mL and was 2.4 ng/mL for males. The proportion of female patients with prolactin elevations ≥5x ULN was 0% for LATUDA-treated patients versus 0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥5x ULN was 0% for LATUDA-treated patients versus 0% for placebo-treated male patients.

Adult patients with schizophrenia:

In the short-term, placebo-controlled studies, the median change from baseline to endpoint in prolactin levels for LATUDA-treated females was -0.2 ng/mL and was 0.5 ng/mL for males. The proportion of female patients with prolactin elevations ≥5x ULN was 5.7% for LATUDA-treated patients versus 2.0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥5x ULN was 1.6% for LATUDA-treated patients versus 0.6% for placebo-treated male patients.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia has been reported during treatment with antipsychotic agents. Agranulocytosis (including fatal cases) has been reported with other agents in the class. Patients with a preexisting low white blood cell count (WBC) or a history of drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy, and LATUDA should be discontinued at the first sign of a decline in WBC in the absence of other causative factors.

Orthostatic Hypotension and Syncope: LATUDA may cause orthostatic hypotension. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension, in patients with known cardiovascular disease or history of cerebrovascular disease and in patients who are antipsychotic-naїve.

Seizures: LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold (e.g., Alzheimer’s dementia).

Potential for Cognitive and Motor Impairment: Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with LATUDA does not affect them adversely.

Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents.  Appropriate care is advised when prescribing LATUDA for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Suicide: The possibility of suicide attempt is inherent in psychotic illness and close supervision of high-risk patients should accompany drug therapy. Prescriptions for LATUDA should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer’s dementia. LATUDA and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

ADVERSE REACTIONS
Commonly observed adverse reactions (≥5% incidence and at least twice the rate of placebo) for LATUDA:

Indications

LATUDA is indicated for:

Before prescribing LATUDA, please read the full Prescribing Information, including Boxed Warnings.