Lurasidone HCL Tablets for Oral Administration (Latuda)
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Lurasidone HCL Tablets for Oral Administration (Latuda)

LATUDA
(lurasidone hydrochloride)

WARNING

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA­RELATED PSYCHOSIS

  • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are atan increased risk of death [See WARNINGS AND PRECAUTIONS].
  • LATUDA is not approved for use in patients with dementia-related psychosis [See WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

LATUDA is an atypical antipsychotic belonging to the chemical class of benzisothiazol derivatives.

Its chemical name is (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride. Its molecular formula is C28H36N4O2S•HCl and its molecular weight is 529.14.

The chemical structure is:

LATUDA (lurasidone hydrochloride)  Structural Formula Illustration

Lurasidone hydrochloride is a white to off-white powder. It is very slightly soluble in water, practically insoluble or insoluble in 0.1 N HCl, slightly soluble in ethanol, sparingly soluble in methanol, practically insoluble or insoluble in toluene and very slightly soluble in acetone.

LATUDA tablets are intended for oral administration only. Each tablet contains 20 mg, 40 mg, 80 mg, or 120 mg of lurasidone hydrochloride.

Inactive ingredients are mannitol, pregelatinized starch, croscarmellose sodium, hypromellose, magnesium stearate, Opadry® and carnauba wax. Additionally, the 80 mg tablet contains yellow ferric oxide and FD&C Blue No.2 Aluminum Lake.

What are the possible side effects of lurasidone (Latuda)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking lurasidone and call your doctor at once if you have a serious side effect such as:

  • dizziness, fainting, fast or pounding heartbeats;
  • agitation, hostility, confusion, thoughts about hurting yourself;
  • seizure (convulsions);
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • high blood sugar (increased thirst, increased urination, hunger, dry mouth,...

Read All Potential Side Effects and See Pictures of Latuda »

What are the precautions when taking lurasidone hcl tablets for oral administration (Latuda)?

See also Warning section.

Before taking lurasidone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems, stroke, breast cancer, diabetes (including family history), obesity, low blood pressure, seizures, low white blood cell count, dementia (such as Alzheimer's Disease), trouble swallowing.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities...

Read All Potential Precautions of Latuda »

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

LATUDA is indicated for the treatment of patients with schizophrenia.

The efficacy of LATUDA in schizophrenia was established in five 6-week controlled studies of adult patients with schizophrenia [see Clinical Studies].

The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see DOSAGE AND ADMINISTRATION]

DOSAGE AND ADMINISTRATION

Schizophrenia

The recommended starting dose of LATUDA is 40 mg once daily. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 40 mg/day to 160 mg/day [see Clinical Studies]. The maximum recommended dose is 160 mg/day.

Administration Instructions

LATUDA should be taken with food (at least 350 calories) [see CLINICAL PHARMACOLOGY].

Dose Modifications in Special Populations

Renal Impairment

Dose adjustment is recommended in moderate (creatinine clearance: 30 to < 50 mL/min) and severe renal impairment (creatinine clearance < 30 mL/min) patients. The recommended starting dose is 20 mg. The dose in these patients should not exceed 80 mg/day [see Use In Specific Populations].

Hepatic Impairment

Dose adjustment is recommended in moderate (Child Pugh Score = 7 to 9) and severe hepatic impairment (Child Pugh Score = 10 to 15) patients. The recommended starting dose is 20 mg. The dose in moderate hepatic impairment patients should not exceed 80 mg/day and the dose in severe hepatic impairment patients should not exceed 40 mg/day [see Use In Specific Populations].

Dose Modifications Due to Drug Interactions

Concomitant Use with Potential CYP3A4 Inhibitors

The dose of LATUDA should not exceed 80 mg/day in combination with a moderate CYP3A4 inhibitor such as diltiazem.. LATUDA should not be used in combination with a strong CYP3A4 inhibitor (e.g., ketoconazole) [see CONTRAINDICATIONS; DRUG INTERACTIONS].

Concomitant Use with Potental CYP3A4 Inducers

LATUDA should not be used in combination with a strong CYP3A4 inducer (e.g., rifampin) [see CONTRAINDICATIONS; DRUG INTERACTIONS].

HOW SUPPLIED

Dosage Forms And Strengths

LATUDA tablets are available in the following shape and color (Table 1) with respective one-sided debossing:

Table 1: LATUDA Tablet Presentations

Tablet Strength Tablet Color/Shape Tablet Markings
20 mg white to off-white round L20
40 mg white to off-white round L40
80 mg pale green oval L80
120 mg white to off-white oval L120

Storage And Handling

LATUDA tablets are white to off-white, round (20 mg or 40 mg), pale green, oval (80 mg) or white to off-white, oval (120 mg)and identified with strength-specific one-sided debossing, “L20” (20 mg), “L40” (40 mg), “L80” (80 mg) or “L120” (120 mg). Tablets are supplied in the following strengths and package configurations (Table 9):

Table 9: Package Configuration for LATUDA Tablets

Tablet Strength Package Configuration NDC Code
20 mg Bottles of 30 63402-302-30
Bottles of 90 63402-302-90
Bottles of 500 63402-302-50
Box of 100 (Hospital Unit Dose) 63402-302-10 Carton
10 blister cards, 10 tablets each 63402-302-01 Blister
40 mg Bottles of 30 63402-304-30
Bottles of 90 63402-304-90
Bottles of 500 63402-304-50
Box of 100 (Hospital Unit Dose) 63402-304-10 Carton
10 blister cards, 10 tablets each 63402-304-01 Blister
80 mg Bottles of 30 63402-308-30
Bottles of 90 63402-308-90
Bottles of 500 63402-308-50
Box of 100 (Hospital Unit Dose) 63402-308-10 Carton
10 blister cards, 10 tablets each 63402-308-01 Blister
120 mg Bottles of 30 63402-312-30
Bottles of 90 63402-312-90
Bottles of 500 63402-312-50
Box of 100 (Hospital Unit Dose) 63402-312-10 Carton
10 blister cards, 10 tablets each 63402-312-01 Blister

Storage

Store LATUDA tablets at 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature].

Manufactured for: Sunovion Pharmaceuticals Inc. Marlborough, MA 01752 USA. Revised: 04/2012

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The information below is derived from a clinical study database for LATUDA consisting of 2905 patients with schizophrenia exposed to one or more doses with a total experience of 985.3 patient-years. Of these patients, 1508 participated in short-term, placebo-controlled schizophrenia studies with doses of 20 mg, 40 mg, 80 mg, 120 mg or 160 mg once daily. A total of 769 LATUDA-treated patients had at least 24 weeks and 371 LATUDA-treated patients had at least 52 weeks of exposure.

Adverse events during exposure to study treatment were obtained by general inquiry and voluntarily reported adverse experiences, as well as results from physical examinations, vital signs, ECGs, weights and laboratory investigations. Adverse experiences were recorded by clinical investigators using their own terminology. In order to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.

The following findings are based on the short-term, placebo-controlled premarketing studies for schizophrenia in which LATUDA was administered at daily doses ranging from 20 to 160 mg (n=1508).

Commonly Observed Adverse Reactions: The most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo) in patients treated with LATUDA were somnolence, akathisia, nausea and parkinsonism.

Adverse Reactions Associated with Discontinuation of Treatment: A total of 9.5% (143/1508) LATUDA-treated patients and 9.3% (66/708) of placebo-treated patients discontinued due to adverse reactions. There were no adverse reactions associated with discontinuation in subjects treated with LATUDA that were at least 2% and at least twice the placebo rate.

Adverse Reactions Occurring at an Incidence of 2% or More in LATUDA-Treated Patients

Adverse reactions associated with the use of LATUDA (incidence of 2% or greater, rounded to the nearest percent and LATUDA incidence greater than placebo) that occurred during acute therapy (up to 6 weeks in patients with schizophrenia) are shown in Table 6.

Table 6: Adverse Reaction in 2% or More of LATUDA-Treated Patients and That Occurred at Greater Incidence than in the Placebo-Treated Patients in Short-term Schizophrenia Studies

Body System or Organ Class Dictionary-derived Term Percentage of Patients
Placebo
(N=708)
Reporting Reaction All LATUDA
(N=1508)
Gastrointestinal Disorders
  Nausea  5 10
  Vomiting 6 8
  Dyspepsia 5 6
  Salivary Hypersecretion < 1 2
Musculoskeletal and Connective Tissue Disorders
  Back Pain 2 3
Nervous System Disorders
  Somnolence* 7 17
  Akathisia 3 13
  Parkinsonism** 5 10
  Dizziness 2 4
  Dystonia*** < 1 5
Psychiatric Disorders
  Insomnia 8 10
  Agitation 4 5
  Anxiety 4 5
  Restlessness 1 2
Note: Figures rounded to the nearest integer
* Somnolence includes adverse event terms: hypersomnia, hypersomnolence, sedation, and somnolence
** Parkinsonism includes adverse event terms: bradykinesia, cogwheel rigidity, drooling, extrapyramidal disorder, hypokinesia, muscle rigidity, parkinsonism, psychomotor retardation, and tremor
*** Dystonia includes adverse event terms: dystonia, oculogyric crisis, oromandibular dystonia, tongue spasm, torticollis, and trismus

Dose-Related Adverse Reactions

In pooled data from the short-term, placebo-controlled, fixed-dose studies, there were no dose-related adverse reactions (greater than 5% incidence) in patients treated with LATUDA across the 20 mg/day to 160 mg/day dose range. However, the frequency of akathisia increased with dose up to 120 mg/day (5.6% LATUDA 20 mg, 10.7% LATUDA 40 mg, 12.3% LATUDA 80 mg, 22.0% 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.

Extrapyramidal Symptoms

In the short-term, placebo-controlled schizophrenia studies, for LATUDA-treated patients, the incidence of reported events related to extrapyramidal symptoms (EPS), excluding akathisia and restlessness, was 13.5% versus 5.8% for placebo-treated patients. The incidence of akathisia for LATUDA-treated patients was 12.9% versus 3.0% for placebo-treated patients. Incidence of EPS by dose is provided in Table 7.

Table 7: Incidence of EPS Compared to Placebo

Adverse Event Term   LATUDA
Placebo
(N=709)
(%)
20 mg/day
(N=71)
(%)
40 mg/day
(N=487)
(%)
80 mg/day
(N=538)
(%)
120 mg/day
(N=291)
(%)
160 mg/day
(N=121)
(%)
All EPS events 9 10 21 23 39 20
All EPS events, excluding Akathisia/Restlessness 7 6 14 13 24 14
  Akathisia 3 6 11 12 22 7
  Dystonia* < 1 0 4 5 7 2
  Parkinsonism** 5 6 9 8 17 11
  Restlessness 1 1 3 1 3 2
Note: Figures rounded to the nearest integer
* Dystonia includes adverse event terms: dystonia, oculogyric crisis, oromandibular dystonia, tongue spasm, torticollis, and trismus
** Parkinsonism includes adverse event terms: bradykinesia, cogwheel rigidity, drooling, extrapyramidal disorder, hypokinesia, muscle rigidity, parkinsonism, psychomotor retardation, and tremor

In the short-term, placebo-controlled schizophrenia studies, data was objectively collected on the Simpson Angus Rating Scale for extrapyramidal symptoms (EPS), the Barnes Akathisia Scale (for akathisia) and the Abnormal Involuntary Movement Scale (for dyskinesias). The mean change from baseline for LATUDA-treated patients was comparable to placebo-treated patients, with the exception of the Barnes Akathisia Scale global score (LATUDA, 0.1; placebo, 0.0). The percentage of patients who shifted from normal to abnormal was greater in LATUDA-treated patients versus placebo for the BAS (LATUDA, 14.4%; placebo, 7.1%) and the SAS (LATUDA, 5.0%; placebo, 2.3%).

Dystonia

Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

In the short-term, placebo-controlled clinical trials, dystonia occurred in 4.2% of LATUDA-treated subjects (0.0% LATUDA 20 mg, 3.5% LATUDA 40 mg, 4.5% LATUDA 80 mg, 6.5% LATUDA 120 mg and 2.5% LATUDA 160 mg) compared to 0.8% of subjects receiving placebo. Seven subjects (0.5%, 7/1508) discontinued clinical trials due to dystonic events – four were receiving LATUDA 80 mg/day and three were receiving LATUDA 120 mg/day.

Other Adverse Reactions Observed During the Premarketing Evaluation of LATUDA

Following is a list of adverse reactions reported by patients treated with LATUDA at multiple doses of ≥ 20 mg once daily during any phase of a study within the database of 2905 patients. The reactions listed are those that could be of clinical importance, as well as reactions that are plausibly drug-related on pharmacologic or other grounds. Reactions listed in Table 6 or those that appear elsewhere in the LATUDA label are not included. Although the reactions reported occurred during treatment with LATUDA, they were not necessarily caused by it.

Reactions are further categorized by organ class and listed in order of decreasing frequency according to the following definitions: those occurring in at least 1/100 patients (frequent) (only those not already listed in the tabulated results from placebo-controlled studies appear in this listing); those occurring in 1/100 to 1/1000 patients (infrequent); and those occurring in fewer than 1/1000 patients (rare).

Blood and Lymphatic System Disorders: Infrequent: anemia;

Cardiac Disorders: Frequent: tachycardia; Infrequent: AV block 1st degree, angina pectoris, bradycardia

Ear and Labyrinth Disorders: Infrequent: vertigo

Eye Disorders: Frequent: blurred vision

Gastrointestinal Disorders: Frequent: abdominal pain, diarrhea; Infrequent: gastritis,

General Disorders and Administrative Site Conditions: Rare: sudden death

Investigations: Frequent: CPK increased

Metabolism and Nutritional System Disorders: Frequent: decreased appetite

Musculoskeletal and Connective Tissue Disorders: Rare: rhabdomyolysis

Nervous System Disorders: Infrequent: cerebrovascular accident, dysarthria,

Psychiatric Disorders: Infrequent: abnormal dreams, panic attack, sleep disorder;

Renal and Urinary Disorders: Infrequent: dysuria; Rare: renal failure

Reproductive System and Breast Disorders: Infrequent: amenorrhea, dysmenorrhea; Rare: breast enlargement, breast pain, galactorrhea, erectile dysfunction

Skin and Subcutaneous Tissue Disorders: Frequent: rash, pruritus; Rare: angioedema

Vascular Disorders: Frequent: hypertension;

Read the Latuda (lurasidone hcl tablets for oral administration) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Potential for Other Drugs to Affect LATUDA

LATUDA is predominantly metabolized by CYP3A4. LATUDA should not be used in combination with strong inhibitors or inducers of this enzyme [see CONTRAINDICATIONS] and dose should be limited when used in combination with moderate inhibitors of CYP3A4 [see DOSAGE AND ADMINISTRATION]. No dose adjustment is needed with concomitant use of lithium (see Figure 1).

Figure 1: Impact of Other Drugs on LATUDA Pharmacokinetics

Impact of Other Drugs on LATUDA Pharmacokinetics - Illustration

Potential for LATUDA to Affect Other Drugs

No adjustment is needed on the dose of lithium, or substrates of P-gp or CYP3A4 when coadministered with LATUDA (Figure 2).

Figure 2: Impact of LATUDA on Other Drugs

Impact of LATUDA on Other Drugs - Illustration

Drug Abuse And Dependence

Controlled Substance

LATUDA is not a controlled substance.

Abuse

LATUDA has not been systematically studied in humans for its potential for abuse or physical dependence or its ability to induce tolerance. While clinical studies with LATUDA did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict the extent to which a CNS-active drug will be misused, diverted and/or abused once it is marketed. Patients should be evaluated carefully for a history of drug abuse, and such patients should be observed carefully for signs of LATUDA misuse or abuse (e.g., development of development of tolerance, drug-seeking behavior, increases in dose).

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 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 rate of death in drug-treated patients was about 4.5%,compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. LATUDA is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING].

Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis

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 [see also BOXED WARNING].

Neuroleptic Malignant Syndrome

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including LATUDA.

Clinical manifestations of NMS are 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 creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. It is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.

The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. If reintroduced, the patient should be carefully monitored, since recurrences of NMS have been reported.

Tardive Dyskinesia

Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements that can develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of developing tardive dyskinesia 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.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, LATUDA should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on LATUDA, drug discontinuation should be considered. However, some patients may require treatment with LATUDA despite the presence of the syndrome.

Metabolic Changes

Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.

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. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Because LATUDA was not marketed at the time these studies were performed, it is not known if LATUDA is associated with this increased risk.

Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. 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 treatment 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.

Pooled data from short-term, placebo-controlled studies are presented in Table 2.

Table 2: Change in Fasting Glucose

  LATUDA
Placebo 20 mg/day 40 mg/day 80 mg/day 120 mg/day 160 mg/day
Mean Change from Baseline (mg/dL)
n=680 n=71 n=478 n=508 n=283 n=113
Serum Glucose 0 -0.6 2.6 -0.4 2.5 2.5
  Proportion of Patients with Shifts to ≥ 126 mg/dL
Serum Glucose 8.30% 11.70% 12.70% 6.80% 10.00% 5.60%
( ≥ 126 mg/dL) (52/628) (7/60) (57/449) (32/472) (26/241) (6/108)

In the uncontrolled, longer-term studies (primarily open-label extension studies), LATUDA was associated with a mean change in glucose of +1.8 mg/dL at week 24 (n=355), +0.8 mg/dL at week 36 (n=299) and +2.3 mg/dL at week 52 (n=307).

Dyslipidemia

Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics. Pooled data from short-term, placebo-controlled studies are presented in Table 3.

Table 3: Change in Fasting Lipids

  LATUDA
Placebo 20 mg/day 40 mg/day 80 mg/day 120 mg/day 160 mg/day
Mean Change from Baseline (mg/dL)
n=660 n=71 n=466 n=499 n=268 n=115
Total cholesterol -5.8 -12.3 -5.7 -6.2 -3.8 -6.9
Triglycerides -13.4 -29.1 -5.1 -13 -3.1 -10.6
  Proportion of Patients with Shifts
Total cholesterol ( ≥ 240 mg/dL) 5.3% (30/571) 13.8% (8/58) 6.2% (25/402) 5.3% (23/434) 3.8% (9/238) 4.0% (4/101)
Triglycerides ( ≥ 200 mg/dL) 10.1% (53/526) 14.3% (7/49) 10.8% (41/379) 6.3% (25/400) 10.5% (22/209) 7.0% (7/100)

In the uncontrolled, longer-term studies (primarily open-label extension studies), LATUDA was associated with a mean change in total cholesterol and triglycerides of -3.8 (n=356) and -15.1 (n=357) mg/dL at week 24, -3.1 (n=303) and -4.8 (n=303) mg/dL at week 36 and -2.5 (n=307) and -6.9 (n=307) mg/dL at week 52, respectively.

Weight Gain

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

Pooled data from short-term, placebo-controlled studies are presented in Table 4. The mean weight gain was 0.43 kg for LATUDA-treated patients compared to -0.02 kg for placebo-treated patients. Change in weight from baseline for olanzapine was 4.15 kg and for quetiapine extended-release was 2.09 kg in Studies 3 and 5 [see Clinical Studies)], respectively. The proportion of patients with a ≥ 7% increase in body weight (at Endpoint) was 4.8% for LATUDA-treated patients versus 3.3% for placebo-treated patients.

Table 4: Mean Change in Weight (kg) from Baseline

  LATUDA
Placebo
(n=696)
20 mg/day
(n=71)
40 mg/day
(n=484)
80 mg/day
(n=526)
120 mg/day
(n=291)
160 mg/day
(n=114)
All Patients -0.02 -0.15 0.22 0.54 0.68 0.6

In the uncontrolled, longer-term studies (primarily open-label extension studies), LATUDA was associated with a mean change in weight of -0.69 kg at week 24 (n=755), -0.59 kg at week 36 (n=443) and -0.73 kg at week 52 (n=377).

Hyperprolactinemia

As with other drugs that antagonize dopamine D2 receptors, LATUDA elevates prolactin levels.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients [see ADVERSE REACTIONS].

In short-term, placebo-controlled studies, the median change from baseline to endpoint in prolactin levels for LATUDA-treated patients was 0.4 ng/mL and was -1.9 ng/mL in the placebo-treated patients. The median change from baseline to endpoint for males was 0.5 ng/mL and for females was -0.2 ng/mL. Median changes for prolactin by dose are shown in Table 5.

Table 5: Median Change in Prolactin (ng/mL) from Baseline

  LATUDA
Placebo 20 mg/day 40 mg/day 80 mg/day 120 mg/day 160 mg/day
All Patients -1.9 (n=672) -1.1 (n=70) -1.4 (n=476) -0.2 (n=495) 3.3 (n=284) 3.3 (n=115)
Females -5.1 (n=200) -0.7 (n=19) -4.0 (n=149) -0.2 (n=150) 6.7 (n=70) 7.1 (n=36)
Males -1.3 (n=472) -1.2 (n=51) -0.7 (n=327) -0.2 (n=345) 3.1 (n=214) 2.4 (n=79)

The proportion of patients with prolactin elevations ≥ 5× upper limit of normal (ULN) was 2.8% for LATUDA-treated patients versus 1.0% for placebo-treated patients. The proportion offemale 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% versus 0.6% for placebo-treated male patients.

In the uncontrolled longer-term studies (primarily open-label extension studies), LATUDA was associated with a median change in prolactin of -0.9 ng/mL at week 24 (n=357), -5.3ng/mL at week 36 (n=190) and -2.2 ng/mL at week 52 (n=307).

Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro , a factor of potential importance if the prescription of these drugs is considered in a patient with previously detected breast cancer. As is common with compounds which increase prolactin release, an increase in mammary gland neoplasia was observed in a LATUDA carcinogenicity study conducted in rats and mice [see Nonclinical Toxicology]. Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans, but the available evidence is too limited to be conclusive.

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.

Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a pre-existing low 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 decline in WBC, in the absence of other causative factors.

Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm3) should discontinue LATUDA and have their WBC followed until recovery.

Orthostatic Hypotension and Syncope

LATUDA may cause orthostatic hypotension, perhaps due to its α1-adrenergic receptor antagonism. The incidence of orthostatic hypotension and syncope events from short-term, placebo-controlled studies was (LATUDA incidence, placebo incidence): orthostatic hypotension [0.3% (5/1508), 0.1% (1/708)] and syncope [0.1% (2/1508), 0%]. Assessment of orthostatic hypotension was defined by vital sign changes ( ≥ 20 mm Hg decrease in systolic blood pressure and ≥ 10 bpm increase in pulse from sitting to standing or supine to standing positions). In short-term clinical trials orthostatic hypotension occurred with a frequency of 0.8% with LATUDA 40 mg, 2.1% with LATUDA 80 mg, 1.7% with LATUDA 120 mg and 0.8% with LATUDA 160 mg compared to 0.7% with placebo.

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (e.g. dehydration, hypovolemia, and treatment with antihypertensive medications), and in patients with known cardiovascular disease (e.g., heart failure, history of myocardial infarction, ischemia, or conduction abnormalities), or cerebrovascular disease.

Seizures

As with other antipsychotic drugs, LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold, e.g., Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in patients 65 years or older.

In short-term, placebo-controlled trials, seizures/convulsions occurred in 1.0% (2/1508) of patients treated with LATUDA compared to 0.1% (1/455) placebo-treated patients.

Potential for Cognitive and Motor Impairment

LATUDA, like other antipsychotics, has the potential to impair judgment, thinking or motor skills.

In short-term, placebo-controlled trials, somnolence was reported by 17.0% (256/1508) of patients treated with LATUDA (15.5% LATUDA 20 mg, 15.6% LATUDA 40 mg, 15.2% LATUDA 80 mg, 26.5% LATUDA 120 mg and 8.3% LATUDA 160 mg/day) compared to 7.1% (50/708) of placebo patients. In these short-term trials, somnolence included: hypersomnia, hypersomnolence, sedation and somnolence.

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 [see PATIENT INFORMATION].

Suicide

The possibility of a 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.

In short-term, placebo-controlled studies in patients with schizophrenia, the incidence of treatment-emergent suicidal ideation was 0.4% (6/1508) for LATUDA-treated patients compared to 0.8% (6/708) on placebo. No suicide attempts or completed suicides were reported in these studies.

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.

Use in Patients with Concomitant Illness

Clinical experience with LATUDA in patients with certain concomitant illnesses is limited [see CLINICAL PHARMACOLOGY].

Patients with Parkinson's Disease or Dementia with Lewy Bodies are reported to have an increased sensitivity to antipsychotic medication. Manifestations of this increased sensitivity include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with the neuroleptic malignant syndrome.

LATUDA has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from premarketing clinical trials. Because of the risk of orthostatic hypotension with LATUDA, caution should be observed in patients with known cardiovascular disease.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

LATUDA increased incidences of malignant mammary gland tumors and pituitary gland adenomas in female mice orally dosed with 30, 100, 300, or 650 mg/kg/day. The lowest dose produced plasma levels (AUC) approximately equal to those in humans receiving the MRHD of 160 mg/day. No increases in tumors were seen in male mice up to the highest dose tested, which produced plasma levels (AUC) 14 times those in humans receiving the MRHD.

LATUDA increased the incidence of mammary gland carcinomas in females rats orally dosed at 12 and 36 mg/kg/day: the lowest dose; 3 mg/kg/day is the no effect dose which produced plasma levels (AUC) 0.4 times those in humans receiving the MRHD. No increases in tumors were seen in male rats up to highest dose tested, which produced plasma levels (AUC) 6 times those in humans receiving the MRHD.

Proliferative and/or neoplastic changes in the mammary and pituitary glands of rodents have been observed following chronic administration of antipsychotic drugs and are considered to be prolactin mediated. The relevance of this increased incidence of prolactin-mediated pituitary or mammary gland tumors in rodents to humans is unknown [see WARNINGS AND PRECAUTIONS].

Mutagenesis

LATUDA did not cause mutation or chromosomal aberration when tested in vitro and in vivo. LATUDA was negative in the Ames gene mutation test, the Chinese Hamster Lung (CHL) cells, and in the in vivo mouse bone marrow micronucleus test up to 2000 mg/kg (61 times the MRHD of 160 mg/day based on body surface area).

Impairment of Fertility

Estrus cycle irregularities were seen in rats orally administered LATUDA at 1.5, 15 and 150mg/kg/day for 15 consecutive days prior to mating, during the mating period, and through day 7 of gestation. The no-effect dose is 0.1 mg/kg which is approximately 0.006 times the MRHD of 160 mg/day based on body surface area. Fertility was reduced only at the highest dose, which was reversible after a 14 day drug-free period. The no-effect dose for reduced fertility was 15 mg/kg, which is approximately equal to the MRHD based on body surface area.

LATUDA had no effect on fertility in male rats treated orally with LATUDA for 64 consecutive days prior to mating and during the mating period at doses up to 150 mg/kg/day (9 times the MRHD based on body surface area).

Use In Specific Populations

Pregnancy

Teratogenic Effects - Pregnancy Category B

LATUDA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-teratogenic Effects

Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder inthese neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Safe use of LATUDA during pregnancy or lactation has not been established; therefore, use of LATUDA in pregnancy, in nursing mothers, or in women of childbearing potential requires that the benefits of treatment be weighed against the possible risks to mother and child.

Animal Data

No adverse developmental effects were seen in a study in which pregnant rats were given LATUDA during the period of organogenesis and continuing through weaning at doses up to 10 mg/kg/day; this dose is approximately half of the MRHD based on body surface area.

No teratogenic effects were seen in studies in which pregnant rats and rabbits were given LATUDA during the period of organogenesis at doses up to 25 and 50 mg/kg/day, respectively. These doses are 1.5 and 6 times, in rats and rabbits respectively, the maximum recommended human dose (MRHD) of 160 mg/day based on body surface area.

Nursing Mothers

LATUDA was excreted in milk of rats during lactation. It is not known whether LATUDA or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, considering risk of drug discontinuation to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of LATUDA in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and older to determine whether or not they respond differently from younger patients. In elderly patients with psychosis (65 to 85), LATUDA concentrations (20 mg/day) were similar to those in young subjects [see CLINICAL PHARMACOLOGY]. No dose adjustment is necessary in elderly patients (Figure 2).

Elderly patients with dementia-related psychosis treated with LATUDA are at an increased risk of death compared to placebo. LATUDA is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING].

Other Patient Factors

The effect of intrinsic patient factors on the pharmacokinetics of LATUDA is presented in Figure

Figure 3: Impact of Other Patient Factors on LATUDA Pharmacokinetics

Impact of Other Patient Factors on LATUDA Pharmacokinetics - Illustration

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Human Experience

In premarketing clinical studies involving 2905 patients, accidental or intentional overdosage of LATUDA was identified in one patient who ingested an estimated 560 mg of LATUDA. This patient recovered without sequelae. This patient resumed LATUDA treatment for an additional two months.

Management of Overdosage

Consult a Certified Poison Control Center for up-to-date guidance and advice. There is no specific antidote to LATUDA, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers.

Cardiovascular monitoring should commence immediately, including continuous electrocardiographic monitoring for possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of LATUDA. Similarly, the alpha-blocking properties of bretylium might be additive to those of LATUDA, resulting in problematic hypotension.

Hypotension and circulatory collapse should be treated with appropriate measures. Epinephrine and dopamine should not be used, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of LATUDA-induced alpha blockade. In case of severe extrapyramidal symptoms, anticholinergic medication should be administered.

Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.

The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.

CONTRAINDICATIONS

LATUDA is contraindicated in the following:

  • Any patient with a known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone [see ADVERSE REACTIONS].
  • Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) [see DRUG INTERACTIONS].
  • Concomitant use with strong CYP3A4 inducers (e.g., rifampin) [see DRUG INTERACTIONS].

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Although the mechanism of action of LATUDA is unknown, the efficacy of LATUDA in schizophrenia could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

Pharmacodynamics

LATUDA is an antagonist with high affinity binding at the dopamine D2 receptors (Ki=0.994 nM) and the 5-hydroxytryptamine (5-HT, serotonin) receptors 5-HT2A (Ki=0.47 nM) and 5-HT7 (Ki=0.495 nM) receptors. It also binds with moderate affinity at the human α2C adrenergic receptors (Ki=10.8 nM), is a partial agonist at serotonin 5-HT1A (Ki=6.38 nM) receptors, and is an antagonist at the α2A adrenergic receptors (Ki=40.7 nM). LATUDA exhibits little or no affinity for histamine H1 and muscarinic M1 receptors (IC50 > 1,000 nM).

ECG Changes

The effects of LATUDA on the QTc interval were evaluated in a randomized, double-blind, multiple-dose, parallel dedicated thorough QT study in 43 patients with schizophrenia or schizoaffective disorder, who were treated with LATUDA doses of 120 mg daily, 600 mg daily and completed the study. The maximum mean (upper 1-sided, 95% CI) increase in baseline-adjusted QTc intervals based on individual correction method (QTcI) was 7.5 (11.7) ms and 4.6 (9.5) ms, for the 120 mg and 600 mg dose groups respectively, observed at 2 to 4 hours after dosing. In this study, there was no apparent dose (exposure)-response relationship.

In short-term, placebo-controlled studies, no post-baseline QT prolongations exceeding 500 msec were reported in patients treated with LATUDA or placebo.

Changes in Laboratory Tests

There were no clinically important differences between LATUDA and placebo in mean change from baseline to endpoint in routine hematology, urinalysis, or serum chemistry.

Creatinine: In short-term, placebo-controlled trials, the mean change from Baseline in creatinine was 0.06 mg/dL for LATUDA-treated patients compared to 0.02 mg/dL for placebo-treated patients. A creatinine shift from normal to high occurred in 3.0% (43/1453) of LATUDA-treated patients and 1.6% (11/681) on placebo. The threshold for high creatinine value varied from > 0.79 to > 1.3 mg/dL based on the centralized laboratory definition for each study [see Dosage in Special Populations; Use In Specific Populations].

Transaminases: The mean changes in AST and ALT for LATUDA- and placebo-treated patients were similar. The proportion of patients with transaminases (AST and ALT) elevations ≥ 3 times ULN was similar for all LATUDA-treated patients (0.6% and 0.8%, respectively) to placebo-treated patients (0.9% and 1.0%, respectively).

Pharmacokinetics

The activity of LATUDA is primarily due to the parent drug. The pharmacokinetics of LATUDA is dose-proportional within a total daily dose range of 20 mg to 160 mg. Steady-state concentrations of LATUDA are reached within 7 days of starting LATUDA.

Following administration of 40 mg of LATUDA, the mean (%CV) elimination half-life was 18 (7) hours.

Absorption and Distribution

LATUDA is absorbed and reaches peak serum concentrations in approximately 1-3 hours. It is estimated that 9-19% of an administered dose is absorbed. Following administration of 40 mg of LATUDA, the mean (%CV) apparent volume of distribution was 6173 (17.2) L. LATUDA is highly bound (~99%) to serum proteins.

In a food effect study, LATUDA mean Cmax and AUC were about 3-times and 2-times, respectively, when administered with food compared to the levels observed under fasting conditions]. LATUDA exposure was not affected as meal size was increased from 350 to 1000 calories and was independent of meal fat content [see DOSAGE AND ADMINISTRATION].

In clinical studies, establishing the safety and efficacy of LATUDA, patients were instructed to take their daily dose with food [see DOSAGE AND ADMINISTRATION].

Metabolism and Elimination

LATUDA is metabolized mainly via CYP3A4. The major biotransformation pathways are oxidative N-dealkylation, hydroxylation of norbornane ring, and S-oxidation. LATUDA is metabolized into two active metabolites (ID-14283 and ID-14326) and two major non-active metabolites (ID-20219 and ID-20220). Based on in vitro studies LATUDA is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. Because LATUDA is not a substrate for CYP1A2, smoking is not expected to have an effect on the pharmacokinetics of LATUDA.

Total excretion of radioactivity in urine and feces combined was approximately 89%, with about 80% recovered in feces and 9% recovered in urine, after a single dose of [14C]-labeled LATUDA.

Following administration of 40 mg of LATUDA, the mean (%CV) apparent clearance was 3902 (18.0) mL/min.

Clinical Studies

Schizophrenia

The efficacy of LATUDA for the treatment of schizophrenia was established in five short-term (6-week), placebo-controlled studies in adult patients (mean age of 38.4 years, range 18-72) who met DSM-IV criteria for schizophrenia. An active control arm (olanzapine or quetiapine extended-release) was included in two studies to assess assay sensitivity.

Several instruments were used for assessing psychiatric signs and symptoms in these studies:

  1. Positive and Negative Syndrome Scale (PANSS), is a multi-item inventory of general psychopathology used to evaluate the effects of drug treatment in schizophrenia. PANSS total scores may range from 30 to 210.
  2. Brief Psychiatric Rating Scale derived (BPRSd), derived from the PANSS, is a multi-item inventory primarily focusing on positive symptoms of schizophrenia, whereas the PANSS includes a wider range of positive, negative and other symptoms of schizophrenia. BPRSd scores may range from 18 to 126.
  3. The Clinical Global Impression severity scale (CGI-S) is a clinician-rated scale that measures the subject's current illness state on a 1 to 7-point scale.

The endpoint associated with each instrument is change from baseline in the total score to the end of week 6. These changes are then compared to placebo changes for the drug and control groups.

The results of the studies follow:

  • In a 6-week, placebo-controlled trial (N=145) involving two fixed doses of LATUDA (40 or 120 mg/day), both doses of LATUDA at Endpoint were superior to placebo on the BPRSd total score, and the CGI-S.
  • In a 6-week, placebo-controlled trial (N=180) involving a fixed dose of LATUDA (80 mg/day), LATUDA at Endpoint was superior to placebo on the BPRSd total score, and the CGI-S.
  • In a 6-week, placebo and active-controlled trial (N=473) involving two fixed doses of LATUDA (40 or 120 mg/day) and an active control (olanzapine), both LATUDA doses and the active control at Endpoint were superior to placebo on the PANSS total score, and the CGI-S.
  • In a 6-week, placebo-controlled trial (N=489) involving three fixed doses of LATUDA (40, 80 or 120 mg/day), only the 80 mg/day dose of LATUDA at Endpoint was superior to placebo on the PANSS total score, and the CGI-S.
  • In a 6-week, placebo and active-controlled trial (N=482) involving two fixed doses of LATUDA (80 or 160 mg/day) and an active control (quetiapine extended-release), both LATUDA doses and the active control at Endpoint were superior to placebo on the PANSS total score, and the CGI-S.

Thus, the efficacy of LATUDA at doses of 40, 80, 120 and 160 mg/day has been established (Table 8).

Table 8: Summary of Results for Primary Efficacy Endpoints

Study Number Primary Endpoint LS Mean (SE)a Difference from Placebo in Change from Baseline
40 mg/day LATUDA 160 mg/day Olanzapine Quetiapine Extended- Release
80 mg/day 120 mg/day 15 mg/day 600 mg/day
1 BPRSd -5.6* (2.1) - -6.7* (2.2) - - -
2 BPRSd - -4.7* (1.8) - - - -
3 PANSS -9.7* (2.9) - -7.5* (3.0) - -12.6** (2.8) -
4 PANSS -2.1 (2.5) -6.4* (2.5) -3.5 (2.5) - - -
5 PANSS - -11.9* (2.6) - -16.2* (2.5) - -17.5** (2.6)
* adjusted p-value ≤ 0.05
** non-adjusted p-value ≤ 0.05
a Least Squares Mean (Standard Error)

Examination of population subgroups based on age (there were few patients over 65), gender and race did not reveal any clear evidence of differential responsiveness.

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Physicians are advised to discuss with patients for whom they prescribe LATUDA all relevant safety information including, but not limited to, the following:

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Patients and caregivers should be advised that elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs are at increased risk of death compared with placebo. LATUDA is not approved for elderly patients with dementia-related psychosis [see BOXED WARNING; WARNINGS AND PRECAUTIONS].

Neuroleptic Malignant Syndrome

Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see WARNINGS AND PRECAUTIONS].

Hyperglycemia and Diabetes Mellitus

Patients should be aware of the symptoms of hyperglycemia (high blood sugar) and diabetes mellitus. Patients who are diagnosed with diabetes, those with risk factors for diabetes, or those that develop these symptoms during treatment should have their blood glucose monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS].

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose [see WARNINGS AND PRECAUTIONS].

Leukopenia/Neutropenia

Patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia should be advised that they should have their CBC monitored while taking LATUDA [see WARNINGS AND PRECAUTIONS].

Interference with Cognitive and Motor Performance

Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that LATUDA therapy does not affect them adversely [see WARNINGS AND PRECAUTIONS].

Pregnancy and Nursing

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with LATUDA [see Use in Specific Populations].

Concomitant Medication and Alcohol

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions. Patients should be advised to avoid alcohol while taking LATUDA [see DRUG INTERACTIONS].

Heat Exposure and Dehydration

Patients should be advised regarding appropriate care in avoiding overheating and dehydration [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Physicians are advised to discuss with patients for whom they prescribe LATUDA all relevant safety information including, but not limited to, the following:

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Patients and caregivers should be advised that elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs are at increased risk of death compared with placebo. LATUDA is not approved for elderly patients with dementia-related psychosis [see BOXED WARNING; WARNINGS AND PRECAUTIONS].

Neuroleptic Malignant Syndrome

Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see WARNINGS AND PRECAUTIONS].

Hyperglycemia and Diabetes Mellitus

Patients should be aware of the symptoms of hyperglycemia (high blood sugar) and diabetes mellitus. Patients who are diagnosed with diabetes, those with risk factors for diabetes, or those that develop these symptoms during treatment should have their blood glucose monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS].

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose [see WARNINGS AND PRECAUTIONS].

Leukopenia/Neutropenia

Patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia should be advised that they should have their CBC monitored while taking LATUDA [see WARNINGS AND PRECAUTIONS].

Interference with Cognitive and Motor Performance

Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that LATUDA therapy does not affect them adversely [see WARNINGS AND PRECAUTIONS].

Pregnancy and Nursing

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with LATUDA [see Use in Specific Populations].

Concomitant Medication and Alcohol

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions. Patients should be advised to avoid alcohol while taking LATUDA [see DRUG INTERACTIONS].

Heat Exposure and Dehydration

Patients should be advised regarding appropriate care in avoiding overheating and dehydration [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 5/10/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Latuda Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

LURASIDONE - ORAL

(loo-RAS-i-done)

COMMON BRAND NAME(S): Latuda

WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as heart failure, pneumonia, stroke) when this medication is used in older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.

USES: This medication is used to treat a certain mental/mood disorder (schizophrenia). Lurasidone helps you to think more clearly, feel less nervous, and take part in everyday life. It may also help to decrease hallucinations (hearing/seeing things that are not there). Lurasidone is a psychiatric medication that belongs to the class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain.

HOW TO USE: Take this medication by mouth with food as directed by your doctor, usually once daily. Dosage is based on your medical condition, other drugs you are taking, and your response to treatment.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Continue taking this medication exactly as prescribed, even if you are feeling better and thinking more clearly. Do not increase your dose or take this drug more often than prescribed. Your symptoms will not improve any faster, and your risk of side effects will increase. Do not stop taking this medication without consulting your doctor.

Tell your doctor if your condition does not improve or if it worsens. It may take several weeks before you feel the full benefit of this medication.

Disclaimer

Latuda Consumer (continued)

SIDE EFFECTS: Drowsiness, dizziness, nausea, shaking, muscle stiffness, weight gain, mask-like facial expression, inability to keep still, and agitation may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Your doctor may order another medication to lessen these effects.

This medication may cause a serious drop in blood pressure, especially when starting this medication. To reduce your risk of side effects from low blood pressure (such as dizziness), get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these serious side effects occur: drooling/trouble swallowing, fainting, fast/irregular heartbeat, signs of infection (such as persistent cough, fever).

Infrequently, this medication may cause face/muscle twitching and uncontrollable movements (tardive dyskinesia). In some cases, this condition may be permanent. Tell your doctor immediately if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.

This drug may rarely make your blood sugar level rise, which can cause or worsen diabetes. Weight gain from this drug may increase the risk of this side effect. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugar level regularly.

In rare cases, lurasidone may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.

This drug may rarely cause a serious (sometimes fatal) nervous system problem (neuroleptic malignant syndrome-NMS). Get medical help right away if you notice any of the following side effects: unexplained fever, stiff muscles, increased sweating, fast/irregular heartbeat, sudden mental/mood changes (such as confusion, loss of consciousness).

Get medical help right away if this serious side effects occur: seizure.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Latuda (lurasidone hcl tablets for oral administration) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: See also Warning section.

Before taking lurasidone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems, stroke, breast cancer, diabetes (including family history), obesity, low blood pressure, seizures, low white blood cell count, dementia (such as Alzheimer's Disease), trouble swallowing.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication may decrease your ability to sweat, making you more likely to get heat stroke. Avoid activities that may cause you to overheat (such as doing strenuous work/exercise in hot weather, using hot tubs). When the weather is hot, drink plenty of fluids and dress lightly. If you become overheated, promptly seek cooler shelter and stop exercising. Get medical help right away if you develop a fever, mental/mood changes, headache, or dizziness.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Do not stop taking this medication unless directed by your doctor. Babies born to mothers who have used this drug during the last 3 months of pregnancy may infrequently develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn anytime during their first month, tell the doctor right away.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Latuda Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Other medications can affect the removal of lurasidone from your body, which may affect how lurasidone works. Examples include diltiazem, azole antifungals (such as ketoconazole, itraconazole), HIV drugs (such as ritonavir), macrolide antibiotics (such as clarithromycin), rifamycins (such as rifampin, rifabutin), antidepressants (such as fluoxetine, paroxetine, nefazodone), among others.

Tell your doctor or pharmacist if you are taking other products that cause dizziness or drowsiness, including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause dizziness or drowsiness. Ask your pharmacist about using those products safely.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as blood sugar level, complete blood count, blood pressure, weight) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised May 2012. Copyright(c) 2012 First Databank, Inc.

Latuda Patient Information Including Side Effects

Brand Names: Latuda

Generic Name: lurasidone (Pronunciation: loo RAS i done)

What is lurasidone (Latuda)?

Lurasidone is an antipsychotic medication. It works by changing the effects of chemicals in the brain.

Lurasidone is used to treat schizophrenia in adults.

Lurasidone may also be used for purposes not listed in this medication guide.

What are the possible side effects of lurasidone (Latuda)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking lurasidone and call your doctor at once if you have a serious side effect such as:

  • dizziness, fainting, fast or pounding heartbeats;
  • agitation, hostility, confusion, thoughts about hurting yourself;
  • seizure (convulsions);
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss);
  • very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
  • trouble swallowing; or
  • twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs.

Less serious side effects may include:

  • drowsiness;
  • feeling restless;
  • nausea, diarrhea, stomach pain, loss of appetite;
  • blurred vision;
  • weight gain;
  • breast swelling or discharge;
  • missed menstrual periods; or
  • decreased sex drive, impotence, or difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Latuda (lurasidone hcl tablets for oral administration) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about lurasidone (Latuda)?

Lurasidone is not for use in psychotic conditions related to dementia. Lurasidone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

You should not use this medication if you are allergic to lurasidone, or if you are also using ketoconazole (Extina, Ketozole, Nizoral, Xolegal) or rifampin (Rifater, Rifadin, Rifamate).

Before you take lurasidone, tell your doctor if you have liver disease, kidney disease, heart disease, high blood pressure, heart rhythm problems, a history of heart attack or stroke, high cholesterol or triglycerides, low white blood cell (WBC) counts, seizures, diabetes, Parkinson's disease, trouble swallowing, or a history of breast cancer or suicidal thoughts.

While you are taking lurasidone, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking lurasidone.

Lurasidone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can increase certain side effects of lurasidone.

Stop using lurasidone and call your doctor at once if you have very stiff (rigid) muscles, high fever, sweating, confusion, fast or pounding heartbeats, feeling like you might pass out, tremors, or twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs.

There are many other drugs that can interact with lurasidone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Side Effects Centers

Latuda Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking lurasidone (Latuda)?

Lurasidone is not for use in psychotic conditions related to dementia. Lurasidone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

You should not use this medication if you are allergic to lurasidone, or if you are also using ketoconazole (Extina, Ketozole, Nizoral, Xolegal) or rifampin (Rifater, Rifadin, Rifamate).

To make sure you can safely take lurasidone, tell your doctor if you have any of these other conditions:

  • liver disease;
  • kidney disease;
  • heart disease, high blood pressure, heart rhythm problems;
  • a history of heart attack or stroke;
  • high cholesterol or triglycerides (a type of fat in the blood);
  • low white blood cell (WBC) counts;
  • a history of breast cancer;
  • seizures or epilepsy;
  • personal or family history of diabetes (lurasidone may raise your blood sugar);
  • a history of suicidal thoughts or actions;
  • Parkinson's disease; or
  • trouble swallowing.

Lurasidone may cause you to have high blood sugar (hyperglycemia). Talk to your doctor if you have any signs of hyperglycemia such as increased thirst or urination, excessive hunger, or weakness. If you are diabetic, check your blood sugar levels on a regular basis while you are taking lurasidone.

FDA pregnancy category B. Lurasidone is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether lurasidone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using lurasidone.

Do not give this medication to a child without medical advice.

How should I take lurasidone (Latuda)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Lurasidone should be taken with food (at least 350 calories).

Use lurasidone regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Store at room temperature away from moisture and heat.

Side Effects Centers

Latuda Patient Information including If I Miss a Dose

What happens if I miss a dose (Latuda)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Latuda)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

What should I avoid while taking lurasidone (Latuda)?

While you are taking lurasidone, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking lurasidone.

Lurasidone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can increase certain side effects of lurasidone.

What other drugs will affect lurasidone (Latuda)?

Before you take lurasidone, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by lurasidone.

Many drugs can interact with lurasidone. Below is just a partial list. Tell your doctor if you are using:

  • bosentan (Tracleer);
  • conivaptan (Vaprisol);
  • dexamethasone (Decadron, Hexadrol);
  • imatinib (Gleevec);
  • isoniazid (for treating tuberculosis);
  • St. John's wort;
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), rifapentine (Priftin), or telithromycin (Ketek);
  • antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend);
  • an antidepressant such as nefazodone;
  • heart or blood pressure medication such as diltiazem (Cartia, Cardizem), nicardipine (Cardene), quinidine (Quin-G), verapamil (Calan, Covera, Isoptin, Verelan), and others;
  • HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva, Atripla), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), saquinavir (Invirase), or ritonavir (Norvir, Kaletra);
  • medicines to treat narcolepsy, such as armodafanil (Nuvigil) or modafanil (Progivil); or
  • seizure medication such as carbamazepine (Carbatrol, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenobarbital (Solfoton), phenytoin (Dilantin), or primidone (Mysoline).

This list is not complete and other drugs may interact with lurasidone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about lurasidone.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 3.01. Revision date: 3/17/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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