Latuda

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 18.5 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to18.6 mg lurasidone. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet). 

 

White to off-white, film-coated round tablets of 6 mm debossed with ‘LA’ 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Latuda is indicated for the treatment of schizophrenia in adults aged 18 years and over. 

 

4.2 Posology and method of administration 

 

Posology 

 

The recommended starting dose is 37 mg of lurasidone once daily. No initial dose titration is required. 

It is effective in a dose range of 37 to 148 mg once daily. Dose increase should be based on physician 

judgement and observed clinical response. The maximum daily dose should not exceed 148 mg. 

 

Patients on doses higher than 111 mg once daily who discontinue their treatment for longer than 

3 days should be restarted on 111 mg once daily and up-titrated to their optimal dose. For all other 

doses patients can be restarted on their previous dose without need for up-titration. 

 

Dose adjustment due to interactions 

A starting dose of 18.5 mg is recommended and the maximum dose of lurasidone should not exceed 

74 mg once daily in combination with moderate CYP3A4 inhibitors. Dose adjustment of lurasidone 

may be necessary in combination with mild and moderate CYP3A4 inducers (see section 4.5). For 

strong CYP3A4 inhibitors and inducers see section 4.3. 

 

Switching between antipsychotic medicinal products 

Due to different pharmacodynamic and pharmacokinetic profiles among antipsychotic medicinal 

products, supervision by a clinician is needed when switching to another antipsychotic product is 

considered medically appropriate. 

 

Elderly people 

Dosing recommendations for elderly patients with normal renal function (CrCl ≥ 80 ml/min) are the 

same as for adults with normal renal function. However, because elderly patients may have diminished 

renal function, dose adjustments may be required according to their renal function status (see “Renal 

impairment” below). 

 

Limited data are available in elderly people treated with higher doses of lurasidone. No data are 

available in elderly people treated with 148 mg of lurasidone. Caution should be exercised when 

treating patients ≥65 years of age with higher doses of lurasidone. 



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Renal impairment 

No dose adjustment of lurasidone is required in patients with mild renal impairment. 

In patients with moderate (Creatinine Clearance (CrCl) ≥ 30 and < 50 ml/min), severe renal 

impairment (CrCL >15 and < 30 ml/min) and End Stage Renal Disease (ESRD) patients 

(CrCl < 15 ml/min), the recommended starting dose is 18.5 mg and the maximum dose should not 

exceed 74 mg once daily. Lurasidone should not be used in patients with ESRD unless the potential 

benefits outweigh the potential risks. If used in ESRD, clinical monitoring is advised. 

 

Hepatic impairment 

No dose adjustment of lurasidone is required in patients with mild hepatic impairment. 

Dose adjustment is recommended in moderate (Child-Pugh Class B) and severe hepatic impairment 

(Child-Pugh Class C) patients. The recommended starting dose is 18.5 mg. The maximum daily dose 

in moderate hepatic impairment patients should not exceed 74 mg and in severe hepatic impairment 

patients should not exceed 37 mg once daily. 

 

Paediatric population 

The safety and efficacy of lurasidone in children aged less than 18 years have not been established. 

Current available data are described in section 5.1 and 5.2, but no recommendation on a posology can 

be made. 

 

Method of administration  

 

Latuda film-coated tablets are for oral use, to be taken once daily together with a meal. 

If taken without food, it is anticipated that lurasidone exposure will be significantly lower as compared 

to when taken with food (see section 5.2). 

 

Latuda tablets should be swallowed whole, in order to mask the bitter taste. Latuda tablets should be 

taken at the same time every day to aid compliance.  

 

4.3 Contraindications 
 

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Concomitant administration of strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, 

ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and strong CYP3A4 inducers (e.g. 

carbamazepine, phenobarbital, phenytoin, rifampicin, St John’s wort (Hypericum perforatum) 

(see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

During antipsychotic treatment, improvement in the patient's clinical condition may take a few days to 

some weeks. Patients should be closely monitored during this period.  

 

Suicidality  

 

The occurrence of suicidal behaviour is inherent in psychotic illnesses and in some cases has been 

reported early after initiation or switch of antipsychotic therapy. Close supervision of high-risk 

patients should accompany antipsychotic therapy. 

 

Parkinson’s disease 

 

If prescribed to patients with Parkinson’s disease, antipsychotic medicinal products may exacerbate 

the underlying parkinsonism symptoms. Physicians should therefore weigh the risks versus the 

benefits when prescribing lurasidone to patients with Parkinson’s disease. 

 



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Extrapyramidal symptoms (EPS) 

 

Medicinal products with dopamine receptor antagonistic properties have been associated with 

extrapyramidal adverse reactions including rigidity, tremors, mask-like face, dystonias, drooling of 

saliva, drooped posture and abnormal gait. In placebo controlled clinical studies in adult patients with 

schizophrenia there was an increased occurrence of EPS following treatment with lurasidone 

compared to placebo. 

 

Tardive dyskinesia 

 

Medicinal products with dopamine receptor antagonistic properties have been associated with the 

induction of tardive dyskinesia characterised by rhythmical involuntary movements, predominantly of 

the tongue and/or face. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all 

antipsychotics, including lurasidone, should be considered.  

 

Cardiovascular disorders/QT prolongation 

 

Caution should be exercised when lurasidone is prescribed in patients with known cardiovascular 

disease or family history of QT prolongation, hypokalaemia, and in concomitant use with other 

medicinal products thought to prolong the QT interval. 

 

Seizures 

 

Lurasidone should be used cautiously in patients with a history of seizures or other conditions that 

potentially lower the seizure threshold.  

 

Neuroleptic malignant syndrome (NMS) 

 

Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic 

instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported 

to occur with lurasidone. Additional signs may include myoglobinuria (rhabdomyolysis) and acute 

renal failure. In this event, lurasidone should be discontinued.  

 

Elderly patients with dementia 

 

Lurasidone has not been studied in elderly patients with dementia. 

 

Overall mortality  

 

In a meta-analysis of 17 controlled clinical trials, elderly patients with dementia treated with other 

atypical antipsychotics, including risperidone, aripiprazole, olanzapine, and quetiapine had an 

increased risk of mortality compared to placebo. 

 

Cerebrovascular accident 

 

An approximately 3-fold increased risk of cerebrovascular adverse reactions has been seen in 

randomised placebo-controlled clinical trials in the dementia population with some atypical 

antipsychotics, including risperidone, aripiprazole and olanzapine. The mechanism for this increased 

risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient 

populations. Lurasidone should be used with caution in elderly patients with dementia who have risk 

factors for stroke. 

 

Venous thromboembolism 

 

Cases of venous thromboembolism (VTE) have been reported with antipsychotic medicinal products. 

Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible 



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risk factors for VTE should be identified before and during treatment with lurasidone and preventive 

measures undertaken. 

 

Hyperprolactinaemia 

 

Lurasidone elevates prolactin levels due to antagonism of dopamine D2 receptors.   Patients should 

be counseled on signs and symptoms of elevated prolactin, such as gynecomastia, 

galactorrhea, amenorrhea and erectile dysfunction. Patient should be advised to seek medical 

attention if they experience any signs and symptoms 
 

Weight gain 

 

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

recommended. 

 

Hyperglycaemia 

 

Rare cases of glucose related adverse reactions, e.g. increase in blood glucose, have been reported in 

clinical trials with lurasidone. Appropriate clinical monitoring is advisable in diabetic patients and in 

patients with risk factors for the development of diabetes mellitus. 

 

Orthostatic hypotension/syncope 

 

Lurasidone may cause orthostatic hypotension, perhaps due to its α1-adrenergic receptor antagonism. 

Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to 

hypotension. 

 

Interaction with grapefruit juice  

 

Grapefruit juice should be avoided during treatment with lurasidone (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Pharmacodynamic interactions 

 

Given the primary central nervous system effects of lurasidone, lurasidone should be used with 

caution in combination with other centrally acting medicinal products and alcohol.  

 

Caution is advised when prescribing lurasidone with medicinal products known to prolong the QT 

interval, e.g. class IA antiarrhythmics (e.g. quinidine, disopyramide) and class III antiarrhythmics (e.g. 

amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e.g. 

mefloquine).  

 

Pharmacokinetic interactions 

 

The concomitant administration of lurasidone and grapefruit juice has not been assessed. Grapefruit 

juice inhibits CYP3A4 and may increase the serum concentration of lurasidone. Grapefruit juice 

should be avoided during treatment with lurasidone. 

 

Potential for other medicinal products to affect lurasidone  

 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors. Lurasidone and its active metabolite ID-14283 are primarily 

metabolised by CYP3A4.  

 



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CYP3A4 inhibitors 

Lurasidone is contraindicated with strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, 

saquinavir, telaprevir, telithromycin, voriconazole) (see section 4.3).  

 

Coadministration of lurasidone with the strong CYP3A4 inhibitor ketoconazole resulted in a 9- and 

6-fold increase in exposure of lurasidone and its active metabolite ID-14283 respectively.  

 

Co-administration of lurasidone and posaconazole (strong CYP3A4 inhibitor) resulted in an 

approximate 4-5 fold increase in lurasidone exposure.  A persistent effect of posaconazole on 

lurasidone exposure was observed up to 2-3 weeks after stop of posaconazole co-administration. 

 

Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 (e.g. 

diltiazem, erythromycin, fluconazole verapamil) may increase exposure to lurasidone. Moderate 

CYP3A4 inhibitors are estimated to result in a 2-5 fold increase in exposure of CYP3A4 substrates. 

 

Coadministration of lurasidone with diltiazem (slow-release formulation), a moderate CYP3A4 

inhibitor, resulted in a 2.2 and 2.4-fold increase in exposure of lurasidone and ID-14283 respectively 

(see section 4.2). The use of an immediate release formulation of diltiazem could result in a larger 

increase in lurasidone exposure. 

 

CYP3A4 inducers 

Lurasidone is contraindicated with strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, 

phenytoin, rifampicin, St John’s wort (Hypericum perforatum)) (see section 4.3). 

 

Coadministration of lurasidone with the strong CYP3A4 inducer rifampicin resulted in a 6-fold 

decrease in exposure of lurasidone. 

 

Coadministration of lurasidone with mild (e.g. armodafinil, amprenavir, aprepitant, prednisone, 

rufinamide) or moderate (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) inducers of 

CYP3A4 would be expected to give a <2-fold reduction in lurasidone exposure during 

co-administration and for up to 2 weeks after discontinuation of mild or moderate CYP3A4 inducers. 

 

When lurasidone is coadministered with mild or moderate CYP3A4 inducers, the efficacy of 

lurasidone needs to be carefully monitored and a dose adjustment may be needed. 

 

Transporters  

Lurasidone is a substrate of P-gp and BCRP in vitro and the in vivo relevance of this is unclear. 

Coadministration of lurasidone with P-gp and BCRP inhibitors may increase exposure to lurasidone. 

 

Potential for lurasidone to affect other medicinal products 

 

Coadministration of lurasidone with midazolam, a sensitive CYP3A4 substrate, resulted in a < 1.5-fold 

increase in midazolam exposure. Monitoring is recommended when lurasidone and CYP3A4 

substrates known to have a narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, 

quinidine, bepridil or ergot alkaloids [ergotamine, dihydroergotamine]) are coadministered.  

 

Coadministration of lurasidone with digoxin (a P-gp substrate) did not increase the exposure to 

digoxin and only slightly increased Cmax (1.3 –fold) and therefore, it is considered that lurasidone can 

be coadministered with digoxin. Lurasidone is an in vitro inhibitor of the efflux transporter P-gp and 

the clinical relevance of intestinal P-gp inhibition cannot be excluded. Concomitant administration of 

the P-gp substrate dabigatran etexilate may result in increased dabigatran plasma concentrations.  

 

Lurasidone is an in vitro inhibitor of the efflux transporter BCRP and the clinical relevance of 

intestinal BCRP inhibition cannot be excluded. Concomitant administration of BCRP substrates may 

result in increases in the plasma concentrations of these substrates. 

 



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Coadministration of lurasidone with lithium indicated that lithium had clinically negligible effects on 

the pharmacokinetics of lurasidone, therefore no dose adjustment of lurasidone is required when 

coadministered with lithium. Lurasidone does not impact concentrations of lithium. 

 

A clinical drug interaction study investigating the effect of coadministration of lurasidone on patients 

taking oral combination contraceptives including norgestimate and ethinyl estradiol, indicated that 

lurasidone had no clinically or statistically meaningful effects on the pharmacokinetics of the 

contraceptive or sex hormone binding globulin (SHBG) levels. Therefore, lurasidone can be 

coadministered with oral contraceptives. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of lurasidone 

in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, 

embryonal/foetal development, parturition and postnatal development (see section 5.3). The potential 

risk for humans is unknown. Lurasidone should not be used during pregnancy unless clearly 

necessary.  

 

Neonates exposed to antipsychotics (including lurasidone) during the third trimester are at risk of 

adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and 

duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, 

somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored 

carefully. 

 

Breast-feeding 

 

Lurasidone was excreted in milk of rats during lactation (see section 5.3). It is not known whether 

lurasidone or its metabolites are excreted in human milk. Breast feeding in women receiving 

lurasidone should be considered only if the potential benefit of treatment justifies the potential risk to 

the child. 

 

Fertility 

 

Studies in animals have shown a number of effects on fertility, mainly related to prolactin increase, 

which are not considered to be relevant to human reproduction (see section 5.3).  

 

4.7 Effects on ability to drive and use machines 

 

Lurasidone has minor influence on the ability to drive and use machines. Patients should be cautioned 

about operating hazardous machines, including motor vehicles, until they are reasonably certain that 

lurasidone does not affect them adversely (see section 4.8). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The safety of lurasidone has been evaluated at doses of 18.5 -148 mg in clinical studies in patients 

with schizophrenia treated for up to 52 weeks and in the post-marketing setting. The most common 

adverse drug reactions (ADRs) (≥ 10%) were akathisia and somnolence, which were dose-related up to 

111 mg daily. 

 

Tabulated summary of adverse reactions 

 

Adverse drug reactions (ADRs) based upon pooled data are shown by system, organ class and by 

preferred term are listed below. The incidence of ADRs reported in clinical trials is tabulated by 



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frequency category. The following terms and frequencies are applied: very common (≥ 1/10), common 

(≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare 

(<1 /10,000) and not known (cannot be estimated from the available data). Within each frequency 

grouping, adverse reactions are presented in order of decreasing seriousness. 

 

Table 1  

 

System 

Organ Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Infections and 

infestations 

  Nasopharyngit

is 

  

Blood and 

lymphatic 

system 

disorders 

   Eosinophilia Leukopenia**** 

Neutropenia**** 

Anemia**** 

Immune 

system 

disorders 

 Hypersensitiv

ity 

   

Metabolism 

and nutrition 

disorders 

 Weight 

increased 

 

Decreased 

appetite 

Blood glucose 

increased 

Hyponatraemi

a 

  

Psychiatric 

disorders  

 

 Insomnia 

Agitation 

Anxiety 

Restlessness 

Nightmare 

Catatonia 

 Suicidal 

behaviour**** 

Panic attack**** 

Sleep 

disorder**** 

Nervous 

system 

disorders 

 

Akathisia 

Somnolenc

e* 

 

Parkinsonism

** 

Dizziness 

Dystonia*** 

Dyskinesia 

Lethargy 

Dysarthria 

Tardive 

dyskinesia 

Neuroleptic 

malignant 

syndrome 

(NMS) 

Convulsion**** 

Eye disorders   Blurred vision   

Ear and 

labyrinth 

disorders 

    Vertigo**** 

Cardiac 

disorders 

  Tachycardia  Angina**** 

AV block first 

degree**** 

Bradycardia**** 

Vascular 

disorders 

  Hypertension 

Hypotension 

Orthostatic 

hypotension 

Hot flush 

Blood 

pressure 

increased 

  



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System 

Organ Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Gastrointestin

al disorders 

 

 Nausea 

Vomiting 

Dyspepsia 

Salivary 

hypersecretio

n 

Dry mouth 

Upper 

abdominal 

pain 

Stomach 

discomfort 

Flatulence 

 

 Diarrhoea****  

Dysphagia****  

Gastritis**** 

Hepatobiliary 

disorders 

  Alanine 

aminotransfer

ase increased 

  

Skin and 

subcutaneous 

tissue 

disorders 

 Rash  

Pruritus 

 

Hyperhidrosis 

 

 

Angioedema 

 

Stevens-Johnson 

syndrome 

Musculoskele

tal and 

connective 

tissue 

disorders 

 

 Musculoskele

tal stiffness 

Blood 

creatine 

phosphokinas

e increase 

Joint stiffness 

Myalgia 

Neck pain 

Back pain 

 

Rhabdomyoly

sis 

 

Renal and 

urinary 

disorders 

 Serum 

creatinine 

increased 

Dysuria 

 

 Renal failure**** 

Pregnancy, 

puerperium 

and perinatal 

conditions 

    Drug withdrawal 

syndrome 

neonatal (see 4.6) 

Reproductive 

system and 

breast 

disorders 

  Blood 

prolactin 

increased 

 Breast 

enlargement**** 

Breast pain**** 

Galactorrhoea***

*  Erectile 

dysfunction****  

Amenorrhoea***

*  

Dysmenorrhoea*

*** 

General 

disorders and 

administratio

n site 

conditions 

 Fatigue Gait 

disturbance 

 Sudden death 

attributable to 

underlying 

cardiovascular 

disease observed 

during the clinical 

development 

programme**** 

*Somnolence includes adverse reaction terms: hypersomnia, hypersomnolence, sedation, and 

somnolence 



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**Parkinsonism includes adverse reaction terms: bradykinesia, cogwheel rigidity, drooling, 

extrapyramidal disorder, hypokinesia, muscle rigidity, parkinsonism, psychomotor retardation, and 

tremor 

***Dystonia includes adverse reaction terms: dystonia, oculogyric crisis, oromandibular dystonia, 

tongue spasm, torticollis, and trismus. 

****ADRs noted in Phase 2 and 3 controlled and uncontrolled studies; however, the incidence of 

occurrence for these are too low to estimate frequencies. 

 

Description of selected adverse reactions 

 

Post marketing reports of clinically serious cases of skin and other hypersensitivity reactions have 

been reported in association with lurasidone treatment, including some reports of Stevens-Johnson 

syndrome. 

 

Events of interest to the class 

Extrapyramidal symptoms (EPS): In the short-term placebo controlled studies, the incidence of 

reported events related to EPS, excluding akathisia and restlessness, was 13.5% for lurasidone-treated 

subjects versus 5.8% for placebo-treated subjects. The incidence of akathisia for lurasidone-treated 

subjects was 12.9% versus 3.0% for placebo-treated subjects. 

 

Dystonia: 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, difficulty swallowing, difficulty 

breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 

more frequently and with greater severity, higher potency and at higher doses of first generation 

antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 

age groups.  

 

Venous thromboembolism: Cases of venous thromboembolism, including cases of pulmonary 

embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs -Frequency 

unknown. 

 

Reporting of suspected adverse reactions  

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the following website: 

www.mhra.gov.uk/yellowcard. 

 

4.9 Overdose 

 

Management of overdose 

 

There is no specific antidote to lurasidone, 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 QT-prolonging effects when administered in 

patients with an acute overdose of lurasidone. Similarly the alpha-blocking properties of bretylium 

might be additive to those of lurasidone, resulting in problematic hypotension. 

 

Hypotension and circulatory collapse should be treated with appropriate measures. Adrenaline and 

dopamine should not be used, or other sympathomimetics with beta agonist activity, since beta 

stimulation may worsen hypotension in the setting of lurasidone-induced alpha blockade. In case of 

severe extrapyramidal symptoms, anticholinergic medicinal products should be administered. 

 

http://www.mhra.gov.uk/yellowcard


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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. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Psycholeptics, antipsychotics. ATC code: N05AE05 

 

Mechanism of action 

 

Lurasidone is a selective blocking agent of dopamine and monoamine effects. Lurasidone binds 

strongly to dopaminergic D2- and to serotonergic 5-HT2A and 5-HT7- receptors with high binding 

affinity of 0.994, 0.47 and 0.495 nM, respectively. It also blocks α2c-adrenergic receptors and 

α2a-adrenergic receptors with a binding affinity of 10.8 and 40.7 nM respectively. Lurasidone also 

exhibits partial agonism at the 5HT-1A receptor with a binding affinity of 6.38 nM. Lurasidone does 

not bind to histaminergic or muscarinic receptors. 

 

The mechanism of action of the minor active metabolite of lurasidone ID-14283 is similar to that of 

lurasidone. 

 

Lurasidone doses ranging from 9 to 74 mg administered to healthy subjects produced a 

dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor ligand, in the caudate, 

putamen and ventral striatum detected by positron emission tomography. 

 

Pharmacodynamic effects 

 

In the main clinical efficacy studies, lurasidone was administered at doses of 37-148 mg lurasidone. 

 

Clinical efficacy 

The efficacy of lurasidone in the treatment of schizophrenia was demonstrated in five multi-centre, 

placebo-controlled, double-blind, 6-week trials in subjects who met Diagnostic and Statistical Manual 

of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia. Lurasidone doses, which 

varied across the five trials, ranged from 37 to 148 mg lurasidone once daily. In the short-term trials, 

the primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Positive 

and Negative Syndrome Scale (PANSS) total scores, a validated multi-item inventory composed of 

five factors to evaluate positive symptoms, negative symptoms, disorganised thoughts, uncontrolled 

hostility/excitement, and anxiety/depression. Lurasidone demonstrated superior efficacy compared 

with placebo across Phase 3 studies (see Table 2). Lurasidone showed significant separation from 

placebo from as early as Day 4. Additionally, lurasidone was superior to placebo on the predefined 

secondary endpoint Clinical Global Impression – Severity (CGI-S) scale. Efficacy was also confirmed 

in a secondary analysis of treatment response (defined as ≥ 30% decrease from Baseline in PANSS 

total score).  

 

Table 2 

Schizophrenia Studies: Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total 

Score - Change From Baseline to Week 6- MMRM for Studies D1050229, D1050231, and D1050233: 

Intent-to-Treat Analysis Set 

 

Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

Study D1050229 N=124 N=121 N=118 N=123 -- -- 



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Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

Baseline Mean 

(SD) 

96.8 

(11.1) 

96.5 

(11.6) 

96.0 

(10.8) 
96.0 (9.7) 

-- -- 

LS Mean Change 

(SE) 
-17.0 

(1.8) 

-19.2 

(1.7) 

-23.4 

(1.8) 

-20.5 

(1.8) 

-- -- 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -2.1 (2.5) -6.4 (2.5) -3.5 (2.5) -- -- 

p-value -- 0.591 0.034 0.391 -- -- 

Study D1050231 N=114 N=118 -- N=118 -- N=121 

Baseline Mean 

(SD) 

95.8 

(10.8) 

96.6 

(10.7) 

-- 97.9 

(11.3) 

-- 96.3 (12.2) 

LS Mean Change 

(SE) 

-16.0 

(2.1) 

-25.7 

(2.0) 

-- -23.6 

(2.1) 

-- -28.7 (1.9) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -9.7 (2.9) -- -7.5 (3.0) -- -12.6 (2.8) 

p-value  -- 0.002 -- 0.022 -- <0.001 

Study D1050233 N=120 -- N=125 -- N=121 N=116 

Baseline Mean 

(SD) 

96.6 

(10.2) 

-- 97.7 (9.7) -- 97.9 

(11.8) 

97.7 (10.2) 

LS Mean Change 

(SE) 

-10.3 

(1.8) 

-- -22.2 

(1.8) 

-- -26.5 

(1.8) 

-27.8 (1.8) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -- -11.9 

(2.6) 

-- -16.2 

(2.5) 

-17.5 (2.6) 

p-value  -- -- <0.001 -- <0.001 <0.001 

(a) Olanzapine 15 mg in Study D1050231, quetiapine extended-release (XR) 600 mg in Study 

D1050233. 

N is number of subjects per model estimate. 

(b) p-values for lurasidone vs. placebo were adjusted for multiple comparisons. P-values for 

olanzapine and quetiapine XR vs. placebo were unadjusted. 

 

In the short-term studies there was no consistent dose-response correlation observed. 

 

Long-term maintenance efficacy of lurasidone (37 to 148 mg lurasidone once daily ) was 

demonstrated in a 12 month non-inferiority trial with quetiapine extended release (200 to 800 mg once 

daily). Lurasidone was non-inferior to quetiapine  extended release in time to relapse of schizophrenia. 

Lurasidone had a small increase from baseline to Month 12 in body weight and body mass index 

(Mean (SD): 0.73 (3.36) kg and 0.28 (1.17) kg/m2, respectively) compared to quetiapine extended 

release (1.23 (4.56) kg and 0.45 (1.63) kg/m2, respectively). Overall, lurasidone had a negligible effect 

on weight and other metabolic parameters including total cholesterol, triglycerides, and glucose levels. 

 

In a long-term safety study clinically stable patients were treated using 37 – 111 mg lurasidone or 

risperidone 2 – 6 mg. In that study the rate of relapse over a 12-month period was 20% for lurasidone 

and 16% for risperidone. This difference neared, but did not reach, statistical significance. 

 

In a long-term trial designed to assess the maintenance of effect, lurasidone was more effective than 

placebo in maintaining symptom control and delaying relapse of schizophrenia. After having been 

treated for an acute episode and stabilized for a minimum of 12 weeks with lurasidone, patients were 

then randomised in a double-blind manner to either continue on lurasidone or on placebo until they 

experienced a relapse in schizophrenia symptoms. In the primary analysis of time to relapse in which 

patients that withdrew without relapse were censored at the time of withdrawal, patients on lurasidone 

showed a significantly longer time to relapse compared with patients on placebo (p=0.039). The 



13 

Kaplan-Meier estimates of the probability of relapse at Week 28 were 42.2% for lurasidone and 51.2% 

for placebo. The probability of all-cause discontinuation at Week 28 were 58.2% for lurasidone and 

69.9% for placebo (p=0.072). 

 

Paediatric population 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

lurasidone in one or more subsets of the paediatric population in schizophrenia (see section 4.2 for 

information on paediatric use). 

 

Bipolar Depression 

 

The short-term efficacy of lurasidone was studied in a 6-week multicentre, randomized, double-blind, 

placebo-controlled, study of children and adolescent patients (10-17 years of age) who met Diagnostic 

and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a major depressive 

episode associated with bipolar I disorder, with or without rapid cycling, and without psychotic features 

(N=350). Patients were randomized to flexibly dosed lurasidone 18-74 mg once daily or placebo.  

 

The primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Children's 

Depression Rating Scale, Revised (CDRS-R) Total Score. The key secondary endpoint was Clinical 

Global Impression – Bipolar Version, Severity of Illness (CGI-BP-S) Depression Score. Statistically 

significant differences favouring lurasidone over placebo were shown for these endpoints for the total 

population studied, beginning at Week 2 and were maintained at each study visit through to the end of 

the study. However, the primary and key secondary efficacy endpoints were not met in younger 

patients (below 15 years of age). Placebo-adjusted LS mean change (95% CI) from Baseline to Week 6 

LOCF in CDRS-R total score for the lurasidone group was -1.8 (-5.6, 2.0) for subjects in the 10- to 14-

year-old age patients and was -8.6 (-12.4, -4.8) for subjects in the 15- to 17-year-old age patients.  

 

The safety profile of lurasidone in children included in this short-term study is in general consistent 

with that observed when treated within the approved indication in adults, however, differences in 

frequency of the most commonly occurred adverse reactions have been observed in paediatric patients 

for nausea (very common), diarrhea (common) and decreased appetite (common), compared with 

adults (common, unknown, and uncommon, respectively). 

 

Table 2.1 Bipolar Depression Paediatric Study: Children's Depression Rating Scale, Revised (CDRS-R) 

Total Score and Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) Depression 

Score (Depression) - Change From Baseline to Week 6 - MMRM for Study D1050326: Intent-to-Treat 

Analysis Set 

Parameters Study Statistic Placebo Lurasidone dose 18.5-74 

mg (a) (b) 

Primary Endpoint: 

CDRS-R Total Score  
 N=170 N=173 

Baseline Mean (SD) 58.6 (8.26) 59.2 (8.24) 

LS Mean Change (SE) -15.3 (1.08) -21.0 (1.06) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -5.7 (1.39; -8.4 to -3.0) 

p-value -- <0.0001 

    

Key Secondary 

Endpoint: CGI-BP-S 

Depression Score 

 N=170 N=173 

Baseline Mean (SD) 4.5 4.6 

LS Mean Change (SE) -1.05 (0.087) -1.49 (0.085) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -0.44 (0.112; -0.66 to -0.22) 

p-value  -- <0.0001 

N is number of subjects. 

(a) p-values for lurasidone vs. placebo were adjusted for multiple comparisons.  

(b) Lurasidone doses of 18.5, 37, 55.5, 74 mg are equivalent to 20, 40, 60 and 80 amounts of lurasidone hydrochloride. 



14 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Lurasidone reaches peak serum concentrations in approximately 1-3 hours.  

 

In a food effect study, lurasidone mean Cmax and AUC increased approximately by 2-3-times and 

1.5-2-times, respectively, when administered with food compared to the levels observed under fasting 

conditions.  

 

Distribution 

 

Following administration of 37 mg of lurasidone, the mean approximate apparent volume of 

distribution was 6000 L. Lurasidone is highly bound (~99%) to serum proteins. 

 

Biotransformation 

 

Lurasidone is metabolised mainly via CYP3A4. The major biotransformation pathways are oxidative 

N-dealkylation, hydroxylation of norbornane ring, and S-oxidation. 

 

Lurasidone is metabolised into two active metabolites (ID-14283 and ID-14326) and two non-active 

metabolites (ID-20219 and ID-20220). Lurasidone and its metabolites ID-14283, ID-14326, ID-20219 

and ID-20220 correspond to approximately 11.4, 4.1, 0.4, 24 and 11% respectively, of serum 

radioactivity respectively. 

 

CYP3A4 is the major enzyme responsible for metabolism of the active metabolite ID-14283. 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors.  

 

Based on in vitro studies lurasidone is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, 

CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. 

 

In vitro, lurasidone demonstrated no direct, or weak inhibition (direct or time-dependent) (IC50>5.9 

μM) of the enzymes cytochrome P450 (CYP)1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, 

CYP2D6, CYP2E1, and CYP3A4. Based on this data, lurasidone is not expected to affect the 

pharmacokinetics of medicinal products that are substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, 

CYP2C19, CYP2D6, and CYP2E1. For administration of medicinal products that are substrates of 

CYP3A4 with a narrow therapeutic range, see section 4.5.  

 

Lurasidone is an in vitro substrate of the efflux transporters P-gp and BCRP. Lurasidone is not subject 

to active uptake transport by OATP1B1 or OATP1B3.  

 

Lurasidone is an inhibitor of P-gp, BCRP and OCT1 in vitro (see section 4.5). Lurasidone is not 

expected to have a clinically relevant inhibitory potential on transporters OATP1B1, OATP1B3, 

OCT2, OAT1, OAT3, MATE1, MATE2K or BSEP based on in vitro data. 

 

Elimination 

 

Following administration of lurasidone, the elimination half-life was 20-40 hours. Following oral 

administration of a radiolabelled dose, approximately 67% dose was recovered in faeces and 19% in 

urine. Urine comprised mostly of a number of metabolites with minimal renal excretion of parent 

compound.  

 

Linearity/non-linearity 

 



15 

The pharmacokinetics of lurasidone is dose-proportional within a total daily dose range of 18.5 mg to 

148 mg. Steady-state concentrations of lurasidone are reached within 7 days of starting lurasidone. 

 

Pharmacokinetics in special patient groups: 

 

Elderly people 

Limited data have been collected in healthy subjects ≥ 65 years. Of the data collected, similar 

exposure was obtained compared with subjects < 65 years. However, an increase in exposure in 

elderly subjects may be expected for patients if they have impaired renal or hepatic function.  

 

Hepatic impairment 

The serum concentrations of lurasidone are increased in healthy subjects with Child-Pugh Class A, B 

and C hepatic impairment with an increased exposure of 1.5-, 1.7- and 3-fold respectively. 

 

Renal impairment 

The serum concentrations of lurasidone are increased in healthy subjects with mild, moderate and 

severe renal impairment with an increased exposure of 1.5, 1.9 and 2.0-fold respectively. Subjects 

with ESRD (CrCl<15 ml/min) have not been investigated. 

 

Gender 

There were no clinically relevant differences between genders in the pharmacokinetics of lurasidone in 

a population pharmacokinetic analysis in patients with schizophrenia. 

 

Race 

There were no clinically relevant differences in the pharmacokinetics of lurasidone in a population 

pharmacokinetic analysis in patients with schizophrenia. It was noted that Asian subjects had 1.5 fold 

increased exposure to lurasidone compared to Caucasian subjects. 

 

Smoking 

Based on in vitro studies utilising human liver enzymes, lurasidone is not a substrate for CYP1A2; 

smoking should, therefore, not have an effect on the pharmacokinetics of lurasidone. 

 

Paediatric population 

The pharmacokinetics of lurasidone in paediatric patients was investigated in 49 children aged 

6-12 years and 56 adolescents aged 13-17 years. Lurasidone was administered as lurasidone 

hydrochloride at daily doses of either 20, 40, 80, 120 mg (6-17 years) or 160 mg (10-17 years only) for 

7 days. There was no clear correlation between obtained plasma exposure and age or body weight. The 

pharmacokinetics of lurasidone in paediatric patients aged 6–17 years was generally comparable to 

those observed in adults. 

 

5.3 Preclinical safety data 

 

Nonclinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Major findings in 

repeat-dose toxicity studies of lurasidone were centrally-mediated endocrine changes resulting from 

serum prolactin elevations in rats, dogs and monkeys. High serum prolactin levels in long-term 

repeat-dose studies in female rats were associated with effects on bones, adrenal glands, and 

reproductive tissues. In a long-term dog repeat-dose study, high serum prolactin levels were associated 

with effects on male and female reproductive tissues. 

 

In rats, lurasidone had no effect on male and female reproduction at oral doses of 150 and 

0.1 mg/kg/day lurasidone hydrochloride, respectively, or on early embryonic development at an oral 

dose of 15 mg/kg/day lurasidone hydrochloride.  

 

A fertility study in female rats resulted in prolonged oestrous cycle and delayed copulation at 

≥1.5 mg/kg/day lurasidone hydrochloride, whilst the copulation and fertility indices, and the numbers 

of corpora lutea, implantations and live foetuses were decreased at 150 mg/kg/day lurasidone 



16 

hydrochloride. These effects were due to the hyperprolactinemia following lurasidone treatment, 

affecting the oestrous cycle and copulatory behaviour as well as the maintenance of corpus luteum of 

the female rats, resulting in a decrease in implantation and the number of live foetuses. These 

prolactin-related effects are not considered to be relevant to human reproduction. 

 

A single dose of 10 mg/kg lurasidone hydrochloride to pregnant rats resulted in fetal exposure. In a 

dose range finding study in pregnant rats, 150 mg/kg/day lurasidone hydrochloride caused fetal growth 

retardation without signs of teratogenicity. Lurasidone was not teratogenic in rats or rabbits at an 

exposure similar to or below the maximum recommended human dose (148 mg lurasidone ). 

 

Lurasidone was excreted in milk of rats during lactation. 

 

Lurasidone was not genotoxic in a battery of tests. Mammary gland and/or pituitary gland tumours 

were observed in the mouse and rat carcinogenicity studies and are most likely due to the increased 

blood prolactin levels. These findings are common in rodents treated with antipsychotic medicinal 

products with dopamine D2 blocking activity and are considered to be rodent-specific.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Core 

 

Mannitol (E 421) 

Starch, pregelatinised  

Croscarmellose sodium (E468) 

Hypromellose 2910 (E 464) 

Magnesium stearate (E 470b) 

 

Tablet coating 

 

Hypromellose 2910 (E 464) 

Titanium dioxide (E 171) 

Macrogol 8000 

Carnauba wax (E 903) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

5 years 

 

6.4 Special precautions for storage 

 

Store in the original package in order to protect from light.  

 

6.5 Nature and contents of container 

 

Cartons contain 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1 or 98 x 1 tablets in aluminium/aluminium 

perforated unit dose blisters. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 



17 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/001-007 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 21 March 2014 

Date of latest renewal: 14 November 2018 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

 

http://www.ema.europa.eu/


18 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 37 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to 37.2 mg lurasidone. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet). 

 

White to off-white, film-coated round tablets of 8 mm debossed with ‘LB’ 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Latuda is indicated for the treatment of schizophrenia in adults aged 18 years and over. 

 

4.2 Posology and method of administration 

 

Posology 

 

The recommended starting dose is 37 mg of lurasidone once daily. No initial dose titration is required. 

It is effective in a dose range of 37 to 148 mg once daily. Dose increase should be based on physician 

judgement and observed clinical response. The maximum daily dose should not exceed 148 mg. 

 

Patients on doses higher than 111 mg once daily who discontinue their treatment for longer than 

3 days should be restarted on 111 mg once daily and up-titrated to their optimal dose. For all other 

doses patients can be restarted on their previous dose without need for up-titration. 

 

Dose adjustment due to interactions 

A starting dose of 18.5 mg is recommended and the maximum dose of lurasidone should not exceed 

74 mg once daily in combination with moderate CYP3A4 inhibitors. Dose adjustment of lurasidone 

may be necessary in combination with mild and moderate CYP3A4 inducers (see section 4.5). For 

strong CYP3A4 inhibitors and inducers see section 4.3. 

 

Switching between antipsychotic medicinal products 

Due to different pharmacodynamic and pharmacokinetic profiles among antipsychotic medicinal 

products, supervision by a clinician is needed when switching to another antipsychotic product is 

considered medically appropriate. 

 

Elderly people 

Dosing recommendations for elderly patients with normal renal function (CrCl ≥ 80 ml/min) are the 

same as for adults with normal renal function. However, because elderly patients may have diminished 

renal function, dose adjustments may be required according to their renal function status (see “Renal 

impairment” below). 

 

Limited data are available in elderly people treated with higher doses of lurasidone. No data are 

available in elderly people treated with 148 mg of lurasidone. Caution should be exercised when 

treating patients ≥65 years of age with higher doses of lurasidone. 



19 

 

Renal impairment 

No dose adjustment of lurasidone is required in patients with mild renal impairment. 

In patients with moderate (Creatinine Clearance (CrCl) ≥ 30 and < 50 ml/min), severe renal 

impairment (CrCL >15 and < 30 ml/min) and End Stage Renal Disease (ESRD) patients 

(CrCl < 15 ml/min), the recommended starting dose is 18.5 mg and the maximum dose should not 

exceed 74 mg once daily. Lurasidone should not be used in patients with ESRD unless the potential 

benefits outweigh the potential risks. If used in ESRD, clinical monitoring is advised. 

 

Hepatic impairment 

No dose adjustment of lurasidone is required in patients with mild hepatic impairment. 

Dose adjustment is recommended in moderate (Child-Pugh Class B) and severe hepatic impairment 

(Child-Pugh Class C) patients. The recommended starting dose is 18.5 mg. The maximum daily dose 

in moderate hepatic impairment patients should not exceed 74 mg and in severe hepatic impairment 

patients should not exceed 37 mg once daily. 

 

Paediatric population 

The safety and efficacy of lurasidone in children aged less than 18 years have not been established. 

Current available data are described in section 5.1 and 5.2, but no recommendation on a posology can 

be made. 

 

Method of administration  

 

Latuda film-coated tablets are for oral use, to be taken once daily together with a meal. 

If taken without food, it is anticipated that lurasidone exposure will be significantly lower as compared 

to when taken with food (see section 5.2). 

 

Latuda tablets should be swallowed whole, in order to mask the bitter taste. Latuda tablets should be 

taken at the same time every day to aid compliance.  

 

4.3 Contraindications 
 

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Concomitant administration of strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, 

ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and strong CYP3A4 inducers (e.g. 

carbamazepine, phenobarbital, phenytoin, rifampicin, St John’s wort (Hypericum perforatum) 

(see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

During antipsychotic treatment, improvement in the patient's clinical condition may take a few days to 

some weeks. Patients should be closely monitored during this period.  

 

Suicidality  

The occurrence of suicidal behaviour is inherent in psychotic illnesses and in some cases has been 

reported early after initiation or switch of antipsychotic therapy. Close supervision of high-risk 

patients should accompany antipsychotic therapy. 

 

Parkinson’s disease 

If prescribed to patients with Parkinson’s disease, antipsychotic medicinal products may exacerbate 

the underlying parkinsonism symptoms. Physicians should therefore weigh the risks versus the 

benefits when prescribing Lurasidone to patients with Parkinson’s disease. 

 

Extrapyramidal symptoms (EPS) 

Medicinal products with dopamine receptor antagonistic properties have been associated with 

extrapyramidal adverse reactions including rigidity, tremors, mask-like face, dystonias, drooling of 



20 

saliva, drooped posture and abnormal gait. In placebo controlled clinical studies in adult patients with 

schizophrenia there was an increased occurrence of EPS following treatment with lurasidone 

compared to placebo. 

 

Tardive dyskinesia 

Medicinal products with dopamine receptor antagonistic properties have been associated with the 

induction of tardive dyskinesia characterised by rhythmical involuntary movements, predominantly of 

the tongue and/or face. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all 

antipsychotics, including lurasidone, should be considered.  

 

Cardiovascular disorders/QT prolongation 

Caution should be exercised when lurasidone is prescribed in patients with known cardiovascular 

disease or family history of QT prolongation, hypokalaemia, and in concomitant use with other 

medicinal products thought to prolong the QT interval. 

 

Seizures 

Lurasidone should be used cautiously in patients with a history of seizures or other conditions that 

potentially lower the seizure threshold.  

 

Neuroleptic malignant syndrome (NMS) 

Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic 

instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported 

to occur lurasidone. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal 

failure. In this event, lurasidone, should be discontinued.  

 

Elderly patients with dementia 

Lurasidone has not been studied in elderly patients with dementia. 

 

Overall mortality  

In a meta-analysis of 17 controlled clinical trials, elderly patients with dementia treated with other 

atypical antipsychotics, including risperidone, aripiprazole, olanzapine, and quetiapine had an 

increased risk of mortality compared to placebo. 

 

Cerebrovascular accident 

An approximately 3-fold increased risk of cerebrovascular adverse reactions has been seen in 

randomised placebo-controlled clinical trials in the dementia population with some atypical 

antipsychotics, including risperidone, aripiprazole and olanzapine. The mechanism for this increased 

risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient 

populations. Lurasidone should be used with caution in elderly patients with dementia who have risk 

factors for stroke. 

 

Venous thromboembolism 

Cases of venous thromboembolism (VTE) have been reported with antipsychotic medicinal products. 

Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible 

risk factors for VTE should be identified before and during treatment with lurasidone and preventive 

measures undertaken. 

 

Hyperprolactinaemia 

Lurasidone elevates prolactin levels due to antagonism of dopamine D2 receptors.  Patients should 

be counseled on signs and symptoms of elevated prolactin, such as gynecomastia, 

galactorrhea, amenorrhea and erectile dysfunction. Patient should be advised to seek medical 

attention if they experience any signs and symptoms. 
Weight gain 

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

recommended. 

 



21 

Hyperglycaemia 

Rare cases of glucose related adverse reactions, e.g. increase in blood glucose, have been reported in 

clinical trials with lurasidone. Appropriate clinical monitoring is advisable in diabetic patients and in 

patients with risk factors for the development of diabetes mellitus. 

 

Orthostatic hypotension/syncope 

Lurasidone may cause orthostatic hypotension, perhaps due to its α1-adrenergic receptor antagonism. 

Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to 

hypotension. 

 

Interaction with grapefruit juice  

Grapefruit juice should be avoided during treatment with lurasidone (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Pharmacodynamic interactions 

 

Given the primary central nervous system effects of lurasidone, lurasidone should be used with 

caution in combination with other centrally acting medicinal products and alcohol.  

 

Caution is advised when prescribing lurasidone with medicinal products known to prolong the QT 

interval, e.g. class IA antiarrhythmics (e.g. quinidine, disopyramide) and class III antiarrhythmics (e.g. 

amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e.g. 

mefloquine).  

 

Pharmacokinetic interactions 

 

The concomitant administration of lurasidone and grapefruit juice has not been assessed. Grapefruit 

juice inhibits CYP 3A4 and may increase the serum concentration of lurasidone. Grapefruit juice 

should be avoided during treatment with lurasidone. 

 

Potential for other medicinal products to affect lurasidone  

 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors. Lurasidone and its active metabolite ID-14283 are primarily 

metabolised by CYP3A4.  

 

CYP3A4 inhibitors 

Lurasidone is contraindicated with strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, 

saquinavir, telaprevir, telithromycin, voriconazole) (see section 4.3).  

 

Coadministration of lurasidone with the strong CYP3A4 inhibitor ketoconazole resulted in a 9- and 

6-fold increase in exposure of lurasidone and its active metabolite ID-14283 respectively.  

 

Co-administration of lurasidone and posaconazole (strong CYP3A4 inhibitor) resulted in an 

approximate 4-5 fold increase in lurasidone exposure.  A persistent effect of posaconazole on 

lurasidone exposure was observed up to 2-3 weeks after stop of posaconazole co-administration. 

 

Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 (e.g. 

diltiazem, erythromycin, fluconazole verapamil) may increase exposure to lurasidone. Moderate 

CYP3A4 inhibitors are estimated to result in a 2-5 fold increase in exposure of CYP3A4 substrates. 

 

Coadministration of lurasidone with diltiazem (slow-release formulation), a moderate CYP3A4 

inhibitor, resulted in a 2.2 and 2.4-fold increase in exposure of lurasidone and ID-14283 respectively 

(see section 4.2). The use of an immediate release formulation of diltiazem could result in a larger 

increase in lurasidone exposure. 



22 

 

CYP3A4 inducers 

Lurasidone is contraindicated with strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, 

phenytoin, rifampicin, St John’s wort (Hypericum perforatum)) (see section 4.3). 

 

Coadministration of lurasidone with the strong CYP3A4 inducer rifampicin resulted in a 6-fold 

decrease in exposure of lurasidone. 

 

Coadministration of lurasidone with mild (e.g. armodafinil, amprenavir, aprepitant, prednisone, 

rufinamide) or moderate (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) inducers of 

CYP3A4 would be expected to give a <2-fold reduction in lurasidone exposure during 

co-administration and for up to 2 weeks after discontinuation of mild or moderate CYP3A4 inducers. 

 

When lurasidone is coadministered with mild or moderate CYP3A4 inducers, the efficacy of 

lurasidone needs to be carefully monitored and a dose adjustment may be needed. 

 

Transporters  

Lurasidone is a substrate of P-gp and BCRP in vitro and the in vivo relevance of this is unclear. 

Coadministration of lurasidone with P-gp and BCRP inhibitors may increase exposure to lurasidone. 

 

Potential for lurasidone to affect other medicinal products 

 

Coadministration of lurasidone with midazolam, a sensitive CYP3A4 substrate, resulted in a < 1.5-fold 

increase in midazolam exposure. Monitoring is recommended when lurasidone and CYP3A4 

substrates known to have a narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, 

quinidine, bepridil or ergot alkaloids [ergotamine, dihydroergotamine]) are coadministered.  

 

Coadministration of lurasidone with digoxin (a P-gp substrate) did not increase the exposure to 

digoxin and only slightly increased Cmax (1.3 –fold) and therefore, it is considered that lurasidone can 

be coadministered with digoxin. Lurasidone is an in vitro inhibitor of the efflux transporter P-gp and 

the clinical relevance of intestinal P-gp inhibition cannot be excluded. Concomitant administration of 

the P-gp substrate dabigatran etexilate may result in increased dabigatran plasma concentrations.  

 

Lurasidone is an in vitro inhibitor of the efflux transporter BCRP and the clinical relevance of 

intestinal BCRP inhibition cannot be excluded. Concomitant administration of BCRP substrates may 

result in increases in the plasma concentrations of these substrates. 

 

Coadministration of lurasidone with lithium indicated that lithium had clinically negligible effects on 

the pharmacokinetics of lurasidone, therefore no dose adjustment of lurasidone is required when 

coadministered with lithium. Lurasidone does not impact concentrations of lithium. 

 

A clinical drug interaction study investigating the effect of coadministration of lurasidone on patients 

taking oral combination contraceptives including norgestimate and ethinyl estradiol, indicated that 

lurasidone had no clinically or statistically meaningful effects on the pharmacokinetics of the 

contraceptive or sex hormone binding globulin (SHBG) levels. Therefore, lurasidone can be 

coadministered with oral contraceptives. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of lurasidone 

in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, 

embryonal/foetal development, parturition and postnatal development (see section 5.3). The potential 

risk for humans is unknown. Lurasidone should not be used during pregnancy unless clearly 

necessary.  

 



23 

Neonates exposed to antipsychotics (including lurasidone) during the third trimester are at risk of 

adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and 

duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, 

somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored 

carefully. 

 

Breast-feeding 

 

Lurasidone was excreted in milk of rats during lactation (see section 5.3). It is not known whether 

lurasidone or its metabolites are excreted in human milk. Breast feeding in women receiving 

lurasidone should be considered only if the potential benefit of treatment justifies the potential risk to 

the child. 

 

Fertility 

 

Studies in animals have shown a number of effects on fertility, mainly related to prolactin increase, 

which are not considered to be relevant to human reproduction (see section 5.3).  

 

4.7 Effects on ability to drive and use machines 

 

Lurasidone has minor influence on the ability to drive and use machines. Patients should be cautioned 

about operating hazardous machines, including motor vehicles, until they are reasonably certain that 

lurasidone does not affect them adversely (see section 4.8). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The safety of lurasidone has been evaluated at doses of 18.5 -148 mg in clinical studies in patients 

with schizophrenia treated for up to 52 weeks and in the post-marketing setting. The most common 

adverse drug reactions (ADRs) (≥ 10%) were akathisia and somnolence, which were dose-related up to 

111 mg daily. 

 

Tabulated summary of adverse reactions 

 

Adverse drug reactions (ADRs) based upon pooled data are shown by system, organ class and by 

preferred term are listed below. The incidence of ADRs reported in clinical trials is tabulated by 

frequency category. The following terms and frequencies are applied: very common (≥ 1/10), common 

(≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare 

(<1 /10,000) and not known (cannot be estimated from the available data). Within each frequency 

grouping, adverse reactions are presented in order of decreasing seriousness. 

 



24 

Table 1  

 

System Organ 

Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Infections and 

infestations 

  Nasopharyngitis   

Blood and 

lymphatic 

system 

disorders 

   Eosinophilia Leukopenia**** 

Neutropenia**** 

Anemia**** 

Immune system 

disorders 

 Hypersensitivity    

Metabolism and 

nutrition 

disorders 

 Weight 

increased 

 

Decreased 

appetite 

Blood glucose 

increased 

Hyponatraemia 

  

Psychiatric 

disorders  

 

 Insomnia 

Agitation 

Anxiety 

Restlessness 

Nightmare 

Catatonia 

 Suicidal 

behaviour**** 

Panic attack**** 

Sleep disorder**** 

Nervous system 

disorders 

 

Akathisia 

Somnolence* 

 

Parkinsonism** 

Dizziness 

Dystonia*** 

Dyskinesia 

Lethargy 

Dysarthria 

Tardive 

dyskinesia 

Neuroleptic 

malignant 

syndrome 

(NMS) 

Convulsion**** 

Eye disorders   Blurred vision   

Ear and 

labyrinth 

disorders 

    Vertigo**** 

Cardiac 

disorders 

  Tachycardia  Angina**** 

AV block first 

degree**** 

Bradycardia**** 

Vascular 

disorders 

  Hypertension 

Hypotension 

Orthostatic 

hypotension 

Hot flush 

Blood pressure 

increased 

  

Gastrointestinal 

disorders 

 

 Nausea 

Vomiting 

Dyspepsia 

Salivary 

hypersecretion 

Dry mouth 

Upper 

abdominal pain 

Stomach 

discomfort 

Flatulence 

 

 Diarrhoea****  

Dysphagia****  

Gastritis**** 

Hepatobiliary 

disorders 

  Alanine 

aminotransferase 

increased 

  



25 

System Organ 

Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Skin and 

subcutaneous 

tissue disorders 

 Rash  

Pruritus 

 

Hyperhidrosis 

 

 

Angioedema 

 

Stevens-Johnson 

syndrome 

Musculoskeletal 

and connective 

tissue disorders 

 

 Musculoskeletal 

stiffness 

Blood creatine 

phosphokinase 

increase 

Joint stiffness 

Myalgia 

Neck pain 

Back pain 

 

Rhabdomyolysis  

Renal and 

urinary 

disorders 

 Serum 

creatinine 

increased 

Dysuria 

 

 Renal failure**** 

Pregnancy, 

puerperium and 

perinatal 

conditions 

    Drug withdrawal 

syndrome neonatal 

(see 4.6) 

Reproductive 

system and 

breast disorders 

  Blood prolactin 

increased 

 Breast 

enlargement**** 

Breast pain**** 

Galactorrhoea****  

Erectile 

dysfunction****  

Amenorrhoea****  

Dysmenorrhoea**** 

General 

disorders and 

administration 

site conditions 

 Fatigue Gait disturbance  Sudden death 

attributable to 

underlying 

cardiovascular 

disease observed 

during the clinical 

development 

programme**** 

*Somnolence includes adverse reaction terms: hypersomnia, hypersomnolence, sedation, and 

somnolence 

**Parkinsonism includes adverse reaction terms: bradykinesia, cogwheel rigidity, drooling, 

extrapyramidal disorder, hypokinesia, muscle rigidity, parkinsonism, psychomotor retardation, and 

tremor 

***Dystonia includes adverse reaction terms: dystonia, oculogyric crisis, oromandibular dystonia, 

tongue spasm, torticollis, and trismus. 

****ADRs noted in Phase 2 and 3 controlled and uncontrolled studies; however, the incidence of 

occurrence for these are too low to estimate frequencies. 

 

Description of selected adverse reactions 

 

Post marketing reports of clinically serious cases of skin and other hypersensitivity reactions have 

been reported in association with lurasidone treatment, including some reports of Stevens-Johnson 

syndrome. 

 

Events of interest to the class 

Extrapyramidal symptoms (EPS): In the short-term placebo controlled studies, the incidence of 

reported events related to EPS, excluding akathisia and restlessness, was 13.5% for lurasidone-treated 

subjects versus 5.8% for placebo-treated subjects. The incidence of akathisia for lurasidone-treated 

subjects was 12.9% versus 3.0% for placebo-treated subjects. 

 



26 

Dystonia: 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, difficulty swallowing, difficulty 

breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 

more frequently and with greater severity, higher potency and at higher doses of first generation 

antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 

age groups.  

 

Venous thromboembolism: Cases of venous thromboembolism, including cases of pulmonary 

embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs -Frequency 

unknown. 

 

Reporting of suspected adverse reactions  

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the following website: 

www.mhra.gov.uk/yellowcard. 

 

4.9 Overdose 

 

Management of overdose 

 

There is no specific antidote to lurasidone, 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 QT-prolonging effects when administered in 

patients with an acute overdose of lurasidone. Similarly the alpha-blocking properties of bretylium 

might be additive to those of lurasidone, resulting in problematic hypotension. 

 

Hypotension and circulatory collapse should be treated with appropriate measures. Adrenaline and 

dopamine should not be used, or other sympathomimetics with beta agonist activity, since beta 

stimulation may worsen hypotension in the setting of lurasidone-induced alpha blockade. In case of 

severe extrapyramidal symptoms, anticholinergic medicinal products 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. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Psycholeptics, antipsychotics. ATC code: N05AE05 

 

Mechanism of action 

 

Lurasidone is a selective blocking agent of dopamine and monoamine effects. Lurasidone binds 

strongly to dopaminergic D2- and to serotonergic 5-HT2A and 5-HT7- receptors with high binding 

affinity of 0.994, 0.47 and 0.495 nM, respectively. It also blocks α2c-adrenergic receptors and 

α2a-adrenergic receptors with a binding affinity of 10.8 and 40.7 nM respectively. Lurasidone also 

exhibits partial agonism at the 5HT-1A receptor with a binding affinity of 6.38 nM. Lurasidone does 

not bind to histaminergic or muscarinic receptors. 

http://www.mhra.gov.uk/yellowcard


27 

 

The mechanism of action of the minor active metabolite of lurasidone ID-14283 is similar to that of 

lurasidone. 

 

Lurasidone doses ranging from 9 to 74 mg administered to healthy subjects produced a 

dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor ligand, in the caudate, 

putamen and ventral striatum detected by positron emission tomography. 

 

Pharmacodynamic effects 

 

In the main clinical efficacy studies, lurasidone was administered at doses of 37-148 mg lurasidone. 

 

Clinical efficacy 

The efficacy of lurasidone in the treatment of schizophrenia was demonstrated in five multi-centre, 

placebo-controlled, double-blind, 6-week trials in subjects who met Diagnostic and Statistical Manual 

of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia. Lurasidone doses, which 

varied across the five trials, ranged from 37 to 148 mg lurasidone  once daily. In the short-term trials, 

the primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Positive 

and Negative Syndrome Scale (PANSS) total scores, a validated multi-item inventory composed of 

five factors to evaluate positive symptoms, negative symptoms, disorganised thoughts, uncontrolled 

hostility/excitement, and anxiety/depression. Lurasidone demonstrated superior efficacy compared 

with placebo across Phase 3 studies (see Table 2). Lurasidone showed significant separation from 

placebo from as early as Day 4. Additionally, lurasidone was superior to placebo on the predefined 

secondary endpoint Clinical Global Impression – Severity (CGI-S) scale. Efficacy was also confirmed 

in a secondary analysis of treatment response (defined as ≥ 30% decrease from Baseline in PANSS 

total score).  

 

Table 2 

Schizophrenia Studies: Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total 

Score - Change From Baseline to Week 6- MMRM for Studies D1050229, D1050231, and D1050233: 

Intent-to-Treat Analysis Set 

 

Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

Study D1050229 N=124 N=121 N=118 N=123 -- -- 

Baseline Mean 

(SD) 

96.8 

(11.1) 

96.5 

(11.6) 

96.0 

(10.8) 
96.0 (9.7) 

-- -- 

LS Mean Change 

(SE) 
-17.0 

(1.8) 

-19.2 

(1.7) 

-23.4 

(1.8) 

-20.5 

(1.8) 

-- -- 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -2.1 (2.5) -6.4 (2.5) -3.5 (2.5) -- -- 

p-value -- 0.591 0.034 0.391 -- -- 

Study D1050231 N=114 N=118 -- N=118 -- N=121 

Baseline Mean 

(SD) 

95.8 

(10.8) 

96.6 

(10.7) 

-- 97.9 

(11.3) 

-- 96.3 (12.2) 

LS Mean Change 

(SE) 

-16.0 

(2.1) 

-25.7 

(2.0) 

-- -23.6 

(2.1) 

-- -28.7 (1.9) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -9.7 (2.9) -- -7.5 (3.0) -- -12.6 (2.8) 

p-value  -- 0.002 -- 0.022 -- <0.001 

Study D1050233 N=120 -- N=125 -- N=121 N=116 

Baseline Mean 

(SD) 

96.6 

(10.2) 

-- 97.7 (9.7) -- 97.9 

(11.8) 

97.7 (10.2) 



28 

Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

LS Mean Change 

(SE) 

-10.3 

(1.8) 

-- -22.2 

(1.8) 

-- -26.5 

(1.8) 

-27.8 (1.8) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -- -11.9 

(2.6) 

-- -16.2 

(2.5) 

-17.5 (2.6) 

p-value  -- -- <0.001 -- <0.001 <0.001 

(a) Olanzapine 15 mg in Study D1050231, quetiapine extended-release (XR) 600 mg in Study 

D1050233. 

N is number of subjects per model estimate. 

(b) p-values for lurasidone vs. placebo were adjusted for multiple comparisons. P-values for 

olanzapine and quetiapine XR vs. placebo were unadjusted. 

 

 

In the short-term studies there was no consistent dose-response correlation observed. 

 

Long-term maintenance efficacy of lurasidone (37 to 148 mg lurasidone once daily) was demonstrated 

in a 12 month non-inferiority trial with quetiapine extended release  (200 to 800 mg once daily). 

Lurasidone was non-inferior to quetiapine extended release in time to relapse of schizophrenia. 

Lurasidone had a small increase from baseline to Month 12 in body weight and body mass index 

(Mean (SD): 0.73 (3.36) kg and 0.28 (1.17) kg/m2, respectively) compared to quetiapine extended 

release (1.23 (4.56) kg and 0.45 (1.63) kg/m2, respectively). Overall, lurasidone had a negligible effect 

on weight and other metabolic parameters including total cholesterol, triglycerides, and glucose levels. 

 

In a long-term safety study clinically stable patients were treated using 37 – 111 mg lurasidone or 

risperidone 2 – 6 mg. In that study the rate of relapse over a 12-month period was 20% for lurasidone 

and 16% for risperidone. This difference neared, but did not reach, statistical significance. 

 

In a long-term trial designed to assess the maintenance of effect, lurasidone was more effective than 

placebo in maintaining symptom control and delaying relapse of schizophrenia. After having been 

treated for an acute episode and stabilized for a minimum of 12 weeks with lurasidone, patients were 

then randomised in a double-blind manner to either continue on lurasidone or on placebo until they 

experienced a relapse in schizophrenia symptoms. In the primary analysis of time to relapse in which 

patients that withdrew without relapse were censored at the time of withdrawal, patients on lurasidone 

showed a significantly longer time to relapse compared with patients on placebo (p=0.039). The 

Kaplan-Meier estimates of the probability of relapse at Week 28 were 42.2% for lurasidone and 51.2% 

for placebo. The probability of all-cause discontinuation at Week 28 were 58.2% for lurasidone and 

69.9% for placebo (p=0.072). 

 

Paediatric population 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

lurasidone in one or more subsets of the paediatric population in schizophrenia (see section 4.2 for 

information on paediatric use). 

 

Bipolar Depression 

 

The short-term efficacy of lurasidone was studied in a 6-week multicentre, randomized, double-blind, 

placebo-controlled, study of children and adolescent patients (10-17 years of age) who met Diagnostic 

and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a major depressive 

episode associated with bipolar I disorder, with or without rapid cycling, and without psychotic features 

(N=350). Patients were randomized to flexibly dosed lurasidone 18-74 mg once daily or placebo.  

 



29 

The primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Children's 

Depression Rating Scale, Revised (CDRS-R) Total Score. The key secondary endpoint was Clinical 

Global Impression – Bipolar Version, Severity of Illness (CGI-BP-S) Depression Score. Statistically 

significant differences favouring lurasidone over placebo were shown for these endpoints for the total 

population studied, beginning at Week 2 and were maintained at each study visit through to the end of 

the study. However, the primary and key secondary efficacy endpoints were not met in younger 

patients (below 15 years of age). Placebo-adjusted LS mean change (95% CI) from Baseline to Week 6 

LOCF in CDRS-R total score for the lurasidone group was -1.8 (-5.6, 2.0) for subjects in the 10- to 14-

year-old age patients and was -8.6 (-12.4, -4.8) for subjects in the 15- to 17-year-old age patients.  

 

The safety profile of lurasidone in children included in this short-term study is in general consistent 

with that observed when treated within the approved indication in adults, however, differences in 

frequency of the most commonly occurred adverse reactions have been observed in paediatric patients 

for nausea (very common), diarrhea (common) and decreased appetite (common), compared with 

adults (common, unknown, and uncommon, respectively). 

 

 

Table 2.1 Bipolar Depression Paediatric Study: Children's Depression Rating Scale, Revised (CDRS-R) 

Total Score and Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) Depression 

Score (Depression) - Change From Baseline to Week 6 - MMRM for Study D1050326: Intent-to-Treat 

Analysis Set 

Parameters Study Statistic Placebo Lurasidone dose 18.5-74 

mg (a) (b) 

Primary Endpoint: 

CDRS-R Total Score  
 N=170 N=173 

Baseline Mean (SD) 58.6 (8.26) 59.2 (8.24) 

LS Mean Change (SE) -15.3 (1.08) -21.0 (1.06) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -5.7 (1.39; -8.4 to -3.0) 

p-value -- <0.0001 

    

Key Secondary 

Endpoint: CGI-BP-S 

Depression Score 

 N=170 N=173 

Baseline Mean (SD) 4.5 4.6 

LS Mean Change (SE) -1.05 (0.087) -1.49 (0.085) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -0.44 (0.112; -0.66 to -0.22) 

p-value  -- <0.0001 

N is number of subjects. 

(a) p-values for lurasidone vs. placebo were adjusted for multiple comparisons.  

(b) Lurasidone doses of 18.5, 37, 55.5, 74 mg are equivalent to 20, 40, 60 and 80 amounts of lurasidone hydrochloride. 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Lurasidone reaches peak serum concentrations in approximately 1-3 hours.  

 

In a food effect study, lurasidone mean Cmax and AUC increased approximately by 2-3-times and 

1.5-2-times, respectively, when administered with food compared to the levels observed under fasting 

conditions.  

 

Distribution 

 

Following administration of 37 mg of lurasidone, the mean approximate apparent volume of 

distribution was 6000 L. Lurasidone is highly bound (~99%) to serum proteins. 

 



30 

Biotransformation 

 

Lurasidone is metabolised mainly via CYP3A4. The major biotransformation pathways are oxidative 

N-dealkylation, hydroxylation of norbornane ring, and S-oxidation. 

 

Lurasidone is metabolised into two active metabolites (ID-14283 and ID-14326) and two non-active 

metabolites (ID-20219 and ID-20220). Lurasidone and its metabolites ID-14283, ID-14326, ID-20219 

and ID-20220 correspond to approximately 11.4, 4.1, 0.4, 24 and 11% respectively, of serum 

radioactivity respectively. 

 

CYP3A4 is the major enzyme responsible for metabolism of the active metabolite ID-14283. 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors.  

 

Based on in vitro studies lurasidone is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, 

CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. 

 

In vitro, lurasidone demonstrated no direct, or weak inhibition (direct or time-dependent) (IC50>5.9 

μM) of the enzymes cytochrome P450 (CYP)1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, 

CYP2D6, CYP2E1, and CYP3A4. Based on this data, lurasidone is not expected to affect the 

pharmacokinetics of medicinal products that are substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, 

CYP2C19, CYP2D6, and CYP2E1. For administration of medicinal products that are substrates of 

CYP3A4 with a narrow therapeutic range, see section 4.5.  

 

Lurasidone is an in vitro substrate of the efflux transporters P-gp and BCRP. Lurasidone is not subject 

to active uptake transport by OATP1B1 or OATP1B3.  

 

Lurasidone is an inhibitor of P-gp, BCRP and OCT1 in vitro (see section 4.5). Lurasidone is not 

expected to have a clinically relevant inhibitory potential on transporters OATP1B1, OATP1B3, 

OCT2, OAT1, OAT3, MATE1, MATE2K or BSEP based on in vitro data. 

 

Elimination 

 

Following administration of lurasidone, the elimination half-life was 20-40 hours. Following oral 

administration of a radiolabelled dose, approximately 67% dose was recovered in faeces and 19% in 

urine. Urine comprised mostly of a number of metabolites with minimal renal excretion of parent 

compound.  

 

Linearity/non-linearity 

 

The pharmacokinetics of lurasidone is dose-proportional within a total daily dose range of 18.5 mg to 

148 mg. Steady-state concentrations of lurasidone are reached within 7 days of starting lurasidone. 

 

Pharmacokinetics in special patient groups: 

 

Elderly people 

Limited data have been collected in healthy subjects ≥ 65 years. Of the data collected, similar 

exposure was obtained compared with subjects < 65 years. However, an increase in exposure in 

elderly subjects may be expected for patients if they have impaired renal or hepatic function.  

 

Hepatic impairment 

The serum concentrations of lurasidone are increased in healthy subjects with Child-Pugh Class A, B 

and C hepatic impairment with an increased exposure of 1.5-, 1.7- and 3-fold respectively. 

 



31 

Renal impairment 

The serum concentrations of lurasidone are increased in healthy subjects with mild, moderate and 

severe renal impairment with an increased exposure of 1.5, 1.9 and 2.0-fold respectively. Subjects 

with ESRD (CrCl<15 ml/min) have not been investigated. 

 

Gender 

There were no clinically relevant differences between genders in the pharmacokinetics of lurasidone in 

a population pharmacokinetic analysis in patients with schizophrenia. 

 

Race 

There were no clinically relevant differences in the pharmacokinetics of lurasidone in a population 

pharmacokinetic analysis in patients with schizophrenia. It was noted that Asian subjects had 1.5-fold 

increased exposure to lurasidone compared to Caucasian subjects. 

 

Smoking 

Based on in vitro studies utilising human liver enzymes, lurasidone is not a substrate for CYP1A2; 

smoking should, therefore, not have an effect on the pharmacokinetics of lurasidone. 

 

Paediatric population 

The pharmacokinetics of lurasidone in paediatric patients was investigated in 49 children aged 

6-12 years and 56 adolescents aged 13-17 years. Lurasidone was administered as lurasidone 

hydrochloride at daily doses of either 20, 40, 80, 120 mg (6-17 years) or 160 mg (10-17 years only) for 

7 days. There was no clear correlation between obtained plasma exposure and age or body weight. The 

pharmacokinetics of lurasidone in paediatric patients aged 6–17 years was generally comparable to 

those observed in adults. 

 

5.3 Preclinical safety data 

 

Nonclinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Major findings in 

repeat-dose toxicity studies of lurasidone were centrally-mediated endocrine changes resulting from 

serum prolactin elevations in rats, dogs and monkeys. High serum prolactin levels in long-term 

repeat-dose studies in female rats were associated with effects on bones, adrenal glands, and 

reproductive tissues. In a long-term dog repeat-dose study, high serum prolactin levels were associated 

with effects on male and female reproductive tissues. 

 

In rats, lurasidone had no effect on male and female reproduction at oral doses of 150 and 

0.1 mg/kg/day lurasidone hydrochloride, respectively, or on early embryonic development at an oral 

dose of 15 mg/kg/day lurasidone hydrochloride.  

 

A fertility study in female rats resulted in prolonged oestrous cycle and delayed copulation at 

≥1.5 mg/kg/day lurasidone hydrochloride, whilst the copulation and fertility indices, and the numbers 

of corpora lutea, implantations and live foetuses were decreased at 150 mg/kg/day lurasidone 

hydrochloride. These effects were due to the hyperprolactinemia following lurasidone treatment, 

affecting the oestrous cycle and copulatory behaviour as well as the maintenance of corpus luteum of 

the female rats, resulting in a decrease in implantation and the number of live foetuses. These 

prolactin-related effects are not considered to be relevant to human reproduction. 

 

A single dose of 10 mg/kg lurasidone hydrochloride to pregnant rats resulted in fetal exposure. In a 

dose range finding study in pregnant rats, 150 mg/kg/day lurasidone hydrochloride caused fetal growth 

retardation without signs of teratogenicity. Lurasidone was not teratogenic in rats or rabbits at an 

exposure similar to or below the maximum recommended human dose (148 mg lurasidone). 

 

Lurasidone was excreted in milk of rats during lactation. 

 

Lurasidone was not genotoxic in a battery of tests. Mammary gland and/or pituitary gland tumours 

were observed in the mouse and rat carcinogenicity studies and are most likely due to the increased 



32 

blood prolactin levels. These findings are common in rodents treated with antipsychotic medicinal 

products with dopamine D2 blocking activity and are considered to be rodent-specific.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Core 

Mannitol (E 421) 

Starch, pregelatinised  

Croscarmellose sodium (E468) 

Hypromellose 2910 (E 464) 

Magnesium stearate (E 470b) 

 

Tablet coating 

Hypromellose 2910 (E 464) 

Titanium dioxide (E 171) 

Macrogol 8000 

Carnauba wax (E 903) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

5 years 

 

6.4 Special precautions for storage 

 

Store in the original package in order to protect from light.  

 

6.5 Nature and contents of container 

 

Cartons contain 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1 or 98 x 1 tablets in aluminium/aluminium 

perforated unit dose blisters. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 



33 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/008-014 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 21 March 2014 

Date of latest renewal: 14 November 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

 

http://www.ema.europa.eu/


34 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 74 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to 74.5 mg lurasidone. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet). 

 

Pale green, film-coated oval tablets of 12 mm x 7 mm debossed with ‘LD’ 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Latuda is indicated for the treatment of schizophrenia in adults aged 18 years and over. 

 

4.2 Posology and method of administration 

 

Posology 

 

The recommended starting dose is 37 mg of lurasidone once daily. No initial dose titration is required. 

It is effective in a dose range of 37 to 148 mg once daily. Dose increase should be based on physician 

judgement and observed clinical response. The maximum daily dose should not exceed 148 mg. 

 

Patients on doses higher than 111 mg once daily who discontinue their treatment for longer than 

3 days should be restarted on 111 mg once daily and up-titrated to their optimal dose. For all other 

doses patients can be restarted on their previous dose without need for up-titration. 

 

Dose adjustment due to interactions 

A starting dose of 18.5 mg is recommended and the maximum dose of lurasidone should not exceed 

74 mg once daily in combination with moderate CYP3A4 inhibitors. Dose adjustment of lurasidone 

may be necessary in combination with mild and moderate CYP3A4 inducers (see section 4.5). For 

strong CYP3A4 inhibitors and inducers see section 4.3. 

 

Switching between antipsychotic medicinal products 

Due to different pharmacodynamic and pharmacokinetic profiles among antipsychotic medicinal 

products, supervision by a clinician is needed when switching to another antipsychotic product is 

considered medically appropriate. 

 

Elderly people 

Dosing recommendations for elderly patients with normal renal function (CrCl ≥ 80 ml/min) are the 

same as for adults with normal renal function. However, because elderly patients may have diminished 

renal function, dose adjustments may be required according to their renal function status (see “Renal 

impairment” below). 

 

Limited data are available in elderly people treated with higher doses of lurasidone. No data are 

available in elderly people treated with 148 mg of lurasidone. Caution should be exercised when 

treating patients ≥65 years of age with higher doses of lurasidone. 



35 

 

Renal impairment 

No dose adjustment of lurasidone is required in patients with mild renal impairment. 

In patients with moderate (Creatinine Clearance (CrCl) ≥ 30 and < 50 ml/min), severe renal 

impairment (CrCL >15 and < 30 ml/min) and End Stage Renal Disease (ESRD) patients 

(CrCl < 15 ml/min), the recommended starting dose is 18.5 mg and the maximum dose should not 

exceed 74 mg once daily. Lurasidone should not be used in patients with ESRD unless the potential 

benefits outweigh the potential risks. If used in ESRD, clinical monitoring is advised. 

 

Hepatic impairment 

No dose adjustment of lurasidone is required in patients with mild hepatic impairment. 

Dose adjustment is recommended in moderate (Child-Pugh Class B) and severe hepatic impairment 

(Child-Pugh Class C) patients. The recommended starting dose is 18.5 mg. The maximum daily dose 

in moderate hepatic impairment patients should not exceed 74 mg and in severe hepatic impairment 

patients should not exceed 37 mg once daily. 

 

Paediatric population 

The safety and efficacy of lurasidone in children aged less than 18 years have not been established. 

Current available data are described in section 5.1 and 5.2, but no recommendation on a posology can 

be made. 

 

Method of administration  

 

Latuda film-coated tablets are for oral use, to be taken once daily together with a meal. 

If taken without food, it is anticipated that lurasidone exposure will be significantly lower as compared 

to when taken with food (see section 5.2). 

 

Latuda tablets should be swallowed whole, in order to mask the bitter taste. Latuda tablets should be 

taken at the same time every day to aid compliance.  

 

4.3 Contraindications 
 

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Concomitant administration of strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, 

ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and strong CYP3A4 inducers (e.g. 

carbamazepine, phenobarbital, phenytoin, rifampicin, St John’s wort (Hypericum perforatum) 

(see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

During antipsychotic treatment, improvement in the patient's clinical condition may take a few days to 

some weeks. Patients should be closely monitored during this period.  

 

Suicidality  

The occurrence of suicidal behaviour is inherent in psychotic illnesses and in some cases has been 

reported early after initiation or switch of antipsychotic therapy. Close supervision of high-risk 

patients should accompany antipsychotic therapy. 

 

Parkinson’s disease 

If prescribed to patients with Parkinson’s disease, antipsychotic medicinal products may exacerbate 

the underlying parkinsonism symptoms. Physicians should therefore weigh the risks versus the 

benefits when prescribing lurasidone to patients with Parkinson’s disease. 

 

Extrapyramidal symptoms (EPS) 

Medicinal products with dopamine receptor antagonistic properties have been associated with 

extrapyramidal adverse reactions including rigidity, tremors, mask-like face, dystonias, drooling of 



36 

saliva, drooped posture and abnormal gait. In placebo controlled clinical studies in adult patients with 

schizophrenia there was an increased occurrence of EPS following treatment with lurasidone 

compared to placebo. 

 

Tardive dyskinesia 

Medicinal products with dopamine receptor antagonistic properties have been associated with the 

induction of tardive dyskinesia characterised by rhythmical involuntary movements, predominantly of 

the tongue and/or face. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all 

antipsychotics, including lurasidone, should be considered.  

 

Cardiovascular disorders/QT prolongation 

Caution should be exercised when lurasidone is prescribed in patients with known cardiovascular 

disease or family history of QT prolongation, hypokalaemia, and in concomitant use with other 

medicinal products thought to prolong the QT interval. 

 

Seizures 

Lurasidone should be used cautiously in patients with a history of seizures or other conditions that 

potentially lower the seizure threshold.  

 

Neuroleptic malignant syndrome (NMS) 

Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic 

instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported 

to occur lurasidone. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal 

failure. In this event, lurasidone should be discontinued.  

 

Elderly patients with dementia 

Lurasidone has not been studied in elderly patients with dementia. 

 

Overall mortality  

In a meta-analysis of 17 controlled clinical trials, elderly patients with dementia treated with other 

atypical antipsychotics, including risperidone, aripiprazole, olanzapine, and quetiapine had an 

increased risk of mortality compared to placebo. 

 

Cerebrovascular accident 

An approximately 3-fold increased risk of cerebrovascular adverse reactions has been seen in 

randomised placebo-controlled clinical trials in the dementia population with some atypical 

antipsychotics, including risperidone, aripiprazole and olanzapine. The mechanism for this increased 

risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient 

populations. Lurasidone should be used with caution in elderly patients with dementia who have risk 

factors for stroke. 

 

Venous thromboembolism 

Cases of venous thromboembolism (VTE) have been reported with antipsychotic medicinal products. 

Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible 

risk factors for VTE should be identified before and during treatment with lurasidone and preventive 

measures undertaken. 

 

Hyperprolactinaemia 

Lurasidone elevates prolactin levels due to antagonism of dopamine D2 receptors.   Patients should 

be counseled on signs and symptoms of elevated prolactin, such as gynecomastia, 

galactorrhea, amenorrhea and erectile dysfunction. Patient should be advised to seek medical 

attention if they experience any signs and symptoms 
 

Weight gain 

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

recommended. 

 



37 

Hyperglycaemia 

Rare cases of glucose related adverse reactions, e.g. increase in blood glucose, have been reported in 

clinical trials with lurasidone. Appropriate clinical monitoring is advisable in diabetic patients and in 

patients with risk factors for the development of diabetes mellitus. 

 

Orthostatic hypotension/syncope 

Lurasidone may cause orthostatic hypotension, perhaps due to its α1-adrenergic receptor antagonism. 

Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to 

hypotension. 

 

Interaction with grapefruit juice  

Grapefruit juice should be avoided during treatment with lurasidone (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Pharmacodynamic interactions 

 

Given the primary central nervous system effects of lurasidone, lurasidone should be used with 

caution in combination with other centrally acting medicinal products and alcohol.  

 

Caution is advised when prescribing lurasidone with medicinal products known to prolong the QT 

interval, e.g. class IA antiarrhythmics (e.g. quinidine, disopyramide) and class III antiarrhythmics (e.g. 

amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e.g. 

mefloquine).  

 

Pharmacokinetic interactions 

 

The concomitant administration of lurasidone and grapefruit juice has not been assessed. Grapefruit 

juice inhibits CYP 3A4 and may increase the serum concentration of lurasidone. Grapefruit juice 

should be avoided during treatment with lurasidone. 

 

Potential for other medicinal products to affect lurasidone  

 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors. Lurasidone and its active metabolite ID-14283 are primarily 

metabolised by CYP3A4.  

 

CYP3A4 inhibitors 

Lurasidone is contraindicated with strong CYP3A4 inhibitors (e.g. boceprevir, clarithromycin, 

cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, 

saquinavir, telaprevir, telithromycin, voriconazole) (see section 4.3).  

 

Coadministration of lurasidone with the strong CYP3A4 inhibitor ketoconazole resulted in a 9- and 

6-fold increase in exposure of lurasidone and its active metabolite ID-14283 respectively.  

 

Co-administration of lurasidone and posaconazole (strong CYP3A4 inhibitor) resulted in an 

approximate 4-5 fold increase in lurasidone exposure.  A persistent effect of posaconazole on 

lurasidone exposure was observed up to 2-3 weeks after stop of posaconazole co-administration. 

 

Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 (e.g. 

diltiazem, erythromycin, fluconazole verapamil) may increase exposure to lurasidone. Moderate 

CYP3A4 inhibitors are estimated to result in a 2-5-fold increase in exposure of CYP3A4 substrates. 

 

Coadministration of lurasidone with diltiazem (slow-release formulation), a moderate CYP3A4 

inhibitor, resulted in a 2.2 and 2.4-fold increase in exposure of lurasidone and ID-14283 respectively 

(see section 4.2). The use of an immediate release formulation of diltiazem could result in a larger 

increase in lurasidone exposure. 



38 

 

CYP3A4 inducers 

Lurasidone is contraindicated with strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, 

phenytoin, rifampicin, St John’s wort (Hypericum perforatum)) (see section 4.3). 

 

Coadministration of lurasidone with the strong CYP3A4 inducer rifampicin resulted in a 6-fold 

decrease in exposure of lurasidone. 

 

Coadministration of lurasidone with mild (e.g. armodafinil, amprenavir, aprepitant, prednisone, 

rufinamide) or moderate (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) inducers of 

CYP3A4 would be expected to give a <2-fold reduction in lurasidone exposure during 

co-administration and for up to 2 weeks after discontinuation of mild or moderate CYP3A4 inducers. 

 

When lurasidone is coadministered with mild or moderate CYP3A4 inducers, the efficacy of 

lurasidone needs to be carefully monitored and a dose adjustment may be needed. 

 

Transporters  

Lurasidone is a substrate of P-gp and BCRP in vitro and the in vivo relevance of this is unclear. 

Coadministration of lurasidone with P-gp and BCRP inhibitors may increase exposure to lurasidone. 

 

Potential for lurasidone to affect other medicinal products 

 

Coadministration of lurasidone with midazolam, a sensitive CYP3A4 substrate, resulted in a < 1.5-fold 

increase in midazolam exposure. Monitoring is recommended when lurasidone and CYP3A4 

substrates known to have a narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, 

quinidine, bepridil or ergot alkaloids [ergotamine, dihydroergotamine]) are coadministered.  

 

Coadministration of lurasidone with digoxin (a P-gp substrate) did not increase the exposure to 

digoxin and only slightly increased Cmax (1.3 –fold) and therefore, it is considered that lurasidone can 

be coadministered with digoxin. Lurasidone is an in vitro inhibitor of the efflux transporter P-gp and 

the clinical relevance of intestinal P-gp inhibition cannot be excluded. Concomitant administration of 

the P-gp substrate dabigatran etexilate may result in increased dabigatran plasma concentrations.  

 

Lurasidone is an in vitro inhibitor of the efflux transporter BCRP and the clinical relevance of 

intestinal BCRP inhibition cannot be excluded. Concomitant administration of BCRP substrates may 

result in increases in the plasma concentrations of these substrates. 

 

Coadministration of lurasidone with lithium indicated that lithium had clinically negligible effects on 

the pharmacokinetics of lurasidone, therefore no dose adjustment of lurasidone is required when 

coadministered with lithium. Lurasidone does not impact concentrations of lithium. 

 

A clinical drug interaction study investigating the effect of coadministration of lurasidone on patients 

taking oral combination contraceptives including norgestimate and ethinyl estradiol, indicated that 

lurasidone had no clinically or statistically meaningful effects on the pharmacokinetics of the 

contraceptive or sex hormone binding globulin (SHBG) levels. Therefore, lurasidone can be 

coadministered with oral contraceptives. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of lurasidone 

in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, 

embryonal/foetal development, parturition and postnatal development (see section 5.3). The potential 

risk for humans is unknown. Lurasidone should not be used during pregnancy unless clearly 

necessary.  

 



39 

Neonates exposed to antipsychotics (including lurasidone) during the third trimester are at risk of 

adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and 

duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, 

somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored 

carefully. 

 

Breast-feeding 

 

Lurasidone was excreted in milk of rats during lactation (see section 5.3). It is not known whether 

lurasidone or its metabolites are excreted in human milk. Breast feeding in women receiving 

lurasidone should be considered only if the potential benefit of treatment justifies the potential risk to 

the child. 

 

Fertility 

 

Studies in animals have shown a number of effects on fertility, mainly related to prolactin increase, 

which are not considered to be relevant to human reproduction (see section 5.3).  

 

4.7 Effects on ability to drive and use machines 

 

Lurasidone has minor influence on the ability to drive and use machines. Patients should be cautioned 

about operating hazardous machines, including motor vehicles, until they are reasonably certain that 

lurasidone does not affect them adversely (see section 4.8). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The safety of lurasidone has been evaluated at doses of 18.5 -148 mg in clinical studies in patients 

with schizophrenia treated for up to 52 weeks and in the post-marketing setting. The most common 

adverse drug reactions (ADRs) (≥ 10%) were akathisia and somnolence, which were dose-related up to 

111 mg daily. 

 

Tabulated summary of adverse reactions 

 

Adverse drug reactions (ADRs) based upon pooled data are shown by system, organ class and by 

preferred term are listed below. The incidence of ADRs reported in clinical trials is tabulated by 

frequency category. The following terms and frequencies are applied: very common (≥ 1/10), common 

(≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare 

(<1 /10,000) and not known (cannot be estimated from the available data). Within each frequency 

grouping, adverse reactions are presented in order of decreasing seriousness. 

 



40 

Table 1  

 

System 

Organ Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Infections and 

infestations 

  Nasopharyngit

is 

  

Blood and 

lymphatic 

system 

disorders 

   Eosinophilia Leukopenia**** 

Neutropenia**** 

Anemia**** 

Immune 

system 

disorders 

 Hypersensitiv

ity 

   

Metabolism 

and nutrition 

disorders 

 Weight 

increased 

 

Decreased 

appetite 

Blood glucose 

increased 

Hyponatraemi

a 

  

Psychiatric 

disorders  

 

 Insomnia 

Agitation 

Anxiety 

Restlessness 

Nightmare 

Catatonia 

 Suicidal 

behaviour**** 

Panic attack**** 

Sleep 

disorder**** 

Nervous 

system 

disorders 

 

Akathisia 

Somnolenc

e* 

 

Parkinsonism

** 

Dizziness 

Dystonia*** 

Dyskinesia 

Lethargy 

Dysarthria 

Tardive 

dyskinesia 

Neuroleptic 

malignant 

syndrome 

(NMS) 

Convulsion**** 

Eye disorders   Blurred vision   

Ear and 

labyrinth 

disorders 

    Vertigo**** 

Cardiac 

disorders 

  Tachycardia  Angina**** 

AV block first 

degree**** 

Bradycardia**** 

Vascular 

disorders 

  Hypertension 

Hypotension 

Orthostatic 

hypotension 

Hot flush 

Blood 

pressure 

increased 

  

Gastrointestin

al disorders 

 

 Nausea 

Vomiting 

Dyspepsia 

Salivary 

hypersecretio

n 

Dry mouth 

Flatulence 

 

 Diarrhoea****  

Dysphagia****  

Gastritis**** 



41 

System 

Organ Class 

Very 

Common  

Common 

 
Uncommon 

 
Rare 

 
Frequency not 

known 

Upper 

abdominal 

pain 

Stomach 

discomfort 

Hepatobiliary 

disorders 

  Alanine 

aminotransfer

ase increased 

  

Skin and 

subcutaneous 

tissue 

disorders 

 Rash  

Pruritus 

 

Hyperhidrosis 

 

 

Angioedema 

 

Stevens-Johnson 

syndrome 

Musculoskele

tal and 

connective 

tissue 

disorders 

 

 Musculoskele

tal stiffness 

Blood 

creatine 

phosphokinas

e increase 

Joint stiffness 

Myalgia 

Neck pain 

Back pain 

 

Rhabdomyoly

sis 

 

Renal and 

urinary 

disorders 

 Serum 

creatinine 

increased 

Dysuria 

 

 Renal failure**** 

Pregnancy, 

puerperium 

and perinatal 

conditions 

    Drug withdrawal 

syndrome 

neonatal (see 4.6) 

Reproductive 

system and 

breast 

disorders 

  Blood 

prolactin 

increased 

 Breast 

enlargement**** 

Breast pain**** 

Galactorrhoea***

*  Erectile 

dysfunction****  

Amenorrhoea***

*  

Dysmenorrhoea*

*** 

General 

disorders and 

administratio

n site 

conditions 

 Fatigue Gait 

disturbance 

 Sudden death 

attributable to 

underlying 

cardiovascular 

disease observed 

during the clinical 

development 

programme**** 

*Somnolence includes adverse reaction terms: hypersomnia, hypersomnolence, sedation, and 

somnolence 

**Parkinsonism includes adverse reaction terms: bradykinesia, cogwheel rigidity, drooling, 

extrapyramidal disorder, hypokinesia, muscle rigidity, parkinsonism, psychomotor retardation, and 

tremor 



42 

***Dystonia includes adverse reaction terms: dystonia, oculogyric crisis, oromandibular dystonia, 

tongue spasm, torticollis, and trismus. 

****ADRs noted in Phase 2 and 3 controlled and uncontrolled studies; however, the incidence of 

occurrence for these are too low to estimate frequencies. 

 

Description of selected adverse reactions 

 

Post marketing reports of clinically serious cases of skin and other hypersensitivity reactions have 

been reported in association with lurasidone treatment, including some reports of Stevens-Johnson 

syndrome. 

 

Events of interest to the class 

Extrapyramidal symptoms (EPS): In the short-term placebo controlled studies, the incidence of 

reported events related to EPS, excluding akathisia and restlessness, was 13.5% for lurasidone-treated 

subjects versus 5.8% for placebo-treated subjects. The incidence of akathisia for lurasidone-treated 

subjects was 12.9% versus 3.0% for placebo-treated subjects. 

 

Dystonia: 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, difficulty swallowing, difficulty 

breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 

more frequently and with greater severity, higher potency and at higher doses of first generation 

antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 

age groups.  

 

Venous thromboembolism: Cases of venous thromboembolism, including cases of pulmonary 

embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs -Frequency 

unknown. 

 

Reporting of suspected adverse reactions  

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the following website: 

www.mhra.gov.uk/yellowcard. 

 

4.9 Overdose 

 

Management of overdose 

 

There is no specific antidote to lurasidone, 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 QT-prolonging effects when administered in 

patients with an acute overdose of lurasidone. Similarly the alpha-blocking properties of bretylium 

might be additive to those of lurasidone, resulting in problematic hypotension. 

 

Hypotension and circulatory collapse should be treated with appropriate measures. Adrenaline and 

dopamine should not be used, or other sympathomimetics with beta agonist activity, since beta 

stimulation may worsen hypotension in the setting of lurasidone-induced alpha blockade. In case of 

severe extrapyramidal symptoms, anticholinergic medicinal products should be administered. 

 

Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal 

together with a laxative should be considered. 

 

http://www.mhra.gov.uk/yellowcard


43 

The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose 

may create a risk of aspiration with induced emesis. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Psycholeptics, antipsychotics. ATC code: N05AE05 

 

Mechanism of action 

 

Lurasidone is a selective blocking agent of dopamine and monoamine effects. Lurasidone binds 

strongly to dopaminergic D2- and to serotonergic 5-HT2A and 5-HT7- receptors with high binding 

affinity of 0.994, 0.47 and 0.495 nM, respectively. It also blocks α2c-adrenergic receptors and 

α2a-adrenergic receptors with a binding affinity of 10.8 and 40.7 nM respectively. Lurasidone also 

exhibits partial agonism at the 5HT-1A receptor with a binding affinity of 6.38 nM. Lurasidone does 

not bind to histaminergic or muscarinic receptors. 

 

The mechanism of action of the minor active metabolite of lurasidone ID-14283 is similar to that of 

lurasidone. 

 

Lurasidone doses ranging from 9 to 74 mg  administered to healthy subjects produced a 

dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor ligand, in the caudate, 

putamen and ventral striatum detected by positron emission tomography. 

 

Pharmacodynamic effects 

 

In the main clinical efficacy studies, lurasidone was administered at doses of 37-148 mg lurasidone. 

 

Clinical efficacy 

The efficacy of lurasidone in the treatment of schizophrenia was demonstrated in five multi-centre, 

placebo-controlled, double-blind, 6-week trials in subjects who met Diagnostic and Statistical Manual 

of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia. Lurasidone doses, which 

varied across the five trials, ranged from 37 to 148 mg lurasidone once daily. In the short-term trials, 

the primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Positive 

and Negative Syndrome Scale (PANSS) total scores, a validated multi-item inventory composed of 

five factors to evaluate positive symptoms, negative symptoms, disorganised thoughts, uncontrolled 

hostility/excitement, and anxiety/depression. Lurasidone demonstrated superior efficacy compared 

with placebo across Phase 3 studies (see Table 2). Lurasidone showed significant separation from 

placebo from as early as Day 4. Additionally, lurasidone was superior to placebo on the predefined 

secondary endpoint Clinical Global Impression – Severity (CGI-S) scale. Efficacy was also confirmed 

in a secondary analysis of treatment response (defined as ≥ 30% decrease from Baseline in PANSS 

total score).  

 

Table 2 

Schizophrenia Studies: Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total 

Score - Change From Baseline to Week 6- MMRM for Studies D1050229, D1050231, and D1050233: 

Intent-to-Treat Analysis Set 

 

Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

Study D1050229 N=124 N=121 N=118 N=123 -- -- 

Baseline Mean 

(SD) 

96.8 

(11.1) 

96.5 

(11.6) 

96.0 

(10.8) 
96.0 (9.7) 

-- -- 



44 

Study Statistic Placebo Lurasidone dose (b)  Active 

Control 

(a) 
37 mg 74 mg 111 mg 148 mg 

LS Mean Change 

(SE) 
-17.0 

(1.8) 

-19.2 

(1.7) 

-23.4 

(1.8) 

-20.5 

(1.8) 

-- -- 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -2.1 (2.5) -6.4 (2.5) -3.5 (2.5) -- -- 

p-value -- 0.591 0.034 0.391 -- -- 

Study D1050231 N=114 N=118 -- N=118 -- N=121 

Baseline Mean 

(SD) 

95.8 

(10.8) 

96.6 

(10.7) 

-- 97.9 

(11.3) 

-- 96.3 (12.2) 

LS Mean Change 

(SE) 

-16.0 

(2.1) 

-25.7 

(2.0) 

-- -23.6 

(2.1) 

-- -28.7 (1.9) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -9.7 (2.9) -- -7.5 (3.0) -- -12.6 (2.8) 

p-value  -- 0.002 -- 0.022 -- <0.001 

Study D1050233 N=120 -- N=125 -- N=121 N=116 

Baseline Mean 

(SD) 

96.6 

(10.2) 

-- 97.7 (9.7) -- 97.9 

(11.8) 

97.7 (10.2) 

LS Mean Change 

(SE) 

-10.3 

(1.8) 

-- -22.2 

(1.8) 

-- -26.5 

(1.8) 

-27.8 (1.8) 

Treatment Difference 

vs. placebo 

      

Estimate (SE) -- -- -11.9 

(2.6) 

-- -16.2 

(2.5) 

-17.5 (2.6) 

p-value  -- -- <0.001 -- <0.001 <0.001 

(a) Olanzapine 15 mg in Study D1050231, quetiapine extended-release (XR) 600 mg in Study 

D1050233. 

N is number of subjects per model estimate. 

(b) p-values for lurasidone vs. placebo were adjusted for multiple comparisons. P-values for 

olanzapine and quetiapine XR vs. placebo were unadjusted. 

 

In the short-term studies there was no consistent dose-response correlation observed. 

 

Long-term maintenance efficacy of lurasidone (37 to 148 mg lurasidone once) was demonstrated in a 

12 month non-inferiority trial with quetiapine extended release (200 to 800 mg once daily). 

Lurasidone was non-inferior to quetiapine extended release in time to relapse of schizophrenia. 

Lurasidone had a small increase from baseline to Month 12 in body weight and body mass index 

(Mean (SD): 0.73 (3.36) kg and 0.28 (1.17) kg/m2, respectively) compared to quetiapine extended 

release (1.23 (4.56) kg and 0.45 (1.63) kg/m2, respectively). Overall, lurasidone had a negligible effect 

on weight and other metabolic parameters including total cholesterol, triglycerides, and glucose levels. 

 

In a long-term safety study clinically stable patients were treated using 37 – 111 mg lurasidone or 

risperidone 2 – 6 mg. In that study the rate of relapse over a 12-month period was 20% for lurasidone 

and 16% for risperidone. This difference neared, but did not reach, statistical significance. 

 

In a long-term trial designed to assess the maintenance of effect, lurasidone was more effective than 

placebo in maintaining symptom control and delaying relapse of schizophrenia. After having been 

treated for an acute episode and stabilized for a minimum of 12 weeks with lurasidone, patients were 

then randomised in a double-blind manner to either continue on lurasidone or on placebo until they 

experienced a relapse in schizophrenia symptoms. In the primary analysis of time to relapse in which 

patients that withdrew without relapse were censored at the time of withdrawal, patients on lurasidone 

showed a significantly longer time to relapse compared with patients on placebo (p=0.039). The 

Kaplan-Meier estimates of the probability of relapse at Week 28 were 42.2% for lurasidone and 51.2% 



45 

for placebo. The probability of all-cause discontinuation at Week 28 were 58.2% for lurasidone and 

69.9% for placebo (p=0.072). 

 

Paediatric population 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

lurasidone in one or more subsets of the paediatric population in schizophrenia (see section 4.2 for 

information on paediatric use). 

 

Bipolar Depression 

 

The short-term efficacy of lurasidone was studied in a 6-week multicentre, randomized, double-blind, 

placebo-controlled, study of children and adolescent patients (10-17 years of age) who met Diagnostic 

and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a major depressive 

episode associated with bipolar I disorder, with or without rapid cycling, and without psychotic features 

(N=350). Patients were randomized to flexibly dosed lurasidone 18-74 mg once daily or placebo.  

 

The primary efficacy endpoint was defined as the mean change from baseline to Week 6 in Children's 

Depression Rating Scale, Revised (CDRS-R) Total Score. The key secondary endpoint was Clinical 

Global Impression – Bipolar Version, Severity of Illness (CGI-BP-S) Depression Score. Statistically 

significant differences favouring lurasidone over placebo were shown for these endpoints for the total 

population studied, beginning at Week 2 and were maintained at each study visit through to the end of 

the study. However, the primary and key secondary efficacy endpoints were not met in younger 

patients (below 15 years of age). Placebo-adjusted LS mean change (95% CI) from Baseline to Week 6 

LOCF in CDRS-R total score for the lurasidone group was -1.8 (-5.6, 2.0) for subjects in the 10- to 14-

year-old age patients and was -8.6 (-12.4, -4.8) for subjects in the 15- to 17-year-old age patients.  

 

The safety profile of lurasidone in children included in this short-term study is in general consistent 

with that observed when treated within the approved indication in adults, however, differences in 

frequency of the most commonly occurred adverse reactions have been observed in paediatric patients 

for nausea (very common), diarrhea (common) and decreased appetite (common), compared with 

adults (common, unknown, and uncommon, respectively). 

 

Table 2.1 Bipolar Depression Paediatric Study: Children's Depression Rating Scale, Revised (CDRS-R) 

Total Score and Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) Depression 

Score (Depression) - Change From Baseline to Week 6 - MMRM for Study D1050326: Intent-to-Treat 

Analysis Set 

Parameters Study Statistic Placebo Lurasidone dose 18.5-74 

mg (a) (b) 

Primary Endpoint: 

CDRS-R Total Score  
 N=170 N=173 

Baseline Mean (SD) 58.6 (8.26) 59.2 (8.24) 

LS Mean Change (SE) -15.3 (1.08) -21.0 (1.06) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -5.7 (1.39; -8.4 to -3.0) 

p-value -- <0.0001 

    

Key Secondary 

Endpoint: CGI-BP-S 

Depression Score 

 N=170 N=173 

Baseline Mean (SD) 4.5 4.6 

LS Mean Change (SE) -1.05 (0.087) -1.49 (0.085) 

Treatment Difference vs. 

placebo 

  

Estimate (SE; 95% CI) -- -0.44 (0.112; -0.66 to -0.22) 

p-value  -- <0.0001 

N is number of subjects. 

(a) p-values for lurasidone vs. placebo were adjusted for multiple comparisons.  

(b) Lurasidone doses of 18.5, 37, 55.5, 74 mg are equivalent to 20, 40, 60 and 80 amounts of lurasidone hydrochloride. 

 



46 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Lurasidone reaches peak serum concentrations in approximately 1-3 hours.  

 

In a food effect study, lurasidone mean Cmax and AUC increased approximately by 2-3-times and 

1.5-2-times, respectively, when administered with food compared to the levels observed under fasting 

conditions.  

 

Distribution 

 

Following administration of 37 mg of lurasidone, the mean approximate apparent volume of 

distribution was 6000 L. Lurasidone is highly bound (~99%) to serum proteins. 

 

Biotransformation 

 

Lurasidone is metabolised mainly via CYP3A4. The major biotransformation pathways are oxidative 

N-dealkylation, hydroxylation of norbornane ring, and S-oxidation. 

 

Lurasidone is metabolised into two active metabolites (ID-14283 and ID-14326) and two non-active 

metabolites (ID-20219 and ID-20220). Lurasidone and its metabolites ID-14283, ID-14326, ID-20219 

and ID-20220 correspond to approximately 11.4, 4.1, 0.4, 24 and 11% respectively, of serum 

radioactivity respectively. 

 

CYP3A4 is the major enzyme responsible for metabolism of the active metabolite ID-14283. 

Lurasidone and its active metabolite ID-14283 both contribute to the pharmacodynamic effect at the 

dopaminergic and serotonergic receptors.  

 

Based on in vitro studies lurasidone is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, 

CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. 

 

In vitro, lurasidone demonstrated no direct, or weak inhibition (direct or time-dependent) 

(IC50>5.9 μM) of the enzymes cytochrome P450 (CYP)1A2, CYP2B6, CYP2C8, CYP2C9, 

CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Based on this data, lurasidone is not expected to affect 

the pharmacokinetics of medicinal products that are substrates of CYP1A2, CYP2B6, CYP2C8, 

CYP2C9, CYP2C19, CYP2D6, and CYP2E1. For administration of medicinal products that are 

substrates of CYP3A4 with a narrow therapeutic range, see section 4.5.  

 

Lurasidone is an in vitro substrate of the efflux transporters P-gp and BCRP. Lurasidone is not subject 

to active uptake transport by OATP1B1 or OATP1B3.  

 

Lurasidone is an inhibitor of P-gp, BCRP and OCT1 in vitro (see section 4.5). Lurasidone is not 

expected to have a clinically relevant inhibitory potential on transporters OATP1B1, OATP1B3, 

OCT2, OAT1, OAT3, MATE1, MATE2K or BSEP based on in vitro data. 

 

Elimination 

 

Following administration of lurasidone, the elimination half-life was 20-40 hours. Following oral 

administration of a radiolabelled dose, approximately 67% dose was recovered in faeces and 19% in 

urine. Urine comprised mostly of a number of metabolites with minimal renal excretion of parent 

compound.  

 

Linearity/non-linearity 

 

The pharmacokinetics of lurasidone is dose-proportional within a total daily dose range of 18.5 mg to 

148 mg. Steady-state concentrations of lurasidone are reached within 7 days of starting lurasidone. 



47 

 

Pharmacokinetics in special patient groups: 

 

Elderly people 

Limited data have been collected in healthy subjects ≥ 65 years. Of the data collected, similar 

exposure was obtained compared with subjects < 65 years. However, an increase in exposure in 

elderly subjects may be expected for patients if they have impaired renal or hepatic function.  

 

Hepatic impairment 

The serum concentrations of lurasidone are increased in healthy subjects with Child-Pugh Class A, B 

and C hepatic impairment with an increased exposure of 1.5-, 1.7- and 3-fold respectively. 

 

Renal impairment 

The serum concentrations of lurasidone are increased in healthy subjects with mild, moderate and 

severe renal impairment with an increased exposure of 1.5, 1.9 and 2.0-fold respectively. Subjects 

with ESRD (CrCl<15 ml/min) have not been investigated. 

 

Gender 

There were no clinically relevant differences between genders in the pharmacokinetics of lurasidone in 

a population pharmacokinetic analysis in patients with schizophrenia. 

 

Race 

There were no clinically relevant differences in the pharmacokinetics of lurasidone in a population 

pharmacokinetic analysis in patients with schizophrenia. It was noted that Asian subjects had 1.5 fold 

increased exposure to lurasidone compared to Caucasian subjects. 

 

Smoking 

Based on in vitro studies utilising human liver enzymes, lurasidone is not a substrate for CYP1A2; 

smoking should, therefore, not have an effect on the pharmacokinetics of lurasidone. 

 

Paediatric population 

The pharmacokinetics of lurasidone in paediatric patients was investigated in 49 children aged 

6-12 years and 56 adolescents aged 13-17 years. Lurasidone was administered as lurasidone 

hydrochloride at daily doses of either 20, 40, 80, 120 mg (6-17 years) or 160 mg (10-17 years only) for 

7 days. There was no clear correlation between obtained plasma exposure and age or body weight. The 

pharmacokinetics of lurasidone in paediatric patients aged 6–17 years was generally comparable to 

those observed in adults. 

 

5.3 Preclinical safety data 

 

Nonclinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Major findings in 

repeat-dose toxicity studies of lurasidone were centrally-mediated endocrine changes resulting from 

serum prolactin elevations in rats, dogs and monkeys. High serum prolactin levels in long-term 

repeat-dose studies in female rats were associated with effects on bones, adrenal glands, and 

reproductive tissues. In a long-term dog repeat-dose study, high serum prolactin levels were associated 

with effects on male and female reproductive tissues. 

 

In rats, lurasidone had no effect on male and female reproduction at oral doses of 150 and 

0.1 mg/kg/day lurasidone hydrochloride, respectively, or on early embryonic development at an oral 

dose of 15 mg/kg/day lurasidone hydrochloride.  

 

A fertility study in female rats resulted in prolonged oestrous cycle and delayed copulation at 

≥1.5 mg/kg/day lurasidone hydrochloride, whilst the copulation and fertility indices, and the numbers 

of corpora lutea, implantations and live foetuses were decreased at 150 mg/kg/day lurasidone 

hydrochloride. These effects were due to the hyperprolactinemia following lurasidone treatment, 

affecting the oestrous cycle and copulatory behaviour as well as the maintenance of corpus luteum of 



48 

the female rats, resulting in a decrease in implantation and the number of live foetuses. These 

prolactin-related effects are not considered to be relevant to human reproduction. 

 

A single dose of 10 mg/kg lurasidone hydrochloride to pregnant rats resulted in fetal exposure. In a 

dose range finding study in pregnant rats, 150 mg/kg/day lurasidone hydrochloride caused fetal growth 

retardation without signs of teratogenicity. Lurasidone was not teratogenic in rats or rabbits at an 

exposure similar to or below the maximum recommended human dose (148 mg lurasidone). 

 

Lurasidone was excreted in milk of rats during lactation. 

 

Lurasidone was not genotoxic in a battery of tests. Mammary gland and/or pituitary gland tumours 

were observed in the mouse and rat carcinogenicity studies and are most likely due to the increased 

blood prolactin levels. These findings are common in rodents treated with antipsychotic medicinal 

products with dopamine D2 blocking activity and are considered to be rodent-specific.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Core 

Mannitol (E 421) 

Starch, pregelatinised  

Croscarmellose sodium (E468) 

Hypromellose 2910 (E 464) 

Magnesium stearate (E 470b) 

 

Tablet coating 

Hypromellose 2910 (E 464) 

Titanium dioxide (E 171) 

Macrogol 8000 

Iron oxide, Yellow (E 172) 

Indigotine (E 132) 

Carnauba wax (E 903) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

5 years 

 

6.4 Special precautions for storage 

 

Store in the original package in order to protect from light.  

 

6.5 Nature and contents of container 

 

Cartons contain 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1 or 98 x 1 tablets in aluminium/aluminium 

perforated unit dose blisters. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 



49 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/015-021 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 21 March 2014 

Date of latest renewal: 14 November 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


50 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



51 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

AndersonBrecon (UK) Ltd. 

Units 2-7 

Wye Valley Business Park 

Brecon Road 

Hay-on-Wye 

Hereford 

HR3 5PG 

United Kingdom 

 

Aziende Chimiche Riunite Angelini Francesco ACRAF SPA 

Via Vecchia del Pinocchio, 22 60100 

Ancona (AN), Italy 

 

Millmount Healthcare Ltd. 

Block-7, City North Business Campus, 

Stamullen, Co. Meath, K32 YD60, 

Ireland 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to medical prescription. 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
The requirements for submission of periodic safety update reports for this medicinal product are 

set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 

Directive 2001/83/EC and any subsequent updates published on the European medicines web-

portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT  

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached.  
 

 



52 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



53 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



54 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 18.5 mg film-coated tablets 

lurasidone  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to18.6 mg lurasidone. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 x 1 film-coated tablets 

28 x 1 film-coated tablets 

30 x 1 film-coated tablets 

56 x 1 film-coated tablets 

60 x 1 film-coated tablets 

90 x 1 film-coated tablets 

98 x 1 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



55 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/001 14 x 1 film-coated tablets 

EU/1/14/913/002 28 x 1 film-coated tablets 

EU/1/14/913/003 30 x 1 film-coated tablets 

EU/1/14/913/004 56 x 1 film-coated tablets 

EU/1/14/913/005 60 x 1 film-coated tablets 

EU/1/14/913/006 90 x 1 film-coated tablets 

EU/1/14/913/007 98 x 1 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Latuda 18.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 



56 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 18.5 mg tablets 

lurasidone  

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

A.C.R.A.F. S.p.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



57 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 37 mg film-coated tablets 

lurasidone  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to 37.2 mg lurasidone. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 x 1 film-coated tablets 

28 x 1 film-coated tablets 

30 x 1 film-coated tablets 

56 x 1 film-coated tablets 

60 x 1 film-coated tablets 

90 x 1 film-coated tablets 

98 x 1 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



58 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/008 14 x 1 film-coated tablets 

EU/1/14/913/009 28 x 1 film-coated tablets 

EU/1/14/913/010 30 x 1 film-coated tablets 

EU/1/14/913/011 56 x 1 film-coated tablets 

EU/1/14/913/012 60 x 1 film-coated tablets 

EU/1/14/913/013 90 x 1 film-coated tablets 

EU/1/14/913/014 98 x 1 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Latuda 37 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 



59 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 37 mg tablets 

lurasidone  

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

A.C.R.A.F. S.p.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



60 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 74 mg film-coated tablets 

lurasidone  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains lurasidone hydrochloride equivalent to 74.5 mg lurasidone.  

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 x 1 film-coated tablets 

28 x 1 film-coated tablets 

30 x 1 film-coated tablets 

56 x 1 film-coated tablets 

60 x 1 film-coated tablets 

90 x 1 film-coated tablets 

98 x 1 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



61 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original package in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/14/913/015 14 x 1 film-coated tablets 

EU/1/14/913/016 28 x 1 film-coated tablets 

EU/1/14/913/017 30 x 1 film-coated tablets 

EU/1/14/913/018 56 x 1 film-coated tablets 

EU/1/14/913/019 60 x 1 film-coated tablets 

EU/1/14/913/020 90 x 1 film-coated tablets 

EU/1/14/913/021 98 x 1 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Latuda 74 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 



62 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Latuda 74 mg tablets 

lurasidone  

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

A.C.R.A.F. S.p.A.  

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



63 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



64 

Package leaflet: Information for the patient 
 

Latuda 18.5 mg film-coated tablets 

Latuda 37 mg film-coated tablets 

Latuda 74 mg film-coated tablets 
lurasidone 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 
1. What Latuda is and what it is used for  

2. What you need to know before you take Latuda 

3. How to take Latuda 

4. Possible side effects  

5. How to store Latuda 

6. Contents of the pack and other information 

 

 

1. What Latuda is and what it is used for 

 

Latuda contains the active substance lurasidone and belongs to a group of medicines called 

antipsychotics. It is used to treat symptoms of schizophrenia in adults aged 18 years or over. 

Lurasidone works by blocking receptors in the brain to which the substances dopamine and serotonin 

attach. Dopamine and serotonin are neurotransmitters (substances that allow nerve cells to 

communicate with each other) that are involved in the symptoms of schizophrenia. By blocking their 

receptors, lurasidone helps to normalise the activity of the brain, reducing the symptoms of 

schizophrenia. 

 

Schizophrenia is a disorder with symptoms such as hearing things, seeing or sensing things that are not 

there, mistaken beliefs, unusual suspiciousness, becoming withdrawn, incoherent speech and 

behaviour and emotional flatness. People with this disorder may also feel depressed, anxious, guilty, 

or tense. This medicine is used to improve your symptoms of schizophrenia. 

 

 

2. What you need to know before you take Latuda 

 

Do NOT take Latuda if you: 

 are allergic to lurasidone or any of the other ingredients of this medicine (listed in section 6) 

 are taking medicines which may affect the level of lurasidone in your blood such as: 
- medicines for fungal infections such as itraconazole, ketoconazole (except as a shampoo), 

posaconazole or voriconazole 

- medicines for an infection such as the antibiotic clarithromycin or telithromycin 
- medicines for HIV infections such as cobicistat, indinavir, nelfinavir, ritonavir, and 

saquinavir 

- boceprevir, and telaprevir (medicines for chronic hepatitis) 
- nefazodone (a medicine for depression)  
- rifampicin (a medicine for tuberculosis)  
- carbamazepine, phenobarbital and phenytoin (medicines for seizures) 
- St John’s wort (Hypericum perforatum) (herbal medicine for depression). 

 



65 

Warnings and precautions  

It may take several days or even weeks before this medicine will have a full effect. Contact your 

doctor if you have questions on this medicine. 

 

Talk to your doctor or pharmacist before taking this medicine, or during treatment, especially if you 

have: 

 Suicidal  thoughts or behaviour  

 Parkinson’s disease or dementia  

 ever been diagnosed with a condition whose symptoms include high temperature and muscle 
stiffness (also known as neuroleptic malignant syndrome) or if you have ever experienced 

rigidity, tremors or problems moving (extrapyramidal symptoms) or abnormal movements of 

the tongue or face (tardive dyskinesia). You should be aware that these conditions may be 

caused by this medicine  

 heart disease or heart disease treatment that makes you prone to low blood pressure or have a 
family history of irregular heart beat (including QT prolongation) 

 a history of seizures (fits) or epilepsy 

 a history of blood clots, or if someone else in your family has a history of blood clots, as 
medicines for schizophrenia have been associated with formation of blood clots  

 enlarged breasts in male (gynecomastia), milky nipple discharge (galactorrhea), absence of 
menstruation (amenorrhea) or erectile dysfunction 

 diabetes or are prone to diabetes  

 decreased kidney function  

 decreased liver function 

 an increase in your weight 

 blood pressure dropping upon your standing up which may cause fainting.  
 

If you have any of these conditions, please talk to your doctor as he/she may want to adjust your dose, 

monitor you more closely or stop treatment with Latuda.  

 

Children and adolescents  

This medicine is not recommended for children and adolescents under 18 years due to the lack of data 

in these patients. 

 

Other medicines and Latuda 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This is especially important if you are taking:  

 

 any medicines that also work in the brain, as their effects could be additive in a negative way 
with the effects of Latuda on your brain  

 medicines that lower blood pressure, as this medicine can also lower blood pressure 

 medicines for Parkinson’s disease and restless legs syndrome (e.g. levodopa) as this medicine 
can reduce their effects 

 medicines containing ergot alkaloid derivatives (used for treating migraines), and other 
medicines including terfenadine and astemizole (used for treating hay fever and other allergic 

conditions), cisapride (used for treating digestive problems), pimozide (used to treating 

psychiatric illnesses), quinidine (used for treating heart conditions), bepridil (used for treating 

chest pain). 

 

Tell your doctor if you take any of these medicines since your doctor may have to change the dose of 

that medicine during treatment with Latuda. 

 

The following medicines may increase the level of lurasidone in your blood: 

 diltiazem (to treat high blood pressure) 

 erythromycin (to treat infections) 

 fluconazole (to treat fungal infections) 

 verapamil (to treat high blood pressure or chest pain). 



66 

 

The following medicines may decrease the level of lurasidone in your blood:  

 amprenavir, efavirenz, etravirine (to treat HIV infection) 

 aprepitant (to treat nausea and vomiting) 

 armodafinil, modafinil (to treat sleepiness) 

 bosentan (to treat high blood pressure or ulcers of the fingers) 

 nafcillin (to treat infections) 

 prednisone (to treat inflammatory disease)  

 rufinamide (to treat seizures).  
 

Tell your doctor if you take any of these medicines since your doctor may change your dose of Latuda. 

 

Latuda with food, drink and alcohol 

Alcohol should be avoided when taking this medicine. This is because alcohol will have an additive 

negative effect. 

Do not drink grapefruit juice while you are taking this medicine. Grapefruit can affect the way this 

medicine works. 

 

Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your 

doctor for advice before taking this medicine.  

 

You should not take this medicine during pregnancy unless this has been agreed with your doctor.  

 

If your doctor decides that the potential benefit of treatment during pregnancy justifies the potential 

risk to your unborn baby, your doctor will monitor your baby closely after birth. This is because the 

following symptoms may occur in newborn babies of mothers that have used lurasidone in the last 

trimester (last three months) of their pregnancy:  

 shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, and 
difficulty in feeding.  

 

If your baby develops any of these symptoms you should contact your doctor.  

 

It is not known if lurasidone passes into breast milk. Talk to your doctor if you are breast-feeding, or if 

you plan to breast-feed.  

 

Driving and using machines  

Sleepiness, dizziness and vision problems may occur during treatment with this medicine (see section 

4, Possible side effects). Do not drive or use any tools or machines until you know that this medicine 

does not affect you in a negative way. 

 

 

3. How to take Latuda 

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

Your dose will be decided by your doctor and may depend on: 

 how well you respond to a dose 

 if you are taking some other medicines (see section 2, Other medicines and Latuda) 

 if you have kidney or liver problems. 
 

The recommended starting dose is 37 mg once a day.  

The dose may be increased or decreased by your doctor within the dose range of 18.5 mg to 148 mg 

once a day. The maximum dose should not exceed 148 mg once a day.  

 



67 

Swallow your tablet(s) whole with water, in order to mask the bitter taste. You should take your dose 

regularly every day at the same time of the day, so that it is easier to remember it. You must take this 

medicine with food or just after eating, as this helps the body to take up the medicine and allows it to 

work better.  

 

If you take more Latuda than you should  
If you take more of this medicine than you should, contact your doctor immediately. You may 

experience sleepiness, tiredness, abnormal body movements, problems with standing and walking, 

dizziness from low blood pressure, and abnormal heart beats. 

  

If you forget to take Latuda 
Do not take a double dose to make up for a forgotten dose. If you miss one dose, take your next dose 

on the day after the missed dose. If you miss two or more doses, contact your doctor.  

 

If you stop taking Latuda 

If you stop taking this medicine you will lose the effects of the medicine. You should not stop this 

medicine unless told to do so by your doctor as your symptoms may return.  

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.  

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them.  

 

If you notice any of the following symptoms seek medical attention immediately:  

 a severe allergic reaction seen as fever, swollen mouth, face, lip or tongue, shortness of breath, 
itching, skin rash and sometimes a drop in blood pressure. These reactions are seen rarely (may 

affect up to 1 in 1,000 people). 

 

 A serious blistering rash affecting the skin, mouth, eyes and genitals (Stevens-Johnson 
syndrome) 

 

 Fever, sweating, muscle stiffness, and reduced consciousness. These could be symptoms of a 
condition known as neuroleptic malignant syndrome. These reactions are seen rarely (may 

affect up to 1 in 1,000 people). 

 

 Blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 
the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in 

breathing. If you notice any of these symptoms seek medical advice immediately. 

 

The following side effects may also happen: 

 

Very common (may affect more than 1 in 10 people): 

 feeling of restlessness and inability to sit still 

 sleepiness. 
 

Common (may affect up to 1 in 10 people):  

 Parkinsonism: This is a medical term that describes many symptoms which include increase in 
saliva secretion or watery mouth, drooling, jerks when bending the limbs, slow, reduced or 

impaired body movements, no expression in the face, muscle tightness, stiff neck, muscle 

stiffness, small, shuffling, hurried steps and lack of normal arm movements when walking, 

persistent blinking in response to tapping of the forehead (an abnormal reflex) 

 speech problems, unusual muscle movements; a collection of symptoms known as 
extrapyramidal symptoms (EPS) which typically will involve unusual purposeless involuntary 

muscle movements. 

 dizziness 



68 

 muscle spasms and stiffness 

 nausea (feeling sick), vomiting (being sick) 

 rash and itching 

 indigestion 

 dry mouth or excess saliva 

 abdominal pain 

 difficulty sleeping, tiredness, agitation and anxiety 

 weight gain 

 increase in creatine phosphokinase (an enzyme in muscles) seen in blood tests  

 increase in creatinine (a marker of kidney function) seen in blood tests. 
 

Uncommon (may affect up to 1 in 100 people):  

 slurred speech 

 nightmares 

 muscle aches 

 joint pains  

 problems walking 

 rigid posture 

 increased blood prolactin, increased blood glucose (blood sugar), increase in some liver 
enzymes, seen in blood tests 

 increased blood pressure  

 blood pressure dropping upon standing up which may cause fainting 

 fast heart beat 

 common cold 

 hot flush 

 blurred vision  

 reduced appetite 

 sweating 

 pain when passing urine. 

 uncontrollable movements of mouth, tongue and limbs (tardive dyskinesia) 

 low blood levels of sodium which can cause tiredness and confusion, muscle twitching, fits and 
coma (hyponatremia). 

 lack of energy (lethargy) 

 gas (flatulence) 

 neck pain 

 back pain 
 

Rare (may affect up to 1 in 1,000 people):  

 Rhabdomyolysis which is the breakdown of muscle fibres that leads to the release of muscle 
fibre contents (myoglobin) into the bloodstream, seen as muscle pain, being sick, being 

confused, an abnormal heart rate and rhythm, and possibly dark urine 

 increase in eosinophils (a type of white blood cell). 

 swelling beneath the skin surface (angioedema) 
 

Not known (frequency cannot be estimated from the available data): 

 reduced levels of white blood cells (which fight infection) and red blood cells (which carry 
oxygen around the body) 

 deliberate injury to oneself 

 sudden feelings of anxiety 

 sleep disorder  

 spinning sensation  

 seizure (fits) 

 chest pain 

 abnormal nerve impulses in the heart  



69 

 slow heart rate 

 diarrhoea 

 difficulty swallowing 

 irritation to lining of stomach 

 kidney failure 

 newborn babies may show the following: agitation, increase or decreases in muscle tone, 
tremor, sleepiness, breathing or feeding problems  

 abnormal breast enlargement, breast pain, milk secretion from breasts 

 problems with erections 

 painful or absence of menstrual periods 

 sudden death associated with heart disease. 
 

In elderly people with dementia, a small increase in the number of deaths has been reported for 

patients Reporting of side effects taking medicines for schizophrenia compared with those not 

receiving these medicines. 

 

Reporting of side effects  

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the following website: 

www.mhra.gov.uk/yellowcard.  By reporting side effects you can help provide more information on 

the safety of this medicine. 

 

 

5. How to store Latuda 

 

Keep this medicine out of the sight and reach of children.  

 

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

 

Store in the original package in order to protect from light.  

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Latuda contains  

 The active substance is lurasidone.  
Each 18.5 mg tablet contains lurasidone hydrochloride equivalent to 18.6 mg lurasidone. 

Each 37 mg tablet contains lurasidone hydrochloride equivalent to 37.2 mg lurasidone. 

Each 74 mg tablet contains lurasidone hydrochloride equivalent to 74.5 mg lurasidone. 

 The other ingredients are mannitol, pregelatinised starch, croscarmellose sodium, hypromellose, 
magnesium stearate (E470b), titanium dioxide (E171), macrogol, yellow iron oxide (E172) 

(present in 74 mg tablets), indigotine (E132) (present in 74 mg tablets) and carnauba wax 

(E903). 

 

What Latuda looks like and contents of the pack 

 Latuda 18.5 mg film-coated tablets are white to off-white, film-coated round tablets debossed 
with “LA” 

 Latuda 37 mg film-coated tablets are white to off-white, film-coated round tablets debossed 
with “LB” 

 Latuda 74 mg film-coated tablets are pale green, film-coated oval tablets debossed with “LD”. 
 

http://www.mhra.gov.uk/yellowcard


70 

Latuda film-coated tablets are available in pack sizes containing 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 

90 x 1 or 98 x 1 film-coated tablet in aluminium/aluminium perforated unit dose blisters. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rome - Italy 

 

Manufacturer 

AndersonBrecon (UK) Ltd. 

Units 2-7 

Wye Valley Business Park 

Brecon Road 

Hay-on-Wye 

Hereford 

HR3 5PG 

United Kingdom 

 

Aziende Chimiche Riunite Angelini Francesco ACRAF SPA 

Via Vecchia del Pinocchio, 22 60100 

Ancona (AN), Italy 

 

Millmount Healthcare Ltd. 

Block-7, City North Business Campus, 

Stamullen, Co. Meath, K32 YD60, 

Ireland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/ Belgique/ Belgien 
Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

 

Lithuania/ Lietuva  
Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com


71 

Bulgaria/ България 

Анджелини Фарма България ЕООД  

бул. Асен Йорданов 10 

София 1592 

Teл.: + 359 2 975 1395 

office@angelini.bg 

 

Luxembourg/ Luxemburg 
Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Czech Republic/ Česká republika 

Angelini Pharma Česká republika s.r.o.  

Páteřní 1216/7  

635 00 Brno, CZ 

Tel: + 420 546 123 111  

info@angelini.cz 

 

Hungary/ Magyarország  

Angelini Pharma Magyarország Kft 

Dayka Gábor u. 3., 214-215. számú iroda 

H-1118 Budapest 

Tel: + 36 1 336 1614 

office@angelini.hu 

Denmark/ Danmark  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Malta  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

 

Germany/ Deutschland  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Netherlands/ Nederland  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Estonia/ Eesti  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Norway/ Norge  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Greece/ Ελλάδα 

ANGELINI PHARMA HELLAS ABEE 

ΠΑΡΑΓΩΓΗΣ & ΕΜΠΟΡΙΑΣ ΦΑΡΜΑΚΩΝ 

Aχαίας 4 & Τροιζηνίας  

GR-14564 Νέα Κηφισιά 

Τηλ: + 30 210 626 9200 

info@angelinipharma.gr 

 

Austria/ Österreich  

Angelini Pharma Österreich GmbH 

Brigittenauer Lände 50-54 

1200 Wien 

Tel: + 43 5 9606 0 

office@angelini.at 

 

Spain/ España 

ANGELINI PHARMA ESPAÑA, S.L. 

C. Osi, 7  

E-08034 Barcelona 

Tel: + 34 93 253 45 00 

 

Poland/ Polska  

Angelini Pharma Polska Sp. z o.o. 

ul. Podleśna 83 

05-552 Łazy  

Tel.: + 48 22 70 28 200 

angelini@angelini.pl 

 

France  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

 

Portugal  

Angelini Farmacêutica, Lda 

Rua João Chagas, 53, Piso 3 

1499-040 Cruz Quebrada- Dafundo 

Tel: + 351 21 414 8300 

apoio.utente@angelini.pt 

 

mailto:office@angelini.bg
mailto:med.infoeu@sunovion.com
mailto:info@angelini.cz
mailto:office@angelini.hu
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:info@angelinipharma.gr
mailto:office@angelini.at
mailto:angelini@angelini.pl
mailto:med.infoeu@sunovion.com
mailto:apoio.utente@angelini.pt


72 

Croatia/ Hrvatska 

Aziende Chimiche Riunite Angelini Francesco 

– A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rim - Italija 

Tel: + 39 06 78 0531 

 

Romania/ România  

Angelini Pharmaceuticals România SRL 

Str. Carol Davila, Nr. 9, Sector 5 

RO-București 050451 

Tel: + 40 21 331 6767 

office@angelini.ro 

 

Ireland  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Slovenia/ Slovenija  

Aziende Chimiche Riunite Angelini Francesco 

– A.C.R.A.F. S.p.A. 

Viale Amelia 70, 00181 

Rim - Italija 

Tel: + 39 06 78 0531 

 

Iceland/ Ísland  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Slovak republic/ Slovenská republika  

Angelini Pharma Slovenská republika s.r.o.  

Júnová 33 

SK-831 01 Bratislava 

Tel: + 421 2 59 207 320 

office@angelini.sk  

 

Italy/ Italia 

Angelini S.p.A 

Viale Amelia 70 

I-00181 Roma 

Tel: + 39 06 78 0531 

 

Suomi/ Finland  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Cyprus/Κύπρος 

ANGELINI PHARMA HELLAS ABEE 

ΠΑΡΑΓΩΓΗΣ & ΕΜΠΟΡΙΑΣ ΦΑΡΜΑΚΩΝ 

Aχαίας 4 & Τροιζηνίας  

GR-14564 Νέα Κηφισιά 

Τηλ: + 30 210 626 9200 

info@angelinipharma.gr 

 

Sweden/ Sverige  

Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

Latvia/ Latvija  
Sunovion Pharmaceuticals Netherlands B.V. 

Prins Bernhardplein 200  

1097 JB Amsterdam, Netherlands 

med.infoeu@sunovion.com 

 

United Kingdom  
Sunovion Pharmaceuticals Europe Ltd.  

Tel: +44 (0) 207 821 2899 

 

 

This leaflet was last revised in MM/YYYY 
 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

mailto:office@angelini.ro
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
mailto:info@angelinipharma.gr
mailto:med.infoeu@sunovion.com
mailto:med.infoeu@sunovion.com
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET