Latuda · 4.4 Special warnings and precautions for use · 1

HOS-096614 · has-adverse-reaction-information · PDF-Seite 8

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, nausea and insomnia. 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 in Table 1 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 (≥ 1/1,000 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). Table 1: Adverse drug reactions (ADRs) Based Upon Pooled Data for Adults System Organ Very Common Uncommon Rare Frequency not Class Commo known n Infections and Nasopharyngiti infestations s Blood and Anaemia Eosinophilia Neutropenia*** lymphatic Leukopenia * system disorders Immune Hypersensitivit system y disorders Metabolism Weight Blood glucose and nutrition increased increased disorders Decreased Hyponatraemia appetite Psychiatric Insomni Agitation Nightmare Suicidal Sleep disorders a Anxiety Catatonia behaviour disorder**** Restlessness Panic attack Nervous Akathisi Somnolence* Lethargy Neuroleptic system a Parkinsonism* Dysarthria malignant disorders * Tardive syndrome Dizziness dyskinesia (NMS) Dystonia*** Syncope Cerebrovascula Dyskinesia Convulsion r accident Eye disorders

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HOS-096610 · has-contraindication-information · PDF-Seite 3

- 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). 3

HOS-096609 · has-indication-information · PDF-Seite 2

Latuda is indicated for the treatment of schizophrenia in adults and adolescent aged 13 years and over.

HOS-096612 · has-interaction-information · PDF-Seite 5

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). 5 Latuda should be used cautiously when co-administered with other serotonergic agents, such as buprenorphine/opioids, MAO inhibitors, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4). 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. 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

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HOS-096613 · has-pregnancy-information · PDF-Seite 7

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).

HOS-096611 · has-warning-information · PDF-Seite 4

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 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-

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