Invega · 4.3 Contraindications · 1

HOS-154168 · has-adverse-reaction-information · PDF-Seite 9

Adults Summary of the safety profile The adverse drug reactions (ADRs) most frequently reported in clinical trials with adults were headache, insomnia, sedation/somnolence, parkinsonism, akathisia, tachycardia, tremor, dystonia, upper respiratory tract infection, anxiety, dizziness, weight increased, nausea, agitation, constipation, vomiting, fatigue, depression, dyspepsia, diarrhoea, dry mouth, toothache, musculoskeletal pain, hypertension, asthenia, back pain, electrocardiogram QT prolonged, and cough. The ADRs that appeared to be dose-related included headache, sedation/somnolence, parkinsonism, akathisia, tachycardia, dystonia, dizziness, tremor, upper respiratory tract infection, dyspepsia, and musculoskeletal pain. In the schizoaffective disorder studies, a greater proportion of subjects in the total INVEGA dose group who were receiving concomitant therapy with an antidepressant or mood stabiliser experienced adverse events as compared to those subjects treated with INVEGA monotherapy. Tabulated list of adverse reactions The following are all the ADRs that were reported in clinical trials and post-marketing experience with paliperidone by frequency category estimated from INVEGA clinical trials in adults. 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. System Organ Adverse Drug Reaction Class Frequency Very Common Uncommon Rare Not known common Infections and bronchitis, upper pneumonia, eye infection, infestations respiratory tract respiratory tract onychomycosis, infection, infection, cystitis, cellulitis, sinusitis, urinary ear infection, acarodermatitis tract infection, tonsillitis influenza Blood and white blood cell agranulocytosisc, lymphatic count decreased, ne

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HOS-154164 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance, risperidone, or to any of the excipients listed in section 6.1.

HOS-154163 · has-indication-information · PDF-Seite 2

INVEGA is indicated for the treatment of schizophrenia in adults and in adolescents 15 years and older. INVEGA is indicated for the treatment of schizoaffective disorder in adults.

HOS-154166 · has-interaction-information · PDF-Seite 7

Caution is advised when prescribing INVEGA with medicines 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). Potential for INVEGA to affect other medicines Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicines that are metabolised by cytochrome P-450 isozymes. In vitro studies indicate that paliperidone is not an inducer of CYP1A2 activity. Given the primary CNS effects of paliperidone (see section 4.8), INVEGA should be used with caution in combination with other centrally acting medicines, e.g., anxiolytics, most antipsychotics, hypnotics, opiates, etc. or alcohol. Paliperidone may antagonise the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson’s disease, the lowest effective dose of each treatment should be prescribed. Because of its potential for inducing orthostatic hypotension (see section 4.4), an additive effect may be observed when INVEGA is administered with other therapeutic agents that have this potential, e.g., other antipsychotics, tricyclics. Caution is advised if paliperidone is combined with other medicines known to lower the seizure threshold (i.e., phenothiazines or butyrophenones, clozapine, tricyclics or SSRIs, tramadol, mefloquine, etc.). No interaction study between INVEGA and lithium has been performed, however, a pharmacokinetic interaction is unlikely to occur. Co-administration of INVEGA 12 mg once daily with divalproex sodium prolonged-release tablets (500 mg to 2,000 mg once daily) did not affect the steady-state pharmacokinetics of valproate. Co-administration of INVEGA with divalproex sodium prolonged-release tablets increased the exposure to paliperidone (see below). 7 Potential for other medicines to affect INVEGA In vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, but there are no indications in vitro nor in vivo that these isozymes play a significant role in the metabolism of paliperidone. Concomitant administration of INVEGA with paroxetine, a potent CYP2D6 inhibitor, showed no clinically significant effect on the pharmacokinetics of paliperidone. In vitro studies have shown that paliperidone i

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HOS-154167 · has-pregnancy-information · PDF-Seite 8

Pregnancy There are no adequate data from the use of paliperidone during pregnancy. Paliperidone was not teratogenic in animal studies, but other types of reproductive toxicity were observed (see section 5.3). Neonates exposed to antipsychotics (including paliperidone) during the third trimester of pregnancy 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. INVEGA should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly. 8 Breast-feeding Paliperidone is excreted in the breast milk to such an extent that effects on the breast-fed infant are likely if therapeutic doses are administered to breast-feeding women. INVEGA should not be used while breast feeding. Fertility There were no relevant effects observed in the non-clinical studies.

HOS-154165 · has-warning-information · PDF-Seite 4

Patients with schizoaffective disorder treated with paliperidone should be carefully monitored for a potential switch from manic to depressive symptoms. QT interval Caution should be exercised when INVEGA is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicines thought to prolong the QT interval. Neuroleptic malignant syndrome Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness, and elevated serum creatine phosphokinase levels has been reported to occur with paliperidone. Additional clinical signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs or symptoms indicative of NMS, all antipsychotics, including INVEGA, should be discontinued. Tardive dyskinesia/extrapyramidal symptoms Medicines 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 INVEGA, should be considered. Caution is warranted in patients receiving both, psychostimulants (e.g., methylphenidate) and paliperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both medications. Gradual withdrawal of stimulant treatment is recommended (see section 4.5). Leucopenia, neutropenia, and agranulocytosis Events of leucopenia, neutropenia, and agranulocytosis have been reported with antipsychotic agents, including INVEGA. Agranulocytosis has been reported very rarely (< 1/10 000 patients) during post-marketing surveillance. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leucopenia/neutropenia should be monitored during the first few months of therapy and discontinuation of INVEGA should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1 x 109/L) should discontinue INVEGA and have their WBC followed until recovery. Hyperglycaemia and diabetes mellitus

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