Xeplion

HOS-095838 · has-adverse-reaction-information · PDF-Seite 30

Summary of the safety profile The adverse reactions most frequently reported in clinical trials were insomnia, headache, anxiety, upper respiratory tract infection, injection site reaction, parkinsonism, weight increased, akathisia, agitation, sedation/somnolence, nausea, constipation, dizziness, musculoskeletal pain, tachycardia, tremor, abdominal pain, vomiting, diarrhoea, fatigue, and dystonia. Of these, akathisia and sedation/somnolence appeared to be dose-related. Tabulated list of adverse reactions The following are all adverse reactions that were reported with paliperidone by frequency category estimated from paliperidone palmitate clinical trials. 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 30 (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); and not known (cannot be estimated from the available data). System Organ Adverse reactions Class Frequency Very Common Uncommon Rare Not knowna common Infections and upper respiratory pneumonia, eye infection, infestations tract infection, bronchitis, respiratory acarodermatitis urinary tract tract infection, infection, influenza sinusitis, cystitis, ear infection, tonsillitis, onychomycosis, cellulitis, subcutaneous abscess Blood and white blood cell count neutropenia, agranulocytosis lymphatic system decreased, anaemia thrombocytopenia disorders , eosinophil count increased Immune system hypersensitivity anaphylactic disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095832 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile The adverse reactions most frequently reported in clinical trials were insomnia, headache, anxiety, upper respiratory tract infection, injection site reaction, parkinsonism, weight increased, akathisia, agitation, sedation/somnolence, nausea, constipation, dizziness, musculoskeletal pain, tachycardia, tremor, abdominal pain, vomiting, diarrhoea, fatigue, and dystonia. Of these, akathisia and sedation/somnolence appeared to be dose-related. Tabulated list of adverse reactions The following are all adverse reactions that were reported with paliperidone by frequency category estimated from paliperidone palmitate clinical trials. 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). System Organ Adverse reactions Class Frequency Very Common Uncommon Rare Not knowna common Infections and upper respiratory pneumonia, bronchitis, eye infection, infestations tract infection, respiratory tract acarodermatitis urinary tract infection, sinusitis, infection, influenza cystitis, ear infection, tonsillitis, onychomycosis, cellulitis, subcutaneous abscess Blood and white blood cell count neutropenia, agranulocytosis lymphatic system decreased, anaemia thrombocytopenia, disorders eosinophil count increased Immune system hypersensitivity anaphylactic disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095828 · has-contraindication-information · PDF-Seite 6

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

HOS-095834 · has-contraindication-information · PDF-Seite 25

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

HOS-095827 · has-indication-information · PDF-Seite 2

Xeplion is indicated for maintenance treatment of schizophrenia in adult patients stabilised with paliperidone or risperidone. In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, Xeplion may be used without prior stabilisation with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed. 2

HOS-095833 · has-indication-information · PDF-Seite 22

Xeplion is indicated for maintenance treatment of schizophrenia in adult patients stabilised with paliperidone or risperidone. In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, Xeplion may be used without prior stabilisation with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed.

HOS-095830 · has-interaction-information · PDF-Seite 9

Caution is advised when prescribing Xeplion 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). This list is indicative and not exhaustive. Potential for Xeplion to affect other medicines Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicinal products that are metabolised by cytochrome P-450 isozymes. Given the primary central nervous system (CNS) effects of paliperidone (see section 4.8), Xeplion should be used with caution in combination with other centrally acting medicinal products, 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 Xeplion is administered with other therapeutic agents that have this potential, e.g., other antipsychotics, tricyclics. Caution is advised if paliperidone is combined with other medicinal products known to lower the seizure threshold (i.e., phenothiazines or butyrophenones, tricyclics or SSRIs, tramadol, mefloquine, etc.). Co-administration of oral paliperidone prolonged release tablets at steady-state (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. No interaction study between Xeplion and lithium has been performed, however, a pharmacokinetic interaction is not likely to occur. Potential for other medicines to affect Xeplion 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 oral paliperidone with paroxetine, a potent CYP2D6 inhibitor, showed no clinically significant effect on the pharmacokinetics of paliperidone. Co-administration of oral paliperidone prolonged release once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095836 · has-interaction-information · PDF-Seite 28

Caution is advised when prescribing Xeplion 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). This list is indicative and not exhaustive. 28 Potential for Xeplion to affect other medicines Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicinal products that are metabolised by cytochrome P-450 isozymes. Given the primary central nervous system (CNS) effects of paliperidone (see section 4.8), Xeplion should be used with caution in combination with other centrally acting medicinal products, 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 Xeplion is administered with other therapeutic agents that have this potential, e.g., other antipsychotics, tricyclics. Caution is advised if paliperidone is combined with other medicinal products known to lower the seizure threshold (i.e., phenothiazines or butyrophenones, tricyclics or SSRIs, tramadol, mefloquine, etc.). Co-administration of oral paliperidone prolonged release tablets at steady-state (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. No interaction study between Xeplion and lithium has been performed, however, a pharmacokinetic interaction is not likely to occur. Potential for other medicines to affect Xeplion 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 oral paliperidone with paroxetine, a potent CYP2D6 inhibitor, showed no clinically significant effect on the pharmacokinetics of paliperidone. Co-administration of oral paliperidone prolonged release once daily with carbamazepine 200

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095831 · has-pregnancy-information · PDF-Seite 10

Pregnancy There are no adequate data from the use of paliperidone during pregnancy. Intramuscularly injected paliperidone palmitate and orally administered paliperidone were not teratogenic in animal studies, but other types of reproductive toxicity were seen (see section 5.3). Neonates exposed to 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. Xeplion should not be used during pregnancy unless clearly necessary. 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. Xeplion should not be used while breast-feeding. Fertility There were no relevant effects observed in the non-clinical studies.

HOS-095837 · has-pregnancy-information · PDF-Seite 30

Pregnancy There are no adequate data from the use of paliperidone during pregnancy. Intramuscularly injected paliperidone palmitate and orally administered paliperidone were not teratogenic in animal studies, but other types of reproductive toxicity were seen (see section 5.3). Neonates exposed to 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. Xeplion should not be used during pregnancy unless clearly necessary. 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. Xeplion should not be used while breast-feeding. Fertility There were no relevant effects observed in the non-clinical studies.

HOS-095829 · has-warning-information · PDF-Seite 6

Use in patients who are in an acutely agitated or severely psychotic state Xeplion should not be used to manage acutely agitated or severely psychotic states when immediate symptom control is warranted. QT interval Caution should be exercised when paliperidone is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products 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, paliperidone should be discontinued. Tardive dyskinesia/extrapyramidal symptoms 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 paliperidone, 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 Xeplion. 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 Xeplion 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 Xeplion and have their WBC followed until recovery. Hyper

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095835 · has-warning-information · PDF-Seite 25

Use in patients who are in an acutely agitated or severely psychotic state Xeplion should not be used to manage acutely agitated or severely psychotic states when immediate symptom control is warranted. QT interval Caution should be exercised when paliperidone is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QT interval. 25 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, paliperidone should be discontinued. Tardive dyskinesia/extrapyramidal symptoms 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 paliperidone, 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 Xeplion. 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 Xeplion 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

Auszug; vollständigen Abschnitt im Original lesen.