Invega

/ Janssen

Schizophrenia: The recommended dose of (paliperidone) Extended-Release Tablets for the treatment of schizophrenia is 6 mg once daily, administered in the morning. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day. In a longer-term study, this product has been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on this product for 6 weeks. this product should be prescribed at the lowest effective dose for maintaining clinical stability and the physician should periodically reevaluate the long-term usefulness of the drug in individual patients.
Schizoaffective Disorder: The recommended dose (paliperidone) Extended-Release Tablets for the treatment of schizoaffective disorder is 6 mg once daily, administered in the morning. Initial dose titration is not required. Some patients may benefit from lower or higher doses within the recommended dose range of 3 to 12 mg once daily. A general trend for greater effects was seen with higher doses. This trend must be weighed against dose-related increase in adverse reactions. Dosage adjustment, if indicated, should occur only after clinical reassessment. Dose increases, if indicated, generally should occur at intervals of more than 4 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.

Treatment of schizophrenia.

Known hypersensitivity to paliperidone, risperidone, or to any components in the formulation.

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 this medical product 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 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 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
Leukopenia, neutropenia, and agranulocytosis– Events of leucopenia, neutropenia, and agranulocytosis have been reported with antipsychotic agents, including paliperidone. 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 leukopenia/neutropenia should be monitored during the first few months of therapy and discontinuation of this medical product 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 this medical product and have their WBC followed until recovery.
Hyperglycemia and diabetes mellitus– Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes have been reported during treatment with paliperidone. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Association with ketoacidosis has been reported very rarely and rarely with diabetic coma. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any atypical antipsychotic should be monitored for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.
Weight gain–Significant weight gain has been reported with paliperidone use. Weight should be monitored regularly.
Hyperprolactinaemia– Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. Paliperidone should be used with caution in patients with possible prolactin-dependent tumours.
Orthostatic hypotension– This medical product should be used with caution in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction or ischaemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration and hypovolemia).
Seizures– Paliperidone should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Potential for gastrointestinal obstruction– this medical product, tablet is non-deformable and does not appreciably change shape in the gastrointestinal tract, this medical product should not ordinarily be administered to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic) or in patients with dysphagia or significant difficulty in swallowing tablets. Due to the controlled-release design of the dosage form, It’s should only be used in patients who are able to swallow the tablet whole.
Conditions with decreased gastro-intestinal transit time– Conditions leading to shorter gastrointestinal transit time, e.g., diseases associated with chronic severe diarrhoea, may result in a reduced absorption of paliperidone.
Renal impairment– The plasma concentrations of paliperidone are increased in patients with renal impairment and, therefore, dosage adjustment may be required in some patients. No data are available in patients with a creatinine clearance below 10 ml/min. Paliperidone should not be used in patients with creatinine clearance below 10 ml/min.
Elderly patients with dementia
Elderly patients with dementia- 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. Among those treated with risperidone, the mortality was 4% compared with 3.1% for placebo.
Cerebrovascular adverse reactions– An approximately 3-fold increased risk of cerebrovascular adverse reactions have 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. paliperidone should be used with caution in elderly patients with dementia who have risk factors for stroke.
Parkinson’s disease and dementia with Lewy bodies– Physicians should weigh the risks versus the benefits when prescribing this medical product to patients with Parkinson’s disease or Dementia with Lewy Bodies (DLB) since both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotics.
Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.
Priapism– Antipsychotic medicinal products (including risperidone) with α-adrenergic blocking effects have been reported to induce priapism. During postmarketing surveillance priapism has also been reported with paliperidone, which is the active metabolite of risperidone. Patients should be informed to seek urgent medical care in case that priapism has not been resolved within 3-4 hours.
Body temperature regulation– Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic medicinal products. Appropriate care is advised when prescribing INVEGA to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
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 this medical product and preventive measures undertaken.
Antiemetic effect– An antiemetic effect was observed in preclinical studies with paliperidone. This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain medicines or of conditions such as intestinal obstruction, Reye’s syndrome, and brain tumour.
Paediatric population– The sedative effect of paliperidone should be closely monitored in this population. A change in the time of administration of paliperidone may improve the impact of sedation on the patient. Because of the potential effects of prolonged hyperprolactinemia on growth and sexual maturation in adolescents, regular clinical evaluation of endocrinological status should be considered, including measurements of height, weight, sexual maturation, monitoring of menstrual functioning, and other potential prolactin-related effects.
Intraoperative Floppy Iris Syndrome– Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with alpha1a-adrenergic antagonist effect, such as paliperidone. IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with alpha1a-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha1 blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.
See prescribing information for full details

Very common: insomnia, parkinsonism, akathisia, sedation/somnolence, headache.
Common: bronchitis, upper respiratory tract infection, sinusitis, urinary tract infection, influenza, weight increased, increased appetite, weight decreased, decreased appetite, mania, agitation, depression, anxiety, dystonia, dizziness, dyskinesia, tremor, vision blurred, atrioventricular block, conduction disorder, electrocardiogram QT prolonged, bradycardia, tachycardia, orthostatic hypotension, hypertension, pharyngolaryngeal pain, cough, nasal congestion, abdominal pain, abdominal discomfort, vomiting, nausea, constipation, diarrhoea, dyspepsia, dry mouth, toothache, transaminases increased, pruritus, rash, musculoskeletal pain, back pain, arthralgia, amenorrhoea, pyrexia, asthenia, fatigue.
See prescribing information for full details

medicines known to prolong the QT interval, e.g., class IA antiarrhythmics, class III antiarrhythmics, some antihistaminics. Other centrally acting medicines, e.g. anxiolytics, most antipsychotics, hypnotics, opiates, etc. or alcohol. Levodopa and other dopamine agonists. Other antipsychotics, tricyclics. Other medicines known to lower the seizure threshold.

Fertility: There were no relevant effects observed in the non-clinical studies.
Pregnancy: There are no adequate data from the use of paliperidone during pregnancy. 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. This medical product should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly
Lactation: 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. This medical product should not be used while breast feeding.

In general, expected signs and symptoms are those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, QT prolongation, and extrapyramidal symptoms. Torsade de pointes and ventricular fibrillation have been reported in association with overdose. In the case of acute overdosage, the possibility of multiple medicinal product involvement should be considered.
Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. There is no specific antidote to paliperidone. General supportive measures should be employed. Establish and maintain a clear airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring for possible arrhythmias. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluid and/or sympathomimetic agents.
Administration of activated charcoal together with a laxative should be considered. In case of severe extrapyramidal symptoms, anticholinergic agents should be administered. Close supervision and monitoring should continue until the patient recovers.