Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Hypersensitivity to the active substance, risperidone, or to any of the excipients listed in section 6.1.
Patients with schizoaffective disorder treated with paliperidone should be carefully monitored for a potential switch from manic to depressive symptoms.
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 (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.
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).
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 × 109/L) should discontinue INVEGA and have their WBC followed until recovery.
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, including INVEGA, 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.
Significant weight gain has been reported with INVEGA use. Weight should be monitored regularly.
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.
Paliperidone may induce orthostatic hypotension in some patients based on its alpha-blocking activity. Based on pooled data from the three, placebo-controlled, 6-week, fixed-dose trials with INVEGA (3, 6, 9, and 12 mg), orthostatic hypotension was reported by 2.5% of subjects treated with INVEGA compared with 0.8% of subjects treated with placebo. INVEGA 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).
INVEGA should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Because the INVEGA tablet is non-deformable and does not appreciably change shape in the gastrointestinal tract, INVEGA 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. There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of medicines in non-deformable controlled-release formulations. Due to the controlled-release design of the dosage form, INVEGA should only be used in patients who are able to swallow the tablet whole.
Conditions leading to shorter gastrointestinal transit time, e.g. diseases associated with chronic severe diarrhoea, may result in a reduced absorption of paliperidone.
The plasma concentrations of paliperidone are increased in patients with renal impairment and, therefore, dosage adjustment may be required in some patients (see sections 4.2 and 5.2). 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.
No data are available in patients with severe hepatic impairment (Child-Pugh class C). Caution is recommended if paliperidone is used in such patients.
INVEGA has not been studied in elderly patients with dementia. The experience from risperidone is considered valid also for paliperidone.
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.
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. INVEGA should be used with caution in elderly patients with dementia who have risk factors for stroke.
Physicians should weigh the risks versus the benefits when prescribing INVEGA 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.
Antipsychotic medicinal products (including risperidone) with α-adrenergic blocking effects have been reported to induce priapism. During post-marketing 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.
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.
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 INVEGA and preventive measures undertaken.
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.
The sedative effect of INVEGA should be closely monitored in this population. A change in the time of administration of INVEGA 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.
During treatment with INVEGA regular examination for extrapyramidal symptoms and other movement disorders should also be conducted.
For specific posology recommendations in the paediatric population see section 4.2.
Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with alpha 1a-adrenergic antagonist effect, such as INVEGA (see section 4.8).
IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with alpha 1a-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha 1 blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially sodium-free.
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).
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).
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 is a P-glycoprotein (P-gp) substrate.
Co-administration of INVEGA once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone likely as a result of induction of renal P-gp by carbamazepine. A minor decrease in the amount of active substance excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration. Larger decreases in plasma concentrations of paliperidone could occur with higher doses of carbamazepine. On initiation of carbamazepine, the dose of INVEGA should be re-evaluated and increased if necessary. Conversely, on discontinuation of carbamazepine, the dose of INVEGA should be re-evaluated and decreased if necessary. It takes 2-3 weeks for full induction to be achieved and upon discontinuation of the inducer the effect wears off over a similar time period. Other medicinal products or herbals which are inducers, e.g. rifampicin and St John’s wort (Hypericum perforatum) may have similar effects on paliperidone.
Medicinal products affecting gastrointestinal transit time may affect the absorption of paliperidone, e.g. metoclopramide.
Co-administration of a single dose of INVEGA 12 mg with divalproex sodium prolonged-release tablets (two 500 mg tablets once daily) resulted in an increase of approximately 50% in the Cmax and AUC of paliperidone. Dosage reduction for INVEGA should be considered when INVEGA is co-administered with valproate after clinical assessment.
Concomitant use of INVEGA with oral risperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive paliperidone exposure.
The combined use of psychostimulants (e.g. methylphenidate) with paliperidone can lead to extrapyramidal symptoms upon change of either or both treatments (see section 4.4).
Interaction studies have only been performed in adults.
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.
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.
There were no relevant effects observed in the non-clinical studies.
Paliperidone can have minor or moderate influence on the ability to drive and use machines due to potential nervous system and visual effects (see section 4.8). Therefore, patients should be advised not to drive or operate machines until their individual susceptibility to INVEGA is known.
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.
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 Class | Adverse Drug Reaction | ||||
|---|---|---|---|---|---|
| Frequency | |||||
| Very common | Common | Uncommon | Rare | Not known | |
| Infections and infestations | bronchitis, upper respiratory tract infection, sinusitis, urinary tract infection, influenza | pneumonia, respiratory tract infection, cystitis, ear infection, tonsillitis | eye infection, onychomycosis, cellulitis, acarodermatitis | ||
| Blood and lymphatic system disorders | white blood cell count decreased, thrombocytopenia, anaemia, haematocrit decreased | agranulocytosisc, neutropenia, eosinophil count increased | |||
| Immune system disorders | anaphylactic reaction, hypersensitivity | ||||
| Endocrine disorders | hyperprolactinaemiaa | inappropriate antidiuretic hormone secretionc, glucose urine present | |||
| Metabolism and nutrition disorders | weight increased, increased appetite, weight decreased, decreased appetite | diabetes mellitusd, hyperglycaemia, waist circumference increased, anorexia, blood triglycerides increased | water intoxication, diabetic ketoacidosisc, hypoglycaemia, polydipsia, blood cholesterol increased | hyperinsulinaemia | |
| Psychiatric disorders | insomniae | mania, agitation, depression, anxiety | sleep disorder, confusional state, libido decreased, anorgasmia, nervousness, nightmare | catatonia, somnambulism, blunted affectc | |
| Nervous system disorders | parkinsonismb, akathisiab, sedation/ somnolence, headache | dystoniab, dizziness, dyskinesiab, tremorb | tardive dyskinesia, convulsione, syncope, psychomotor hyperactivity, dizziness postural, disturbance in attention, dysarthria, dysgeusia, hypoaesthesia, paresthaesia | neuroleptic malignant syndrome, cerebral ischaemia, unresponsive to stimulic, loss of consciousness, depressed level of consciousnessc, diabetic comac balance disorder, coordination abnormal, head titubationc | |
| Eye disorders | vision blurred | photophobia, conjunctivitis, dry eye | glaucoma, eye movement disorderc, eye rollingc, lacrimation increased, ocular hyperaemia | ||
| Ear and labyrinth disorders | vertigo, tinnitus, ear pain | ||||
| Cardiac disorders | atrioventricular block, conduction disorder, electrocardiogram QT prolonged, bradycardia, tachycardia | sinus arrhythmia, electrocardiogram abnormal, palpitations | atrial fibrillation, postural orthostatic tachycardia syndromec | ||
| Vascular disorders | orthostatic hypotension, hypertension | hypotension | pulmonary embolism, venous thrombosis, ischaemia, flushing | ||
| Respiratory, thoracic and mediastinal disorders | pharyngolaryngeal pain, cough, nasal congestion | dyspnoea, wheezing, epistaxis | sleep apnoea syndrome, hyperventilation, pneumonia aspiration, respiratory tract congestion, dysphonia | pulmonary congestion | |
| Gastrointestinal disorders | abdominal pain, abdominal discomfort, vomiting, nausea, constipation, diarrhoea, dyspepsia, dry mouth, toothache | swollen tongue, gastroenteritis, dysphagia, flatulence | pancreatitisc, intestinal obstruction, ileus, faecal incontinence, faecalomac, cheilitis | ||
| Hepatobiliary disorders | transaminases increased | gamma-glutamyltran sferase increased, hepatic enzyme increased | jaundice | ||
| Skin and subcutaneous tissue disorders | pruritus, rash | urticaria, alopecia, eczema, acne | angioedema, drug eruptionc, hyperkeratosis, dry skin, erythema, skin discolouration, seborrhoeic dermatitis, dandruff | ||
| Musculoskeletal and connective tissue disorders | musculoskeletal pain, back pain, arthralgia | blood creatine phosphokinase increased, muscle spasms, joint stiffness, joint swelling, muscular weakness, neck pain | rhabdomyolysisc, posture abnormalc | ||
| Renal and urinary disorders | urinary incontinence, pollakiuria, urinary retention, dysuria | ||||
| Pregnancy, puerperium and perinatal conditions | drug withdrawal syndrome neonatal (see section 4.6)c | ||||
| Reproductive system and breast disorders | amenorrhoea | erectile dysfunction, ejaculation disorder, menstrual disordere, galactorrhoea, sexual dysfunction, breast pain, breast discomfort | priapismc, menstruation delayedc, gynaecomastia, breast engorgement, breast enlargementc, breast discharge, vaginal discharge | ||
| General disorders | pyrexia, asthenia, fatigue | face oedema, oedemae, chills, body temperature increased, gait abnormal, thirst, chest pain, chest discomfort, malaise | hypothermiac, body temperature decreasedc, drug withdrawal syndromec, indurationc | ||
| Injury, poisoning and procedural complications | fall | ||||
a Refer to ‘Hyperprolactinaemia’ below.
b Refer to ‘Extrapyramidal symptoms’ below.
c Not observed in INVEGA clinical studies but observed in post-marketing environment with paliperidone
d In placebo-controlled pivotal trials, diabetes mellitus was reported in 0.05% in INVEGA-treated subjects compared to a rate of 0% in placebo group. Overall incidence from all clinical trials was 0.14% in all INVEGA-treated subjects
e Insomnia includes: initial insomnia, middle insomnia; Convulsion includes: grand mal convulsion; Oedema includes: generalised oedema, oedema peripheral, pitting oedema. Menstrual disorder includes: menstruation irregular, oligomenorrhoea
Paliperidone is the active metabolite of risperidone, therefore, the adverse reaction profiles of these compounds (including both the oral and injectable formulations) are relevant to one another. In addition to the above adverse reactions, the following adverse reactions have been noted with the use of risperdone products and can be expected to occur with INVEGA.
Psychiatric disorders: sleep-related eating disorder.
Nervous system disorders: cerebrovascular disorder.
Eye disorders: floppy iris syndrome (intraoperative).
Respiratory, thoracic and mediastinal disorders: rales.
In schizophrenia clinical trials, there was no difference observed between placebo and the 3 and 6 mg doses of INVEGA. Dose dependence for EPS was seen with the two higher doses of INVEGA (9 and 12 mg). In the schizoaffective disorder studies, the incidence of EPS was observed at a higher rate than placebo in all dose groups without a clear relationship to dose.
EPS included a pooled analysis of the following terms: Parkinsonism (includes salivary hypersecretion, musculoskeletal stiffness, parkinsonism, drooling, cogwheel rigidity, bradykinesia, hypokinesia, masked facies, muscle tightness, akinesia, nuchal rigidity, muscle rigidity, parkinsonian gait, and glabellar reflex abnormal, parkinsonian rest tremor), akathisia (includes akathisia, restlessness, hyperkinesia, and restless leg syndrome), dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis, and myoclonus), dystonia (includes dystonia, hypertonia, torticollis, muscle contractions involuntary, muscle contracture, blepharospasm, oculogyration, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue spasm, and trismus), and tremor. It should be noted that a broader spectrum of symptoms are included that do not necessarily have an extrapyramidal origin.
In schizophrenia clinical trials, the proportions of subjects meeting a weight gain criterion of ≥7% of body weight were compared, revealing a similar incidence of weight gain for INVEGA 3 mg and 6 mg compared with placebo, and a higher incidence of weight gain for INVEGA 9 mg and 12 mg compared with placebo.
In schizoaffective disorder clinical trials, a higher percentage of INVEGA-treated subjects (5%) had an increase in body weight of ≥7% compared with placebo-treated subjects (1%). In the study that examined two dose groups (see section 5.1), the increase in body weight of ≥7% was 3% in the lower-dose (3-6 mg) group, 7% in the higher-dose (9-12 mg) group, and 1% in the placebo group.
In schizophrenia clinical trials, increases in serum prolactin were observed with INVEGA in 67% of subjects. Adverse reactions that may suggest increase in prolactin levels (e.g. amenorrhoea, galactorrhoea, menstrual disturbances, gynaecomastia) were reported overall in 2% of subjects. Maximum mean increases of serum prolactin concentrations were generally observed on day 15 of treatment, but remained above baseline levels at study endpoint.
QT prolongation, ventricular arrythmias (ventricular fibrillation, ventricular tachycardia), sudden unexplained death, cardiac arrest and Torsade de pointes may occur with antipsychotics. Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown.
Paliperidone is the active metabolite of risperidone. The safety profile of risperidone may be pertinent.
In a study conducted in elderly subjects with schizophrenia, the safety profile was similar to that seen in non-elderly subjects. INVEGA has not been studied in elderly patients with dementia. In clinical trials with some other atypical antipsychotics, increased risks of death and cerebrovascular accidents have been reported (see section 4.4).
In one short-term and two longer-term studies with paliperidone prolonged-release tablets conducted in adolescents 12 years and older with schizophrenia, the overall safety profile was similar to that seen in adults. In the pooled adolescent schizophrenia population (12 years and older, N=545) exposed to INVEGA, the frequency and type of undesirable effects were similar to those in adults except for the following ADRs that were reported more frequently in adolescents receiving INVEGA than adults receiving INVEGA (and more frequently than placebo): sedation/somnolence, parkinsonism, weight increase, upper respiratory tract infection, akathisia, and tremor were reported very commonly (≥1/10) in adolescents; abdominal pain, galactorrhoea, gynaecomastia, acne, dysarthria, gastroenteritis, epistaxis, ear infection, blood triglyceride increased, and vertigo were reported commonly (≥1/100, <1/10) in adolescents.
In the short-term, placebo-controlled, fixed-dose adolescent study, the incidence of EPS was higher than placebo for all doses of INVEGA with an increased frequency of EPS at higher doses. Across all adolescent studies, EPS was more common in adolescents than in adults for each INVEGA dose.
In the short-term, placebo-controlled, fixed-dose adolescent study, a higher percentage of INVEGA-treated subjects (6-19% depending on dose) had an increase in body weight of ≥7% compared to placebo-treated subjects (2%). There was no clear dose relationship. In the long-term 2-year study, the subjects who were exposed to INVEGA during both the double-blind and open-label studies reported a modest weight gain (4.9 kg).
In adolescents, weight gain should be assessed against that expected with normal growth.
In the up to 2-year, open-label treatment study of INVEGA in adolescents with schizophrenia, incidence of elevated serum prolactin levels occurred in 48% of females and 60% of males. Adverse reactions that may suggest increase in prolactin levels (e.g. amenorrhoea, galactorrhoea, menstrual disturbances, gynaecomastia) were reported overall in 9.3% of subjects.
Reporting suspected adverse reactions after authorisation of the medical 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 national reporting system listed in Appendix V.
Not applicable.
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