The short-term efficacy of INVEGA (3 to 15 mg once daily) was established in three placebo-controlled and active-controlled (olanzapine), 6-week, fixed-dose trials in non-elderly adult subjects (mean age of 37) who met DSM-IV criteria for schizophrenia:
Please see Hyperglycemia and Diabetes warning below.
The information below is derived from a clinical trial database for INVEGA consisting of 2720 patients and/or normal subjects exposed to one or more doses of INVEGA for the treatment of schizophrenia.
Of these 2720 patients, 2054 were patients who received INVEGA while participating in multiple dose, effectiveness trials. The conditions and duration of treatment with INVEGA varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and flexible-dose studies, and short-term and longer-term exposure. Adverse events were assessed by collecting adverse events and performing physical examinations, vital signs, weights, laboratory analyses and ECGs.
Adverse events during exposure were obtained by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.
The stated frequencies of adverse events represent the proportions of individuals who experienced a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
The information presented in these sections was derived from pooled data from the three placebo-controlled, 6-week, fixed-dose studies based on subjects with schizophrenia who received INVEGA at daily doses within the recommended range of 3 to 12 mg (n = 850).
Table 1 enumerates the pooled incidences of treatment-emergent adverse events that were spontaneously reported in the three placebo-controlled, 6-week, fixed-dose studies, listing those events that occurred in 2% or more of subjects treated with INVEGA in any of the dose groups, and for which the incidence in INVEGA-treated subjects in any of the dose groups was greater than the incidence in subjects treated with placebo.
| Percentage of Patients Reporting Event | |||||
| INVEGA | |||||
| Placebo | 3 mg once daily |
6 mg once daily |
9 mg once daily |
12 mg once daily |
|
| Body System or Organ Class | (N=355) | (N=127) | (N=235) | (N=246) | (N=242) |
| Dictionary-Derived Term | |||||
| Percentage of subjects with adverse events |
66 | 72 | 66 | 70 | 76 |
| Cardiac disorders | |||||
| Atrioventricular block first degree | 1 | 2 | 0 | 2 | 1 |
| Bundle branch block | 2 | 3 | 1 | 3 | <1 |
| Sinus arrhythmia | 0 | 2 | 1 | 1 | <1 |
| Tachycardia | 7 | 14 | 12 | 12 | 14 |
| Eye disorders | |||||
| Vision blurred | 1 | 1 | <1 | 0 | 2 |
| Gastrointestinal disorders | |||||
| Abdominal pain upper | 1 | 1 | 3 | 2 | 2 |
| Dry mouth | 1 | 2 | 3 | 1 | 3 |
| Dyspepsia | 4 | 2 | 3 | 2 | 5 |
| Nausea | 5 | 6 | 4 | 4 | 4 |
| Salivary hypersecretion | <1 | 0 | <1 | 1 | 4 |
| General disorders | |||||
| Asthenia | 1 | 1 | <1 | 2 | 2 |
| Fatigue | 1 | 2 | 1 | 2 | 2 |
| Pyrexia | 1 | 1 | <1 | 2 | 2 |
| Investigations | |||||
| Blood insulin increased | 1 | 2 | 1 | 1 | <1 |
| Blood pressure increased | 1 | 2 | <1 | <1 | 1 |
| Electrocardiogram QT corrected interval progonged | 3 | 3 | 4 | 3 | 5 |
| Electrocardiogram T wave abnormal | 1 | 2 | 1 | 2 | 1 |
| Musculoskeletal and connective tissue disorders | |||||
| Back pain | 1 | 1 | 1 | 1 | 2 |
| Pain in extremity | 1 | 0 | 1 | 0 | 2 |
| Nervous system disorders | |||||
| Akathisia | 4 | 4 | 3 | 8 | 10 |
| Dizziness | 4 | 6 | 5 | 4 | 5 |
| Dystonia | 1 | 1 | 1 | 5 | 4 |
| Extrapyramidal disorder | 2 | 5 | 2 | 7 | 7 |
| Headache | 12 | 11 | 12 | 14 | 14 |
| Hypertonia | 1 | 2 | 1 | 4 | 3 |
| Parkinsonism | 0 | 0 | <1 | 2 | 1 |
| Somnolence | 7 | 6 | 9 | 10 | 11 |
| Tremor | 3 | 3 | 3 | 4 | 3 |
| Psychiatric disorders | |||||
| Anxiety | 8 | 9 | 7 | 6 | 5 |
| Respiratory, thoracic and mediastinal disorders | |||||
| Cough | 1 | 3 | 2 | 3 | 2 |
| Vascular disorders | |||||
| Orthostatic hypotension | 1 | 2 | 1 | 2 | 4 |
| * Table includes adverse events that were reported in 2% or more of subjects in any of the INVEGA® dose groups and which occurred at greaer incidence than in the placebo group. Data are pooled from three studies: one study included once-daily INVEGA® doses of 3 and 9 mg; the second study included 6,9, and 12 mg; and the third study included 6 and 12 mg (see CLINICAL PHARMACOLOGY: Clinical Trials). Events for which the INVEGA® incidence was equal to or less than placebo are not listed in the table, but included the following: constipation, diarrhea, vomiting, nasopharyngitis, agitation, and insomnia. | |||||
In the trials cited above, what were the effects on:
What was the incidence or risk of:
What were the rates of:
Incidence of weight gain >7% similar to that for placebo.

Please see Hyperglycemia and Diabetes warning below.
Please see full Prescribing Information for INVEGA

Please see Hyperglycemia and Diabetes warning below.
Please see full Prescribing Information for INVEGA.
In a study in subjects with moderate hepatic impairment (Child-Pugh class B), the plasma concentrations of free paliperidone were similar to those of healthy subjects, although total paliperidone exposure decreased because of a decrease in protein binding. Consequently, no dose adjustment is required in patients with mild or moderate hepatic impairment. The effect of severe hepatic impairment is unknown.
Like other drugs that antagonize dopamine D2 receptors, paliperidone elevates prolactin levels and the elevation persists during chronic administration. Paliperidone has a prolactin-elevating effect similar to that seen with RISPERDAL® (risperidone), a drug that is associated with higher levels of prolactin than other antipsychotic drugs.
Hyperprolactinemia, regardless of etiology, may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.
Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is considered in a patient with previously detected breast cancer. An increase in the incidence of pituitary gland, mammary gland, and pancreatic islet cell neoplasia (mammary adenocarcinomas, pituitary and pancreatic adenomas) was observed in the risperidone carcinogenicity studies conducted in mice and rats (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility). Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans, but the available evidence is too limited to be conclusive.
Please see full Prescribing Information for INVEGA and RISPERDAL.

INVEGA delivered discontinuation rates due to adverse events that are similar to those for placebo across all doses.

Please see full Prescribing Information for INVEGA.
For additional medical or clinical information, please call our Customer Communications Center at
1-800-JANSSEN (1-800-526-7736), 9 AM - 5 PM (ET), Monday through Friday.
INVEGA is contraindicated in patients with a known hypersensitivity to paliperidone, to risperidone, or to any components in the INVEGA formulation.
For warnings, including Boxed Warning on Increased Mortality in Elderly Patients with Dementia-Related Psychosis, see the full US Prescribing Information under WARNINGS.
For more on Safety, please see the full US Prescribing Information under PRECAUTIONS, ADVERSE REACTIONS, and OVERDOSAGE.