Risperdal/Risperdal Consta Adverse Reactions

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of risperidone based on the comprehensive assessment of the available adverse event information. A causal relationship with risperidone cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical trial data:Risperdal: The safety of RISPERDAL was evaluated from a clinical trial database consisting of 9803 patients exposed to one or more doses of RISPERDAL for the treatment of various psychiatric disorders in adults, elderly patients with dementia, and pediatrics. Of these 9803 patients, 2687 were patients who received RISPERDAL while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with RISPERDAL varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 3 years) exposures.
The majority of all adverse reactions were mild to moderate in severity.
Double-blind, placebo-controlled data - Adult patients: Adverse reactions reported by ≥ 1% of RISPERDAL-treated adult patients in nine 3- to 8-week double-blind, placebo-controlled trials are shown in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

Double-blind, Placebo-controlled data - Elderly patients with dementia: Adverse reactions reported by ≥ 1% of RISPERDAL-treated elderly patients with dementia in six 4- to 12-week double-blind, placebo-controlled trials are shown in Table 2. Table 2 includes only those adverse reactions that are either not listed in Table 1 or those adverse reactions that occurred at ≥ 2 times the frequency of the adverse reactions listed in Table 1. (See Table 2.)

Click on icon to see table/diagram/image

Double-blind, placebo-controlled data - Pediatric patients: Adverse reactions reported by ≥ 1% of RISPERDAL-treated pediatric patients in eight 3- to 8-week double-blind, placebo-controlled trials are shown in Table 3. Table 3 includes only those adverse reactions that are either not listed in Table 1 or those adverse reactions that occurred at ≥ 2 times the frequency of the adverse reactions listed in Table 1. (See Table 3.)

Click on icon to see table/diagram/image

Risperdal Consta: The safety of RISPERDAL CONSTA was evaluated from a clinical trial database consisting of 2392 patients exposed to one or more doses of RISPERDAL CONSTA for the treatment of schizophrenia. Of these 2392 patients, 332 were patients who received RISPERDAL CONSTA while participating in a 12-week double-blind, placebo-controlled trial. A total of 202 of the 332 were schizophrenic patients who received 25 mg or 50 mg RISPERDAL CONSTA. The conditions and duration of treatment with RISPERDAL CONSTA in the other clinical trials varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 4 years) exposures. In addition to the studies in patients with schizophrenia, safety data are presented from a trial assessing the efficacy and safety of RISPERDAL CONSTA when administered as adjunctive maintenance treatment in patients with bipolar disorder and when administered as monotherapy for the treatment of bipolar I disorder.
In the monotherapy study for the maintenance treatment of bipolar I disorder, the subjects in this multicenter, double-blind, placebo-controlled study were adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who were stable on risperidone (oral or long-acting injection), were stable on other antipsychotics or mood stabilizers, or were experiencing an acute episode. After a 3-week period of treatment with open-label oral risperidone (n=440), subjects who demonstrated an initial response to oral risperidone in this period and those who were stable on risperidone (oral or long-acting injection) at study entry entered into a 26-week stabilization period of open-label RISPERDAL CONSTA (n=501). Subjects who demonstrated a maintained response during this period were then randomized into a 24-month double-blind, placebo-controlled period in which they received RISPERDAL CONSTA (n=154) or placebo (n=149) as monotherapy. Subjects who relapsed or who completed the double-blind period could choose to enter an 8-week open-label RISPERDAL CONSTA extension period (n=160).
In the adjunctive maintenance treatment study involving patients with bipolar disorder, the subjects in this multicenter, double-blind, placebo-controlled study were adult patients who met DSM-IV criteria for Bipolar Disorder Type I or II and who experienced at least 4 episodes of mood disorder requiring psychiatric/clinical intervention in the previous 12 months, including at least 2 episodes in the 6 months prior to the start of the study. At the start of this study, all patients (n=275) entered into a 16-week open-label treatment phase in which they received RISPERDAL CONSTA in addition to continuing their treatment as usual, which consisted of various mood stabilizers, antidepressants, and/or anxiolytics. Patients who reached remission at the end of this 16-week open-label treatment phase (n=139) were then randomized into a 52-week double-blind, placebo-controlled phase in which they received RISPERDAL CONSTA (n=72) or placebo (n=67) as adjunctive treatment in addition to continuing their treatment as usual. Patients who did not reach remission at the end of the 16-week open-label treatment phase could choose to continue to receive RISPERDAL CONSTA as adjunctive therapy in an open-label manner, in addition to continuing their treatment as usual, for up to an additional 36 weeks as clinically indicated for a total period of up to 52 weeks; these patients (n=70) were also included in the evaluation of safety.
The majority of all adverse reactions were mild to moderate in severity.
Double-Blind, Placebo-Controlled Data - Schizophrenia: Adverse reactions reported by ≥ 2% of RISPERDAL CONSTA- treated patients with schizophrenia in one 12-week double-blind, placebo-controlled trial are shown in Table 4. (See Table 4.)

Click on icon to see table/diagram/image

Double-Blind, Placebo-Controlled Data - Bipolar Disorder: Table 5 lists the treatment-emergent adverse reactions reported in 2% or more of RISPERDAL CONSTA-treated patients in the 24-month double-blind, placebo-controlled treatment period of the trial assessing the efficacy and safety of RISPERDAL CONSTA when administered as monotherapy for maintenance treatment in patients with bipolar I disorder. (See Table 5.)

Click on icon to see table/diagram/image

Table 6 lists the treatment-emergent adverse reactions reported in ≥ 4% of patients in the 52-week double-blind, placebo-controlled treatment phase of a trial assessing the efficacy and safety of RISPERDAL CONSTA when administered as adjunctive maintenance treatment in patients with bipolar disorder. (See Table 6.)

Click on icon to see table/diagram/image

Other clinical trial data: Risperdal: 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. This subsection includes additional adverse reactions reported with risperidone and/or paliperidone in clinical trials. Adverse reactions reported with risperidone and/or paliperidone by ≥ 1% of RISPERDAL-treated subjects in a pooled dataset of 23 double-blind, placebo-controlled pivotal studies (9 in adults, 6 in elderly patients with dementia, and 8 in pediatric patients) are shown in Table 7. (See Table 7.)

Click on icon to see table/diagram/image

Adverse reactions reported with risperidone and/or paliperidone by < 1% of RISPERDAL-treated subjects in a pooled dataset of 23 double-blind, placebo-controlled pivotal studies (9 in adults, 6 in elderly patients with dementia, and 8 in paediatric patients) are shown in Table 8. (See Table 8.)

Click on icon to see table/diagram/image

Adverse reactions reported with risperidone and/or paliperidone in other clinical trials but not reported by RISPERDAL-treated subjects in a pooled dataset of 23 double-blind, placebo-controlled pivotal studies are shown in Table 9. (See Table 9.)

Click on icon to see table/diagram/image

Risperdal Consta: 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. This subsection includes additional adverse reactions reported with risperidone and/or paliperidone in clinical trials. Adverse reactions reported with risperidone and/or paliperidone by ≥ 2% of RISPERDAL CONSTA-treated subjects with schizophrenia are shown in Table 10. (See Table 10.)

Click on icon to see table/diagram/image

Adverse reactions reported with risperidone and/or paliperidone by < 2% of RISPERDAL CONSTA-treated subjects with schizophrenia are shown in Table 11. (See Table 11.)

Click on icon to see table/diagram/image

Adverse reactions reported with risperidone and/or paliperidone in other clinical trials but not reported by RISPERDAL CONSTA (25 mg or 50 mg)-treated subjects with schizophrenia are shown in Table 12. (See Table 12.)

Click on icon to see table/diagram/image

Postmarketing Data: Adverse events first identified as adverse reactions during postmarketing experience with risperidone and/or paliperidone are included in Tables 13 and 14. In the table, the frequencies are provided according to the following convention: 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, including isolated reports; Unknown: Cannot be estimated from the available data.
In Tables 13 and 14, adverse reactions are presented by frequency category based on incidence in clinical trials, when known.
Risperdal: (See Table 13.)

Click on icon to see table/diagram/image

Risperdal Consta: (See Table 14.)

Click on icon to see table/diagram/image

Very rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA have been reported during postmarketing experience in patients who have previously tolerated oral risperidone.