14.3 Bipolar Mania — Combination Therapy
The efficacy of risperidone with concomitant lithium or
valproate in the treatment of acute manic or mixed episodes was established in
one controlled trial in adult patients who met the DSM-IV criteria for Bipolar I
Disorder. This trial included patients with or without psychotic features and
with or without a rapid-cycling course.
- In this 3-week placebo-controlled combination trial, 148 in- or outpatients
on lithium or valproate therapy with inadequately controlled manic or mixed
symptoms were randomized to receive risperidone, placebo, or an active
comparator, in combination with their original therapy. Risperidone, in a dose
range of 1-6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.8
mg/day), combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L
to 1.4 mEq/L or 50 mcg/mL to 120 mcg/mL, respectively) was superior to lithium
or valproate alone in the reduction of YMRS total score.
- In a second 3-week placebo-controlled combination trial, 142 in- or
outpatients on lithium, valproate, or carbamazepine therapy with inadequately
controlled manic or mixed symptoms were randomized to receive risperidone or
placebo, in combination with their original therapy. Risperidone, in a dose
range of 1-6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.7
mg/day), combined with lithium, valproate, or carbamazepine (in therapeutic
ranges of 0.6 mEq/L to 1.4 mEq/L for lithium, 50 mcg/mL to 125 mcg/mL for
valproate, or 4-12 mcg/mL for carbamazepine, respectively) was not superior to
lithium, valproate, or carbamazepine alone in the reduction of YMRS total score.
A possible explanation for the failure of this trial was induction of
risperidone and 9-hydroxyrisperidone clearance by carbamazepine, leading to
subtherapeutic levels of risperidone and 9-hydroxyrisperidone.
14.4 Irritability Associated with Autistic Disorder
Short-Term Efficacy
The efficacy of risperidone in the treatment of irritability associated with
autistic disorder was established in two 8-week, placebo-controlled trials in
children and adolescents (aged 5 to 16 years) who met the DSM-IV criteria for
autistic disorder. Over 90% of these subjects were under 12 years of age and
most weighed over 20 kg (16-104.3 kg).
Efficacy was evaluated using two assessment scales: the Aberrant Behavior
Checklist (ABC) and the Clinical Global Impression — Change (CGI-C) scale. The
primary outcome measure in both trials was the change from baseline to endpoint
in the Irritability subscale of the ABC (ABC-I). The ABC-I subscale measured the
emotional and behavioral symptoms of autism, including aggression towards
others, deliberate self-injuriousness, temper tantrums, and quickly changing
moods. The CGI-C rating at endpoint was a co-primary outcome measure in one of
the studies.
The results of these trials are as follows:
- In one of the 8-week, placebo-controlled trials, children and adolescents
with autistic disorder (n=101), aged 5 to 16 years, received twice daily doses
of placebo or risperidone 0.5-3.5 mg/day on a weight-adjusted basis.
Risperidone, starting at 0.25 mg/day or 0.5 mg/day depending on baseline weight
(< 20 kg and > 20 kg, respectively) and titrated to clinical response (mean
modal dose of 1.9 mg/day, equivalent to 0.06 mg/kg/day), significantly improved
scores on the ABC-I subscale and on the CGI-C scale compared with placebo.
- In the other 8-week, placebo-controlled trial in children with autistic
disorder (n=55), aged 5 to 12 years, risperidone 0.02 to 0.06 mg/kg/day given
once or twice daily, starting at 0.01 mg/kg/day and titrated to clinical
response (mean modal dose of 0.05 mg/kg/day, equivalent to 1.4 mg/day),
significantly improved scores on the ABC-I subscale compared with
placebo.
Long-Term Efficacy
Following completion of the first 8-week double-blind study, 63 patients
entered an open-label study extension where they were treated with risperidone
for 4 or 6 months (depending on whether they received risperidone or placebo in
the double-blind study). During this open-label treatment period, patients were
maintained on a mean modal dose of risperidone of 1.8-2.1 mg/day (equivalent to
0.05 — 0.07 mg/kg/day).
Patients who maintained their positive response to risperidone (response was
defined as > 25% improvement on the ABC-I subscale and a CGI-C rating of ‘much
improved’ or ‘very much improved’) during the 4-6 month open-label treatment
phase for about 140 days, on average, were randomized to receive risperidone or
placebo during an 8-week, double-blind withdrawal study (n=39 of the 63
patients). A pre-planned interim analysis of data from patients who completed
the withdrawal study (n=32), undertaken by an independent Data Safety Monitoring
Board, demonstrated a significantly lower relapse rate in the risperidone group
compared with the placebo group. Based on the interim analysis results, the
study was terminated due to demonstration of a statistically significant effect
on relapse prevention. Relapse was defined as > 25% worsening on the most recent
assessment of the ABC-I subscale (in relation to baseline of the randomized
withdrawal phase).
16 HOW SUPPLIED/STORAGE AND HANDLING
Risperidone Tablets, USP 0.25 mg are yellow, oblong shaped,
biconvex film coated tablets debossed with ‘0.25’ on one side and ‘1035’ on
other side.
Bottles of 30 | NDC 54868-6201-1 |
Bottles of 60 | NDC 54868-6201-0 |
Risperidone Tablets, USP 0.5 mg are red, oblong shaped, biconvex film coated
tablets debossed with ‘R 0.50’ on one side and ‘1036’ on other side.
Bottles of 30 | NDC 54868-6082-0 |
Bottles of 90 | NDC 54868-6082-1 |
Bottles of 30 | NDC 54868-5918-1 |
Bottles of 60 | NDC 54868-5918-0 |
Bottles of 30 | NDC 54868-6243-0 |
16.1 Storage and Handling
Store at 20°- 25°C (68° — 77°F); excursions permitted to 15° —
30°C (59° — 86°F). [See USP Controlled Room Temperature]. PROTECT FROM MOISTURE.
Keep out of reach of children. Dispense in a tight, light-resistant
container.
17 PATIENT COUNSELING INFORMATION
Physicians are advised to discuss the following issues with
patients for whom they prescribe risperidone:
17.1 Orthostatic Hypotension
Patients should be advised of the risk of orthostatic
hypotension, especially during the period of initial dose titration [see Warnings and Precautions (5.7)].
17.2 Interference with Cognitive and Motor Performance
Since risperidone has the potential to impair judgment,
thinking, or motor skills, patients should be cautioned about operating
hazardous machinery, including automobiles, until they are reasonably certain
that risperidone therapy does not affect them adversely [see
Warnings and Precautions (5.9)].
17.3 Pregnancy
Patients should be advised to notify their physician if
they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations
(8.1)].
17.4 Nursing
Patients should be advised not to breast-feed an infant if
they are taking risperidone [see Use in
Specific Populations (8.3)].
17.5 Concomitant Medication
Patients should be advised to inform their physicians if
they are taking, or plan to take, any prescription or over-the-counter drugs,
since there is a potential for interactions [see Drug Interactions (7)].
17.6 Alcohol
Patients should be advised to inform their physicians if
they are taking, or plan to take, any prescription or over-the-counter drugs,
since there is a potential for interactions [see Drug Interactions (7)].
Manufactured by:
TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA.
For:
TORRENT PHARMA INC., 5380 Holiday Terrace, Suite 40, Kalamazoo, Michigan
49009.
8025923 Revised
October 2010
Relabeling and Repackaging by:
Physicians Total Care, Inc.
Tulsa, OK 74146
PRINCIPAL DISPLAY PANEL
Risperidone Tablets, USP 0.25 mg
Risperidone Tablets, USP 0.5 mg
Risperidone Tablets, USP 1 mg
Risperidone Tablets, USP 2 mg
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RISPERIDONE risperidone tablet |
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RISPERIDONE risperidone tablet |
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RISPERIDONE risperidone tablet |
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Revised: 10/2009 Physicians Total Care, Inc
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.
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