A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Risperdal Indications, Dosage, Storage, Stability - Risperidone
Risperdal Indications, Dosage, Storage, Stability - Risperidone
INDICATIONS AND USAGE
Schizophrenia
RISPERDAL® (risperidone) is indicated for the
treatment of schizophrenia.
The efficacy of RISPERDAL® in schizophrenia
was established in short-term (6- to 8-weeks) controlled trials of schizophrenic
inpatients (see CLINICAL PHARMACOLOGY).
The efficacy of RISPERDAL® in delaying relapse
was demonstrated in schizophrenic patients who had been clinically stable for
at least 4 weeks before initiation of treatment with RISPERDAL® or
an active comparator and who were then observed for relapse during a period
of 1 to 2 years (see CLINICAL PHARMACOLOGY
– Clinical Trials). Nevertheless, the physician who elects to use RISPERDAL®
for extended periods should periodically re-evaluate the long-term usefulness
of the drug for the individual patient (see DOSAGE
AND ADMINISTRATION).
Bipolar Mania
Monotherapy
RISPERDAL® is indicated for the short-term treatment
of acute manic or mixed episodes associated with Bipolar I Disorder.
The efficacy of RISPERDAL® was established in
two placebo-controlled trials (3-week) with patients meeting DSM-IV criteria
for Bipolar I Disorder who currently displayed an acute manic or mixed episode
with or without psychotic features (see CLINICAL
PHARMACOLOGY).
Combination Therapy
The combination of RISPERDAL® with lithium or
valproate is indicated for the short-term treatment of acute manic or mixed
episodes associated with Bipolar I Disorder.
The efficacy of RISPERDAL® in combination with
lithium or valproate was established in one placebo-controlled (3-week) trial
with patients meeting DSM-IV criteria for Bipolar I Disorder who currently displayed
an acute manic or mixed episode with or without psychotic features (see CLINICAL
PHARMACOLOGY).
The effectiveness of RISPERDAL® for longer-term
use, that is, for more than 3 weeks of treatment of an acute episode, and for
prophylactic use in mania, has not been systematically evaluated in controlled
clinical trials. Therefore, physicians who elect to use RISPERDAL®
for extended periods should periodically re-evaluate the long-term risks
and benefits of the drug for the individual patient (see DOSAGE
AND ADMINISTRATION).
DOSAGE AND ADMINISTRATION
Schizophrenia
Usual Initial Dose
RISPERDAL® (risperidone) can be administered
on either a BID or a QD schedule. In early clinical trials, RISPERDAL®
was generally administered at 1 mg BID initially, with increases in increments
of 1mg BID on the second and third day, as tolerated, to a target dose of 3
mg BID by the third day. Subsequent controlled trials have indicated that total
daily risperidone doses of up to 8 mg on a QD regimen are also safe and effective.
However, regardless of which regimen is employed, in some patients a slower
titration may be medically appropriate. Further dosage adjustments, if indicated,
should generally occur at intervals of not less than 1week, since steady state
for the active metabolite would not be achieved for approximately 1 week in
the typical patient. When dosage adjustments are necessary, small dose increments/decrements
of 1-2mg are recommended.
Efficacy in schizophrenia was demonstrated in a dose range
of 4 to16 mg/day in the clinical trials supporting effectiveness of RISPERDAL®;
however, maximal effect was generally seen in a range of 4 to 8 mg/day. Doses
above 6 mg/day for BID dosing were not demonstrated to be more efficacious than
lower doses, were associated with more extrapyramidal symptoms and other adverse
effects, and are not generally recommended. In a single study supporting QD
dosing, the efficacy results were generally stronger for 8 mg than for 4 mg.
The safety of doses above 16 mg/day has not been evaluated in clinical trials.
Maintenance Therapy
While there is no body of evidence available to answer the
question of how long the schizophrenic patient treated with RISPERDAL®
should remain on it, the effectiveness of RISPERDAL® 2
mg/day to 8 mg/day at delaying relapse was demonstrated in a controlled trial
in patients who had been clinically stable for at least 4 weeks and were then
followed for a period of 1 to 2 years. In this trial, RISPERDAL® was
administered on a QD schedule, at 1 mg QD initially, with increases to 2 mg
QD on the second day, and to a target dose of 4 mg QD on the third day (see
CLINICAL PHARMACOLOGY – Clinical Trials).
Nevertheless, patients should be periodically reassessed to determine the need
for maintenance treatment with an appropriate dose.
Reinitiation of Treatment in Patients Previously Discontinued
Although there are no data to specifically address reinitiation
of treatment, it is recommended that when restarting patients who have had an
interval off RISPERDAL®, the initial titration schedule should
be followed.
Switching From Other Antipsychotics
There are no systematically collected data to specifically
address switching schizophrenic patients from other antipsychotics to RISPERDAL®,
or concerning concomitant administration with other antipsychotics. While immediate
discontinuation of theprevious antipsychotic treatment may be acceptable for
some schizophrenic patients, more gradual discontinuation may be most appropriate
for others. In all cases, the period of overlapping antipsychotic administration
should be minimized. When switching schizophrenic patients from depotantipsychotics,
if medically appropriate, initiate RISPERDAL® therapy in place
of thenextscheduled injection. The need for continuing existing EPS medication
should be re-evaluated periodically.
Bipolar Mania
Usual Dose
Risperidone should be administered on a once daily schedule,
starting with 2 mg to 3 mg per day. Dosage adjustments, if indicated, should
occur at intervals of not less than 24 hours and in dosage increments/decrements
of 1 mg per day, as studied in the short-term, placebo-controlled trials. In
these trials, short-term (3 week) anti-manic efficacy was demonstrated in a
flexible dosage range of 1-6 mg per day (see CLINICAL
PHARMACOLOGY – Clinical Trials). RISPERDAL®
doses higher than 6 mg per day were not studied.
Maintenance Therapy
There is no body of evidence available from controlled trials
to guide a clinician in the longer-term management of a patient who improves
during treatment of an acute manic episode with risperidone. While it is generally
agreed that pharmacological treatment beyond an acute response in mania is desirable,
both for maintenance of the initial response and for prevention of new manic
episodes, there are no systematically obtained data to support the use of risperidone
in such longer-term treatment (i.e., beyond 3 weeks).
Pediatric Use
Safety and effectiveness of RISPERDAL® in pediatric
patients with schizophrenia or acute mania associated with Bipolar I Disorder
have not been established.
Dosage in Special Populations
The recommended initial dose is 0.5 mg BID in patients who
are elderly or debilitated, patients with severe renal or hepatic impairment,
and patients either predisposed to hypotension or for whom hypotension would
pose a risk. Dosage increases in these patients should be in increments of no
more than 0.5 mg BID. Increases to dosages above 1.5 mg BID should generally
occur at intervals of at least 1 week. In some patients, slower titration may
be medically appropriate.
Elderly or debilitated patients, and patients with renal impairment,
may have less ability to eliminate RISPERDAL® than normal adults.
Patients with impaired hepatic function may have increases in the free fraction
of risperidone, possibly resulting in an enhanced effect (see CLINICAL
PHARMACOLOGY). Patients with a predisposition to hypotensive reactions
or for whom such reactions would pose a particular risk likewise need to be
titrated cautiously and carefully monitored (see PRECAUTIONS).
If a once-a-day dosing regimen in the elderly or debilitated patient is being
considered, it is recommended that the patient be titrated on a twice-a-day
regimen for 2-3 days at the target dose. Subsequent switches to a once-a-day
dosing regimen can be done thereafter.
Co-Administration of RISPERDAL® with Certain
Other Medications
Co-administration of carbamazepine and other enzyme inducers
(e.g., phenytoin, rifampin, phenobarbital) with risperidone would be expected
to cause decreases in the plasma concentrations of active moiety (the sum of
risperidone and 9-hydroxyrisperidone), which could lead to decreased efficacy
of risperidone treatment. The dose of risperidone needs to be titrated accordingly
for patients receiving these enzyme inducers, especially during initiation or
discontinuation of therapy with these inducers (see CLINICAL
PHARMACOLOGY and PRECAUTIONS).
Fluoxetine and paroxetine have been shown to increase the plasma
concentration of risperidone 2.5-2.8 fold and 3-9 fold respectively. Fluoxetine
did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine
lowered the concentration of 9-hydroxyrisperidone an average of 13%. The dose
of risperidone needs to be titrated accordingly when fluoxetine or paroxetine
is co-administered (see CLINICAL PHARMACOLOGY
and PRECAUTIONS).
Directions for Use of RISPERDAL® M-TAB™
Orally Disintegrating Tablets
RISPERDAL® M-TAB™ Orally Disintegrating
Tablets are supplied in blister packs of 4 tablet units each.
Tablet Accessing
Do not open the blister until ready to administer. For single
tablet removal, separate one of the four blister units by tearing apart at the
perforations. Bend the corner where indicated. Peel back foil to expose the
tablet. DO NOT push the tablet through the foil because this could damage the
tablet.
Tablet Administration
Using dry hands, remove the tablet from the blister unit and
immediately place the entire RISPERDAL® M-TAB™ Orally Disintegrating
Tablet on the tongue. The RISPERDAL® M-TAB™ Orally Disintegrating
Tablet should be consumed immediately, as the tablet cannot be stored once removed
from the blister unit. RISPERDAL® M-TAB™ Orally Disintegrating
Tablets disintegrate in the mouth within seconds and can be swallowed subsequently
with or without liquid. Patients should not attempt to split or to chew the
tablet.
HOW SUPPLIED
RISPERDAL® (risperidone) tablets are imprinted
"JANSSEN", and either "Ris" and the strength "0.25",
"0.5", or "R" and the strength "1", "2",
"3", or "4".
0.25 mg dark yellow tablet: bottles of 60 NDC 50458-301-04,
bottles of 500 NDC 50458-301-50, hospital unit dose packs of 100 NDC 50458-301-01.
0.5 mg red-brown tablet: bottles of 60 NDC 50458-302-06, bottles
of 500 NDC 50458-302-50, hospital unit dose packs of 100 NDC 50458-302-01.
1 mg white tablet: bottles of 60 NDC 50458-300-06, blister
pack of 100 NDC 50458-300-01, bottles of 500 NDC 50458-300-50.
2 mg orange tablet: bottles of 60 NDC 50458-320-06, blister
pack of 100 NDC 50458-320-01, bottles of 500 NDC 50458-320-50.
3 mg yellow tablet: bottles of 60 NDC 50458-330-06, blister
pack of 100 NDC 50458-330-01, bottles of 500 NDC 50458-330-50.
4 mg green tablet: bottles of 60 NDC 50458-350-06, blister
pack of 100 NDC 50458-350-01.
RISPERDAL® (risperidone) 1 mg/mL oral solution
(NDC 50458-305-03) is supplied in 30 mL bottles with a calibrated (in milligrams
and milliliters) pipette. The minimum calibrated volume is 0.25 mL, while the
maximum calibrated volume is 3 mL. Tests indicate that RISPERDAL® (risperidone)
oral solution is compatible in the following beverages: water, coffee, orange
juice, and low-fat milk; it is NOT compatible with either cola or tea, however.
RISPERDAL® M-TAB™ (risperidone) Orally
Disintegrating Tablets are etched on one side with "R0.5", "R1",
and "R2", respectively, and are packaged in blister packs of 4 (2
X 2) tablets.
0.5 mg light coral, round, biconvex tablets: 7 blister packages
per box, NDC 50458-395-28, long-term care packaging of 30 tablets NDC 50458-395-30.
1 mg light coral, square, biconvex tablets: 7 blister packages
per box, NDC 50458-315-28, long-term care packaging of 30 tablets NDC 50458-315-30.
2 mg light coral, round, biconvex tablets: 7 blister packages
per box, NDC 50458-325-28.
Storage and Handling
RISPERDAL® tablets should be stored at controlled
room temperature 15°-25°C (59°-77°F). Protect from light and moisture. Keep
out of reach of children.
RISPERDAL® 1 mg/mL oral solution should be stored
at controlled room temperature 15°-25°C (59°-77°F). Protect from light and freezing.
Keep out of reach of children.
RISPERDAL® M-TAB™ Orally Disintegrating
Tablets should be stored at controlled room temperature 15°-25°C (59°-77°F).
Keep out of reach of children.
7503226 US Patent 4,804,663 December 2003 ©
Janssen 2003 RISPERDAL® tablets are manufactured by: JOLLC, Gurabo,
Puerto Rico or Janssen-Cilag, SpA, Latina, Italy RISPERDAL® oral
solution is manufactured by: Janssen Pharmaceutica N.V.
Beerse, Belgium
RISPERDAL® M-TAB™
Orally Disintegrating Tablets are manufactured by: JOLLC, Gurabo, Puerto
Rico RISPERDAL® tablets, RISPERDAL® M-TAB™
Orally Disintegrating Tablets, and oral solution are distributed by: Janssen
Pharmaceutica Products, L.P. Titusville, NJ 08560
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