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Risperdal

Risperdal

Generic

Name

risperidone

Dosage

Form

tablets

orally

disintegrating

tablets

oral

solution

Medically

reviewed

on

Sep

Overview

Side

Effects

Dosage

Professional

Tips

Interactions

On

This

Page

Boxed

Warning

Indications

and

Usage

Dosage

and

Administration

Dosage

Forms

and

Strengths

Contraindications

Warnings

and

Precautions

Adverse

Reactions

Drug

Interactions

Use

In

Specific

Populations

Drug

Abuse

and

Dependence

Overdosage

Description

Clinical

Pharmacology

Nonclinical

Toxicology

Clinical

Studies

How

SuppliedStorage

and

Handling

Patient

Counseling

Information

WARNING

INCREASED

MORTALITY

IN

ELDERLY

PATIENTS

WITH

DEMENTIARELATED

PSYCHOSIS

Elderly

patients

with

dementiarelated

psychosis

treated

with

antipsychotic

drugs

are

at

an

increased

risk

of

death

Risperdal

is

not

approved

for

the

treatment

of

patients

with

dementiarelated

psychosis

see

Warnings

and

Precautions

Indications

and

Usage

for

Risperdal

See

also

Ingrezza

Schizophrenia

Risperdal

risperidone

is

indicated

for

the

treatment

of

schizophrenia

Efficacy

was

established

in

shortterm

trials

in

adults

shortterm

trials

in

adolescents

ages

to

years

and

one

longterm

maintenance

trial

in

adults

see

Clinical

Studies

Bipolar

Mania

Monotherapy

Risperdal

is

indicated

for

the

treatment

of

acute

manic

or

mixed

episodes

associated

with

Bipolar

I

Disorder

Efficacy

was

established

in

shortterm

trials

in

adults

and

one

shortterm

trial

in

children

and

adolescents

ages

to

years

see

Clinical

Studies

Adjunctive

Therapy

Risperdal

adjunctive

therapy

with

lithium

or

valproate

is

indicated

for

the

treatment

of

acute

manic

or

mixed

episodes

associated

with

Bipolar

I

Disorder

Efficacy

was

established

in

one

shortterm

trial

in

adults

see

Clinical

Studies

Irritability

Associated

with

Autistic

Disorder

Risperdal

is

indicated

for

the

treatment

of

irritability

associated

with

autistic

disorder

including

symptoms

of

aggression

towards

others

deliberate

selfinjuriousness

temper

tantrums

and

quickly

changing

moods

Efficacy

was

established

in

shortterm

trials

in

children

and

adolescents

ages

to

years

see

Clinical

Studies

Risperdal

Dosage

and

Administration

Table

Recommended

Daily

Dosage

by

Indication

Initial

Dose

Titration

Increments

Target

Dose

Effective

Dose

Range

Schizophrenia

adults

mg

to

mg

to

mg

to

mg

Schizophrenia

adolescents

mg

to

mg

mg

to

mg

Bipolar

mania

adults

to

mg

mg

to

mg

to

mg

Bipolar

mania

children

and

adolescents

mg

to

mg

to

mg

to

mg

Irritability

in

autistic

disorder

mg

Can

increase

to

mg

by

Day

body

weight

less

than

kg

mg

Can

increase

to

mg

by

Day

body

weight

greater

than

or

equal

to

kg

After

Day

at

intervals

of

weeks

mg

body

weight

less

than

kg

mg

body

weight

greater

than

or

equal

to

kg

mg

body

weight

less

than

kg

mg

body

weight

greater

than

or

equal

to

kg

to

mg

Severe

Renal

and

Hepatic

Impairment

in

Adults

use

a

lower

starting

dose

of

mg

twice

daily

May

increase

to

dosages

above

mg

twice

daily

at

intervals

of

one

week

or

longer

Schizophrenia

Adults

Usual

Initial

Dose

Risperdal

can

be

administered

once

or

twice

daily

Initial

dosing

is

mg

per

day

May

increase

the

dose

at

intervals

of

hours

or

greater

in

increments

of

to

mg

per

day

as

tolerated

to

a

recommended

dose

of

to

mg

per

day

In

some

patients

slower

titration

may

be

appropriate

Efficacy

has

been

demonstrated

in

a

range

of

mg

to

mg

per

day

However

doses

above

mg

per

day

for

twice

daily

dosing

were

not

demonstrated

to

be

more

efficacious

than

lower

doses

were

associated

with

more

extrapyramidal

symptoms

and

other

adverse

see

Clinical

Studies

Adolescents

The

initial

dose

is

mg

once

daily

administered

as

a

singledaily

dose

in

the

morning

or

evening

The

dose

may

be

adjusted

at

intervals

of

hours

or

greater

in

increments

of

mg

or

mg

per

day

as

tolerated

to

a

recommended

dose

of

mg

per

day

Although

efficacy

has

been

demonstrated

in

studies

of

adolescent

patients

with

schizophrenia

at

doses

between

mg

to

mg

per

day

no

additional

benefit

was

observed

above

mg

per

day

and

higher

doses

were

associated

with

more

adverse

events

Doses

higher

than

mg

per

day

have

Patients

experiencing

persistent

somnolence

may

benefit

from

administering

half

the

daily

dose

twice

daily

Maintenance

Therapy

While

it

is

unknown

how

long

a

patient

with

schizophrenia

should

remain

on

Risperdal

the

effectiveness

of

Risperdal

mg

per

day

to

mg

per

day

at

delaying

relapse

was

demonstrated

in

a

controlled

trial

in

adult

patients

who

had

been

clinically

stable

for

at

least

weeks

and

were

then

followed

for

a

period

of

to

years

see

Clinical

Studies

Both

adult

and

adolescent

patients

who

respond

acutely

should

generally

be

maintained

on

their

effective

dose

beyond

the

acute

episode

Patients

should

be

periodically

reassessed

to

determine

the

need

for

maintenance

treatment

Reinitiation

of

Treatment

in

Patients

Previously

Discontinued

Although

there

are

no

data

to

specifically

address

reinitiation

of

treatment

it

is

recommended

that

after

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

treating

patients

with

concomitant

antipsychotics

Bipolar

Mania

Usual

Dose

Adults

The

initial

dose

range

is

mg

to

mg

per

day

The

dose

may

be

adjusted

at

intervals

of

hours

or

greater

in

increments

of

mg

per

day

The

effective

dose

range

is

mg

to

mg

per

day

as

studied

in

the

shortterm

placebocontrolled

trials

In

these

trials

shortterm

week

antimanic

efficacy

was

demonstrated

in

a

flexible

dosage

range

of

mg

to

mg

per

day

see

Clinical

Studies

Risperdal

doses

higher

than

mg

per

day

were

not

studied

Pediatrics

The

initial

dose

is

mg

once

daily

administered

as

a

singledaily

dose

in

the

morning

or

evening

The

dose

may

be

adjusted

at

intervals

of

hours

or

greater

in

increments

of

mg

or

mg

per

day

as

tolerated

to

the

recommended

target

dose

of

mg

to

mg

per

day

Although

efficacy

has

been

demonstrated

in

studies

of

pediatric

patients

with

bipolar

mania

at

doses

between

mg

and

mg

per

day

no

additional

benefit

was

observed

above

mg

per

day

and

higher

doses

were

associated

with

more

adverse

events

Doses

higher

than

Patients

experiencing

persistent

somnolence

may

benefit

from

administering

half

the

daily

dose

twice

daily

Maintenance

Therapy

There

is

no

body

of

evidence

available

from

controlled

trials

to

guide

a

clinician

in

the

longerterm

management

of

a

patient

who

improves

during

treatment

of

an

acute

manic

episode

with

Risperdal

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

Risperdal

in

such

longerterm

treatment

ie

beyond

weeks

The

physician

who

elects

to

use

Risperdal

for

extended

periods

should

periodically

reevaluate

the

longterm

risks

and

benefits

of

the

drug

for

the

individual

patient

Irritability

Associated

with

Autistic

Disorder

Pediatrics

Children

and

Adolescents

The

dosage

of

Risperdal

should

be

individualized

according

to

the

response

and

tolerability

of

the

patient

The

total

daily

dose

of

Risperdal

can

be

administered

once

daily

or

half

the

total

daily

dose

can

be

administered

twice

daily

For

patients

with

body

weight

less

than

kg

initiate

dosing

at

mg

per

day

For

patients

with

body

weight

greater

than

or

equal

to

kg

initiate

dosing

at

mg

per

day

After

a

minimum

of

four

days

the

dose

may

be

increased

to

the

recommended

dose

of

mg

per

day

for

patients

less

than

kg

and

mg

per

day

for

patients

greater

than

or

equal

to

kg

Maintain

this

dose

for

a

minimum

of

days

In

patients

not

achieving

sufficient

clinical

response

the

dose

may

be

increased

at

intervals

of

Once

sufficient

clinical

response

has

been

achieved

and

maintained

consider

gradually

lowering

the

dose

to

achieve

the

optimal

balance

of

efficacy

and

safety

The

physician

who

elects

to

use

Risperdal

for

extended

periods

should

periodically

reevaluate

the

longterm

risks

and

benefits

of

the

drug

for

the

individual

patient

Patients

experiencing

persistent

somnolence

may

benefit

from

a

oncedaily

dose

administered

at

bedtime

or

administering

half

the

daily

dose

twice

daily

or

a

reduction

of

the

dose

Dosing

in

Patients

with

Severe

Renal

or

Hepatic

Impairment

For

patients

with

severe

renal

impairment

CLcr

mLmin

or

hepatic

impairment

points

on

Child

Pugh

System

the

initial

starting

dose

is

mg

twice

daily

The

dose

may

be

increased

in

increments

of

mg

or

less

administered

twice

daily

For

doses

above

mg

twice

daily

increase

in

intervals

of

one

week

or

greater

see

Use

in

Specific

Populations

and

Dose

Adjustments

for

Specific

Drug

Interactions

When

Risperdal

is

coadministered

with

enzyme

inducers

eg

carbamazepine

the

dose

of

Risperdal

should

be

increased

up

to

double

the

patients

usual

dose

It

may

be

necessary

to

decrease

the

Risperdal

dose

when

enzyme

inducers

such

as

carbamazepine

are

discontinued

see

Drug

Interactions

Similar

effect

may

be

expected

with

coadministration

of

Risperdal

with

other

enzyme

inducers

eg

phenytoin

rifampin

and

phenobarbital

When

fluoxetine

or

paroxetine

is

coadministered

with

Risperdal

the

dose

of

Risperdal

should

be

reduced

The

Risperdal

dose

should

not

exceed

mg

per

day

in

adults

when

coadministered

with

these

drugs

When

initiating

therapy

Risperdal

should

be

titrated

slowly

It

may

be

necessary

to

increase

the

Risperdal

dose

when

enzyme

inhibitors

such

as

fluoxetine

or

paroxetine

are

discontinued

see

Drug

Interactions

Administration

of

Risperdal

Oral

Solution

Risperdal

Oral

Solution

can

be

administered

directly

from

the

calibrated

pipette

or

can

be

mixed

with

a

beverage

prior

to

administration

Risperdal

Oral

Solution

is

compatible

in

the

following

beverages

water

coffee

orange

juice

and

lowfat

milk

it

is

NOT

compatible

with

either

cola

or

tea

Directions

for

Use

of

Risperdal

MTAB

Orally

Disintegrating

Tablets

Tablet

Accessing

Risperdal

MTAB

Orally

Disintegrating

Tablets

mg

mg

and

mg

Risperdal

MTAB

Orally

Disintegrating

Tablets

mg

mg

and

mg

are

supplied

in

blister

packs

of

tablets

each

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

Risperdal

MTAB

Orally

Disintegrating

Tablets

mg

and

mg

Risperdal

MTAB

Orally

Disintegrating

Tablets

mg

and

mg

are

supplied

in

a

childresistant

pouch

containing

a

blister

with

tablet

each

The

childresistant

pouch

should

be

torn

open

at

the

notch

to

access

the

blister

Do

not

open

the

blister

until

ready

to

administer

Peel

back

foil

from

the

side

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

MTAB

Orally

Disintegrating

Tablet

on

the

tongue

The

Risperdal

MTAB

Orally

Disintegrating

Tablet

should

be

consumed

immediately

as

the

tablet

can

not

be

stored

once

removed

from

the

blister

unit

Risperdal

MTAB

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

Dosage

Forms

and

Strengths

Risperdal

Tablets

are

available

in

the

following

strengths

and

colors

mg

dark

yellow

mg

redbrown

mg

white

mg

orange

mg

yellow

and

mg

green

All

are

capsule

shaped

and

imprinted

with

JANSSEN

on

one

side

and

either

Ris

Ris

or

on

the

other

side

according

to

their

respective

strengths

Risperdal

Oral

Solution

is

available

in

a

mgmL

strength

Risperdal

MTAB

Orally

Disintegrating

Tablets

are

available

in

the

following

strengths

colors

and

shapes

mg

light

coral

round

mg

light

coral

square

mg

coral

square

mg

coral

round

and

mg

coral

round

All

are

biconvex

and

etched

on

one

side

with

or

according

to

their

respective

strengths

Contraindications

Risperdal

is

contraindicated

in

patients

with

a

known

hypersensitivity

to

either

risperidone

or

paliperidone

or

to

any

of

the

excipients

in

the

Risperdal

formulation

Hypersensitivity

reactions

including

anaphylactic

reactions

and

angioedema

have

been

reported

in

patients

treated

with

risperidone

and

in

patients

treated

with

paliperidone

Paliperidone

is

a

metabolite

of

risperidone

Warnings

and

Precautions

Increased

Mortality

in

Elderly

Patients

with

DementiaRelated

Psychosis

Elderly

patients

with

dementiarelated

psychosis

treated

with

antipsychotic

drugs

are

at

an

increased

risk

of

death

Analyses

of

placebocontrolled

trials

modal

duration

of

weeks

largely

in

patients

taking

atypical

antipsychotic

drugs

revealed

a

risk

of

death

in

drugtreated

patients

of

between

to

times

the

risk

of

death

in

placebotreated

patients

Over

the

course

of

a

typical

controlled

trial

the

rate

of

death

in

drugtreated

patients

was

about

compared

to

a

rate

of

about

in

the

placebo

group

Although

the

causes

of

death

were

varied

most

of

the

deaths

appeared

to

be

either

cardiovascular

In

two

of

four

placebocontrolled

trials

in

elderly

patients

with

dementiarelated

psychosis

a

higher

incidence

of

mortality

was

observed

in

patients

treated

with

furosemide

plus

Risperdal

when

compared

to

patients

treated

with

Risperdal

alone

or

with

placebo

plus

furosemide

No

pathological

mechanism

has

been

identified

to

explain

this

finding

and

no

consistent

pattern

for

cause

of

death

was

observed

Risperdal

risperidone

is

not

approved

for

the

treatment

of

dementiarelated

psychosis

see

Boxed

Warning

Cerebrovascular

Adverse

Reactions

Including

Stroke

in

Elderly

Patients

with

DementiaRelated

Psychosis

Cerebrovascular

adverse

reactions

eg

stroke

transient

ischemic

attack

including

fatalities

were

reported

in

patients

mean

age

years

range

in

trials

of

risperidone

in

elderly

patients

with

dementiarelated

psychosis

In

placebocontrolled

trials

there

was

a

significantly

higher

incidence

of

cerebrovascular

adverse

events

in

patients

treated

with

risperidone

compared

to

patients

treated

with

placebo

Risperdal

is

not

approved

for

the

treatment

of

patients

with

dementiarelated

psychosis

see

Boxed

Warning

and

Warnings

and

Precautions

Neuroleptic

Malignant

Syndrome

Antipsychotic

drugs

including

Risperdal

can

cause

a

potentially

fatal

symptom

complex

referred

to

as

Neuroleptic

Malignant

Syndrome

NMS

Clinical

manifestations

of

NMS

include

hyperpyrexia

muscle

rigidity

altered

mental

status

and

autonomic

instability

irregular

pulse

or

blood

pressure

tachycardia

diaphoresis

and

cardiac

dysrhythmia

Additional

signs

may

include

elevated

creatine

phosphokinase

CPK

myoglobinuria

rhabdomyolysis

and

acute

renal

failure

The

diagnostic

evaluation

of

patients

with

this

syndrome

is

complicated

In

arriving

at

a

diagnosis

it

is

important

to

identify

cases

in

which

the

clinical

presentation

includes

both

serious

medical

illness

eg

pneumonia

systemic

infection

etc

and

untreated

or

inadequately

treated

extrapyramidal

signs

and

symptoms

EPS

Other

important

considerations

in

the

differential

diagnosis

include

central

anticholinergic

toxicity

heat

stroke

drug

fever

and

primary

central

nervous

system

pathology

The

management

of

NMS

should

include

immediate

discontinuation

of

antipsychotic

drugs

and

other

drugs

not

essential

to

concurrent

therapy

intensive

symptomatic

treatment

and

medical

monitoring

and

treatment

of

any

concomitant

serious

medical

problems

for

which

specific

treatments

are

available

There

is

no

general

agreement

about

specific

pharmacological

treatment

regimens

for

uncomplicated

NMS

If

a

patient

requires

antipsychotic

drug

treatment

after

recovery

from

NMS

the

potential

reintroduction

of

drug

therapy

should

be

carefully

considered

The

patient

should

be

carefully

monitored

since

recurrences

of

NMS

have

been

reported

Tardive

Dyskinesia

A

syndrome

of

potentially

irreversible

involuntary

dyskinetic

movements

may

develop

in

patients

treated

with

antipsychotic

drugs

The

risk

of

developing

tardive

dyskinesia

and

the

likelihood

that

it

will

become

irreversible

are

believed

to

increase

as

the

duration

of

treatment

and

the

total

cumulative

dose

of

antipsychotic

drugs

administered

to

the

patient

increase

However

the

syndrome

can

develop

although

much

less

commonly

after

relatively

brief

treatment

periods

at

low

doses

The

syndrome

may

remit

partially

or

completely

if

antipsychotic

treatment

is

withdrawn

Antipsychotic

treatment

itself

however

may

suppress

or

partially

suppress

the

signs

and

symptoms

of

the

syndrome

and

thereby

may

possibly

mask

the

underlying

process

The

effect

that

symptomatic

suppression

has

upon

the

longterm

course

of

the

syndrome

is

unknown

Given

these

considerations

prescribe

Risperdal

in

a

manner

that

is

most

likely

to

minimize

the

occurrence

of

tardive

dyskinesia

Chronic

antipsychotic

treatment

should

generally

be

reserved

for

patients

who

suffer

from

a

chronic

illness

that

is

known

to

respond

to

antipsychotic

drugs

and

for

whom

alternative

equally

effective

but

potentially

less

harmful

treatments

are

not

available

or

appropriate

In

patients

who

do

require

chronic

treatment

the

smallest

dose

and

the

shortest

duration

of

treatment

producing

a

satisfactory

clinical

response

should

be

sought

The

need

for

continued

treatment

should

be

reassessed

periodically

If

signs

and

symptoms

of

tardive

dyskinesia

appear

in

a

patient

treated

with

Risperdal

consider

drug

discontinuation

However

some

patients

may

require

treatment

with

Risperdal

despite

the

presence

of

the

syndrome

Metabolic

Changes

Atypical

antipsychotic

drugs

have

been

associated

with

metabolic

changes

that

may

increase

cardiovascularcerebrovascular

risk

These

metabolic

changes

include

hyperglycemia

dyslipidemia

and

body

weight

gain

While

all

of

the

drugs

in

the

class

have

been

shown

to

produce

some

metabolic

changes

each

drug

has

its

own

specific

risk

profile

Hyperglycemia

and

Diabetes

Mellitus

Hyperglycemia

and

diabetes

mellitus

in

some

cases

extreme

and

associated

with

ketoacidosis

or

hyperosmolar

coma

or

death

have

been

reported

in

patients

treated

with

atypical

antipsychotics

including

Risperdal

Assessment

of

the

relationship

between

atypical

antipsychotic

use

and

glucose

abnormalities

is

complicated

by

the

possibility

of

an

increased

background

risk

of

diabetes

mellitus

in

patients

with

schizophrenia

and

the

increasing

incidence

of

diabetes

mellitus

in

the

general

population

Given

these

confounders

the

relationship

between

atypical

antipsychotic

use

and

hyperglycemiarelated

adverse

events

is

not

completely

understood

However

epidemiological

studies

suggest

an

increased

risk

of

treatmentemergent

hyperglycemiarelated

adverse

events

in

patients

treated

with

the

atypical

antipsychotics

Precise

risk

estimates

for

hyperglycemiarelated

adverse

events

in

patients

treated

with

atypical

antipsychotics

are

not

available

Patients

with

an

established

diagnosis

of

diabetes

mellitus

who

are

started

on

atypical

antipsychotics

including

Risperdal

should

be

monitored

regularly

for

worsening

of

glucose

control

Patients

with

risk

factors

for

diabetes

mellitus

eg

obesity

family

history

of

diabetes

who

are

starting

treatment

with

atypical

antipsychotics

including

Risperdal

should

undergo

fasting

blood

glucose

testing

at

the

beginning

of

treatment

and

periodically

during

treatment

Any

patient

treated

with

atypical

antipsychotics

including

Risperdal

should

be

monitored

for

symptoms

of

hyperglycemia

including

polydipsia

polyuria

polyphagia

and

weakness

Patients

who

develop

symptoms

of

hyperglycemia

during

treatment

with

atypical

antipsychotics

including

Risperdal

should

undergo

fasting

blood

glucose

testing

In

some

cases

hyperglycemia

has

resolved

when

the

atypical

antipsychotic

including

Risperdal

was

discontinued

however

some

patients

required

continuation

of

antidiabetic

treatment

despite

discontinuation

of

Risperdal

Pooled

data

from

three

doubleblind

placebocontrolled

schizophrenia

studies

and

four

doubleblind

placebocontrolled

bipolar

monotherapy

studies

are

presented

in

Table

Table

Change

in

Random

Glucose

from

Seven

PlaceboControlled

to

Fixed

or

FlexibleDose

Studies

in

Adult

Subjects

with

Schizophrenia

or

Bipolar

Mania

Risperdal

Placebo

mgday

mgday

Mean

change

from

baseline

mgdL

Serum

Glucose

Proportion

of

patients

with

shifts

Serum

Glucose

mgdL

to

mgdL

In

longerterm

controlled

and

uncontrolled

studies

Risperdal

was

associated

with

a

mean

change

in

glucose

of

mgdL

at

Week

and

mgdL

at

Week

Data

from

the

placebocontrolled

to

study

in

children

and

adolescents

with

schizophrenia

years

of

age

bipolar

mania

years

of

age

or

autistic

disorder

to

years

of

age

are

presented

in

Table

Table

Change

in

Fasting

Glucose

from

Three

PlaceboControlled

to

FixedDose

Studies

in

Children

and

Adolescents

with

Schizophrenia

years

of

age

Bipolar

Mania

years

of

age

or

Autistic

Disorder

to

years

of

age

Risperdal

Placebo

mgday

Mean

change

from

baseline

mgdL

Serum

Glucose

Proportion

of

patients

with

shifts

Serum

Glucose

mgdL

to

mgdL

In

longerterm

uncontrolled

openlabel

extension

pediatric

studies

Risperdal

was

associated

with

a

mean

change

in

fasting

glucose

of

mgdL

at

Week

Dyslipidemia

Undesirable

alterations

in

lipids

have

been

observed

in

patients

treated

with

atypical

antipsychotics

Pooled

data

from

placebocontrolled

to

week

fixed

or

flexibledose

studies

in

adult

subjects

with

schizophrenia

or

bipolar

mania

are

presented

in

Table

Table

Change

in

Random

Lipids

from

Seven

PlaceboControlled

to

Fixed

or

FlexibleDose

Studies

in

Adult

Subjects

with

Schizophrenia

or

Bipolar

Mania

Risperdal

Placebo

mgday

mgday

Mean

change

from

baseline

mgdL

Cholesterol

Change

from

baseline

Triglycerides

Change

from

baseline

Proportion

of

patients

With

Shifts

Cholesterol

mgdL

to

mgdL

Triglycerides

mgdL

to

mgdL

In

longerterm

controlled

and

uncontrolled

studies

Risperdal

was

associated

with

a

mean

change

in

a

nonfasting

cholesterol

of

mgdL

at

Week

and

mgdL

at

Week

and

b

nonfasting

triglycerides

of

mgdL

at

Week

Pooled

data

from

placebocontrolled

to

fixeddose

studies

in

children

and

adolescents

with

schizophrenia

years

of

age

bipolar

mania

years

of

age

or

autistic

disorder

years

of

age

are

presented

in

Table

Table

Change

in

Fasting

Lipids

from

Three

PlaceboControlled

to

FixedDose

Studies

in

Children

and

Adolescents

with

Schizophrenia

Years

of

Age

Bipolar

Mania

Years

of

Age

or

Autistic

Disorder

to

Years

of

Age

Risperdal

Placebo

mgday

Mean

change

from

baseline

mgdL

Cholesterol

Change

from

baseline

LDL

Change

from

baseline

HDL

Change

from

baseline

Triglycerides

Change

from

baseline

Proportion

of

patients

with

shifts

Cholesterol

mgdL

to

mgdL

LDL

mgdL

to

mgdL

HDL

mgdL

to

mgdL

Triglycerides

mgdL

to

mgdL

In

longerterm

uncontrolled

openlabel

extension

pediatric

studies

Risperdal

was

associated

with

a

mean

change

in

a

fasting

cholesterol

of

mgdL

at

Week

b

fasting

LDL

of

mgdL

at

Week

c

fasting

HDL

of

mgdL

at

Week

and

d

fasting

triglycerides

of

mgdL

at

Week

Weight

Gain

Weight

gain

has

been

observed

with

atypical

antipsychotic

use

Clinical

monitoring

of

weight

is

recommended

Data

on

mean

changes

in

body

weight

and

the

proportion

of

subjects

meeting

a

weight

gain

criterion

of

or

greater

of

body

weight

from

placebocontrolled

to

week

fixed

or

flexibledose

studies

in

adult

subjects

with

schizophrenia

or

bipolar

mania

are

presented

in

Table

Table

Mean

Change

in

Body

Weight

kg

and

the

Proportion

of

Subjects

with

Gain

in

Body

Weight

From

Seven

PlaceboControlled

to

Fixed

or

FlexibleDose

Studies

in

Adult

Subjects

With

Schizophrenia

or

Bipolar

Mania

Risperdal

Placebo

mgday

mgday

Weight

kg

Change

from

baseline

Weight

Gain

increase

from

baseline

In

longerterm

controlled

and

uncontrolled

studies

Risperdal

was

associated

with

a

mean

change

in

weight

of

kg

at

Week

and

kg

at

Week

Data

on

mean

changes

in

body

weight

and

the

proportion

of

subjects

meeting

the

criterion

of

gain

in

body

weight

from

nine

placebocontrolled

to

fixeddose

studies

in

children

and

adolescents

with

schizophrenia

years

of

age

bipolar

mania

years

of

age

autistic

disorder

years

of

age

or

other

psychiatric

disorders

years

of

age

are

presented

in

Table

Table

Mean

Change

in

Body

Weight

kg

and

the

Proportion

of

Subjects

With

Gain

in

Body

Weight

From

Nine

PlaceboControlled

to

FixedDose

Studies

in

Children

and

Adolescents

With

Schizophrenia

Years

of

Age

Bipolar

Mania

Years

of

Age

Autistic

Disorder

to

Years

of

Age

or

Other

Psychiatric

Disorders

Years

of

Age

Placebo

Risperdal

mgday

Weight

kg

Change

from

baseline

Weight

Gain

increase

from

baseline

In

longerterm

uncontrolled

openlabel

extension

pediatric

studies

Risperdal

was

associated

with

a

mean

change

in

weight

of

kg

at

Week

and

kg

at

Week

In

a

longterm

openlabel

extension

study

in

adolescent

patients

with

schizophrenia

weight

increase

was

reported

as

a

treatmentemergent

adverse

event

in

of

patients

In

adolescent

patients

with

schizophrenia

a

mean

increase

of

kg

was

observed

after

months

of

Risperdal

treatment

The

majority

of

that

increase

was

observed

within

the

first

months

The

average

percentiles

at

baseline

and

months

respectively

were

and

for

weight

and

for

height

and

and

for

body

mass

index

In

longterm

openlabel

trials

studies

in

patients

with

autistic

disorder

or

other

psychiatric

disorders

a

mean

increase

of

kg

after

months

of

Risperdal

treatment

was

observed

which

was

higher

than

the

expected

normal

weight

gain

approximately

to

kg

per

year

adjusted

for

age

based

on

Centers

for

Disease

Control

and

Prevention

normative

data

The

majority

of

that

increase

occurred

within

the

first

months

of

exposure

to

Risperdal

The

average

percentiles

at

baseline

and

months

respectively

were

and

for

weight

and

for

height

and

and

for

body

mass

index

In

one

placebocontrolled

trial

in

children

and

adolescent

patients

with

acute

manic

or

mixed

episodes

of

bipolar

I

disorder

increases

in

body

weight

were

higher

in

the

Risperdal

groups

than

the

placebo

group

but

not

dose

related

kg

in

the

Risperdal

mg

group

kg

in

the

Risperdal

mg

group

and

kg

in

the

placebo

group

A

similar

trend

was

observed

in

the

mean

change

from

baseline

in

body

mass

index

When

treating

pediatric

patients

with

Risperdal

for

any

indication

weight

gain

should

be

assessed

against

that

expected

with

normal

growth

Hyperprolactinemia

As

with

other

drugs

that

antagonize

dopamine

D

receptors

Risperdal

elevates

prolactin

levels

and

the

elevation

persists

during

chronic

administration

Risperdal

is

associated

with

higher

levels

of

prolactin

elevation

than

other

antipsychotic

agents

Hyperprolactinemia

may

suppress

hypothalamic

GnRH

resulting

in

reduced

pituitary

gonadotropin

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

prolactinelevating

compounds

Longstanding

hyperprolactinemia

when

associated

with

hypogonadism

may

lead

to

decreased

bone

density

in

both

female

and

male

subjects

Tissue

culture

experiments

indicate

that

approximately

onethird

of

human

breast

cancers

are

prolactin

dependent

in

vitro

a

factor

of

potential

importance

if

the

prescription

of

these

drugs

is

contemplated

in

a

patient

with

previously

detected

breast

cancer

An

increase

in

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

Nonclinical

Toxicology

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

the

available

evidence

is

considered

too

limited

to

be

conclusive

at

this

time

Orthostatic

Hypotension

Risperdal

may

induce

orthostatic

hypotension

associated

with

dizziness

tachycardia

and

in

some

patients

syncope

especially

during

the

initial

dosetitration

period

probably

reflecting

its

alphaadrenergic

antagonistic

properties

Syncope

was

reported

in

of

Risperdal

treated

patients

in

Phase

and

studies

in

adults

with

schizophrenia

The

risk

of

orthostatic

hypotension

and

syncope

may

be

minimized

by

limiting

the

initial

dose

to

mg

total

either

once

daily

or

mg

twice

daily

in

normal

adults

and

mg

twice

daily

in

the

elderly

and

patients

with

renal

or

hepatic

impairment

see

Dosage

and

Administration

Monitoring

of

orthostatic

vital

signs

should

be

considered

in

patients

for

whom

this

is

of

concern

A

dose

reduction

should

be

considered

if

hypotension

occurs

Risperdal

should

be

used

with

particular

caution

in

patients

with

known

cardiovascular

disease

history

of

myocardial

infarction

or

ischemia

heart

failure

or

conduction

abnormalities

cerebrovascular

disease

and

conditions

which

would

predispose

patients

to

hypotension

eg

dehydration

and

hypovolemia

Clinically

significant

hypotension

has

been

observed

with

concomitant

use

of

Risperdal

and

antihypertensive

medication

Falls

Somnolence

postural

hypotension

motor

and

sensory

instability

have

been

reported

with

the

use

of

antipsychotics

including

Risperdal

which

may

lead

to

falls

and

consequently

fractures

or

other

fallrelated

injuries

For

patients

particularly

the

elderly

with

diseases

conditions

or

medications

that

could

exacerbate

these

effects

assess

the

risk

of

falls

when

initiating

antipsychotic

treatment

and

recurrently

for

patients

on

longterm

antipsychotic

therapy

Leukopenia

Neutropenia

and

Agranulocytosis

Class

Effect

In

clinical

trial

andor

postmarketing

experience

events

of

leukopenianeutropenia

have

been

reported

temporally

related

to

antipsychotic

agents

including

Risperdal

Agranulocytosis

has

also

been

reported

Possible

risk

factors

for

leukopenianeutropenia

include

preexisting

low

white

blood

cell

count

WBC

and

history

of

druginduced

leukopenianeutropenia

Patients

with

a

history

of

a

clinically

significant

low

WBC

or

a

druginduced

leukopenianeutropenia

should

have

their

complete

blood

count

CBC

monitored

frequently

during

the

first

few

months

of

therapy

and

discontinuation

of

Risperdal

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

should

discontinue

Risperdal

and

have

their

WBC

followed

until

recovery

Potential

for

Cognitive

and

Motor

Impairment

Somnolence

was

a

commonly

reported

adverse

reaction

associated

with

Risperdal

treatment

especially

when

ascertained

by

direct

questioning

of

patients

This

adverse

reaction

is

doserelated

and

in

a

study

utilizing

a

checklist

to

detect

adverse

events

of

the

highdose

patients

Risperdal

mgday

reported

somnolence

compared

to

of

placebo

patients

Direct

questioning

is

more

sensitive

for

detecting

adverse

events

than

spontaneous

reporting

by

which

of

Risperdal

mgday

patients

and

of

placebo

patients

reported

somnolence

as

an

adverse

reaction

Since

Risperdal

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

Risperdal

therapy

does

not

affect

them

adversely

Seizures

During

premarketing

testing

in

adult

patients

with

schizophrenia

seizures

occurred

in

of

Risperdal

treated

patients

two

in

association

with

hyponatremia

Risperdal

should

be

used

cautiously

in

patients

with

a

history

of

seizures

Dysphagia

Esophageal

dysmotility

and

aspiration

have

been

associated

with

antipsychotic

drug

use

Aspiration

pneumonia

is

a

common

cause

of

morbidity

and

mortality

in

patients

with

advanced

Alzheimers

dementia

Risperdal

and

other

antipsychotic

drugs

should

be

used

cautiously

in

patients

at

risk

for

aspiration

pneumonia

see

Boxed

Warning

and

Warnings

and

Precautions

Priapism

Priapism

has

been

reported

during

postmarketing

surveillance

Severe

priapism

may

require

surgical

intervention

Body

Temperature

Regulation

Disruption

of

body

temperature

regulation

has

been

attributed

to

antipsychotic

agents

Both

hyperthermia

and

hypothermia

have

been

reported

in

association

with

oral

Risperdal

use

Caution

is

advised

when

prescribing

for

patients

who

will

be

exposed

to

temperature

extremes

Patients

with

Phenylketonuria

Inform

patients

that

Risperdal

MTAB

Orally

Disintegrating

Tablets

contain

phenylalanine

Phenylalanine

is

a

component

of

aspartame

Each

mg

Risperdal

MTAB

Orally

Disintegrating

Tablet

contains

mg

phenylalanine

each

mg

Risperdal

MTAB

Orally

Disintegrating

Tablet

contains

mg

phenylalanine

each

mg

Risperdal

MTAB

Orally

Disintegrating

Tablet

contains

mg

phenylalanine

each

mg

Risperdal

MTAB

Orally

Disintegrating

Tablet

contains

mg

phenylalanine

and

each

mg

Risperdal

MTAB

Orally

Disintegrating

Tablet

contains

mg

phenylalanine

Adverse

Reactions

The

following

are

discussed

in

more

detail

in

other

sections

of

the

labeling

Increased

mortality

in

elderly

patients

with

dementiarelated

psychosis

see

Boxed

Warning

and

Warnings

and

Precautions

Cerebrovascular

adverse

events

including

stroke

in

elderly

patients

with

dementiarelated

psychosis

see

Warnings

and

Precautions

Neuroleptic

malignant

syndrome

see

Warnings

and

Precautions

Tardive

dyskinesia

see

Warnings

and

Precautions

Metabolic

Changes

Hyperglycemia

and

diabetes

mellitus

Dyslipidemia

and

Weight

Gain

see

Warnings

and

Precautions

Hyperprolactinemia

see

Warnings

and

Precautions

Orthostatic

hypotension

see

Warnings

and

Precautions

Falls

see

Warnings

and

Precautions

Leukopenia

neutropenia

and

agranulocytosis

see

Warnings

and

Precautions

Potential

for

cognitive

and

motor

impairment

see

Warnings

and

Precautions

Seizures

see

Warnings

and

Precautions

Dysphagia

see

Warnings

and

Precautions

Priapism

see

Warnings

and

Precautions

Disruption

of

body

temperature

regulation

see

Warnings

and

Precautions

Patients

with

Phenylketonuria

see

Warnings

and

Precautions

The

most

common

adverse

reactions

in

clinical

trials

and

twice

placebo

were

parkinsonism

akathisia

dystonia

tremor

sedation

dizziness

anxiety

blurred

vision

nausea

vomiting

upper

abdominal

pain

stomach

discomfort

dyspepsia

diarrhea

salivary

hypersecretion

constipation

dry

mouth

increased

appetite

increased

weight

fatigue

rash

nasal

congestion

upper

respiratory

tract

infection

nasopharyngitis

and

pharyngolaryngeal

pain

The

most

common

adverse

reactions

that

were

associated

with

discontinuation

from

clinical

trials

causing

discontinuation

in

of

adults

andor

of

pediatrics

were

nausea

somnolence

sedation

vomiting

dizziness

and

akathisia

see

Adverse

Reactions

Discontinuations

Due

to

Adverse

Reactions

The

data

described

in

this

section

are

derived

from

a

clinical

trial

database

consisting

of

adult

and

pediatric

patients

exposed

to

one

or

more

doses

of

Risperdal

for

the

treatment

of

schizophrenia

bipolar

mania

autistic

disorder

and

other

psychiatric

disorders

in

pediatrics

and

elderly

patients

with

dementia

Of

these

patients

were

patients

who

received

Risperdal

while

participating

in

doubleblind

placebocontrolled

trials

The

conditions

and

duration

of

treatment

with

Risperdal

varied

greatly

and

included

in

overlapping

categories

doubleblind

fixed

and

flexibledose

placebo

or

activecontrolled

studies

and

openlabel

phases

of

studies

inpatients

and

outpatients

and

shortterm

up

to

weeks

and

longerterm

up

to

years

exposures

Safety

was

assessed

by

collecting

adverse

events

and

performing

physical

examinations

vital

signs

body

weights

laboratory

analyses

and

ECGs

Clinical

Trials

Experience

Because

clinical

trials

are

conducted

under

widely

varying

conditions

adverse

reaction

rates

observed

in

the

clinical

trials

of

a

drug

can

not

be

directly

compared

to

rates

in

the

clinical

trials

of

another

drug

and

may

not

reflect

the

rates

observed

in

clinical

practice

CommonlyObserved

Adverse

Reactions

in

DoubleBlind

PlaceboControlled

Clinical

Trials

Schizophrenia

Adult

Patients

with

Schizophrenia

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

adult

patients

with

schizophrenia

in

three

to

doubleblind

placebocontrolled

trials

Table

Adverse

Reactions

in

of

Risperdal

Treated

Adult

Patients

and

greater

than

placebo

with

Schizophrenia

in

DoubleBlind

PlaceboControlled

Trials

Percentage

of

Patients

Reporting

Reaction

Risperdal

SystemOrgan

Class

Adverse

Reaction

mg

per

day

mg

per

day

Placebo

Parkinsonism

includes

extrapyramidal

disorder

musculoskeletal

stiffness

parkinsonism

cogwheel

rigidity

akinesia

bradykinesia

hypokinesia

masked

facies

muscle

rigidity

and

Parkinsons

disease

Akathisia

includes

akathisia

and

restlessness

Dystonia

includes

dystonia

muscle

spasms

muscle

contractions

involuntary

muscle

contracture

oculogyration

tongue

paralysis

Tremor

includes

tremor

and

parkinsonian

rest

tremor

Cardiac

Disorders

Tachycardia

Eye

Disorders

Vision

blurred

Gastrointestinal

Disorders

Nausea

Constipation

Dyspepsia

Dry

mouth

Abdominal

discomfort

Salivary

hypersecretion

Diarrhea

General

Disorders

Fatigue

Chest

pain

Asthenia

Infections

and

Infestations

Nasopharyngitis

Upper

respiratory

tract

infection

Sinusitis

Urinary

tract

infection

Investigations

Blood

creatine

phosphokinase

increased

Heart

rate

increased

Musculoskeletal

and

Connective

Tissue

Disorders

Back

pain

Arthralgia

Pain

in

extremity

Nervous

System

Disorders

Parkinsonism

Akathisia

Sedation

Dizziness

Dystonia

Tremor

Dizziness

postural

Psychiatric

Disorders

Insomnia

Anxiety

Respiratory

Thoracic

and

Mediastinal

Disorders

Nasal

congestion

Dyspnea

Epistaxis

Skin

and

Subcutaneous

Tissue

Disorders

Rash

Dry

skin

Vascular

Disorders

Orthostatic

hypotension

Pediatric

Patients

with

Schizophrenia

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

pediatric

patients

with

schizophrenia

in

a

doubleblind

placebocontrolled

trial

Table

Adverse

Reactions

in

of

Risperdal

Treated

Pediatric

Patients

and

greater

than

placebo

with

Schizophrenia

in

a

DoubleBlind

Trial

Percentage

of

Patients

Reporting

Reaction

Risperdal

SystemOrgan

Class

Adverse

Reaction

mg

per

day

mg

per

day

Placebo

Parkinsonism

includes

extrapyramidal

disorder

muscle

rigidity

musculoskeletal

stiffness

and

hypokinesia

Akathisia

includes

akathisia

and

restlessness

Dystonia

includes

dystonia

and

oculogyration

Gastrointestinal

Disorders

Salivary

hypersecretion

Nervous

System

Disorders

Sedation

Parkinsonism

Tremor

Akathisia

Dizziness

Dystonia

Psychiatric

Disorders

Anxiety

CommonlyObserved

Adverse

Reactions

in

DoubleBlind

PlaceboControlled

Clinical

Trials

Bipolar

Mania

Adult

Patients

with

Bipolar

Mania

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

adult

patients

with

bipolar

mania

in

four

doubleblind

placebocontrolled

monotherapy

trials

Table

Adverse

Reactions

in

of

Risperdal

Treated

Adult

Patients

and

greater

than

placebo

with

Bipolar

Mania

in

DoubleBlind

PlaceboControlled

Monotherapy

Trials

Percentage

of

Patients

Reporting

Reaction

SystemOrgan

Class

Adverse

Reaction

Risperdal

mg

per

day

Placebo

Parkinsonism

includes

extrapyramidal

disorder

parkinsonism

musculoskeletal

stiffness

hypokinesia

muscle

rigidity

muscle

tightness

bradykinesia

cogwheel

rigidity

Akathisia

includes

akathisia

and

restlessness

Tremor

includes

tremor

and

parkinsonian

rest

tremor

Dystonia

includes

dystonia

muscle

spasms

oculogyration

torticollis

Eye

Disorders

Vision

blurred

Gastrointestinal

Disorders

Nausea

Diarrhea

Salivary

hypersecretion

Stomach

discomfort

General

Disorders

Fatigue

Nervous

System

Disorders

Parkinsonism

Sedation

Akathisia

Tremor

Dizziness

Dystonia

Lethargy

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

adult

patients

with

bipolar

mania

in

two

doubleblind

placebocontrolled

adjuvant

therapy

trials

Table

Adverse

Reactions

in

of

Risperdal

Treated

Adult

Patients

and

greater

than

placebo

with

Bipolar

Mania

in

DoubleBlind

PlaceboControlled

Adjunctive

Therapy

Trials

Percentage

of

Patients

Reporting

Reaction

SystemOrgan

Class

Risperdal

Mood

Stabilizer

Placebo

Mood

Stabilizer

Adverse

Reaction

Parkinsonism

includes

extrapyramidal

disorder

hypokinesia

and

bradykinesia

Akathisia

includes

hyperkinesia

and

akathisia

Cardiac

Disorders

Palpitations

Gastrointestinal

Disorders

Dyspepsia

Nausea

Diarrhea

Salivary

hypersecretion

General

Disorders

Chest

pain

Infections

and

Infestations

Urinary

tract

infection

Nervous

System

Disorders

Parkinsonism

Sedation

Akathisia

Dizziness

Tremor

Lethargy

Psychiatric

Disorders

Anxiety

Respiratory

Thoracic

and

Mediastinal

Disorders

Pharyngolaryngeal

pain

Cough

Pediatric

Patients

with

Bipolar

Mania

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

pediatric

patients

with

bipolar

mania

in

a

doubleblind

placebocontrolled

trial

Table

Adverse

Reactions

in

of

Risperdal

Treated

Pediatric

Patients

and

greater

than

placebo

with

Bipolar

Mania

in

DoubleBlind

PlaceboControlled

Trials

Percentage

of

Patients

Reporting

Reaction

Risperdal

SystemOrgan

Class

Adverse

Reaction

mg

per

day

mg

per

day

Placebo

Parkinsonism

includes

musculoskeletal

stiffness

extrapyramidal

disorder

bradykinesia

and

nuchal

rigidity

Dystonia

includes

dystonia

laryngospasm

and

muscle

spasms

Akathisia

includes

restlessness

and

akathisia

Eye

Disorders

Vision

blurred

Gastrointestinal

Disorders

Abdominal

pain

upper

Nausea

Vomiting

Diarrhea

Dyspepsia

Stomach

discomfort

General

Disorders

Fatigue

Metabolism

and

Nutrition

Disorders

Increased

appetite

Nervous

System

Disorders

Sedation

Dizziness

Parkinsonism

Dystonia

Akathisia

Psychiatric

Disorders

Anxiety

Respiratory

Thoracic

and

Mediastinal

Disorders

Pharyngolaryngeal

pain

Skin

and

Subcutaneous

Tissue

Disorders

Rash

CommonlyObserved

Adverse

Reactions

in

DoubleBlind

PlaceboControlled

Clinical

Trials

Autistic

Disorder

Table

lists

the

adverse

reactions

reported

in

or

more

of

Risperdal

treated

pediatric

patients

treated

for

irritability

associated

with

autistic

disorder

in

two

doubleblind

placebocontrolled

trials

and

one

doubleblind

placebocontrolled

study

Table

Adverse

Reactions

in

of

Risperdal

Treated

Pediatric

Patients

and

greater

than

placebo

Treated

for

Irritability

Associated

with

Autistic

Disorder

in

DoubleBlind

PlaceboControlled

Trials

Percentage

of

Patients

Reporting

Reaction

SystemOrgan

Class

Risperdal

mgday

Placebo

Adverse

Reaction

Parkinsonism

includes

musculoskeletal

stiffness

extrapyramidal

disorder

muscle

rigidity

cogwheel

rigidity

and

muscle

tightness

Gastrointestinal

Disorders

Vomiting

Constipation

Dry

mouth

Nausea

Salivary

hypersecretion

General

Disorders

and

Administration

Site

Conditions

Fatigue

Pyrexia

Thirst

Infections

and

Infestations

Nasopharyngitis

Rhinitis

Upper

respiratory

tract

infection

Investigations

Weight

increased

Metabolism

and

Nutrition

Disorders

Increased

appetite

Nervous

System

Disorders

Sedation

Drooling

Headache

Tremor

Dizziness

Parkinsonism

Renal

and

Urinary

Disorders

Enuresis

Respiratory

Thoracic

and

Mediastinal

Disorders

Cough

Rhinorrhea

Nasal

congestion

Skin

and

Subcutaneous

Tissue

Disorders

Rash

Other

Adverse

Reactions

Observed

During

the

Clinical

Trial

Evaluation

of

Risperidone

The

following

additional

adverse

reactions

occurred

across

all

placebocontrolled

activecontrolled

and

openlabel

studies

of

Risperdal

in

adults

and

pediatric

patients

Blood

and

Lymphatic

System

Disorders

anemia

granulocytopenia

neutropenia

Cardiac

Disorders

sinus

bradycardia

sinus

tachycardia

atrioventricular

block

first

degree

bundle

branch

block

left

bundle

branch

block

right

atrioventricular

block

Ear

and

Labyrinth

Disorders

ear

pain

tinnitus

Endocrine

Disorders

hyperprolactinemia

Eye

Disorders

ocular

hyperemia

eye

discharge

conjunctivitis

eye

rolling

eyelid

edema

eye

swelling

eyelid

margin

crusting

dry

eye

lacrimation

increased

photophobia

glaucoma

visual

acuity

reduced

Gastrointestinal

Disorders

dysphagia

fecaloma

fecal

incontinence

gastritis

lip

swelling

cheilitis

aptyalism

General

Disorders

edema

peripheral

thirst

gait

disturbance

influenzalike

illness

pitting

edema

edema

chills

sluggishness

malaise

chest

discomfort

face

edema

discomfort

generalized

edema

drug

withdrawal

syndrome

peripheral

coldness

feeling

abnormal

Immune

System

Disorders

drug

hypersensitivity

Infections

and

Infestations

pneumonia

influenza

ear

infection

viral

infection

pharyngitis

tonsillitis

bronchitis

eye

infection

localized

infection

cystitis

cellulitis

otitis

media

onychomycosis

acarodermatitis

bronchopneumonia

respiratory

tract

infection

tracheobronchitis

otitis

media

chronic

Investigations

body

temperature

increased

blood

prolactin

increased

alanine

aminotransferase

increased

electrocardiogram

abnormal

eosinophil

count

increased

white

blood

cell

count

decreased

blood

glucose

increased

hemoglobin

decreased

hematocrit

decreased

body

temperature

decreased

blood

pressure

decreased

transaminases

increased

Metabolism

and

Nutrition

Disorders

decreased

appetite

polydipsia

anorexia

Musculoskeletal

and

Connective

Tissue

Disorders

joint

stiffness

joint

swelling

musculoskeletal

chest

pain

posture

abnormal

myalgia

neck

pain

muscular

weakness

rhabdomyolysis

Nervous

System

Disorders

balance

disorder

disturbance

in

attention

dysarthria

unresponsive

to

stimuli

depressed

level

of

consciousness

movement

disorder

transient

ischemic

attack

coordination

abnormal

cerebrovascular

accident

speech

disorder

syncope

loss

of

consciousness

hypoesthesia

tardive

dyskinesia

dyskinesia

cerebral

ischemia

cerebrovascular

disorder

neuroleptic

malignant

syndrome

diabetic

coma

head

titubation

Psychiatric

Disorders

agitation

blunted

affect

confusional

state

middle

insomnia

nervousness

sleep

disorder

listlessness

libido

decreased

and

anorgasmia

Renal

and

Urinary

Disorders

enuresis

dysuria

pollakiuria

urinary

incontinence

Reproductive

System

and

Breast

Disorders

menstruation

irregular

amenorrhea

gynecomastia

galactorrhea

vaginal

discharge

menstrual

disorder

erectile

dysfunction

retrograde

ejaculation

ejaculation

disorder

sexual

dysfunction

breast

enlargement

Respiratory

Thoracic

and

Mediastinal

Disorders

wheezing

pneumonia

aspiration

sinus

congestion

dysphonia

productive

cough

pulmonary

congestion

respiratory

tract

congestion

rales

respiratory

disorder

hyperventilation

nasal

edema

Skin

and

Subcutaneous

Tissue

Disorders

erythema

skin

discoloration

skin

lesion

pruritus

skin

disorder

rash

erythematous

rash

papular

rash

generalized

rash

maculopapular

acne

hyperkeratosis

seborrheic

dermatitis

Vascular

Disorders

hypotension

flushing

Additional

Adverse

Reactions

Reported

with

Risperdal

CONSTA

The

following

is

a

list

of

additional

adverse

reactions

that

have

been

reported

during

the

premarketing

evaluation

of

Risperdal

CONSTA

regardless

of

frequency

of

occurrence

Cardiac

Disorders

bradycardia

Ear

and

Labyrinth

Disorders

vertigo

Eye

Disorders

blepharospasm

Gastrointestinal

Disorders

toothache

tongue

spasm

General

Disorders

and

Administration

Site

Conditions

pain

Infections

and

Infestations

lower

respiratory

tract

infection

infection

gastroenteritis

subcutaneous

abscess

Injury

and

Poisoning

fall

Investigations

weight

decreased

gammaglutamyltransferase

increased

hepatic

enzyme

increased

Musculoskeletal

Connective

Tissue

and

Bone

Disorders

buttock

pain

Nervous

System

Disorders

convulsion

paresthesia

Psychiatric

Disorders

depression

Skin

and

Subcutaneous

Tissue

Disorders

eczema

Vascular

Disorders

hypertension

Discontinuations

Due

to

Adverse

Reactions

Schizophrenia

Adults

Approximately

of

Risperdal

treated

patients

in

doubleblind

placebocontrolled

trials

discontinued

treatment

due

to

an

adverse

reaction

compared

with

who

were

receiving

placebo

The

adverse

reactions

associated

with

discontinuation

in

or

more

Risperdal

treated

patients

were

Table

Adverse

Reactions

Associated

With

Discontinuation

in

or

More

Risperdal

Treated

Adult

Patients

in

Schizophrenia

Trials

Risperdal

Adverse

Reaction

mgday

mgday

Placebo

Dizziness

Nausea

Vomiting

Parkinsonism

Somnolence

Dystonia

Agitation

Abdominal

pain

Orthostatic

hypotension

Akathisia

Discontinuation

for

extrapyramidal

symptoms

including

Parkinsonism

akathisia

dystonia

and

tardive

dyskinesia

was

in

placebotreated

patients

and

in

active

controltreated

patients

in

a

doubleblind

placebo

and

activecontrolled

trial

Schizophrenia

Pediatrics

Approximately

of

Risperdal

treated

patients

discontinued

treatment

due

to

an

adverse

reaction

in

a

doubleblind

placebocontrolled

trial

compared

with

placebotreated

patients

The

adverse

reactions

associated

with

discontinuation

for

at

least

one

Risperdal

treated

patient

were

dizziness

somnolence

sedation

lethargy

anxiety

balance

disorder

hypotension

and

palpitation

Bipolar

Mania

Adults

In

doubleblind

placebocontrolled

trials

with

Risperdal

as

monotherapy

approximately

of

Risperdal

treated

patients

discontinued

treatment

due

to

an

adverse

event

compared

with

approximately

of

placebotreated

patients

The

adverse

reactions

associated

with

discontinuation

in

Risperdal

treated

patients

were

Table

Adverse

Reactions

Associated

With

Discontinuation

in

or

More

Risperdal

Treated

Adult

Patients

in

Bipolar

Mania

Clinical

Trials

Adverse

Reaction

Risperdal

mgday

Placebo

Parkinsonism

Lethargy

Dizziness

Alanine

aminotransferase

increased

Aspartate

aminotransferase

increased

Bipolar

Mania

Pediatrics

In

a

doubleblind

placebocontrolled

trial

of

Risperdal

treated

patients

discontinued

due

to

an

adverse

reaction

compared

with

of

placebotreated

patients

The

adverse

reactions

associated

with

discontinuation

in

more

than

one

Risperdal

treated

pediatric

patient

were

nausea

somnolence

sedation

and

vomiting

Autistic

Disorder

Pediatrics

In

the

two

placebocontrolled

trials

in

pediatric

patients

treated

for

irritability

associated

with

autistic

disorder

one

Risperdal

treated

patient

discontinued

due

to

an

adverse

reaction

Parkinsonism

and

one

placebotreated

patient

discontinued

due

to

an

adverse

event

Dose

Dependency

of

Adverse

Reactions

in

Clinical

Trials

Extrapyramidal

Symptoms

Data

from

two

fixeddose

trials

in

adults

with

schizophrenia

provided

evidence

of

doserelatedness

for

extrapyramidal

symptoms

associated

with

Risperdal

treatment

Two

methods

were

used

to

measure

extrapyramidal

symptoms

EPS

in

an

trial

comparing

fixed

doses

of

Risperdal

and

mgday

including

a

Parkinsonism

score

mean

change

from

baseline

from

the

Extrapyramidal

Symptom

Rating

Scale

and

incidence

of

spontaneous

complaints

of

EPS

Table

Dose

Groups

Placebo

Risperdal

mg

Risperdal

mg

Risperdal

mg

Risperdal

mg

Parkinsonism

EPS

Incidence

Similar

methods

were

used

to

measure

extrapyramidal

symptoms

EPS

in

an

trial

comparing

fixed

doses

of

Risperdal

and

mgday

Table

Dose

Groups

Risperdal

mg

Risperdal

mg

Risperdal

mg

Risperdal

mg

Risperdal

mg

Parkinsonism

EPS

Incidence

Dystonia

Class

Effect

Symptoms

of

dystonia

prolonged

abnormal

contractions

of

muscle

groups

may

occur

in

susceptible

individuals

during

the

first

few

days

of

treatment

Dystonic

symptoms

include

spasm

of

the

neck

muscles

sometimes

progressing

to

tightness

of

the

throat

swallowing

difficulty

difficulty

breathing

andor

protrusion

of

the

tongue

While

these

symptoms

can

occur

at

low

doses

they

occur

more

frequently

and

with

greater

severity

with

high

potency

and

at

higher

doses

of

first

generation

antipsychotic

drugs

An

elevated

risk

of

acute

dystonia

is

observed

in

males

and

younger

age

groups

Other

Adverse

Reactions

Adverse

event

data

elicited

by

a

checklist

for

side

effects

from

a

large

study

comparing

fixed

doses

of

Risperdal

and

mgday

were

explored

for

doserelatedness

of

adverse

events

A

CochranArmitage

Test

for

trend

in

these

data

revealed

a

positive

trend

for

the

following

adverse

reactions

somnolence

vision

abnormal

dizziness

palpitations

weight

increase

erectile

dysfunction

ejaculation

disorder

sexual

function

abnormal

fatigue

and

skin

discoloration

Changes

in

Body

Weight

Weight

gain

was

observed

in

shortterm

controlled

trials

and

longerterm

uncontrolled

studies

in

adult

and

pediatric

patients

see

Warnings

and

Precautions

Adverse

Reactions

and

Use

in

Specific

Populations

Changes

in

ECG

Parameters

Betweengroup

comparisons

for

pooled

placebocontrolled

trials

in

adults

revealed

no

statistically

significant

differences

between

risperidone

and

placebo

in

mean

changes

from

baseline

in

ECG

parameters

including

QT

QTc

and

PR

intervals

and

heart

rate

When

all

Risperdal

doses

were

pooled

from

randomized

controlled

trials

in

several

indications

there

was

a

mean

increase

in

heart

rate

of

beat

per

minute

compared

to

no

change

for

placebo

patients

In

shortterm

schizophrenia

trials

higher

doses

of

risperidone

mgday

were

associated

with

a

higher

mean

increase

in

heart

rate

compared

to

placebo

beats

per

minute

In

pooled

placebocontrolled

acute

mania

trials

in

adults

there

were

small

decreases

in

mean

heart

rate

similar

among

all

treatment

groups

In

the

two

placebocontrolled

trials

in

children

and

adolescents

with

autistic

disorder

aged

years

mean

changes

in

heart

rate

were

an

increase

of

beats

per

minute

in

the

Risperdal

groups

and

beats

per

minute

in

the

placebo

group

There

were

no

other

notable

ECG

changes

In

a

placebocontrolled

acute

mania

trial

in

children

and

adolescents

aged

years

there

were

no

significant

changes

in

ECG

parameters

other

than

the

effect

of

Risperdal

to

transiently

increase

pulse

rate

beats

per

minute

In

two

controlled

schizophrenia

trials

in

adolescents

aged

years

there

were

no

clinically

meaningful

changes

in

ECG

parameters

including

corrected

QT

intervals

between

treatment

groups

or

within

treatment

groups

over

time

Postmarketing

Experience

The

following

adverse

reactions

have

been

identified

during

postapproval

use

of

risperidone

Because

these

reactions

are

reported

voluntarily

from

a

population

of

uncertain

size

it

is

not

always

possible

to

reliably

estimate

their

frequency

or

establish

a

causal

relationship

to

drug

exposure

These

adverse

reactions

include

alopecia

anaphylactic

reaction

angioedema

atrial

fibrillation

cardiopulmonary

arrest

diabetic

ketoacidosis

in

patients

with

impaired

glucose

metabolism

dysgeusia

hypoglycemia

hypothermia

ileus

inappropriate

antidiuretic

hormone

secretion

intestinal

obstruction

jaundice

mania

pancreatitis

pituitary

adenoma

precocious

puberty

pulmonary

embolism

QT

prolongation

sleep

apnea

syndrome

sleeprelated

eating

disorder

somnambulism

sudden

death

thrombocytopenia

thrombotic

thrombocytopenic

purpura

urinary

retention

and

water

Drug

Interactions

Pharmacokineticrelated

Interactions

The

dose

of

Risperdal

should

be

adjusted

when

used

in

combination

with

enzyme

inhibitors

eg

fluoxetine

and

paroxetine

and

enzyme

inducers

eg

carbamazepine

see

Table

and

Dosage

and

Administration

Dose

adjustment

is

not

recommended

for

Risperdal

when

coadministered

with

ranitidine

cimetidine

amitriptyline

or

erythromycin

see

Table

Table

Summary

of

Effect

of

Coadministered

Drugs

on

Exposure

to

Active

Moiety

Risperidone

in

Healthy

Subjects

or

Patients

with

Schizophrenia

Coadministered

Drug

Dosing

Schedule

Effect

on

Active

Moiety

Risperidone

Ratio

Risperidone

Dose

Recommendation

Coadministered

Drug

Risperidone

AUC

C

max

Change

relative

to

reference

Enzyme

Inhibitors

Fluoxetine

mgday

or

mg

twice

daily

Reevaluate

dosing

Do

not

exceed

mgday

Paroxetine

mgday

mgday

Reevaluate

dosing

Do

not

exceed

mgday

mgday

mgday

mgday

mgday

Enzyme

inducers

Inducers

Carbamazepine

mgday

mg

twice

daily

Titrate

dose

upwards

Do

not

exceed

twice

the

patients

usual

dose

Enzyme

Inhibitors

Ranitidine

mg

twice

daily

mg

single

dose

Dose

adjustment

not

needed

Cimetidine

mg

twice

daily

mg

single

dose

Dose

adjustment

not

needed

Erythromycin

mg

four

times

daily

mg

single

dose

Dose

adjustment

not

needed

Other

Drugs

Amitriptyline

mg

twice

daily

mg

twice

daily

Dose

adjustment

not

needed

Effect

of

Risperidone

on

Other

Drugs

Lithium

Repeated

oral

doses

of

Risperdal

mg

twice

daily

did

not

affect

the

exposure

AUC

or

peak

plasma

concentrations

C

max

of

lithium

Dose

adjustment

for

lithium

is

not

recommended

Valproate

Repeated

oral

doses

of

Risperdal

mg

once

daily

did

not

affect

the

predose

or

average

plasma

concentrations

and

exposure

AUC

of

valproate

mgday

in

three

divided

doses

compared

to

placebo

However

there

was

a

increase

in

valproate

peak

plasma

concentration

C

max

after

concomitant

administration

of

Risperdal

Dose

adjustment

for

valproate

is

not

recommended

Digoxin

Risperdal

mg

twice

daily

did

not

show

a

clinically

relevant

effect

on

the

pharmacokinetics

of

digoxin

Dose

adjustment

for

digoxin

is

not

recommended

Pharmacodynamicrelated

Interactions

CentrallyActing

Drugs

and

Alcohol

Given

the

primary

CNS

effects

of

risperidone

caution

should

be

used

when

Risperdal

is

taken

in

combination

with

other

centrallyacting

drugs

and

alcohol

Drugs

with

Hypotensive

Effects

Because

of

its

potential

for

inducing

hypotension

Risperdal

may

enhance

the

hypotensive

effects

of

other

therapeutic

agents

with

this

potential

Levodopa

and

Dopamine

Agonists

Risperdal

may

antagonize

the

effects

of

levodopa

and

dopamine

agonists

Clozapine

Chronic

administration

of

clozapine

with

Risperdal

may

decrease

the

clearance

of

risperidone

USE

IN

SPECIFIC

POPULATIONS

Pregnancy

Pregnancy

Exposure

Registry

There

is

a

pregnancy

exposure

registry

that

monitors

pregnancy

outcomes

in

women

exposed

to

atypical

antipsychotics

including

Risperdal

during

pregnancy

Healthcare

providers

are

encouraged

to

register

patients

by

contacting

the

National

Pregnancy

Registry

for

Atypical

Antipsychotics

at

or

online

at

httpwomensmentalhealthorgclinicalandresearchprogramspregnancyregistry

Risk

Summary

Neonates

exposed

to

antipsychotic

drugs

during

the

third

trimester

of

pregnancy

are

at

risk

for

extrapyramidal

andor

withdrawal

symptoms

following

delivery

see

Clinical

Considerations

Overall

available

data

from

published

epidemiologic

studies

of

pregnant

women

exposed

to

risperidone

have

not

established

a

drugassociated

risk

of

major

birth

defects

miscarriage

or

adverse

maternal

or

fetal

outcomes

see

Data

There

are

risks

to

the

mother

associated

with

untreated

schizophrenia

or

bipolar

I

disorder

and

with

exposure

to

antipsychotics

including

Risperdal

during

pregnancy

see

Clinical

Considerations

Oral

administration

of

risperidone

to

pregnant

mice

caused

cleft

palate

at

doses

to

times

the

maximum

recommended

human

dose

MRHD

with

maternal

toxicity

observed

at

MRHD

based

on

mgm

body

surface

area

Risperidone

was

not

teratogenic

in

rats

or

rabbits

at

doses

up

to

times

the

MRHD

based

on

mgm

body

surface

area

Increased

stillbirths

and

decreased

birth

weight

occurred

after

oral

risperidone

administration

to

pregnant

rats

at

the

MRHD

based

on

mgm

body

surface

area

Learning

was

impaired

in

offspring

of

rats

when

the

dams

were

dosed

at

the

MRHD

and

offspring

mortality

increased

at

doses

to

times

the

MRHD

based

on

mgm

body

surface

area

The

estimated

background

risk

of

major

birth

defects

and

miscarriage

for

the

indicated

population

is

unknown

All

pregnancies

have

a

background

risk

of

birth

defect

loss

or

other

adverse

outcomes

In

the

US

general

population

the

estimated

background

risk

of

major

birth

defects

and

miscarriage

in

clinically

recognized

pregnancies

is

and

respectively

Clinical

Considerations

Diseaseassociated

maternal

andor

embryofetal

risk

There

is

a

risk

to

the

mother

from

untreated

schizophrenia

or

bipolar

I

disorder

including

increased

risk

of

relapse

hospitalization

and

suicide

Schizophrenia

and

bipolar

I

disorder

are

associated

with

increased

adverse

perinatal

outcomes

including

preterm

birth

It

is

not

known

if

this

is

a

direct

result

of

the

illness

or

other

comorbid

factors

FetalNeonatal

Adverse

Reactions

Extrapyramidal

andor

withdrawal

symptoms

including

agitation

hypertonia

hypotonia

tremor

somnolence

respiratory

distress

and

feeding

disorder

have

been

reported

in

neonates

who

were

exposed

to

antipsychotic

drugs

including

Risperdal

during

the

third

trimester

of

pregnancy

These

symptoms

have

varied

in

severity

Monitor

neonates

for

extrapyramidal

andor

withdrawal

symptoms

and

manage

symptoms

appropriately

Some

neonates

recovered

within

hours

or

days

without

specific

treatment

others

required

prolonged

hospitalization

Data

Human

Data

Published

data

from

observational

studies

birth

registries

and

case

reports

on

the

use

of

atypical

antipsychotics

during

pregnancy

do

not

report

a

clear

association

with

antipsychotics

and

major

birth

defects

A

prospective

observational

study

including

women

treated

with

risperidone

demonstrated

placental

passage

of

risperidone

A

retrospective

cohort

study

from

a

Medicaid

database

of

women

exposed

to

antipsychotics

during

pregnancy

did

not

indicate

an

overall

increased

risk

for

major

birth

defects

There

was

a

small

increase

in

the

risk

of

major

birth

defects

CI

and

of

cardiac

malformations

CI

in

a

subgroup

of

Animal

Data

Oral

administration

of

risperidone

to

pregnant

mice

during

organogenesis

caused

cleft

palate

at

mgkgday

which

is

times

the

MRHD

of

mgday

based

on

mgm

body

surface

area

maternal

toxicity

occurred

at

times

the

MRHD

Risperidone

was

not

teratogenic

when

administered

orally

to

rats

at

to

mgkgday

and

rabbits

at

to

mgkgday

which

are

up

to

times

the

MRHD

of

mgday

risperidone

based

on

mgm

body

surface

area

Learning

was

impaired

in

offspring

of

rats

dosed

orally

throughout

pregnancy

at

mgkgday

which

is

times

the

MRHD

and

neuronal

cell

death

increased

in

fetal

brains

of

offspring

of

rats

dosed

during

pregnancy

at

and

mgkgday

which

are

and

times

the

MRHD

based

on

mgm

body

surface

area

postnatal

development

and

growth

of

the

offspring

were

also

delayed

Rat

offspring

mortality

increased

during

the

first

days

of

lactation

when

pregnant

rats

were

dosed

throughout

gestation

at

to

mgkgday

which

are

to

times

the

MRHD

of

mgday

based

on

mgm

body

surface

area

It

is

not

known

whether

these

deaths

were

due

to

a

direct

effect

on

the

fetuses

or

pups

or

to

effects

on

the

dams

a

noeffect

dose

could

not

be

determined

The

rate

of

stillbirths

was

increased

at

mgkg

or

times

the

MRHD

based

on

mgm

body

surface

area

In

a

rat

crossfostering

study

the

number

of

live

offspring

was

decreased

the

number

of

stillbirths

increased

and

the

birth

weight

was

decreased

in

offspring

of

drugtreated

pregnant

rats

In

addition

the

number

of

deaths

increased

by

Day

among

offspring

of

drugtreated

pregnant

rats

regardless

of

whether

or

not

the

offspring

were

crossfostered

Risperidone

also

appeared

to

impair

maternal

behavior

in

that

offspring

body

weight

gain

and

survival

from

Day

to

of

lactation

were

reduced

in

offspring

born

to

control

but

reared

by

drugtreated

dams

All

of

these

effects

occurred

at

mgkg

which

is

times

and

the

only

dose

tested

in

the

study

Lactation

Risk

Summary

Limited

data

from

published

literature

reports

the

presence

of

risperidone

and

its

metabolite

in

human

breast

milk

at

relative

infant

dose

ranging

between

and

of

the

maternal

weightadjusted

dosage

There

are

reports

of

sedation

failure

to

thrive

jitteriness

and

extrapyramidal

symptoms

tremors

and

abnormal

muscle

movements

in

breastfed

infants

exposed

to

risperidone

see

Clinical

Considerations

There

is

no

information

on

the

effects

of

risperidone

on

milk

production

The

developmental

and

health

benefits

of

breastfeeding

should

be

considered

along

with

the

mothers

clinical

need

for

Risperdal

and

any

potential

adverse

effects

on

the

breastfed

child

from

Risperdal

or

from

the

mothers

underlying

condition

Clinical

Considerations

Infants

exposed

to

Risperdal

through

breastmilk

should

be

monitored

for

excess

sedation

failure

to

thrive

jitteriness

and

extrapyramidal

symptoms

tremors

and

abnormal

muscle

movements

Females

and

Males

of

Reproductive

Potential

Infertility

Females

Based

on

the

pharmacologic

action

of

risperidone

receptor

antagonism

treatment

with

Risperdal

may

result

in

an

increase

in

serum

prolactin

levels

which

may

lead

to

a

reversible

reduction

in

fertility

in

females

of

reproductive

potential

see

Warnings

and

Precautions

Pediatric

Use

Approved

Pediatric

Indications

Schizophrenia

The

efficacy

and

safety

of

Risperdal

in

the

treatment

of

schizophrenia

were

demonstrated

in

adolescents

aged

years

in

two

shortterm

and

weeks

respectively

doubleblind

controlled

trials

see

Indications

and

Usage

Adverse

Reactions

and

Clinical

Studies

Additional

safety

and

efficacy

information

was

also

assessed

in

one

longterm

openlabel

extension

study

in

of

these

adolescent

patients

with

schizophrenia

Safety

and

effectiveness

of

Risperdal

in

children

less

than

years

of

age

with

schizophrenia

have

not

been

established

Bipolar

I

Disorder

The

efficacy

and

safety

of

Risperdal

in

the

shortterm

treatment

of

acute

manic

or

mixed

episodes

associated

with

Bipolar

I

Disorder

in

children

and

adolescent

patients

aged

years

were

demonstrated

in

one

doubleblind

placebocontrolled

trial

see

Indications

and

Usage

Adverse

Reactions

and

Clinical

Studies

Safety

and

effectiveness

of

Risperdal

in

children

less

than

years

of

age

with

bipolar

disorder

have

not

been

established

Autistic

Disorder

The

efficacy

and

safety

of

Risperdal

in

the

treatment

of

irritability

associated

with

autistic

disorder

were

established

in

two

doubleblind

placebocontrolled

trials

in

children

and

adolescent

patients

aged

to

years

see

Indications

and

Usage

Adverse

Reactions

and

Clinical

Studies

Additional

safety

information

was

also

assessed

in

a

longterm

study

in

patients

with

autistic

disorder

or

in

short

and

longterm

studies

in

more

than

pediatric

patients

with

psychiatric

disorders

other

than

autistic

disorder

schizophrenia

or

bipolar

mania

who

were

of

similar

age

and

weight

and

who

received

similar

dosages

of

Risperdal

as

patients

treated

for

irritability

associated

with

autistic

disorder

A

third

study

was

a

multicenter

randomized

doubleblind

placebocontrolled

fixeddose

study

to

evaluate

the

efficacy

and

safety

of

a

lower

than

recommended

dose

of

risperidone

in

subjects

to

years

of

age

with

autistic

disorder

and

associated

irritability

and

related

behavioral

symptoms

There

were

two

weightbased

fixed

doses

of

risperidone

highdose

and

lowdose

The

high

dose

was

mg

per

day

for

patients

weighing

to

kg

and

it

was

mg

per

day

for

patients

weighing

kg

The

low

dose

was

mg

per

day

for

patients

for

patients

weighing

to

kg

and

Adverse

Reactions

in

Pediatric

Patients

Tardive

Dyskinesia

In

clinical

trials

in

children

and

adolescents

treated

with

Risperdal

patients

were

reported

to

have

tardive

dyskinesia

which

resolved

on

discontinuation

of

Risperdal

treatment

see

also

Warnings

and

Precautions

Weight

Gain

Weight

gain

has

been

observed

in

children

and

adolescents

during

treatment

with

Risperdal

Clinical

monitoring

of

weight

is

recommended

during

treatment

Data

derive

from

shortterm

placebocontrolled

trials

and

longerterm

uncontrolled

studies

in

pediatric

patients

ages

to

years

with

schizophrenia

bipolar

disorder

autistic

disorder

or

other

psychiatric

disorders

In

the

shortterm

trials

to

weeks

the

mean

weight

gain

for

Risperdal

treated

patients

was

kg

compared

to

kg

for

placebotreated

patients

In

these

trials

approximately

of

the

Risperdal

group

had

weight

gain

compared

to

in

the

placebo

group

In

longerterm

uncontrolled

openlabel

pediatric

studies

the

mean

weight

gain

was

kg

at

Week

and

kg

at

Week

see

Warnings

and

Precautions

and

Adverse

Reactions

Somnolence

Somnolence

was

frequently

observed

in

placebocontrolled

clinical

trials

of

pediatric

patients

with

autistic

disorder

Most

cases

were

mild

or

moderate

in

severity

These

events

were

most

often

of

early

onset

with

peak

incidence

occurring

during

the

first

two

weeks

of

treatment

and

transient

with

a

median

duration

of

days

Somnolence

was

the

most

commonly

observed

adverse

reaction

in

the

clinical

trial

of

bipolar

disorder

in

children

and

adolescents

as

well

as

in

the

schizophrenia

trials

in

adolescents

As

was

seen

in

the

autistic

disorder

trials

these

adverse

reactions

were

most

often

of

early

onset

and

transient

in

duration

see

Adverse

Reactions

and

Patients

experiencing

persistent

somnolence

may

benefit

from

a

change

in

dosing

regimen

see

Dosage

and

Administration

and

Hyperprolactinemia

Risperdal

has

been

shown

to

elevate

prolactin

levels

in

children

and

adolescents

as

well

as

in

adults

see

Warnings

and

Precautions

In

doubleblind

placebocontrolled

studies

of

up

to

weeks

duration

in

children

and

adolescents

aged

to

years

with

autistic

disorder

or

psychiatric

disorders

other

than

autistic

disorder

schizophrenia

or

bipolar

mania

of

patients

who

received

Risperdal

had

elevated

prolactin

levels

compared

to

of

patients

who

received

placebo

Similarly

in

placebocontrolled

trials

in

children

and

adolescents

aged

to

years

with

bipolar

disorder

or

adolescents

aged

to

years

with

schizophrenia

of

patients

who

received

Risperdal

had

elevated

levels

of

prolactin

compared

to

of

patients

on

placebo

Increases

were

dosedependent

and

generally

greater

in

females

than

in

males

across

indications

In

clinical

trials

in

children

and

adolescents

galactorrhea

was

reported

in

of

Risperdal

treated

patients

and

gynecomastia

was

reported

in

of

Risperdal

treated

patients

Growth

and

Sexual

Maturation

The

longterm

effects

of

Risperdal

on

growth

and

sexual

maturation

have

not

been

fully

evaluated

in

children

and

adolescents

Juvenile

Animal

Studies

Juvenile

dogs

were

treated

with

oral

risperidone

from

weeks

to

of

age

equivalent

to

the

period

of

childhood

through

adolescence

in

humans

at

doses

of

or

mgkgday

which

are

and

times

the

MRHD

of

mgday

for

children

based

on

mgm

body

surface

area

Bone

length

and

density

were

decreased

with

a

noeffect

dose

of

mgkgday

this

dose

produced

plasma

AUC

of

risperidone

plus

its

active

metabolite

paliperidone

that

were

similar

to

those

in

children

and

adolescents

receiving

the

MRHD

of

mgday

In

addition

sexual

maturation

was

delayed

at

all

doses

in

both

males

and

females

The

above

effects

showed

little

or

no

reversibility

in

females

after

a

week

drugfree

recovery

period

Juvenile

rats

treated

with

oral

risperidone

from

days

to

of

age

equivalent

to

the

period

of

infancy

through

adolescence

in

humans

showed

impaired

learning

and

memory

performance

reversible

only

in

females

with

a

noeffect

dose

of

mgkgday

which

is

times

the

MRHD

of

mgday

for

children

based

on

mgm

body

surface

area

This

dose

produced

plasma

AUC

of

risperidone

plus

paliperidone

about

half

the

exposure

observed

in

humans

at

the

MRHD

No

other

consistent

effects

on

neurobehavioral

or

reproductive

development

were

seen

up

to

the

highest

tested

dose

of

mgkgday

which

is

time

the

MRHD

and

produced

plasma

AUC

of

risperidone

plus

paliperidone

that

were

about

two

thirds

of

those

observed

in

humans

at

the

MRHD

of

mgday

for

children

Geriatric

Use

Clinical

studies

of

Risperdal

in

the

treatment

of

schizophrenia

did

not

include

sufficient

numbers

of

patients

aged

and

over

to

determine

whether

or

not

they

respond

differently

than

younger

patients

Other

reported

clinical

experience

has

not

identified

differences

in

responses

between

elderly

and

younger

patients

In

general

a

lower

starting

dose

is

recommended

for

an

elderly

patient

reflecting

a

decreased

pharmacokinetic

clearance

in

the

elderly

as

well

as

a

greater

frequency

of

decreased

hepatic

renal

or

cardiac

function

and

of

concomitant

disease

or

other

drug

therapy

see

Clinical

Pharmacology

and

Dosage

and

Administration

While

elderly

patients

exhibit

a

greater

tendency

to

orthostatic

hypotension

its

risk

in

the

elderly

may

be

minimized

by

limiting

the

initial

dose

to

mg

twice

daily

followed

by

careful

titration

see

Warnings

and

Precautions

Monitoring

of

orthostatic

vital

signs

should

be

considered

in

patients

for

whom

this

is

of

concern

This

drug

is

substantially

excreted

by

the

kidneys

and

the

risk

of

toxic

reactions

to

this

drug

may

be

greater

in

patients

with

impaired

renal

function

Because

elderly

patients

are

more

likely

to

have

decreased

renal

function

care

should

be

taken

in

dose

selection

and

it

may

be

useful

to

monitor

renal

function

see

Dosage

and

Administration

Renal

Impairment

In

patients

with

moderate

to

severe

Clcr

to

mLmin

renal

disease

clearance

of

the

sum

of

risperidone

and

its

active

metabolite

decreased

by

compared

to

young

healthy

subjects

Risperdal

doses

should

be

reduced

in

patients

with

renal

disease

see

Dosage

and

Administration

Hepatic

Impairment

While

the

pharmacokinetics

of

risperidone

in

subjects

with

liver

disease

were

comparable

to

those

in

young

healthy

subjects

the

mean

free

fraction

of

risperidone

in

plasma

was

increased

by

about

because

of

the

diminished

concentration

of

both

albumin

and

α

acid

glycoprotein

Risperdal

doses

should

be

reduced

in

patients

with

liver

disease

see

Dosage

and

Administration

Patients

with

Parkinsons

Disease

or

Lewy

Body

Dementia

Patients

with

Parkinsons

Disease

or

Dementia

with

Lewy

Bodies

can

experience

increased

sensitivity

to

Risperdal

Manifestations

can

include

confusion

obtundation

postural

instability

with

frequent

falls

extrapyramidal

symptoms

and

clinical

features

consistent

with

neuroleptic

malignant

syndrome

Drug

Abuse

and

Dependence

Controlled

Substance

Risperdal

risperidone

is

not

a

controlled

substance

Abuse

Risperdal

has

not

been

systematically

studied

in

animals

or

humans

for

its

potential

for

abuse

While

the

clinical

trials

did

not

reveal

any

tendency

for

any

drugseeking

behavior

these

observations

were

not

systematic

and

it

is

not

possible

to

predict

on

the

basis

of

this

limited

experience

the

extent

to

which

a

CNSactive

drug

will

be

misused

diverted

andor

abused

once

marketed

Consequently

patients

should

be

evaluated

carefully

for

a

history

of

drug

abuse

and

such

patients

should

be

observed

closely

for

signs

of

Risperdal

misuse

or

abuse

eg

development

of

tolerance

increases

in

dose

drugseeking

behavior

Dependence

Risperdal

has

not

been

systematically

studied

in

animals

or

humans

for

its

potential

for

tolerance

or

physical

dependence

Overdosage

Human

Experience

Premarketing

experience

included

eight

reports

of

acute

Risperdal

overdosage

with

estimated

doses

ranging

from

to

mg

and

no

fatalities

In

general

reported

signs

and

symptoms

were

those

resulting

from

an

exaggeration

of

the

drugs

known

pharmacological

effects

ie

drowsiness

and

sedation

tachycardia

and

hypotension

and

extrapyramidal

symptoms

One

case

involving

an

estimated

overdose

of

mg

was

associated

with

hyponatremia

hypokalemia

prolonged

QT

and

widened

QRS

Another

case

involving

an

estimated

overdose

of

mg

was

associated

with

a

seizure

Postmarketing

experience

includes

reports

of

acute

Risperdal

overdosage

with

estimated

doses

of

up

to

mg

In

general

the

most

frequently

reported

signs

and

symptoms

are

those

resulting

from

an

exaggeration

of

the

drugs

known

pharmacological

effects

ie

drowsiness

sedation

tachycardia

hypotension

and

extrapyramidal

symptoms

Other

adverse

reactions

reported

since

market

introduction

related

to

Risperdal

overdose

include

prolonged

QT

interval

and

convulsions

Torsade

de

pointes

has

been

reported

in

association

with

combined

overdose

of

Risperdal

and

paroxetine

Management

of

Overdosage

For

the

most

up

to

date

information

on

the

management

of

Risperdal

overdosage

contact

a

certified

poison

control

center

or

wwwpoisonorg

Provide

supportive

care

including

close

medical

supervision

and

monitoring

Treatment

should

consist

of

general

measures

employed

in

the

management

of

overdosage

with

any

drug

Consider

the

possibility

of

multiple

drug

overdosage

Ensure

an

adequate

airway

oxygenation

and

ventilation

Monitor

cardiac

rhythm

and

vital

signs

Use

supportive

and

symptomatic

measures

There

is

no

specific

antidote

to

Risperdal

Risperdal

Description

Risperdal

contains

risperidone

an

atypical

antipsychotic

belonging

to

the

chemical

class

of

benzisoxazole

derivatives

The

chemical

designation

is

Its

molecular

formula

is

C

H

FN

O

and

its

molecular

weight

is

The

structural

formula

is

Risperidone

is

a

white

to

slightly

beige

powder

It

is

practically

insoluble

in

water

freely

soluble

in

methylene

chloride

and

soluble

in

methanol

and

N

HCl

Risperdal

Tablets

are

for

oral

administration

and

available

in

mg

dark

yellow

mg

redbrown

mg

white

mg

orange

mg

yellow

and

mg

green

strengths

Risperdal

tablets

contain

the

following

inactive

ingredients

colloidal

silicon

dioxide

hypromellose

lactose

magnesium

stearate

microcrystalline

cellulose

propylene

glycol

sodium

lauryl

sulfate

and

starch

corn

The

mg

mg

mg

mg

and

mg

tablets

also

contain

talc

and

titanium

dioxide

The

mg

tablets

contain

yellow

iron

oxide

the

mg

tablets

contain

red

iron

oxide

the

mg

tablets

contain

FDC

Yellow

No

Aluminum

Lake

the

mg

and

mg

tablets

contain

DC

Yellow

No

the

mg

tablets

contain

FDC

Blue

No

Aluminum

Lake

Risperdal

is

also

available

as

a

mgmL

oral

solution

Risperdal


Home

Vet

advantus

imidacloprid

soft

chew

advantus

imidacloprid

soft

chew

This

page

contains

information

on

advantus

imidacloprid

soft

chew

for

veterinary

use

The

information

provided

typically

includes

the

following

advantus

imidacloprid

soft

chew

Indications

Warnings

and

cautions

for

advantus

imidacloprid

soft

chew

Direction

and

dosage

information

for

advantus

imidacloprid

soft

chew

advantus

imidacloprid

soft

chew

This

treatment

applies

to

the

following

species

Dogs

imidacloprid

soft

chew

Manufacturer

Bayer

Animal

Health

advantus

is

a

flavored

soft

chew

for

dogs

and

puppies

weeks

of

age

and

older

and

weighing

pounds

or

greater

Active

Ingredients

advantus

contains

mg

or

mg

of

imidacloprid

Use

advantus

kills

adult

fleas

and

is

indicated

for

the

treatment

of

flea

infestations

on

dogs

and

puppies

weeks

of

age

and

older

and

weighing

pounds

or

greater

Warnings

Not

for

human

use

Keep

this

and

all

drugs

out

of

the

reach

of

children

and

pets

Side

Effects

Side

effects

seen

with

this

drug

include

vomiting

decreased

appetite

decreased

energy

soft

stools

and

difficulty

walking

Directions

You

should

weigh

your

dog

before

giving

this

medication

to

make

sure

you

are

using

the

right

size

for

your

dog

Do

not

give

to

puppies

younger

than

weeks

of

age

or

to

dogs

weighing

less

than

pounds

Do

not

give

more

than

one

tablet

a

day

Use

the

table

to

find

the

right

dose

for

your

dog

Dosing

Table

Body

Weight

Dose

Soft

Chew

Strength

lbs

One

Soft

Chew

mg

imidacloprid

lbs

One

Soft

Chew

mg

imidacloprid

To

give

advantus

place

the

soft

chew

directly

in

your

dogs

mouth

or

allow

your

dog

to

take

the

soft

chew

from

your

hand

Watch

closely

to

ensure

your

dog

swallows

the

soft

chew

A

single

dose

kills

adult

fleas

on

your

dog

Because

advantus

does

not

have

an

effect

on

fleas

in

the

environment

your

dog

may

become

reinfested

with

fleas

If

your

dog

becomes

reinfested

you

can

safely

repeat

treatment

as

often

as

once

a

day

Contact

your

veterinarian

if

you

have

any

questions

about

flea

infestations

on

your

dog

Treat

all

pets

in

your

household

with

a

flea

protection

product

advantus

should

only

be

given

to

dogs

QuestionsComments

Call

Bayer

at

To

report

side

effects

call

Bayer

Veterinary

Services

at

For

additional

information

for

reporting

side

effects

for

animal

drugs

contact

FDA

at

or

online

at

httpwwwfdagovAnimalVeterinarySafetyHealth

Other

Information

Contact

your

veterinarian

if

your

dog

ingests

more

than

the

recommended

dose

of

advantus

advantus

has

not

been

tested

in

pregnant

or

nursing

dogs

advantus

starts

to

kill

fleas

within

hour

A

study

demonstrated

that

advantus

achieves

greater

than

effectiveness

against

adult

fleas

within

hours

advantus

may

be

used

together

with

other

products

including

heartworm

preventatives

corticosteroids

antibiotics

vaccines

deworming

medications

and

shampoos

advantus

does

not

protect

against

ticks

or

mosquitoes

Flea

Infestations

on

Dogs

Treatment

of

flea

infestations

is

important

to

your

dogs

health

Fleas

in

your

dogs

environment

can

reinfest

your

dog

Therefore

you

may

need

to

treat

with

advantus

more

than

one

time

The

following

diagram

illustrates

the

fleas

life

cycle

and

where

advantus

works

Fleas

reproduce

rapidly

A

single

female

flea

may

produce

up

to

eggs

over

her

lifetime

Eggs

hatch

and

may

grow

into

adults

in

only

three

weeks

Adult

female

fleas

feed

by

ingesting

blood

from

your

dog

and

lay

eggs

that

drop

off

from

your

dogs

coat

Within

days

larvae

hatch

from

these

eggs

and

live

undetected

in

your

dogs

surroundings

such

as

in

the

carpet

and

bedding

Fleas

can

emerge

to

reinfest

your

pet

continuing

the

life

cycle

When

these

new

fleas

are

seen

on

your

dog

treat

with

advantus

If

you

have

any

questions

about

flea

treatment

or

medical

problems

associated

with

flea

infestations

consult

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veterinarian

Storage

Information

Store

at

temperatures

between

and

How

Supplied

advantus

is

available

in

two

strengths

mg

or

mg

imidacloprid

Both

strengths

are

packaged

in

count

bottles

containing

flavored

soft

chews

or

count

bottles

containing

flavored

soft

chews

NADA

Approved

by

FDA

Bayer

Healthcare

LLC

Animal

Health

Division

Shawnee

Mission

KS

USA

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in

Spain

Bayer

regd

the

Bayer

Cross

regd

and

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trademarks

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Bayer

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use

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United

States

of

America

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intended

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provide

adequate

information

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use

Before

using

or

dispensing

any

product

read

and

carefully

observe

the

label

directions

BAYER

HEALTHCARE

LLC

Animal

Health

Division

PO

BOX

SHAWNEE

MISSION

KS

Customer

Service

Tel

Customer

Service

Fax

Website

wwwbayerahcom

Every

effort

has

been

made

to

ensure

the

accuracy

of

the

advantus

imidacloprid

soft

chew

information

published

above

However

it

remains

the

responsibility

of

the

readers

to

familiarize

themselves

with

the

product

information

contained

on

the

US

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or

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insert

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Use our interactive Itinerary Planner to map your perfect Passport weekend Sonoma Wine Countrys Premier Wine Food Festival Interactive Passport Itinerary Planner How to use the planner 1 Browse the 2019 Participating Wineries below the map 2 When you see a winery youre interested in click to read a sneak peak on their theme 3 If you decide this is a MustSee select Add to Itinerary 4 Now you can add in your starting location be it your home or hotel as well as your ending location 5 Click the small x next to the winerys name if you no longer want them included on your itinerary 6 Once youve made your perfect Passport Adventure select Print Itinerary or Send by email to save 7 Last step is to wait eagerly until April 27th 28th See you in April Tickets go on sale to the public on February 1st at 10am pst As an event we do not accept buses larger than 24passengers Please note that not all of our wineries are able to accommodate any size buses or limos If you plan on travelling with a group please check the winery description above to ensure they can accommodate your party or reference this document 2018 information check back for updated information Click here to download the 2018 Passport Themes Themes for the 30th Anniversary event will be released early 2019 Tickets go on sale to the public on February 1st at 10am pst Use DCVPassport to stay up on all things Passport and join the conversation drycreekvalleywines drycreekvalley drycreekvalley

O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O