Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Neuroleptic Malignant Syndrome
(Additions and/or revisions underlined)
Neuroleptic
Malignant Syndrome (NMS), a potentially fatal symptom complex, has been
reported in association with antipsychotic drugs. Clinical manifestations of
NMS are hyperpyrexia, muscle rigidity, altered mental status including
delirium, and autonomic instability (irregular pulse or blood pressure,
tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may
include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and
acute renal failure.
If
NMS is suspected, immediately discontinue RISPERDAL CONSTA and provide symptomatic
treatment and monitoring.
5.4 Tardive Dyskinesia
(Additions and/or revisions underlined)
Tardive dyskinesia, a syndrome consisting of
potentially irreversible, involuntary, dyskinetic movements, may develop in
patients treated with antipsychotic drugs. Although the prevalence of the
syndrome appears to be highest among the elderly, especially elderly women, it
is impossible to predict which patients will develop the syndrome.
The
risk of developing tardive dyskinesia and the likelihood that it will become
irreversible increase with the duration of treatment and the cumulative
dose .
The syndrome can develop after relatively brief treatment periods, even
at low doses. It may also occur after discontinuation of treatment.
Tardive
dyskinesia may remit, partially or completely, if antipsychotic treatment
is discontinued. Antipsychotic treatment, itself, however, may suppress
(or partially suppress) the signs and symptoms of the syndrome,
possibly masking the underlying process. The effect that symptomatic
suppression has upon the long-term course of the syndrome is unknown.
Given
these considerations, RISPERDAL CONSTA® should
be prescribed in a manner that is most likely to minimize the occurrence of
tardive dyskinesia. Chronic antipsychotic treatment should generally be
reserved for patients: (1) who suffer from a chronic illness that is
known to respond to antipsychotic drugs, and (2) for whom alternative, equally
effective, but potentially less harmful treatments are not available or
appropriate. In patients who do require chronic treatment, the lowest
dose and the shortest duration of treatment producing a satisfactory clinical
response. Periodically reassess the need for continued treatment.
6
Adverse Reactions
(Additions and/or revisions
underlined)
The following are discussed in
more detail in other sections of the labeling:
- Increased mortality in elderly patients with dementia-related psychosis
[see Boxed Warning and Warnings and
Precautions (5.1)]
6.2 Postmarketing Experience
(Additions and/or revisions underlined)
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 possible to reliably estimate their frequency:
agranulocytosis, alopecia, anaphylactic reaction, angioedema, atrial
fibrillation, blood cholesterol increased, blood triglycerides increased, catatonia,
diabetes mellitus, diabetic ketoacidosis in patients with impaired glucose
metabolism, drug withdrawal syndrome neonatal, dysgeusia, hypoglycemia,
hypothermia, ileus, inappropriate antidiuretic hormone secretion, intestinal
obstruction, jaundice, mania, pancreatitis, priapism, QT prolongation, sleep
apnea syndrome, somnambulism, Stevens-Johnson syndrome and toxic epidermal
necrolysis (SJS/TEN), thrombocytopenia, thrombotic thrombocytopenic purpura,
urinary retention, and water intoxication. In addition, the following adverse
reactions have been observed during postapproval use of RISPERDAL CONSTA:
cerebrovascular disorders, including cerebrovascular accidents, and diabetes
mellitus aggravated.
Retinal
artery occlusion after injection of RISPERDAL CONSTA has been reported during postmarketing
surveillance. This has been reported in the presence of abnormal arteriovenous
anastomosis.
Serious
injection site reactions including abscess, cellulitis, cyst, hematoma,
necrosis, nodule, and ulcer have been reported with RISPERDAL CONSTA during postmarketing
surveillance. Isolated cases required surgical
intervention.
Very
rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA have been reported during
postmarketing experience in patients who have previously tolerated oral
risperidone.
Postmarketing
cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported
in patients concomitantly taking methylphenidate and risperidone when there was
an increase or decrease in dosage, initiation, or discontinuation of either or
both medications.
7
Drug Interactions
7.6 Methylphenidate
(Newly added subsection)
Concomitant
use with methylphenidate, when there is change in dosage of either medication,
may increase the risk of extrapyramidal symptoms (EPS). Monitor for symptoms of
EPS with concomitant use of RISPERDAL CONSTA and methylphenidate [see Adverse Reactions (6.2)].
8
Use in Specific Populations
8.1 Pregnancy
(Extensive changes; please refer to
label)
8.6 Renal or Hepatic Impairment
(Newly added subsection)
In patients
with renal or hepatic impairment, carefully titrate with oral risperidone prior
to initiating treatment with RISPERDAL CONSTA [see Dosage
and Administration (2.4)].
Patients
with renal impairment may have less ability to eliminate risperidone than
patients with normal renal function. Patients with impaired hepatic function
may have an increase in the free fraction of risperidone, possibly resulting in
an enhanced effect [see Clinical
Pharmacology (12.3)].
8.7 Patients
with Parkinson’s Disease or Lewy Body Dementia
(Newly added subsection)
Patients
with Parkinson’s Disease or Dementia with Lewy Bodies can experience increased
sensitivity to RISPERDAL CONSTA. Manifestations can include confusion,
obtundation, postural instability with frequent falls, extrapyramidal symptoms,
and clinical features consistent with neuroleptic malignant syndrome.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Extensive changes; please refer to label)
Approved Drug Label (PDF)
6
Adverse Reactions
6.8 Postmarketing Experience
(Additions and/or
revisions underlined)
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 possible to reliably estimate their frequency: agranulocytosis,
alopecia, anaphylactic reaction, angioedema, atrial fibrillation, blood cholesterol
increased, blood triglycerides increased, diabetes mellitus, diabetic ketoacidosis
in patients with impaired glucose metabolism, drug withdrawal syndrome neonatal,
dysgeusia, hypoglycemia, hypothermia, ileus, inappropriate antidiuretic hormone
secretion, intestinal obstruction, jaundice, mania, pancreatitis, priapism, QT prolongation,
sleep apnea syndrome, somnambulism, Stevens-Johnson syndrome and toxic epidermal
necrolysis (SJS/TEN), thrombocytopenia, urinary retention, and water intoxication.
In addition, the following adverse reactions have been observed during postapproval
use of RISPERDAL CONSTA®: cerebrovascular disorders, including cerebrovascular accidents,
and diabetes mellitus aggravated.
Retinal
artery occlusion after injection of RISPERDAL CONSTA® has been reported during postmarketing
surveillance. This has been reported in the presence of abnormal arteriovenous anastomosis.
Serious
injection site reactions including abscess, cellulitis, cyst, hematoma, necrosis,
nodule, and ulcer have been reported with RISPERDAL CONSTA® during postmarketing
surveillance. Isolated cases required surgical intervention.
Very
rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA® have
been reported during postmarketing experience in patients who have previously tolerated
oral risperidone.
Approved Drug Label (PDF)
6
Adverse Reactions
6.8 Postmarketing Experience
(Additions and/or
revisions are underlined)
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 possible
to reliably estimate their frequency: agranulocytosis, alopecia, anaphylactic reaction, angioedema, atrial fibrillation, blood cholesterol increased, blood triglycerides increased, diabetes mellitus, diabetic
ketoacidosis in patients with impaired glucose metabolism, drug withdrawal syndrome neonatal, dysgeusia, hypoglycemia, hypothermia, ileus, inappropriate antidiuretic hormone secretion, intestinal obstruction, jaundice, mania, pancreatitis, priapism, QT prolongation, sleep
apnea syndrome, somnambulism, thrombocytopenia, urinary
retention, and water intoxication. In addition,
the following adverse reactions
have been observed
during postapproval use of RISPERDAL CONSTA®: cerebrovascular disorders, including cerebrovascular
accidents, and diabetes mellitus
aggravated.
…
Approved Drug Label (PDF)
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and Lactation
Labeling Rule (PLLR) Conversion; Extensive revisions-please refer to label)
8.2 Lactation
(Pregnancy and Lactation Labeling Rule (PLLR)
Conversion; Additions and/or revisions
are underlined)
Risk Summary
Limited data from published literature reports the presence
of risperidone and its metabolite, 9- hydroxyrisperidone, in human breast milk
at relative infant dose ranging between 2.3% and 4.7% of the maternal
weight-adjusted dosage. There are reports of sedation, failure to thrive,
jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements)
in breastfed infants exposed to risperidone.
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 mother’s clinical need for RISPERDAL® and any potential adverse effects on the breastfed child
from RISPERDAL® or from the mother’s 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).
8.3 Females and Males of Reproductive Potential
(Newly Added Subsection)
Infertility
Females
Based on the pharmacologic action of risperidone (D2
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.
8.4 Pediatric Use
(Additions and/or revisions
are underlined)
Juvenile Animal Studies
Juvenile dogs were treated with oral
risperidone from weeks 10 to 50 of age (equivalent to the period of
childhood through adolescence in humans), at doses of 0.31, 1.25, or 5
mg/kg/day, which are 1.2, 3.4, and 13.5 times the MRHD of 6 mg/day for
children, based on mg/m2 body surface area. Bone length and density were
decreased with a no-effect dose of 0.31 mg/kg/day; this dose
produced plasma AUC of risperidone
plus its active
metabolite paliperidone (9-hydroxy-risperidone) that were
similar to those in children and adolescents receiving the MRHD of 6 mg/day. 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
12 week drug-free recovery period.
In Juvenile rats, treated with oral risperidone from
days 12 to 50 of age (equivalent to the period of infancy through
adolescence in humans) showed impaired learning and memory performance
(reversible only in females), with a no-effect dose of 0.63
mg/kg/day which is 0.5 times the MRHD of 6 mg/day for children, based on
mg/m2 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 1.25 mg/kg/day which is 1 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 6 mg/day for
children.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions
are underlined)
Pregnancy
Advise patients to notify their healthcare provider if they
become pregnant or intend to become pregnant during treatment with RISPERDAL®. Advise patients that RISPERDAL® may cause extrapyramidal and/or withdrawal symptoms in a
neonate. Advise patients that there is a pregnancy registry that monitors
pregnancy outcomes in women exposed to RISPERDAL® during pregnancy.
Lactation
Advise breastfeeding women using RISPERDAL® to monitor infants for somnolence, failure to thrive,
jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle
movements) and to seek medical care if they notice these signs.
Infertility
Advise females of reproductive potential that RISPERDAL® may impair fertility due to an increase in serum prolactin
levels. The effects on fertility are reversible.
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