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 RISPERDALâ 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. Whether antipsychotic drug
products differ in their potential to cause tardive dyskinesia is unknown.
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, RISPERDALâ 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, use the lowest dose and the shortest duration of
treatment producing a satisfactory
clinical response. Periodically reassess the need for continued treatment.
If
signs and symptoms of tardive dyskinesia appear in a patient on
RISPERDALâ,
drug discontinuation should be considered. However, some patients may
require treatment with RISPERDALâ despite the presence of the syndrome.
5.7 Orthostatic
Hypotension
(Additions and/or revisions underlined)
RISPERDALâ may induce orthostatic hypotension
associated with dizziness, tachycardia, and in some patients, syncope,
especially during the initial dose-titration period, probably reflecting its
alpha-adrenergic antagonistic properties. Syncope was reported in 0.2% (6/2607)
of RISPERDALâ-treated
patients in Phase 2 and 3 studies in adults with schizophrenia. The risk of
orthostatic hypotension and syncope may be minimized by limiting the initial
dose to 2 mg total (either once daily or 1 mg twice daily) in normal adults and
0.5 mg twice daily in the elderly and patients with renal or hepatic impairment
[see Dosage and Administration (2.1, 2.4)]
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. RISPERDALâ 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, e.g.,
dehydration and hypovolemia., and in the elderly and patients
with renal or hepatic impairment. Monitoring of orthostatic vital signs should
be considered if hypotension occurs. Clinically significant hypotension has
been observed with concomitant use of RISPERDALâ and
antihypertensive medication.
6
Adverse Reactions
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 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, catatonia, 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, somnambulism, Stevens-Johnson
syndrome and toxic epidermal necrolysis (SJS/TEN), sudden death,
thrombocytopenia, thrombotic thrombocytopenic purpura, urinary retention, and
water intoxication.
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
7.2 Pharmacodynamic-related Interactions
(Additions and/or revisions underlined)
Centrally
-Acting
Drugs and Alcohol
Given the primary
CNS effects of risperidone, caution should be used when RISPERDAL is taken in combination with other
centrally -acting 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.
Methylphenidate
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 and methylphenidate [see Adverse Reactions (6.2)].
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
6.2 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 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, somnambulism, Stevens-Johnson
syndrome and toxic epidermal necrolysis (SJS/TEN), sudden death, thrombocytopenia,
thrombotic thrombocytopenic purpura, urinary retention, and water intoxication.
Approved Drug Label (PDF)
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions
and/or revisions are underlined)
…
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, somnambulism, sudden death,
thrombocytopenia, thrombotic thrombocytopenic purpura, urinary
retention, and water intoxication.
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.
Get Email Alerts |
Guide
