Approved Drug Label (PDF)
5
Warnings and Precautions
5.11 Leukopenia, Neutropenia, and Agranulocytosis
(Additions and/or revisions underlined)
In
clinical trial and/or postmarketing experience, events of
leukopenia/neutropenia have been reported temporally related to antipsychotic
agents, including INVEGA®.
Agranulocytosis has also been reported.
Possible
risk factors for leukopenia/neutropenia include pre-existing low white blood
cell count (WBC)/absolute neutrophil count (ANC) and history of
drug-induced leukopenia/neutropenia. In patients with a history of a
clinically significant low WBC/ANC or a drug-induced
leukopenia/neutropenia, perform a complete blood count (CBC) frequently
during the first few months of therapy. In such patients, consider
discontinuation of INVEGA® at
the first sign of a clinically significant decline in WBC in the absence of
other causative factors.
Monitor
patients with clinically significant neutropenia for fever or other
symptoms or signs of infection and treat promptly if such symptoms or
signs occur. Discontinue INVEGA® in patients with severe neutropenia
(absolute neutrophil count < 1000/mm3)
and follow their WBC until recovery.
5.12 Potential for Cognitive and Motor Impairment
(Additions and/or revisions underlined)
Somnolence,
sedation, and dizziness were reported as adverse reactions in
subjects treated with INVEGA® [see Adverse Reactions (6.2)].
Antipsychotics, including INVEGA®,
have the potential to impair judgment, thinking, or motor skills. Patients
should be cautioned about performing activities requiring mental alertness,
such as operating hazardous machinery or operating a motor vehicle, until they
are reasonably certain that paliperidone therapy does not adversely affect
them.
5.16 Body Temperature Regulation
(Additions and/or revisions underlined)
Disruption
of the body’s ability to reduce core body temperature has been attributed to
antipsychotic agents. Appropriate care is advised when prescribing INVEGA® to patients who will
be experiencing conditions which may contribute to an elevation in core body
temperature, e.g., exercising strenuously, exposure to extreme heat, receiving
concomitant medication with anticholinergic activity, or being subject to
dehydration.
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, including paliperidone.
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 INVEGA and provide symptomatic
treatment and monitoring.
5.5 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 appear to increase with 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 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 long-term course of the syndrome is unknown.
Given
these considerations, INVEGA® 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.
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions and/or revisions underlined)
The
following adverse reactions have been identified during postapproval use of
INVEGA®; because these
reactions were reported voluntarily from a population of uncertain size, it is
not possible to reliably estimate their frequency: angioedema, catatonia,
ileus, priapism, somnambulism, swollen tongue, tardive dyskinesia, thrombotic
thrombocytopenic purpura, urinary incontinence, urinary retention
8
Use in Specific Populations
8.8 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 INVEGA®.
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)
5
Warnings and Precautions
5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis
(Additions
and/or revisions are underlined)
Elderly patients with dementia-related
psychosis treated with antipsychotic
drugs are at an increased risk of death. Analyses of 17 placebo-controlled
trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic
drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times
the risk of death in placebo-treated patients. Over the course of a typical 10-week
controlled trial, the rate of death in drug-treated patients was about 4.5%, compared
to a rate of about 2.6% in the placebo group. Although the causes of death were
varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure,
sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest
that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic
drugs may increase mortality. The extent to which the findings of increased mortality
in observational studies may be attributed to the antipsychotic
drug as opposed to some
characteristic(s) of the patients is not clear.
INVEGA® (paliperidone) is not approved for the treatment
of dementia-related psychosis.
6
Adverse Reactions
6.1 Overall Adverse Reaction Profile
(Additions and/or
revisions are underlined)
- Patients with Concomitant
Illness
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 report the presence
of paliperidone in human breast milk. There is no information on the effects
on the breastfed infant, or the effects on milk production; however, there are reports
of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors
and abnormal muscle movements) in breastfed infants exposed to paliperidone’s parent
compound, risperidone. The developmental and health benefits of breastfeeding
should be considered along with the mother’s clinical need for INVEGA® and any
potential adverse effects on the breastfed child from INVEGA® or from the mother’s
underlying condition.
Clinical Considerations
Infants exposed to INVEGA ® 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 paliperidone (D2 receptor
antagonism), treatment with INVEGA® 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
In a study in which juvenile rats were treated with oral paliperidone
from days 24 to 73 of age, a reversible impairment of performance in a test of learning
and memory was seen, in females only, with a no-effect dose of 0.63 mg/kg/day, which
produced plasma levels (AUC) of paliperidone similar to those in adolescents at MRHD of 12 mg/day…
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 INVEGA®. Advise patients that INVEGA® 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 INVEGA® during pregnancy.
Lactation
Advise breastfeeding
women using INVEGA® 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 INVEGA® may impair fertility due to an increase
in serum prolactin levels. The effects on fertility are reversible.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.10 Falls
(Newly added
subsection)
Somnolence,
postural hypotension, motor and sensory instability have been reported with the
use of antipsychotics, including INVEGA, which may lead to falls and,
consequently, fractures or other fall-related 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 long-term antipsychotic
therapy.
6
Adverse Reactions
6.1 Overall Adverse Reaction Profile
(Additions and/or revisions are underlined)
The following
adverse reactions are discussed in more detail in other sections of the
labeling:
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