Paliperidone -@- Antipsychotic agent - Benzisoxazole- (Sep 2008)
Drug Name:Paliperidone -@- Antipsychotic agent - Benzisoxazole- (Sep 2008)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Centrally-acting drugs: Due to CNS effects, use caution in combination.
Avoid alcohol.
.
Drugs that may cause orthostatic hypotension:
An additive effect may be observed when co-administered with INVEGAR.
.
Co-administration with carbamazepine decreased mean steady-state
Cmax and AUC of paliperidone by approximately 37%.
Adjust dose of INVEGAR if necessary based on clinical assessment.
.
Co-administration of divalproex sodium increased Cmax and AUC
of paliperidone by approximately 50%.
Adjust dose of INVEGAR if necessary based on clinical assessment.
Indication:
U.S.FDA APPROVED FROM 01-01-08 TO 31-12-08
Drug name Indication Date of Approval
205. Paliperidone ER Tablet 3mg/6mg/9mg 26-09-08
For the acute and maintenance treatment of
schizophrenia
INVEGA® (paliperidone) Extended-Release Tablets
Initial U.S. Approval: 2006
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
DEMENTIA-RELATED PSYCHOSIS
See full prescribing information for complete boxed warning.
Elderly patients with dementia-related psychosis treated with antipsychotic
drugs are at an increased risk of death. INVEGA® is not approved for use
in patients with dementia-related psychosis. (5.1)
RECENT MAJOR CHANGES
Indications and Usage, Schizoaffective Disorder (1.2) July 2009
Dosage and Administration, Schizoaffective Disorder (2.2) July 2009
Dosage and Administration, Dosage in Special Populations,
Renal Impairment (2.5) July 2009
Warnings and Precautions, Leukopenia, Neutropenia, and
Agranulocytosis (5.10) July 2009
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
1.Paliperidone ER Tablet 14-11-2009
12mg - Addl.Stgth
Same as approved
2.Paliperidone ER Tablet 26-09-2008
3mg/6mg/9mg
For the acute Maintenance treatment of Schizophrenia
3.Paliperidone ER tablets 1.5mg 04-03-2009
Addl.Stgth
same as approved
Schizophrenia
Adverse Reaction:
The most common adverse reactions (incidence . 5% and at least twice
that for placebo) were extrapyramidal symptoms, tachycardia, and
akathisia in the schizophrenia trials, and extrapyramidal symptoms,
somnolence, dyspepsia, constipation, weight increased,
and nasopharyngitis in the schizoaffective disorder trials.
Contra-Indications:
CONTRAINDICATIONS
Known hypersensitivity to paliperidone, risperidone, or to any components
in the formulation
WARNINGS AND PRECAUTIONS
Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with
Dementia-Related Psychosis: Increased incidence of cerebrovascular
adverse reactions (e.g. stroke, transient ischemic attack, including fatalities).
INVEGA® is not approved for use in patients with dementia-related psychosis
Neuroleptic Malignant Syndrome :
Manage with immediate discontinuation of drug and close monitoring
QT Prolongation:
Increase in QT interval, avoid use with drugs that also increase
QT interval and in patients with risk factors for prolonged QT interval
Tardive Dyskinesia:
Discontinue drug if clinically appropriate
.
Hyperglycemia and Diabetes Mellitus:
Monitor glucose regularly in patients with and at risk for diabetes
.
Hyperprolactinemia:
Prolactin elevations occur and persist during chronic administration
Gastrointestinal Narrowing:
Obstructive symptoms may result in patients with gastrointestinal disease
.
Orthostatic Hypotension and Syncope:
Use with caution in patients with known cardiovascular or cerebrovascular
disease and patients predisposed to hypotension
.
Leukopenia, Neutropenia, and Agranulocytosis: has been reported with
antipsychotics, including INVEGAR.
Patients with a history of a clinically significant low white blood
cell count (WBC) or a drug-induced leukopenia/neutropenia should
have their complete blood count (CBC) monitored frequently
during the first few months of therapy and discontinuation of INVEGAR
should be considered at the first sign of a clinically significant
decline in WBC in the absence of other causative factors.
.
Potential for Cognitive and Motor Impairment :
Use caution when operating machinery
Seizures:
Use cautiously in patients with a history of seizures or with conditions
that lower the seizure threshold
.
Suicide:
Closely supervise high-risk patients
Dosages/ Overdosage Etc:
Schizophrenia
Dosage-
6mg once daily in the morning taken consistently in fasting or fed state
Adjust dose as pere response Range 3 - 12mg once daily
Below 18 years not recommended
INDICATIONS AND USAGE
INVEGA® is an atypical antipsychotic agent indicated for the
acute and maintenance treatment of schizophrenia
acute treatment of schizoaffective disorder as monotherapy
acute treatment of schizoaffective disorder as an adjunct to mood
stabilizers and/or antidepressants
DOSAGE AND ADMINISTRATION
For schizophrenia: 6 mg extended-release tablet administered in the morning
with or without food. Initial dose titration is not required.
Some patients may benefit from either higher doses up to 12 mg/day
or a lower dose of 3 mg/day. If clinical assessment warrants, increas
the dose at increments of 3 mg/day at intervals of more than 5 days.
Maximum recommended dose is 12 mg/day.
For schizoaffective disorder: 6 mg extended-release tablet administered in the
morning with or without food. Initial dose titration is not required.
Some patients may benefit from lower or higher doses within the
recommended dose range of 3 to 12 mg once daily.
If clinical assessment warrants, increase the dose at increments
of 3 mg/day at intervals of more than 4 days.
Maximum recommended dose is 12 mg/day.
Tablet should be swallowed whole and should not be chewed,
divided, or crushed.
Patients may notice tablet-shaped shell in their stool.
DOSAGE FORMS AND STRENGTHS
Tablets: 1.5 mg, 3 mg, 6 mg, and 9 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Physicians are advised to discuss the following issues with patients for whom
they prescribe INVEGA®.
1. Orthostatic Hypotension
Patients should be advised that there is risk of orthostatic hypotension, particularly
at the time of initiating treatment, re-initiating treatment, or increasing the dose
2. Interference with Cognitive and Motor Performance
As INVEGA® 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 INVEGA® therapy does not affect them
adversely
.
3. Pregnancy
Patients should be advised to notify their physician if they become pregnant or intend
to become pregnant during treatment with INVEGA®.
4. Nursing
Caution should be exercised when INVEGA® is administered to a nursing woman.
The known benefits of breastfeeding should be weighed against the unknown risks
of infant exposure to paliperidone.
5. Concomitant Medication
Patients should be advised to inform their physicians if they are taking, or plan to
take, any prescription or over-the-counter drugs, as there is a potential for
interactions
6. Alcohol
Patients should be advised to avoid alcohol while taking INVEGA®
7. Heat Exposure and Dehydration
Patients should be advised regarding appropriate care in avoiding overheating
and dehydration
8. Administration
Patients should be informed that INVEGA® should be swallowed whole with the
aid of liquids.
Tablets should not be chewed, divided, or crushed.
The medication is contained within a nonabsorbable shell designed to release
the drug at a controlled rate.
The tablet shell, along with insoluble core components , is eliminated from the body;
patients should not be concerned if they occasionally notice something that looks
like a tablet in their stool
.
Manufactured by:
ALZA Corporation
Vacaville, CA 95688
OR
Janssen Cilag Manufacturing, LLC
Gurabo, Puerto Rico 00778
Manufactured for:
Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action
Paliperidone is the major active metabolite of risperidone. The mechanism of action
of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown,
but it has been proposed that the drugs therapeutic activity in schizophrenia
is mediated through a combination of central dopamine Type 2 (D2) and
serotonin Type 2 (5HT2A) receptor antagonism.
2. Pharmacokinetics
Following a single dose, the plasma concentrations of paliperidone gradually rise
to reach peak plasma concentration (Cmax) approximately 24 hours after dosing.
The pharmacokinetics of paliperidone following INVEGA® administration
are dose-proportional within the available dose range.
The terminal elimination half-life of paliperidone is approximately 23 hours.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
.
Renal impairment:
Dosing must be individualized according to renal function status.
For mild renal impairment (creatinine clearance
.50 mL/min to < 80 mL/min), the recommended initial dose is 3 mg/day,
which may be increased to a maximum of 6 mg/day based on clinical
response and tolerability.
For moderate to severe renal impairment (creatinine clearance .10 mL/min
to <50 mL/min), the recommended initial dose is1.5 mg mg/day, which may
be increased to a maximum of 3 mg/day after clinical reassessment.
As INVEGAR has not been studied in patients with creatinine clearance
< 10 mL/min, use is not recommended in such patients.
.
Elderly:
same as for younger adults (adjust dose according to renal function status).
.
Nursing Mothers: Limited data.
.
Pediatric Use:
safety and effectiveness not established in patients less than 18 years of age.
