Brexpiprazole - Rexulti-@- (July 2015) - Antipsychotic
Drug Name:Brexpiprazole - Rexulti-@- (July 2015) - Antipsychotic
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:
Factors: Dosage Adjustments for REXULTI
Strong CYP2D6* or CYP3A4 inhibitors
Administer half of usual dose
Strong/moderate CYP2D6 with Strong/moderate CYP3A4 inhibitors
Administer a quarter of usual dose
Known CYP2D6 Poor Metabolizers taking strong/moderate CYP3A4 inhibitors
Administer a quarter of usual dose
Strong CYP3A4 inducers
Double the usual dose and further adjust based on clinical response
* REXULTI may be administered without dosage adjustment in patients
with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine).
Indication:
REXULTIR (brexpiprazole) tablets, for oral use
Initial U.S. Approval: 2015
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL
THOUGHTS AND BEHAVIORS
See full prescribing information for complete boxed warning.
.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs
are at increased risk of death. REXULTI is not approved for the treatment of patients
with dementia-related psychosis (5.1).
.
Antidepressants increase the risk of suicidal thoughts and behaviors in patients
aged 24 years and younger. Monitor for clinical worsening and emergence of
suicidal thoughts and behaviors (5.2).
.
Safety and effectiveness of REXULTI have not been established in
pediatric patients (8.4).
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.17
Drug Name - Brexpiprazole
Active Ingredient- Rexulti
Date of approval - 7/10/2015
FDA-approved use - To treat schizophrenia and as an add on to an
Antidepressant to treat depressive disorder
Approved by US FDA on 7/10/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
REXULTI is an atypical antipsychotic indicated for:
Use as an adjunctive therapy to antidepressants for the treatment of major depressiv
disorder (MDD)
Treatment of schizophrenia
Adverse Reaction:
Most common adverse reactions were:
MDD: Weight increased and akathisia (.5% and at least twice the rate for placebo)
Schizophrenia: Weight increased (.4% and at least twice the rate for placebo)
Contra-Indications:
CONTRAINDICATIONS
Known hypersensitivity to REXULTI or any of its components
WARNINGS AND PRECAUTIONS
Cerebrovascular Adverse Reactions in Elderly Patients with
Dementia-Related Psychosis:
Increased incidence of cerebrovascular adverse reactions
(e.g. stroke, transient ischemic attack)
Neuroleptic Malignant Syndrome: Manage with immediate discontinuation
and close monitoring
.
Tardive Dyskinesia: Discontinue if clinically appropriate
.
Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus,
dyslipidemia and weight gain
Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts
(CBC) in patients with pre-existing low white blood cell count (WBC)
or history of leukopenia or neutropenia.
Consider discontinuing REXULTI if a clinically significant decline in WBC occurs
in absence of other causative factors
.
Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure
and warn patients with known cardiovascular or cerebrovascular disease,
and risk of dehydration or syncope
.
Seizures: Use cautiously in patients with a history of seizures or with conditions
that lower the seizure threshold
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
REXULTI is an atypical antipsychotic indicated for:
Use as an adjunctive therapy to antidepressants for the treatment of major depressiv
disorder (MDD)
Treatment of schizophrenia
DOSAGE AND ADMINISTRATION.
Administer REXULTI once daily with or without food
Indication
Major depressive disorder (MDD)
Starting dose 0.5 mg/day or 1 mg/day
Recomended dose 2 mg/day
Maximum dose 3 mg/day
Schizophrenia
Starting dose 1 mg/day
Recommended dose 2 to 4 mg/day
Maximum dose 4 mg/day
.
Moderate to Severe Hepatic Impairment (Child-Pugh score .7): Maximum
.
Moderate to Severe Hepatic Impairment (Child-Pugh score .7):
Maximum recommended dosage is 2 mg once daily for patients with MDD
and 3 mg once daily for patients with schizophrenia
.
Moderate, Severe or End-Stage Renal Impairment (CLcr<60 mL /minute):
Maximum recommended dosage is 2 mg once daily for patients with MDD
and 3 mg once daily for patients with schizophrenia
.
Known CYP2D6 Poor Metabolizers: Reduce the usual dosage by half
DOSAGE FORMS AND STRENGTHS
Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).
Suicidal Thoughts and Behaviors
Advise patients and caregivers to look for the emergence of suicidality, especially
early during treatment and when the dosage is adjusted up or down and instruct
them to report such symptoms to the healthcare provider
Dosage and Administration
Advise patients that REXULTI can be taken with or without food.
Advise patients regarding importance of following dosage escalation instructions
.
Neuroleptic Malignant Syndrome (NMS)
Counsel patients about a potentially fatal adverse reaction -
Neuroleptic Malignant Syndrome (NMS) that has been reported in association
with administration of antipsychotic drugs.
Advise patients to contact a health care provider or report to the emergency room
if they experience signs or symptoms of NMS
Tardive Dyskinesia
Counsel patients on the signs and symptoms of tardive dyskinesia and to contact
their health care provider if these abnormal movements occur
.
Metabolic Changes
Educate patients about the risk of metabolic changes, how to recognize symptoms
of hyperglycemia and diabetes mellitus, and the need for specific monitoring,
including blood glucose, lipids, and weight
.
Leukopenia, Neutropenia and Agranulocytosis
Advise patients with a pre-existing low WBC or a history of drug induced
leukopenia/neutropenia that they should have their CBC monitored while taking
REXULTI
Orthostatic Hypotension and Syncope
Educate patients about the risk of orthostatic hypotension and syncope especially
early in treatment, and also at times of re-initiating treatment or increases in dosage
Heat Exposure and Dehydration
Counsel patients regarding appropriate care in avoiding overheating and dehydration
.
Interference with Cognitive and Motor Performance
Caution patients about performing activities requiring mental alertness, such as
operating hazardous machinery or operating a motor vehicle, until they are
reasonably certain that REXULTI therapy does not adversely affect their ability
to engage in such activities
Concomitant Medications
Advise patients to inform their health care providers of any changes to their current
prescription or over-the-counter medications because there is a potential
for clinically significant interactions
Pregnancy
Advise patients that third trimester use of REXULTI may cause extrapyramidal
and/or withdrawal symptoms in a neonate and to notify their healthcare provider
with a known or suspected pregnancy. Advise patients that there is a pregnancy
exposure registry that monitors pregnancy outcomes in women exposed to
REXULTI during pregnancy
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
The mechanism of action of brexpiprazole in the treatment of major depressive disorder
or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated
through a combination of partial agonist activity at serotonin 5-HT1A and dopamine
D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.
2. Pharmacokinetics
Absorption
After single dose administration of REXULTI tablets, the peak plasma brexpiprazole
concentrations occurred within 4 hours after administration; and the absolute
oral bioavailability was 95%. Brexpiprazole steady-state concentrations were attained
within 10-12 days of dosing
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Adequate and well-controlled studies have not been conducted with REXULTI in pregnant
women to inform drug-associated risks. However, neonates whose mothers are exposed
to antipsychotic drugs, like REXULTI, during the third trimester of pregnancy are at
risk for extrapyramidal and/or withdrawal symptoms.
2. Lactation
Risk Summary
Lactation studies have not been conducted to assess the presence of brexpiprazole
in human milk, the effects of brexpiprazole on the breastfed infant, or the effects of
brexpiprazole on milk production. Brexpiprazole is present in rat milk.
3.Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Antidepressants
increased the risk of suicidal thoughts and behaviors in pediatric patients
.
4. Geriatric Use
Clinical studies of the efficacy REXULTI did not include any patients aged 65 or older
to determine whether they respond differently from younger patients. In general, dose
selection for an elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, and cardiac
function, concomitant diseases, and other drug therapy.