ARIPIPRAZOLE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ARIPIPRAZOLE (UNII: 82VFR53I78) (ARIPIPRAZOLE - UNII:82VFR53I78)

Available from:

Preferred Pharmaceuticals Inc.

INN (International Name):

ARIPIPRAZOLE

Composition:

ARIPIPRAZOLE 15 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Aripiprazole Oral Tablets are indicated for the treatment of: Aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions ( 6.2) ]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) . Overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . There are risks to the mother associated with untreated schizophrenia, bipolar I disorder, or major depressive disorder, and with exposure to antipsychotics, including aripiprazole, during pregnancy (see Clinical Considerations) . In animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 19 times, respectively, the maximum recommended human dose (MRHD) of 30 mg/day based on mg/m 2 body  surface area, produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. Oral and intravenous aripiprazole administration during the pre- and post- natal period in rats at doses 10 times the MRHD based on mg/m 2  body surface area, produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A retrospective study from a Medicaid database of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data In animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits. In pregnant rats treated orally with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are approximately 1, 3 and 10 times the MRHD of 30 mg/day based on mg/m 2  body surface area, a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes, were observed at 10 times the MRHD. Delayed skeletal ossification was observed at 3 and 10 times the MRHD. Delivered offspring had increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed at 10 times the MRHD (the other dose groups were not examined for these findings). Postnatally, delayed vaginal opening was seen at 3 and 10 times the MRHD. Impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) were observed at 10 times the MRHD; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. In pregnant rats injected intravenously with aripiprazole during organogenesis at doses of 3, 9, and 27 mg/kg/day, which are 1, 3, and 9 times the MRHD of 30 mg/day based on mg/m 2  body surface area, decreased fetal weight and delayed skeletal ossification were observed at 9 times the MRHD; this dose also caused maternal toxicity. In pregnant rabbits treated orally with aripiprazole during organogenesis at doses of 10, 30, and 100 mg/kg/day which are 6, 19, and 65 times the MRHD of 30 mg/day based on mg/m 2  body surface area, decreased maternal food consumption, and increased abortions as well as increased fetal mortality were observed at 65 times the MRHD. Decreased fetal weight and increased incidence of fused sternebrae were observed at 19 and 65 times the MRHD. In pregnant rabbits injected intravenously with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are 2, 6, and 19 times the MRHD of 30 mg/day based on mg/m 2  body surface area, decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification were observed at 19 times the MRHD; this dose also caused maternal toxicity. The fetal no-effect dose was 10 mg/kg/day, which is 6 times the MRHD. In rats treated orally with aripiprazole peri- and post-natally from gestation Day 17 through postpartum Day 21 at doses of 3, 10, and 30 mg/kg/day which are 1, 3, and 10 times the MRHD of 30 mg/day based on mg/m 2  body surface area slight maternal toxicity and slightly prolonged gestation were observed at 10 times the MRHD. An increase in stillbirths and, decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. In rats injected intravenously with aripiprazole from gestation Day 6 through lactation Day 20 at doses of 3, 8, and 20 mg/kg/day, which are 1, 3, and 6 times the MRHD of 30 mg/day based on mg/m 2  body surface area, increased stillbirths were observed at 3 and 6 times the MRHD; and decreases in early postnatal pup weight and survival were observed at 6 times the MRHD; these doses also caused some maternal toxicity. There were no effects on postnatal behavioral and reproductive development. Risk Summary Limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. There are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for aripiprazole and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition.  Safety and effectiveness in pediatric patients with major depressive disorder or agitation associated with schizophrenia or bipolar mania have not been established. The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients, 10 to 17 years of age, were similar to those in adults after correcting for the differences in body weight [see Clinical Pharmacology ( 12.3) ] . Schizophrenia Safety and effectiveness in pediatric patients with schizophrenia were established in a 6 week, placebo-controlled clinical trial in 202 pediatric patients aged 13 to 17 years [see Dosage and Administration ( 2.1), Adverse Reactions ( 6.1) , and Clinical Studies ( 14.1) ] . Although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. Bipolar I Disorder Safety and effectiveness in pediatric patients with bipolar mania were established in a 4 week, placebo-controlled clinical trial in 197 pediatric patients aged 10 to 17 years [see Dosage and Administration ( 2.2), Adverse Reactions ( 6.1) , and Clinical Studies ( 14.2)] . Although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. The efficacy of adjunctive aripiprazole with concomitant lithium or valproate in the treatment of manic or mixed episodes in pediatric patients has not been systematically evaluated. However, such efficacy and lack of pharmacokinetic interaction between aripiprazole and lithium or valproate can be extrapolated from adult data, along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. Irritability Associated with Autistic Disorder Safety and effectiveness in pediatric patients demonstrating irritability associated with autistic disorder were established in two 8 week, placebo-controlled clinical trials in 212 pediatric patients aged 6 to 17 years [see Indications and Usage ( 1), Dosage and Administration ( 2.4), Adverse Reactions ( 6.1) , and Clinical Studies ( 14.4)] . A maintenance trial was conducted in pediatric patients (6 to 17 years of age) with irritability associated with autistic disorder. The first phase of this trial was an open-label, flexibly dosed (aripiprazole 2 to 15 mg/day) phase in which patients were stabilized (defined as >25% improvement on the ABC-I subscale, and a CGI-I rating of "much improved" or "very much improved") on aripiprazole for 12 consecutive weeks. Overall, 85 patients were stabilized and entered the second, 16 week, double-blind phase where they were randomized to either continue aripiprazole treatment or switch to placebo. In this trial, the efficacy of aripiprazole for the maintenance treatment of irritability associated with autistic disorder was not established. Tourette's Disorder Safety and effectiveness of aripiprazole in pediatric patients with Tourette's Disorder were established in one 8 week (aged 7 to 17 years) and one 10 week trial (aged 6 to 18 years) in 194 pediatric patients [see Dosage and Administration ( 2.5), Adverse Reactions ( 6.1), and Clinical Studies ( 14.5) ]. Maintenance efficacy in pediatric patients has not been systematically evaluated. Juvenile Animal Studies Aripiprazole in juvenile rats caused mortality, CNS clinical signs, impaired memory and learning, and delayed sexual maturation when administered at oral doses of 10, 20, 40 mg/kg/day from weaning (21 days old) through maturity (80 days old). At 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other CNS signs were observed in both genders. In addition, delayed sexual maturation was observed in males. At all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. The changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. A No Observed Adverse Effect Level (NOAEL) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (AUC 0 to 24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All drug-related effects were reversible after a 2 month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. Aripiprazole in juvenile dogs (2 months old) caused CNS clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. Mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. A NOAEL could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (AUC 0 to 24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All drug-related effects were reversible after a 2 month recovery period. No dosage adjustment is recommended for elderly patients [see Boxed Warning,Warnings and Precautions ( 5.1) , and Clinical Pharmacology ( 12.3) ] . Of the 13,543 patients treated with oral aripiprazole in clinical trials, 1,073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. Placebo-controlled studies of oral aripiprazole in schizophrenia, bipolar mania, or major depressive disorder did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Aripiprazole is not approved for the treatment of patients with psychosis associated with Alzheimer's disease [see Boxed Warning and Warnings and Precautions ( 5.1) ] . Dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high aripiprazole concentrations. Approximately 8% of Caucasians and 3 to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see Dosage and Administration ( 2.7) and Clinical Pharmacology ( 12.3) ]. No dosage adjustment for aripiprazole is required on the basis of a patient's hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute) [see Clinical Pharmacology ( 12.3) ] . No dosage adjustment for aripiprazole is required on the basis of a patient's sex, race, or smoking status [see Clinical Pharmacology ( 12.3) ] . Aripiprazole is not a controlled substance. Aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). In physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed.

Product summary:

Aripiprazole tablets, USP 15 mg are white to off-white, round, uncoated tablets, debossed with "15" on one side and "19" on other side Bottles of 20                           NDC 68788-7006-2 Bottles of 30                           NDC 68788-7006-3 Bottles of 60                           NDC 68788-7006-6 Bottles of 90                           NDC 68788-7006-9 Bottles of 100                         NDC 68788-7006-1 Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Preferred Pharmaceuticals Inc.
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Repackaged By: Preferred Pharmaceuticals Inc.
MEDICATION GUIDE
Aripiprazole (AR-i-PIP-ra-zole) Tablets, USP
What is the most important information I should know about
aripiprazole tablets?
(For other side effects, also see "What are the possible side effects
of aripiprazole tablets?").
Serious side effects may happen when you take aripiprazole tablets,
including:
● Increased risk of death in elderly patients with dementia-related
psychosis: Medicines like
aripiprazole tablets can raise the risk of death in elderly people who
have lost touch with reality
(psychosis) due to confusion and memory loss (dementia). Aripiprazole
tablets are not approved for the
treatment of patients with dementia-related psychosis.
● Risk of suicidal thoughts or actions: Antidepressant medicines,
depression and other serious mental
illnesses, and suicidal thoughts or actions:
•
Antidepressant medicines may increase suicidal thoughts or actions in
some children, teenagers,
and young adults within the first few months of treatment.
•
Depression and other serious mental illnesses are the most important
causes of suicidal thoughts
and actions. Some people may have a particularly high risk of having
suicidal thoughts or actions.
These include people who have (or have a family history of) bipolar
illness (also called manic-
depressive illness) or suicidal thoughts or actions.
•
How can I watch for and try to prevent suicidal thoughts and actions
in myself or a family
member?
•
Pay close attention to any changes, especially sudden changes, in
mood, behaviors, thoughts, or
feelings. This is very important when an antidepressant medicine is
started or when the dose is
changed.
•
Call the healthcare provider right away to report new or sudden
changes in mood, behavior,
thoughts or feelings.
•
Keep all follow-up visits with the healthcare provider as scheduled.
Call the healthcare provider
between visits as needed, especially if you have concerns about
symptoms.
Call a healthcare provider r

Summary of Product characteristics

ARIPIPRAZOLE- ARIPIPRAZOLE TABLET
PREFERRED PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ARIPIPRAZOLE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ARIPIPRAZOLE TABLETS.
ARIPIPRAZOLE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2002
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
PSYCHOSIS AND SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT
DRUGS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
•
•
INDICATIONS AND USAGE
Aripiprazole Tablets are an atypical antipsychotic. The oral
formulations are indicated for:
•
•
•
•
•
DOSAGE AND ADMINISTRATION
Initial Dose
Recommended
Dose
Maximum Dose
Schizophrenia – adults ( 2.1)
10 to 15
mg/day
10 to 15 mg/day
30 mg/day
Schizophrenia – adolescents (
2.1)
2 mg/day
10 mg/day
30 mg/day
Bipolar mania – adults:
monotherapy ( 2.2)
15 mg/day
15 mg/day
30 mg/day
Bipolar mania – adults: adjunct
to lithium or valproate ( 2.2)
10 to 15
mg/day
15 mg/day
30 mg/day
Bipolar mania – pediatric
patients: monotherapy or as an
adjunct to lithium or valproate (
2.2)
2 mg/day
10 mg/day
30 mg/day
Major Depressive Disorder –
Adults adjunct to
antidepressants ( 2.3)
2 to 5 mg/day
5 to 10 mg/day
15 mg/day
Irritability associated with
autistic disorder – pediatric
patients ( 2.4)
2 mg/day
5 to 10 mg/day
15 mg/day
Tourette's
disorder – ( 2.5)
Patients ˂ 50 kg 2 mg/day
5 mg/day
10 mg/day
Patients ≥ 50
2 mg/day
10 mg/day
20 mg/day
Elderly patients with dementia-related psychosis treated with
antipsychotic drugs are at an
increased risk of death. Aripiprazole is not approved for the
treatment of patients with dementia-
related psychosis. ( 5.1)
Increased risk of suicidal thinking and behavior in children,
adolescents, and young adults taking
antidepressants. Monitor for worsening and emergence of suicidal
thoughts and behaviors. ( 5.3)
Schizophrenia ( 14.1)
Acute Treatment of Manic and Mixed Episodes associated with Bip