ARISTADA INITIO- aripiprazole lauroxil injection, suspension, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

aripiprazole lauroxil (UNII: B786J7A343) (aripiprazole lauroxil - UNII:B786J7A343)

Available from:

Alkermes, Inc.

Administration route:

INTRAMUSCULAR

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

ARISTADA INITIO, in combination with oral aripiprazole, is indicated for the initiation of ARISTADA when used for the treatment of schizophrenia in adults. ARISTADA INITIO is contraindicated in patients with a known hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions (6)]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA INITIO during pregnancy. For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Limited published data on aripiprazole use in pregnant women are not sufficient to inform any drug-associated risks for birth defects or miscarriage. No teratogenicity was observed in animal reproductive studies with intramuscular administration of aripiprazole lauroxil to rats and rabbits during organogenesis at doses up to 8 and 23 times, respectively, the maximum recommended human dose (MRHD) of 675 mg based on body surface area (mg/m2 ). However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats and rabbits [see Data]. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Advise pregnant women of the potential risk to a fetus. Clinical Considerations 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 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 recover within hours or days without specific treatment; others required prolonged hospitalization. Data Animal Data for ARISTADA (Aripiprazole Lauroxil) Aripiprazole lauroxil did not cause adverse developmental or maternal effects in rats or rabbits when administered intramuscularly during the period of organogenesis at doses of 18, 49, or 144 mg/animal in pregnant rats which are approximately 1 to 8 times the MRHD of 675 mg based on mg/m2 , and at doses of 241, 723, and 2893 mg/animal in pregnant rabbits which are approximately 2 to 23 times the MRHD based on mg/m2 . However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats and rabbits [see Data below] . Animal Data for Aripiprazole Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day which are approximately 1 to 10 times the oral MRHD of 30 mg/day based on mg/m2 of aripiprazole during the period of organogenesis. Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight, and undescended testes. Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD based on mg/m2 . At 3 and 10 times the oral MRHD based on mg/m2 , delivered offspring had decreased body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). A low incidence of diaphragmatic hernia was also seen in the fetuses exposed to the highest dose. Postnatally, delayed vaginal opening was seen at 3 and 10 times the oral MRHD based on mg/m2 and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) along with some maternal toxicity were seen at the highest dose; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral MRHD based on mg/m2 of aripiprazole during the period of organogenesis decreased maternal food consumption and increased abortions were seen at the highest dose as well as increased fetal mortality. Decreased fetal weight and increased incidence of fused sternebrae were observed at 3 and 11 times the oral MRHD based on AUC. In rats treated with oral doses of 3, 10, and 30 mg/kg/day which are 1 to 10 times the oral MRHD based on mg/m2 of aripiprazole perinatally and postnatally (from day 17 of gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged gestation were seen at the highest dose. An increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. Risk Summary Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ARISTADA INITIO and any potential adverse effects on the breastfed infant from ARISTADA INITIO or from the underlying maternal condition. Safety and effectiveness of ARISTADA INITIO in pediatric patients have not been established. Safety and effectiveness of ARISTADA INITIO in patients >65 years of age have not been evaluated. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA INITIO is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1, 5.2)]. Approximately 8% of Caucasians and 3-8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM). Avoid use of ARISTADA INITIO in these patients because dosage adjustments are not possible (it is only available in one strength in a single-dose pre-filled syringe) [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)] . No dosage adjustment for ARISTADA INITIO is required based on 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 ARISTADA INITIO is required on the basis of a patient's sex, race, or smoking status [see Clinical Pharmacology (12.3)] .

Product summary:

ARISTADA INITIO extended-release injectable suspension is available in a strength of 675 mg in 2.4 mL. The kit contains a 5-mL pre-filled syringe containing ARISTADA INITIO as a sterile white to off-white aqueous extended-release injectable suspension with safety needles. Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (between 59°F and 86°F). Do not freeze.

Authorization status:

New Drug Application

Patient Information leaflet

ARISTADA INITIO- ARIPIPRAZOLE LAUROXIL INJECTION, SUSPENSION, EXTENDED
RELEASE
Alkermes, Inc.
----------
This Medication Guide has been approved by the U.S. Food and
Drug Administration
Revised 12/2023
MEDICATION GUIDE
ARISTADA INITIO® (air-is-TAH-dah i-ni'-she-oh)
(aripiprazole lauroxil)
extended-release injectable suspension, for intramuscular use
What is the most important information I should know about ARISTADA
INITIO?
ARISTADA INITIO may cause serious side effects, including:
•
Increased risk of death in elderly people with dementia-related
psychosis. ARISTADA INITIO
increases the risk of death in elderly people who have lost touch with
reality (psychosis) due to
confusion and memory loss (dementia). ARISTADA INITIO is not for the
treatment of people
with dementia-related psychosis.
What is ARISTADA INITIO?
ARISTADA INITIO is a prescription medicine given as a one-time
injection and is used in combination
with oral aripiprazole to start ARISTADA treatment, or re-start
ARISTADA treatment after a missed
dose, when ARISTADA is used for the treatment of schizophrenia in
adults.
It is not known if ARISTADA INITIO is safe and effective in children.
Do not receive ARISTADA INITIO if you are allergic to aripiprazole or
any of the ingredients in
ARISTADA INITIO. See the end of this Medication Guide for a complete
list of ingredients in
ARISTADA INITIO.
Before you receive ARISTADA INITIO, tell your healthcare provider
about all of your medical
conditions, including if you:
•
have not taken ABILIFY®, ABILIFY MAINTENA® or any aripiprazole
product before
•
have or had heart problems or a stroke
•
have diabetes or high blood sugar or a family history of diabetes or
high blood sugar. Your
healthcare provider should check your blood sugar before you receive
ARISTADA INITIO.
•
have or had low or high blood pressure
•
have or had seizures (convulsions)
•
have or had a low white blood cell count
•
are pregnant or plan to become pregnant. It is not known if ARISTADA
INITIO will harm your
unborn baby.
•
If

Summary of Product characteristics

ARISTADA INITIO- ARIPIPRAZOLE LAUROXIL INJECTION, SUSPENSION, EXTENDED
RELEASE
ALKERMES, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ARISTADA INITIO SAFELY
AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ARISTADA INITIO
.
ARISTADA INITIO (ARIPIPRAZOLE LAUROXIL) EXTENDED-RELEASE INJECTABLE
SUSPENSION, FOR
INTRAMUSCULAR USE
INITIAL U.S. APPROVAL: 2015
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. (5.1)
ARISTADA INITIO IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH
DEMENTIA-RELATED
PSYCHOSIS. (5.1)
INDICATIONS AND USAGE
ARISTADA INITIO, in combination with oral aripiprazole, is indicated
for the initiation of ARISTADA when
used for the treatment of schizophrenia in adults (1).
DOSAGE AND ADMINISTRATION
Administer one 675 mg injection of ARISTADA INITIO and one 30 mg dose
of oral aripiprazole in
conjunction with the first ARISTADA injection (2.1).
ARISTADA INITIO is only to be used as a single dose and is not for
repeated dosing (2.1).
Administer ARISTADA INITIO by intramuscular injection in either the
deltoid or gluteal muscle by a
healthcare professional (2.1).
For patients naïve to aripiprazole, establish tolerability with oral
aripiprazole prior to initiating treatment
with ARISTADA INITIO (2.1).
See Dosage and Administration for detailed preparation and
administration instructions (2.4).
Avoid use in known CYP2D6 poor metabolizers (2.3, 7.1).
Avoid use with strong CYP2D6 or CYP 3A4 inhibitors and strong CYP3A4
inducers (2.3, 7.1).
ARISTADA INITIO is not interchangeable with ARISTADA (2.1, 5.3).
DOSAGE FORMS AND STRENGTHS
Extended-release injectable suspension: 675 mg single-dose pre-filled
syringe (3).
CONTRAINDICATIONS
Known hypersensitivity to aripiprazole (4).
WARNINGS AND PRECAUTIONS
_Cerebrovascular Adverse Rea