Dosage & Administration
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Aristada & Aristada Initio Prescribing Information
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ].
ARISTADA is indicated for the treatment of schizophrenia in adults [see Clinical Studies ].
Recommended Dosage
ARISTADA is only to be administered as an intramuscular injection by a healthcare professional. For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ARISTADA. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability. Refer to the prescribing information of oral aripiprazole for the recommended dosage and administration of the oral formulation.
There are two ways to initiate treatment with ARISTADA:
- Option #1: Administer one intramuscular injection of ARISTADA INITIO 675 mg (in either the deltoid or gluteal muscle) and one dose of oral aripiprazole 30 mg in conjunction with the first ARISTADA injection.
- The first ARISTADA injection may be administered on the same day as ARISTADA INITIO or up to 10 days thereafter. See the ARISTADA INITIO prescribing information for additional information regarding administration of ARISTADA INITIO.
- Avoid injecting both ARISTADA INITIO and ARISTADA concomitantly into the same deltoid or gluteal muscle.
- Option #2: Administer 21 consecutive days of oral aripiprazole in conjunction with the first ARISTADA injection.
Depending on individual patient's needs, treatment with ARISTADA can be initiated at a dose of 441 mg, 662 mg or 882 mg administered monthly, 882 mg administered every 6 weeks or 1064 mg administered every 2 months. The 441 mg, 662 mg, 882 mg and 1064 mg doses correspond to 300 mg, 450 mg, 600 mg and 724 mg of aripiprazole, respectively [see Clinical Pharmacology ].
| Dose | Dosing Frequency | Site of Intramuscular Injection |
|---|---|---|
| 441 mg | Monthly | Deltoid or Gluteal |
| 662 mg | Monthly | Gluteal |
| 882 mg | Monthly or every 6 weeks | Gluteal |
| 1064 mg | Every 2 months | Gluteal |
Use the following ARISTADA doses for patients who are stabilized on oral aripiprazole, as shown in Table 2.
| Oral Aripiprazole Dose | Intramuscular ARISTADA Dose |
|---|---|
| 10 mg per day | 441 mg every month |
| 15 mg per day | 662 mg every month 882 mg every 6 weeks 1064 mg every 2 months |
| 20 mg or higher per day | 882 mg every month |
In conjunction with the first ARISTADA injection, administer a single injection of ARISTADA INITIO and one dose of oral aripiprazole 30 mg, or continue treatment with oral aripiprazole for 21 consecutive days [see Recommended Dosage( 2.1)].
Adjust the ARISTADA dose as needed. When making dose and dosing interval adjustments, consider the pharmacokinetics and prolonged-release characteristics of ARISTADA [see Clinical Pharmacology( 12.3)].
Missed Doses
When a dose of ARISTADA is missed, administer the next injection of ARISTADA as soon as possible. Depending on the time elapsed since the last ARISTADA injection, supplement the next ARISTADA injection as recommended in Table 3 below.
| Dose of Patient's Last ARISTADA Injection | Length of Time Since Last Injection | ||
|---|---|---|---|
a The patient should supplement with the same dose of oral aripiprazole as when the patient began ARISTADA (see Table 2). | |||
| 441 mg | ≤ 6 weeks | > 6 and ≤ 7 weeks | > 7 weeks |
| 662 mg | ≤ 8 weeks | > 8 and ≤ 12 weeks | > 12 weeks |
| 882 mg | ≤ 8 weeks | > 8 and ≤ 12 weeks | > 12 weeks |
| 1064 mg | ≤ 10 weeks | > 10 and ≤ 12 weeks | > 12 weeks |
| Dosage and Administration for Re-initiation of ARISTADA | No Supplementation Required | Supplement with a Single Dose of ARISTADA INITIO OR 7 Days of Oral Aripiprazolea | Re-initiate with a Single Dose of ARISTADA INITIO and a Single Dose of Oral Aripiprazole 30 mg OR supplement with 21 Days of Oral Aripiprazolea |
Early Dosing
The recommended ARISTADA dosing interval is monthly for the 441 mg, 662 mg and 882 mg doses, every 6 weeks for the 882 mg dose, or every 2 months for the 1064 mg dose and should be maintained. In the event of early dosing, an ARISTADA injection should not be given earlier than 14 days after the previous injection.
Dose Adjustments for CYP450 Considerations
Refer to the prescribing information for oral aripiprazole for recommendations regarding dosage adjustments due to drug interactions, for the first 21 days when the patient is taking 21 days of oral aripiprazole concomitantly with the first dose of ARISTADA. Avoid initiating ARISTADA treatment with ARISTADA INITIO in patients requiring dose adjustments.
Once stabilized on ARISTADA, refer to the dosing recommendations below for patients taking strong CYP2D6 inhibitors, strong CYP3A4 inhibitors, or strong CYP3A4 inducers:
- No dosage changes recommended for ARISTADA, if CYP450 modulators are added for less than 2 weeks.
- Make dose changes to ARISTADA if CYP450 modulators are added for greater than 2 weeks (see Table 4).
| Concomitant Medicine | Dose Change for ARISTADAa |
|---|---|
a For the 882 mg dose administered every 6 weeks and the 1064 mg administered every 2 months, the next lower strength should be 441 mg administered monthly. | |
| Strong CYP3A4 Inhibitor | Reduce the dose of ARISTADA to the next lower strength. No dosage adjustment is necessary in patients taking 441 mg ARISTADA, if tolerated. For patients known to be poor metabolizers of CYP2D6: Reduce dose to 441 mg from 662 mg, 882 mg, or 1064 mg. No dosage adjustment is necessary in patients taking 441 mg ARISTADA, if tolerated. |
| Strong CYP2D6 Inhibitor | Reduce the dose of ARISTADA to the next lower strength. No dosage adjustment is necessary in patients taking 441 mg ARISTADA, if tolerated. For patients known to be poor metabolizers of CYP2D6: No dose adjustment required. |
| Both Strong CYP3A4 Inhibitor and Strong CYP2D6 Inhibitor | Avoid use for patients at 662 mg, 882 mg, or 1064 mg dose. No dosage adjustment is necessary in patients taking 441 mg ARISTADA, if tolerated. |
| CYP3A4 Inducers | No dose adjustment for 662 mg, 882 mg, or 1064 mg dose; increase the 441 mg dose to 662 mg. |
Important Administration Instructions
The kit contains a syringe containing ARISTADA sterile aqueous extended-release injectable suspension and 2 or 3 safety needles depending on dose (a 2-inch 20 gauge needle with yellow needle hub, a 1 ½-inch 20 gauge needle with yellow needle hub, and a 1-inch 21 gauge needle with green needle hub (441 mg kit only)) for intramuscular injection. All materials should be stored at room temperature.
A | 5 mL syringe containing ARISTADA sterile aqueous extended-release injectable suspension
B | 20 gauge needle, 2-inch with yellow needle hub
C | 20 gauge needle, 1½-inch with yellow needle hub
D | 21 gauge needle, 1-inch with green needle hub
1. TAP and vigorously SHAKE the syringe.
1a. Tap the syringe at least 10 times to dislodge any material which may have settled.
1b. Shake the syringe vigorously for a minimum of 30 seconds to ensure a uniform suspension. If the syringe is not used within 15 minutes, shake again for 30 seconds.
2. SELECT the injection needle.
2a. Select injection site.
2b. Select needle length based on injection site. For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided.
| Injection Site | Needle Length |
| 441 mg dose | |
| Deltoid | 21 gauge, 1-inch or 20 gauge, 1½-inch |
| Gluteal | 20 gauge, 1½-inch or 20 gauge, 2-inch |
| 662 mg dose | |
| Gluteal | 20 gauge, 1½-inch or 20 gauge, 2-inch |
| 882 mg dose | |
| Gluteal | 20 gauge, 1½-inch or 20 gauge, 2-inch |
| 1064 mg dose | |
| Gluteal | 20 gauge, 1½-inch or 20 gauge, 2-inch |
[see Dosage and Administration( 2.1)]
3. ATTACH the injection needle.
Attach the appropriate needle securely with a clockwise twisting motion. Do NOT overtighten. Overtightening could lead to needle hub cracking.
4. PRIME the syringe to remove air.
4a. Bring the syringe into upright position and tap the syringe to bring air to the top.
4b. Depress the plunger rod to remove air until a few drops are released. It is normal to see small air bubbles remaining in the syringe.
5. Inject in a RAPID and CONTINUOUS manner. Product requires a RAPID injection. Do not hesitate. Administer the entire content intramuscularly. Do not inject by any other route.
6. DISPOSE of the needle. Cover the needle by pressing the safety device. Dispose of used and unused items in a proper waste container.
ARISTADA is a white to off-white aqueous extended-release injectable suspension provided in a single-dose pre-filled syringe.
ARISTADA is available as described in Table 6.
| Dose Strength | Volume | Inject Intramuscularly | Color Label |
|---|---|---|---|
| 441 mg | 1.6 mL | Deltoid or Gluteal Muscle | Light Blue |
| 662 mg | 2.4 mL | Gluteal Muscle Only | Green |
| 882 mg | 3.2 mL | Gluteal Muscle Only | Burgundy |
| 1064 mg | 3.9 mL | Gluteal Muscle Only | Dark Blue |
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA 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, including ARISTADA, 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 (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 outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including ARISTADA, during pregnancy (see Clinical Considerations). Aripiprazole exposure during pregnancy may decrease milk supply in the post-partum period [see Use in Specific Populations ].
No teratogenicity was observed in animal reproductive studies with intramuscular administration of aripiprazole lauroxil to rats and rabbits during organogenesis at doses up to 5 and 15 times, respectively, the maximum recommended human dose (MRHD) of 1,064 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 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. Schizophrenia is 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.
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 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 0.6 to 5 times the MRHD of 1064 mg on mg/m2 basis, and at doses of 241, 723, and 2893 mg/animal in pregnant rabbits which are approximately 1 to 15 times the MRHD on mg/m2 basis. 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 on mg/m2 basis 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 on mg/m2 basis.
At 3 and 10 times the oral MRHD on mg/m2 basis, 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 on mg/m2 basis 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 on mg/m2 basis 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 on mg/m2 basis 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.
Lactation
Risk Summary
Aripiprazole is present in human breast milk. Based on published case reports and pharmacovigilance reports, aripiprazole exposure during pregnancy and/or the postpartum period may lead to clinically relevant decreases in milk supply which may be reversible with discontinuation of the drug. There are also reports of aripiprazole exposure during pregnancy and no maternal milk supply in the post-partum period. Effects on milk supply may be mediated through decreases in prolactin levels, which have been observed [see Adverse Reactions ]. Monitor the breastfeed infant for dehydration and lack of appropriate weight gain. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ARISTADA and any potential adverse effects on the breastfed infant from ARISTADA or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness of ARISTADA in patients <18 years of age have not been evaluated.
Geriatric Use
Safety and effectiveness of ARISTADA 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 is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ].
CYP2D6 Poor Metabolizers
Dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high aripiprazole concentrations. Approximately 8% of Caucasians and 3-8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see Dosage and Administration( 2.4), Clinical Pharmacology ( 12.3)].
Hepatic and Renal Impairment
No dosage adjustment for ARISTADA 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)].
Other Specific Populations
No dosage adjustment for ARISTADA is required on the basis of a patient's sex, race, or smoking status [see Clinical Pharmacology( 12.3)].
ARISTADA is contraindicated in patients with a known hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions].