Dosage & Administration
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Abilify Asimtufii Prescribing Information
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ABILIFY ASIMTUFII is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1)].
ABILIFY ASIMTUFII is indicated:
- for the treatment of schizophrenia in adults
- for maintenance monotherapy treatment of bipolar I disorder in adults
Important Administration Information
For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ABILIFY ASIMTUFII. Due to the half-life of oral aripiprazole (i.e., 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively), it may take up to 2 weeks to fully assess tolerability.
ABILIFY ASIMTUFII must be administered as an intramuscular gluteal injection by a healthcare professional. Do not administer by any other route.
For detailed preparation and administration instructions, [see Dosage and Administration (2.5)].
Recommended Dosage for ABILIFY ASIMTUFII
The recommended dosage of ABILIFY ASIMTUFII is 960 mg, administered once every 2 months (56 days after previous injection).
Patients Receiving Oral Antipsychotics
There are two ways to initiate treatment with ABILIFY ASIMTUFII in patients receiving oral antipsychotics:
1-day initiation:
- Administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle, one injection of Abilify Maintena 400 mg in a separate gluteal or deltoid muscle, and one dose of oral aripiprazole 20 mg, on the first day of treatment with ABILIFY ASIMTUFII.
- Do not administer both injections into the same muscle.
14-day initiation:
- Administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle and continue treatment with oral aripiprazole (10 mg to 20 mg) for 14 consecutive days.
- For patients already stable on another oral antipsychotic (and known to tolerate aripiprazole), administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle and continue treatment with the oral antipsychotic for 14 consecutive days.
Patients Receiving Abilify Maintena
For patients receiving Abilify Maintena 400 mg (once monthly dosing), administer ABILIFY ASIMTUFII 960 mg (once every 2 month dosing) in place of the next scheduled injection of the Abilify Maintena. The first ABILIFY ASIMTUFII injection may be administered in place of the second, or later injection of Abilify Maintena.
If there are adverse reactions with the ABILIFY ASIMTUFII 960 mg dosage, the dosage may be reduced to 720 mg once every 2 months.
Patients may be given the ABILIFY ASIMTUFII injection up to 2 weeks before or 2 weeks after the 2-month scheduled timepoint.
Missed Doses
If more than 8 weeks and less than 14 weeks have elapsed since the last injection, administer the next dose of ABILIFY ASIMTUFII as soon as possible. The once every 2 month schedule should be resumed.
If more than 14 weeks have elapsed since the last injection, restart treatment with either 1-day initiation or 14-day initiation with ABILIFY ASIMTUFII [see Dosage and Administration (2.2)].
Dosage Modifications for Cytochrome P450 Considerations
Dosage adjustments for patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant strong CYP3A4 inhibitors or CYP2D6 inhibitors for more than 14 days are described in Table 1.
If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the dosage of ABILIFY ASIMTUFII may need to be increased to the previous dose.
Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.
| Factors | Dosage Recommendation |
|---|---|
| |
| CYP2D6 Poor Metabolizers | |
| Known CYP2D6 Poor Metabolizers | 720 mg once every 2 months * |
| Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors | Avoid use |
| Patients Taking 960 mg of ABILIFY ASIMTUFII | |
| Concomitant use of ABILIFY ASIMTUFII with Strong CYP2D6 inhibitors | 720 mg once every 2 months * |
| Concomitant use of ABILIFY ASIMTUFII with Strong CYP3A4 inhibitors | 720 mg once every 2 months * |
| Concomitant use of ABILIFY ASIMTUFII with Strong CYP2D6 and Strong CYP3A4 inhibitors | Avoid use |
| Concomitant use of ABILIFY ASIMTUFII with CYP3A4 inducers | Avoid use |
Preparation and Administration Instructions
- Read the complete instructions for preparation and administration below and consider referring to the separate Healthcare Provider "Instructions for Use" for additional preparation and administration considerations.
- To be prepared and administered by a healthcare professional only.
- For gluteal intramuscular injection only. Do not administer by any other route.
- Prior to administration, visually inspect ABILIFY ASIMTUFII pre-filled syringe for particulate matter and discoloration. The suspension should appear to be a uniform, homogeneous suspension that is opaque and milky-white in color. Do not use ABILIFY ASIMTUFII pre-filled syringe if the suspension is discolored, or particulate matter is present
- Each kit contains one sterile pre-filled syringe containing ABILIFY ASIMTUFII 720 mg or 960 mg and two safety needles:
- One sterile 1 ½ inch, 22 gauge needle (in black packaging)
- One sterile 2 inch, 21 gauge needle (in green packaging)
- Each kit contains one sterile pre-filled syringe containing ABILIFY ASIMTUFII 720 mg or 960 mg and two safety needles:
Preparation Prior to Administration
- Remove the ABILIFY ASIMTUFII pre-filled syringe from the package.
- Tap the syringe on your hand at least 10 (ten) times (Figure 1).
- After tapping, shake the syringe vigorously for at least 10 (ten) seconds, until the medication is uniform (Figure 2).
Figure 1 Figure 2 
Select the appropriate needle
Needle selection is determined by patient body type.
For gluteal intramuscular administration only.
- For non-obese patients - 22-gauge, 1.5-inch (38 mm) safety needle with needle protection device (needle in black packaging)
- For obese patients - 21-gauge, 2-inch (51 mm) safety needle with needle protection device (needle in green packaging)
Attach the needle
- Twist and pull off the pre-filled syringe tip-cap (Figure 3).
- While holding the base of the needle, ensure the needle is firmly seated on the safety device with a push. Gently twist clockwise until SECURELY fitted (Figure 3).
Figure 3 
Expel Air
- When you are ready to administer the injection of ABILIFY ASIMTUFII, hold the pre-filled syringe upright and remove the needle-cap straight up (Figure 4). Do not twist the needle-cap, as this may loosen the needle from the syringe.
Figure 4 
- Slowly advance the plunger rod upward to expel the air and until the suspension fills needle base (Figure 5).
Figure 5 
Inject the dose
- Slowly inject the entire contents of the pre-filled syringe intramuscularly into the gluteal muscle of the patient (Figure 6).
Do not administer by any other route.
Do not massage the injection site.
| Figure 6 |
 |
Disposal Procedure
- After the injection, press the safety shield on a hard surface to cover and lock shield over the needle (Figures 7 and 8)
Figure 7 Figure 8 
- Immediately discard used syringe and the unused needle in an approved sharps container.
- The unused needle should not be saved for future use.
Extended-release injectable suspension: sterile, white to off-white, aqueous suspension in a single-dose, pre-filled syringe.
| Dose Strength | Volume | Label Color | Syringe Tip Wrap |
|---|---|---|---|
| 720 mg | 2.4 mL | Light Blue | Aqua |
| 960 mg | 3.2 mL | Pink | Light Blue |
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ABILIFY ASIMTUFII, 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-research-programs/pregnancyregistry/.
Risk Summary
Neonates exposed to antipsychotic drugs, including ABILIFY ASIMTUFII, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms (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 or bipolar I disorder and with exposure to antipsychotics, including ABILIFY ASIMTUFII, during pregnancy (see Clinical Considerations). Aripiprazole exposure during pregnancy may decrease milk supply in the post-partum period [see Use in Specific Populations (8.2)].
In animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 11 times, respectively, the maximum recommended human oral dose (MRHD) 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 oral MRHD produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (see Data).
The background risk of major birth defects and miscarriage for the indicated population are 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.
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 oral aripiprazole, during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Data
Animal Data
No developmental toxicity studies were conducted with intramuscular aripiprazole suspension.
In animal oral or intravenous studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits.
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). 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 rats treated with aripiprazole intravenously at doses of 3, 9, and 27 mg/kg/day, which are 1 to 9 times the oral MRHD on mg/m2 basis, during the period of organogenesis, decreased fetal weight and delayed skeletal ossification were seen at the highest dose which also caused 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 of aripiprazole on mg/m2 basis 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 pregnant rabbits receiving aripiprazole injection intravenously at doses of 3, 10, and 30 mg/kg/day, which are 2 to 19 times the oral MRHD on mg/m2 basis during the period of organogenesis, the highest dose caused pronounced maternal toxicity that resulted in decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification. The fetal no-effect dose was 5 times the human exposure at the oral MRHD based on AUC and is 6 times the oral MRHD on mg/m2 basis.
In rats treated with oral doses of 3, 10, and 30 mg/kg/day, which are 1 to 10 times the oral MRHD of aripiprazole on a mg/m2 basis, peri- and post-natally (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.
In rats treated with aripiprazole intravenously at doses of 3, 8, and 20 mg/kg/day which are 1 to 6 times the oral MRHD on mg/m2 basis from Day 6 of gestation through Day 20 postpartum, increased stillbirths were seen at 3 and 6 times the oral MRHD on mg/m2 basis, and decreases in early postnatal pup weight and survival were seen at the highest dose; these doses produced some maternal toxicity. There were no effects on postnatal behavioral and reproductive development.
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 (6.1)]. Monitor the breastfed infant for dehydration and lack of appropriate weight gain. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ABILIFY ASIMTUFII and any potential adverse effects on the breastfed infant from ABILIFY ASIMTUFII or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness of ABILIFY ASIMTUFII in pediatric patients have not been established.
Juvenile Animal Studies
No juvenile animal studies were conducted with intramuscular aripiprazole suspension. A study with oral aripiprazole in juvenile rats caused mortality, CNS clinical signs, impaired memory and learning, and delayed sexual maturation when administered at 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 (AUC0-24) for aripiprazole or its major active metabolite in adolescents at the maximum recommended oral 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 (AUC0-24) for aripiprazole or its major active metabolite in adolescents at the maximum recommended oral pediatric dose of 15 mg/day. All drug-related effects were reversible after a 2-month recovery period.
Geriatric Use
Clinical studies of ABILIFY ASIMTUFII did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data have not identified differences in responses between the elderly and younger patients [see Clinical Pharmacology (12.3)]. 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, or cardiac function, and of concomitant disease or other drug therapy.
In single-dose and multiple-dose pharmacokinetic studies with oral aripiprazole, there was no detectable age effect in the population pharmacokinetic analysis in schizophrenia patients [see Clinical Pharmacology (12.3)]. No dosage adjustments are recommended based on age alone. ABILIFY ASIMTUFII is not approved for the treatment of patients with dementia-related psychosis [see also Boxed Warning and Warnings and Precautions (5.1)].
CYP2D6 Poor Metabolizers
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 (2.4)].
ABILIFY ASIMTUFII is contraindicated in patients with a known hypersensitivity to aripiprazole, or any of the excipients. Hypersensitivity reactions ranging from pruritus/urticaria to anaphylaxis have been reported in patients receiving aripiprazole [see Adverse Reactions (6.1)].