ABILIFY MAINTENA

ABILIFY MAINTENA- aripiprazole
Otsuka America Pharmaceutical, Inc.

1 INDICATIONS AND USAGE

ABILIFY MAINTENA (aripiprazole) is indicated for:

• Treatment of schizophrenia in adults [see Clinical Studies (14.1)]
• Maintenance monotherapy treatment of bipolar I disorder in adults [see Clinical Studies (14.2)]

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Overview for the Treatment of Schizophrenia and Maintenance Monotherapy of Bipolar I Disorder

ABILIFY MAINTENA is only to be administered by intramuscular injection by a healthcare professional. The recommended starting and maintenance dose of ABILIFY MAINTENA is 400 mg monthly (no sooner than 26 days after the previous injection).

For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ABILIFY MAINTENA. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

After the first ABILIFY MAINTENA injection, administer oral aripiprazole (10 mg to 20 mg) for 14 consecutive days to achieve therapeutic aripiprazole concentrations during initiation of therapy. For patients already stable on another oral antipsychotic (and known to tolerate aripiprazole), after the first ABILIFY MAINTENA injection, continue treatment with the antipsychotic for 14 consecutive days to maintain therapeutic antipsychotic concentrations during initiation of therapy.

If there are adverse reactions with the 400-mg dosage, consider reducing the dosage to 300 mg once monthly.

2.2 Dosage Adjustments for Missed Doses

If the second or third doses are missed:

• If more than 4 weeks and less than 5 weeks have elapsed since the last injection, administer the injection as soon as possible.
• If more than 5 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection.

If the fourth or subsequent doses are missed:

• If more than 4 weeks and less than 6 weeks have elapsed since the last injection, administer the injection as soon as possible.
• If more than 6 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection.

2.3 Dosage Adjustments for Cytochrome P450 Considerations

Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days (see Table 1). Dosage adjustments for 200 mg and 160 mg are obtained only by using the 300-mg or 400-mg strength vials for intramuscular deltoid or gluteal injection.

If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the ABILIFY MAINTENA dosage may need to be increased [see Dosage and Administration (2.1)].

Avoid the concomitant use of CYP3A4 inducers with ABILIFY MAINTENA for greater than 14 days because the blood levels of aripiprazole are decreased and may be below the effective levels.

Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Table 1: Dose Adjustments of ABILIFY MAINTENA in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers for Greater than 14 days

Factors	Adjusted Dose
* 200-mg and 160-mg dosage adjustments are obtained only by using the 300-mg or 400-mg strength vials.
CYP2D6 Poor Metabolizers
Known CYP2D6 Poor Metabolizers	300 mg
Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors	200 mg *
Patients Taking 400 mg of ABILIFY MAINTENA
Strong CYP2D6 or CYP3A4 inhibitors	300 mg
CYP2D6 and CYP3A4 inhibitors	200 mg *
CYP3A4 inducers	Avoid use
Patients Taking 300 mg of ABILIFY MAINTENA
Strong CYP2D6 or CYP3A4 inhibitors	200 mg *
CYP2D6 and CYP3A4 inhibitors	160 mg *
CYP3A4 inducers	Avoid use

ABILIFY MAINTENA comes in two types of kits. See instructions for reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe [see Dosage and Administration (2.5)] , and 2) Vials [see Dosage and Administration (2.6)].

2.4 Different Aripiprazole Formulations and Kits

There are two aripiprazole formulations for intramuscular use with different dosages, dosing frequencies, and indications. ABILIFY MAINTENA is a long-acting aripiprazole formulation with 4-week dosing intervals indicated for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder in adults. In contrast, aripiprazole injection (9.75 mg per vial) is a short-acting formulation indicated for agitation in patients with schizophrenia or mania. Do not substitute these products. Refer to the prescribing information for aripiprazole injection for more information about aripiprazole injection.

ABILIFY MAINTENA comes in two types of kits. See instructions for reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe available in 300-mg or 400-mg strength syringes [see Dosage and Administration (2.5)] , and 2) Single-use vials available in 300-mg or 400-mg strength vials [see Dosage and Administration (2.6)].

The 200-mg and 160-mg dosage adjustments are obtained only by using the 300-mg or 400-mg strength vials.

2.5 Pre-filled Dual Chamber Syringe: Preparation and Administration Instructions

Preparation Prior to Reconstitution

For deep intramuscular deltoid or gluteal injection by healthcare professionals only. Do not administer by any other route. Inject full syringe contents immediately following reconstitution. Administer once monthly.

Lay out and confirm that components listed below are provided in the kit:

• One ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe (400 mg or 300 mg as appropriate) for extended-release injectable suspension containing lyophilized powder and Sterile Water for Injection
• One 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients
• One 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients
• One 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

Reconstitution of Lyophilized Powder in Pre-filled Dual Chamber Syringe

Reconstitute at room temperature.

a)

Push plunger rod slightly to engage threads. And then, rotate plunger rod until the rod stops rotating to release diluent. After plunger rod is at complete stop, middle stopper will be at the indicator line (see Figure 1).

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Figure 1

b)

Vertically shake the syringe vigorously for 20 seconds until drug is uniformly milky-white (see Figure 2).

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Figure 2

c)

Visually inspect the syringe for particulate matter and discoloration prior to administration. The reconstituted ABILIFY MAINTENA suspension should appear to be a uniform, homogeneous suspension that is opaque and milky-white in color.

Injection Procedure

Use appropriate aseptic techniques throughout injection procedure. For deep intramuscular injection only.

a)

Twist and pull off Over-cap and Tip-cap (see Figure 3).

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Figure 3

b)

Select appropriate needle (see Figure 4).

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Figure 4

For deltoid administration:

• 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for non-obese patients
• 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for obese patients

For gluteal administration:

• 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for non-obese patients
• 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for obese patients

c)

While holding the needle cap, ensure the needle is firmly seated on the safety device with a push. Twist clockwise until SNUGLY fitted (see Figure 5).

Figure 5

d)

Then PULL needle-cap straight up (see Figure 6).

Figure 6

e)

Hold syringe UPRIGHT and ADVANCE PLUNGER ROD SLOWLY TO EXPEL THE AIR. Expel air until suspension fills needle base. If it’s not possible to advance plunger rod to expel the air, check that plunger rod is rotated to a complete stop (see Figure 7).

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Figure 7

f)

Inject slowly into the deltoid or gluteal muscle. Do not massage the injection site.

Disposal Procedure

a)

Engage the needle safety device and safely discard all kit components (see Figure 8). ABILIFY MAINTENA pre-filled dual chamber syringe is for single-use only.

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Figure 8

b)

Rotate sites of injections between the two deltoid or gluteal muscles.