ABILIFY MAINTENA 720 mg / 960 mg Prolonged-release suspension for injection Ref.[116141] Active ingredients: Aripiprazole

Posology

For patients who have never taken aripiprazole, tolerability with aripiprazole must be established prior to initiating treatment with Abilify Maintena.

Titration of the dose for Abilify Maintena is not required.

Starting regimen

The recommended starting dosing regimen when transitioning from Abilify Maintena 400 mg once monthly is Abilify Maintena 960 mg no sooner than 26 days after previous injection of Abilify Maintena 400 mg. Abilify Maintena 960 mg should then be dosed once every 2 months (every 56 days).

Initiation may also be started by following one of two additional regimens:

• One injection start: On the day of initiation following oral therapy, one injection of Abilify Maintena 960 mg should be administered and treatment with 10 mg to 20 mg oral aripiprazole per day for 14 consecutive days should be continued to maintain therapeutic aripiprazole concentrations during initiation of therapy.
• Two injection start: On the day of initiation following oral therapy, one injection of Abilify Maintena 960 mg and one injection of Abilify Maintena 400 mg should be administered at two different injection sites (see method of administration), along with one 20 mg dose of oral aripiprazole.

Dosing interval and dosing adjustments

After the injection start, the recommended maintenance dose is one injection of Abilify Maintena 960 mg every second month. Inject Abilify Maintena 960 mg once every two months as a single injection 56 days after the previous injection. Patients may be given the injection up to 2 weeks before or 2 weeks after the scheduled 2-month dose.

If there are adverse reactions with the Abilify Maintena 960 mg dose, reduction to Abilify Maintena 720 mg once every two months should be considered.

Missed doses

If more than 8 weeks and less than 14 weeks have elapsed since the last injection, the next dose of Abilify Maintena 960 mg/720 mg should be administered as soon as possible. The once every two months schedule should then be resumed. If more than 14 weeks have elapsed since the last injection, the next dose of Abilify Maintena 960 mg/720 mg should be administered with concomitant oral aripiprazole for 14 days or with 2 separate injections (one each of Abilify Maintena 960 mg and Abilify Maintena 400 mg or one each Abilify Maintena 720 mg and Abilify Maintena 300 mg) administered together with one 20 mg oral aripiprazole dose. The once every two months schedule should then be resumed.

Special populations

Elderly

The safety and efficacy of Abilify Maintena 960 mg/720 mg in the treatment of schizophrenia in patients 65 years of age or older has not been established (see section 4.4). No recommendations on dosing can be made.

Renal impairment

No dose adjustment is required for patients with renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment is required for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, the data available are insufficient to establish recommendations. In these patients dosing should be managed cautiously. Oral formulation should be preferred (see section 5.2).

Known CYP2D6 poor metabolisers

In patients who are known to be CYP2D6 poor metabolisers:

• Patients transitioning from Abilify Maintena 300 mg once monthly: The starting dose should be one injection of Abilify Maintena 720 mg g, no sooner than 26 days after previous injection of Abilify Maintena 300 mg.
• One injection start (following transition from oral therapy): The starting dose should be one injection of Abilify Maintena 720 mg and treatment should be continued with the prescribed dose of oral aripiprazole per day for 14 consecutive days.
• Two injection start (following transition from oral therapy): The starting dose should be 2 separate injections; one Abilify Maintena 720 mg and one Abilify Maintena 300 mg injection, together with a single dose of 20 mg oral aripiprazole (see method of administration).

Thereafter, a maintenance dose of Abilify Maintena 720 mg should be administered once every two months as a single injection.

Maintenance dose adjustments due to interactions with CYP2D6 and/or CYP3A4 inhibitors and/or CYP3A4 inducers

Maintenance dose adjustments should be made in patients taking concomitant strong CYP3A4 inhibitors or strong CYP2D6 inhibitors for more than 14 days. If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the dose may need to be increased to the previous dose (see section 4.5). In case of adverse reactions despite dose adjustments of Abilify Maintena 960 mg, the necessity of concomitant use of CYP2D6 or CYP3A4 inhibitor should be reassessed.

Concomitant use of CYP3A4 inducers with Abilify Maintena 960 mg/720 mg for more than 14 days should be avoided because the blood levels of aripiprazole are decreased and may be below the effective levels (see section 4.5).

Abilify Maintena 960 mg/720 mg should not be used in patients who are known to be CYP2D6 poor metabolisers and concomitantly use a strong CYP2D6 and/or CYP3A4 inhibitor.

Table 1. Maintenance dose adjustments of Abilify Maintena in patients who are taking concomitant strong CYP2D6 inhibitors, strong CYP3A4 inhibitors, and/or CYP3A4 inducers for more than 14 days:

^* Avoid use in patients who already take 720 mg, e.g. due to adverse rections to the higher dose.

Paediatric population

The safety and efficacy of Abilify Maintena 960 mg/720 mg in children and adolescents aged 0 to 17 years have not been established. No data are available.

Method of administration

Abilify Maintena 960 mg and 720 mg is only intended for gluteal intramuscular injection and must not be administered intravenously or subcutaneously. It must only be administered by a healthcare professional.

The suspension must be injected slowly as a single injection (doses must not be divided) into the gluteal muscle, alternating the injections between the right and left side. Care must be taken to avoid inadvertent injection into a blood vessel.

If initiating with any of the options that require two injections (one Abilify Maintena 960 mg or 720 mg and one Abilify Maintena 400 mg or 300 mg ), inject into two different sites. DO NOT inject both injections concomitantly into the same gluteal muscle.

Full instructions for use and handling of Abilify Maintena 960 mg/720 mg are provided in the package leaflet (information intended for healthcare professionals).

No cases of overdose associated with adverse reactions were reported in clinical studies with aripiprazole. While experience with aripiprazole overdose is limited, among the few cases of overdose (accidental or intentional) reported in clinical trials and post marketing experience with oral aripiprazole, the highest estimated ingestion was a total of 1260 mg with no fatalities.

The potential for dose dumping has been evaluated by simulation of aripiprazole plasma concentrations after an Abilify Maintena 960 mg dose is entirely absorbed in the systemic circulation. Based on the results of the simulation, if dose dumping would occur, aripiprazole concentrations may reach up to 13.5 times the concentrations that are achieved by a therapeutic dose of Abilify Maintena 960 mg without dose dumping. Furthermore, aripiprazole concentrations following dose dumping would decline within 5 days to concentrations normally observed following the administration of Abilify Maintena 960 mg.

Signs and symptoms

Care must be taken to avoid inadvertent injection of this medicinal product into a blood vessel. Following any confirmed or suspected accidental overdose/inadvertent intravenous administration with aripiprazole, close observation of the patient is needed. The potentially medically significant signs and symptoms observed in overdose included lethargy, increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea.

Management of overdose

There is no specific antidote to aripiprazole. Management of overdose should concentrate on supportive care, including close medical supervision and monitoring. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures. Treatment should consist of general measures employed in the management of overdose with any medicinal product. Consider the possibility of multiple medicinal product overdose. Consider the long-acting nature of the medicinal product and the long elimination half-life of aripiprazole when assessing treatment needs and recovery.

3 years.

Do not freeze.

Pre-filled syringe (cyclic-olefin-copolymer) with bromobutyl plunger stopper and bromobutyl tip-cap and polypropylene plunger rod and finger grip.

Abilify Maintena 960 mg prolonged-release suspension for injection in pre-filled syringe:

Each 960 mg pack contains one pre-filled syringe, and two sterile safety needles: one 38 mm (1.5 inch) 22 gauge and one 51 mm (2 inch) 21 gauge.

Abilify Maintena 720 mg prolonged-release suspension for injection in pre-filled syringe:

Each 720 mg pack contains one pre-filled syringe, and two sterile safety needles: one 38 mm (1.5 inch) 22 gauge and one 51 mm (2 inch) 21 gauge.

Tap the syringe on your hand at least 10 times. After tapping, shake the syringe vigorously for at least 10 seconds.

Gluteal muscle administration:

The recommended needle for gluteal administration is a 38 mm (1.5 inch), 22 gauge sterile safety needle; for obese patients (Body mass index >28 kg/m²), a 51 mm (2 inch), 21 gauge sterile safety needle should be used.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Full instructions for use and handling of Abilify Maintena 960 mg/720 mg are provided in the package leaflet (information intended for healthcare professionals).