Aripiprazole

Qualitative and quantitative composition

Tablets

Each tablet contains 5 mg of aripiprazole

Each tablet contains 10 mg of aripiprazole

Each tablet contains 15 mg of aripiprazole

Each tablet contains 20 mg of aripiprazole

Each tablet contains 30 mg of aripiprazole

Oral disintegrating tablets

Each oral disintegrating tablet contains 10 mg of aripiprazole

Each oral disintegrating tablet contains 30 mg of aripiprazole

For a full list of excipients, see section 5.1.

 

Clinical particulars

Therapeutic indications

ARIPIPRAZOLE is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older.

ARIPIPRAZOLE is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment (see section 5.1).

ARIPIPRAZOLE is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older (see section 5.1).

 

Posology and method of administration

Posology

Adults:

Schizophrenia: the recommended starting dose for ARIPIPRAZOLE is 10 or 15 mg/day with a maintenance dose of 15 mg/day administered on a once-a-day schedule without regard to meals.

ARIPIPRAZOLE is effective in a dose range of 10 to 30 mg/day. Enhanced efficacy at doses higher than a daily dose of 15 mg has not been demonstrated although individual patients may benefit from a higher dose. The maximum daily dose should not exceed 30 mg.

Manic episodes in Bipolar I Disorder: the recommended starting dose for ARIPIPRAZOLE is 15 mg administered on a once-a-day schedule without regard to meals as monotherapy or combination therapy (see section 4.1). Some patients may benefit from a higher dose. The maximum daily dose should not exceed 30 mg.

Recurrence prevention of manic episodes in Bipolar I Disorder: for preventing recurrence of manic episodes in patients who have been receiving aripiprazole as monotherapy or combination therapy, continue therapy at the same dose. Adjustments of daily dosage, including dose reduction should be considered on the basis of clinical status.

Paediatric population:

Schizophrenia in adolescents aged 15 years and older: the recommended dose for ARIPIPRAZOLE is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be initiated at 2 mg (using ARIPIPRAZOLE oral solution 1 mg/ml) for 2 days, titrated to 5 mg for 2 additional days to reach the recommended daily dose of 10 mg. When appropriate, subsequent dose increases should be administered in 5 mg increments without exceeding the maximum daily dose of 30 mg (see section 4.1).

ARIPIPRAZOLE is effective in a dose range of 10 to 30 mg/day. Enhanced efficacy at doses higher than a daily dose of 10 mg has not been demonstrated although individual patients may benefit from a higher dose.

ARIPIPRAZOLE is not recommended for use in patients with schizophrenia below 15 years of age due to insufficient data on safety and efficacy (see sections 3.8 and 4.1).

Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older: the recommended dose for ARIPIPRAZOLE is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be initiated at 2 mg (using ARIPIPRAZOLE oral solution 1 mg/ml) for 2 days, titrated to 5 mg for 2 additional days to reach the recommended daily dose of 10 mg.

The treatment duration should be the minimum necessary for symptom control and must not exceed 12 weeks. Enhanced efficacy at doses higher than a daily dose of 10 mg has not been demonstrated, and a daily dose of 30 mg is associated with a substantially higher incidence of significant undesirable effects including EPS related events, somnolence, fatigue and weight gain (see section 3.8). Doses higher than 10 mg/day should therefore only be used in exceptional cases and with close clinical monitoring (see sections 3.4, 3.8 and 4.1).

Younger patients are at increased risk of experiencing adverse events associated with aripiprazole. Therefore, ARIPIPRAZOLE is not recommended for use in patients below 13 years of age (see sections 3.8 and 4.1).

Irritability associated with autistic disorder: the safety and efficacy of ARIPIPRAZOLE in children and adolescents aged below 18 years have not yet been established. Currently available data are described in section 4.1 but no recommendation on a posology can be made.

Patients with hepatic impairment: no dosage adjustment is required for patients with mild to 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. However, the maximum daily dose of 30 mg should be used with caution in patients with severe hepatic impairment (see section 4.2).

Patients with renal impairment: no dosage adjustment is required in patients with renal impairment.

Elderly: the effectiveness of ARIPIPRAZOLE in the treatment of schizophrenia and Bipolar I Disorder in patients aged 65 years and older has not been established. Owing to the greater sensitivity of this population, a lower starting dose should be considered when clinical factors warrant (see section 3.4).

Gender: no dosage adjustment is required for female patients as compared to male patients (see section 4.2).

Smoking status: according to the metabolic pathway of ARIPIPRAZOLE no dosage adjustment is required for smokers (see section 3.5).

Dose adjustments due to interactions:

When concomitant administration of potent CYP3A4 or CYP2D6 inhibitors with aripiprazole occurs, the aripiprazole dose should be reduced. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased (see section 3.5).

When concomitant administration of potent CYP3A4 inducers with aripiprazole occurs, the aripiprazole dose should be increased. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose should then be reduced to the recommended dose (see section 3.5).

Method of administration

ARIPIPRAZOLE tablets, oral disintegrating tablets are for oral use.

The oral disintegrating tablet should be placed in the mouth on the tongue, where it will rapidly disperse in saliva. It can be taken with or without liquid. Removal of the intact oral disintegrating tablet from the mouth is difficult. Since the oral disintegrating tablet is fragile, it should be taken immediately on opening the blister. Alternatively, disperse the tablet in water and drink the resulting suspension.

ARIPIPRAZOLEoral disintegrating tablets may be used as an alternative to ARIPIPRAZOLE tablets for patients who have difficulty swallowing ARIPIPRAZOLE tablets (see section 4.2).

Fertility, pregnancy and lactation

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with aripiprazole. Due to insufficient safety information in humans and concerns raised by animal reproductive studies, this medicinal product should not be used in pregnancy unless the expected benefit clearly justifies the potential risk to the foetus.

Neonates exposed to antipsychotics (including aripiprazole) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. These complications have varied in severity; while in some cases symptoms have been self-limited; in other cases neonates have required intensive care unit support and prolonge hospitalization.

These products should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.”

Consequently, newborns should be monitored carefully.

It is not known whether aripiprazole is excreted in human milk. Patients should be advised not to breast feed if they are taking aripiprazole.

Effects on ability to drive and use machines

As with other antipsychotics, patients should be cautioned about operating hazardous machines, including motor vehicles, until they are reasonably certain that aripiprazole does not affect them adversely. Some paediatric patients with Bipolar I Disorder have an increased incidence of somnolence and fatigue (see section 3.8).