Each orodispersible tablet contains 10, 15 mg of aripiprazole.
Excipient with known effect: aspartame (E951).
Pharmacotherapeutic group: Antipsychotics. ATC code: N05AX12.
Pharmacology: Pharmacodynamics: Mechanism of action: It has been proposed that aripiprazole's efficacy in schizophrenia and Bipolar I Disorder is mediated through a combination of partial agonism at dopamine D2 and serotonin 5HT1a receptors and antagonism of serotonin 5HT2a receptors.
Clinical efficacy and safety: Adults: Schizophrenia: In three short-term (4 to 6 weeks) placebo-controlled trials involving 1,228 schizophrenic adult patients, presenting with positive or negative symptoms, aripiprazole was associated with statistically significantly greater improvements in psychotic symptoms compared to placebo.
Aripiprazole is effective in maintaining the clinical improvement during continuation therapy in adult patients who have shown an initial treatment response. In a haloperidol-controlled trial, the proportion of responder patients maintaining response to medicinal product at 52-weeks was similar in both groups (aripiprazole 77% and haloperidol 73%). The overall completion rate was significantly higher for patients on aripiprazole (43%) than for haloperidol (30%). Actual scores in rating scales used as secondary endpoints, including PANSS and the Montgomery-Asberg Depression Rating Scale showed a significant improvement over haloperidol.
Manic episodes in Bipolar I Disorder: In two 3-week, flexible-dose, placebo-controlled monotherapy trials involving patients with a manic or mixed episode of Bipolar I Disorder, aripiprazole demonstrated superior efficacy to placebo in reduction of manic symptoms over 3 weeks. These trials included patients with or without psychotic features and with or without a rapid-cycling course.
The most common treatment-emergent adverse events among patients receiving 30 mg were extrapyramidal disorder (28.3%), somnolence (27.3%), headache (23.2%), and nausea (14.1%). Mean weight gain in the 30 weeks treatment-interval was 2.9 kg as compared to 0.98 kg in patients treated with placebo.
Pharmacokinetics: Aripiprazole orodispersible tablet is bioequivalent to aripiprazole tablets, with a similar rate and extent of absorption. Aripiprazole orodispersible tablets may be used as an alternative to aripiprazole tablets.
Absorption: Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3-5 hours after dosing. Aripiprazole undergoes minimal pre-systemic metabolism. The absolute oral bioavailability of the tablet formulation is 87%. There is no effect of a high fat meal on the pharmacokinetics of aripiprazole.
Distribution: Aripiprazole is widely distributed throughout the body with an apparent volume of distribution of 4.9 l/kg, indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole and dehydro-aripiprazole are greater than 99% bound to serum proteins, binding primarily to albumin.
Biotransformation: Aripiprazole is extensively metabolised by the liver primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalysed by CYP3A4. Aripiprazole is the predominant medicinal product moiety in systemic circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.
Elimination: The mean elimination half-lives for aripiprazole are approximately 75 hours in extensive metabolisers of CYP2D6 and approximately 146 hours in poor metabolisers of CYP2D6.
The total body clearance of aripiprazole is 0.7 ml/min/kg, which is primarily hepatic.
Following a single oral dose of [14C]-labelled aripiprazole, approximately 27% of the administered radioactivity was recovered in the urine and approximately 60% in the faeces. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% was recovered unchanged in the faeces.
Paediatric population: The pharmacokinetics of aripiprazole and dehydro-aripiprazole in paediatric patients 10 to 17 years of age were similar to those in adults after correcting for the differences in body weights.
Pharmacokinetics in special patient group: Elderly: There are no differences in the pharmacokinetics of aripiprazole between healthy elderly and younger adult subjects, nor is there any detectable effect of age in a population pharmacokinetic analysis in schizophrenic patients.
Gender: There are no differences in the pharmacokinetics of aripiprazole between healthy male and female subjects nor is there any detectable effect of gender in a population pharmacokinetic analysis in schizophrenic patients.
Smoking: Population pharmacokinetic evaluation has revealed no evidence of clinically significant effects from smoking on the pharmacokinetics of aripiprazole.
Race: Population pharmacokinetic evaluation showed no evidence of race-related differences on the pharmacokinetics of aripiprazole.
Renal impairment: The pharmacokinetic characteristics of aripiprazole and dehydro-aripiprazole were found to be similar in patients with severe renal disease compared to young healthy subjects.
Hepatic impairment: A single-dose study in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B, and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of aripiprazole and dehydro-aripiprazole, but the study included only 3 patients with Class C liver cirrhosis, which is insufficient to draw conclusions on their metabolic capacity.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.
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 Pharmacology: Pharmacodynamics under Actions).
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 Pharmacology: Pharmacodynamics under Actions).
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.
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. 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.
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.
Dose adjustments due to interactions: When concomitant administration of strong 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 Interactions). When concomitant administration of strong 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 Interactions).
Method of administration: Aripiprazole orodispersible tablets are for oral use.
The orodispersible 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 orodispersible tablet from the mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening the blister. Alternatively, disperse the tablet in water and drink the resulting suspension.
Orodispersible tablets or oral solution may be used as an alternative to aripiprazole tablets for patients who have difficulty swallowing aripiprazole tablets (see Pharmacology: Pharmacokinetics under Actions).
Hypersensitivity to the active substance or to any of the excipients listed in Description.
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored throughout this period.
Pregnancy: There are no adequate and well-controlled trials of aripiprazole in pregnant women. Congenital anomalies have been reported; however, causal relationship with aripiprazole could not be established.
Breast-feeding: Aripiprazole is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility: Aripiprazole did not impair fertility based on data from reproductive toxicity studies.
Summary of the safety profile:
The most commonly reported adverse reactions in placebo-controlled trials are akathisia and nausea each occurring in more than 3% of patients treated with oral aripiprazole.
Do not store above 30°C. Store in the original package in order to protect from moisture.
Shelf life: 24 months.
N05AX12 - aripiprazole ; Belongs to the class of other antipsychotics.
Orodispersible tab 10 mg x 30's. 15 mg x 30's.