Presentation and Status in Health Basket
28 X 5 mg
28 X 10 mg
28 X 15 mg
28 X 30 mg
Adults: Schizophrenia: the recommended starting dose 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. this product 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 is 15 mg administered on a once-a-day schedule without regard to meals as monotherapy or combination therapy. 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.
Adjunctive Treatment of Major Depressive Disorder: Dose Selection: The recommended starting dose as adjunctive treatment for patients already taking an antidepressant is 2 mg/day to 5 mg/day. The efficacy as an adjunctive therapy for major depressive disorder was established within a dose range of 2 mg/day to 15 mg/day. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week .
Maintenance Treatment: The efficacy of this product for the adjunctive maintenance treatment of major depressive disorder has not been evaluated. While there is no body of evidence available to answer the question of how long the patient treated with this product should be maintained, patients should be periodically reassessed to determine the continued need for maintenance treatment.
Paediatric population: Schizophrenia in adolescents 15 years and older: the recommended dose for this product is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be initiated at 2 mg 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 this product 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 in adolescents although individual patients may benefit from a higher dose. this product is not recommended for use in patients below 15 years of age due to insufficient data on safety and efficacy .
Irritability associated with autistic disorder: the safety and efficacy in children and adolescents below 18 years of age have not yet been established.
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.
Patients with renal impairment: no dosage adjustment is required in patients with renal impairment.
Elderly: the effectiveness of this product in the treatment of schizophrenia and Bipolar I Disorder in patients 65 years of age or older has not been established. Owing to the greater sensitivity of this population,a lower starting dose should be considered when clinical factors warrant.
Gender: no dosage adjustment is required for female patients as compared to male patients.
Smoking status: according to the metabolic pathway of this product no dosage adjustment is required for smokers.
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. 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.
For full details see prescribing information.
– Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). Efficacy was established in two 6-week trials in adults with MDD who had an inadequate response to antidepressant therapy during the current episode.
– Treatment of irritability associated with autistic disorder. Efficacy was established in two 8-week trials in pediatric patients (aged 6 to 17 years) with irritability associated with autistic disorder (including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods).
Hypersensitivity to the active substance or to any of the excipients.
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. The occurrence of suicidal behaviour is inherent in psychotic illnesses and mood disorders and in some cases has been reported early after initiation or switch of antipsychotic therapy, including treatment with aripiprazole. Close supervision of high-risk patients should accompany antipsychotic therapy. Results of an epidemiological study suggested that there was no increased risk of suicidality with aripiprazole compared to other antipsychotics among adult patients with schizophrenia or bipolar disorder. There are insufficient paediatric data to evaluate this risk in younger patients (below 18 years of age), but there is evidence that the risk of suicide persists beyond the first 4 weeks of treatment for atypical antipsychotics, including aripiprazole.
Cardiovascular disorders: Aripiprazole should be used with caution in patients with known cardiovascular disease (history of myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medicinal products) or hypertension, including accelerated or malignant.Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs.
Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with ARIPLY and preventive measures undertaken.
Conduction abnormalities: In clinical trials of aripiprazole, the incidence of QT prolongation was comparable to placebo. As with other antipsychotics, aripiprazole should be used with caution in patients with a family history of QT prolongation.
Tardive dyskinesia: in clinical trials of one year or less duration, there were uncommon reports of treatment emergent dyskinesia during treatment with aripiprazole. If signs and symptoms of tardive dyskinesia appear in a patient on this product, dose reduction or discontinuation should be considered. These symptoms can temporally deteriorate or can even arise after discontinuation of treatment.
Other extrapyramidal symptoms: in paediatric clinical trials of aripiprazole akathisia and parkinsonism were observed. If signs and symptoms of other EPS appear in a patient taking this product, dose reduction and close clinical monitoring should be considered.
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex associated with antipsychotic medicinal products. In clinical trials, rare cases of NMS were reported during treatment with aripiprazole. Clinical manifestations of NMS are
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. However, elevated creatine phosphokinase and rhabdomyolysis, not necessarily in association with NMS, have also been reported. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicinal products, including this product, must be discontinued.
Seizure: in clinical trials, uncommon cases of seizure were reported during treatment with aripiprazole. Therefore, aripiprazole should be used with caution in patients who have a history of seizure disorder or have conditions associated with seizures.
For full details see prescribing information.
Uncontrollable twitching or jerking movements, headache, tiredness, vomiting, nausea, an uncomfortable feeling in the stomach, constipation, increased production of saliva, lightheadedness, trouble sleeping, anxiety and restlessness, blurred vision, dizziness (especially when getting up suddenly from a lying or sitting position), fast heartbeat, depression.
For full details see prescribing information.
Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is taken in combination with alcohol or other CNS medicinal products with overlapping adverse reactions such as sedation.If aripiprazole is administered concomitantly with medicinal products known to cause QT prolongation or electrolyte imbalance, caution should be used.Potential for other medicinal products to affect this product: A gastric acid blocker, the H2 antagonist famotidine, reduces aripiprazole rate of absorption but this effect is deemed not clinically relevant. Aripiprazole is metabolised by multiple pathways involving the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required for smokers.In a clinical trial in healthy subjects, a potent inhibitor of CYP2D6 (quinidine) increased aripiprazole AUC by 107%, while Cmax was unchanged. The AUC and Cmax of dehydro-aripiprazole, the active metabolite, decreased by 32% and 47%. dose should be reduced to approximately one-half of its prescribed dose when concomitant administration of this product with quinidine occurs. Other potent inhibitors of CYP2D6, such as fluoxetine and paroxetine, may be expected to have similar effects & similar dose reductions should therefore be applied.In a clinical trial in healthy subjects, a potent inhibitor of CYP3A4 (ketoconazole) increased aripiprazole AUC and Cmax by 63% and 37%, respectively. The AUC and Cmax of dehydro-aripiprazole increased by 77% and 43%, respectively. In CYP2D6 poor metabolisers, concomitant use of potent inhibitors of CYP3A4 may result in higher plasma concentrations of aripiprazole compared to that in CYP2D6 extensive metabolizers. When considering concomitant administration of ketoconazole or other
potent CYP3A4 inhibitors with this product, potential benefits should outweigh the potential risks to the patient. When concomitant administration of ketoconozole with this product occurs, dose should be reduced to approximately one-half of its prescribed dose. Other potent inhibitors of CYP3A4, such as itraconazole and HIV protease inhibitors, may be expected to have similar effects and similar dose reductions should therefore be applied. Upon discontinuation of the CYP2D6 or 3A4 inhibitor, the dosage should be increased to the level prior to the initiation of the concomitant therapy When weak inhibitors of CYP3A4 (e.g., diltiazem or escitalopram) or CYP2D6 are usedconcomitantly with this product, modest increases in aripiprazole concentrations might be expected.
For full details see prescribing information.
Pregnancy and Lactation
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.Animal studies could not exclude potential developmental toxicity. 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, tremor,somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.
Lactation: Aripiprazole is excreted in human breast milk. Patients should be advised not to breast feed if they are taking aripiprazole.
In clinical trials and post-marketing experience, accidental or intentional acute overdose of aripiprazole alone was identified in adult patients with reported estimated doses up to 1,260 mg with no fatalities. The potentially medically important signs and symptoms observed included lethargy, increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea. In addition, reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been received with no fatalities. The potentially medically serious signs and symptoms reported included somnolence, transient loss of consciousness and extrapyramidal symptoms.Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. The possibility of multiple medicinal product involvement should be considered. Therefore cardiovascular monitoring should be started immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Following any confirmed or suspected overdose with aripiprazole, close medical supervision and monitoring should continue until the patient recovers. Activated charcoal (50 g), administered one hour after aripiprazole, decreased aripiprazole Cmax by about 41% and AUC by about 51%, suggesting that charcoal may be effective in the treatment of overdose.Although there is no information on the effect of haemodialysis in treating an overdose with aripiprazole, haemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins.