Each tablet contains: Aripiprazole 5 mg; Aripiprazole 10 mg; Aripiprazole 15 mg.
Aripiprazole, 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril is referred to as a dopamine-serotonin stabilizer. The empirical formula is C23H27Cl2N3O2 and its molecular weight is 448.38.
Pharmacology: Mechanism of Action: The mechanism of action of aripiprazole, as with other drugs having efficacy in Schizophrenia and agitation associated with Schizophrenia is unknown. However, it has been proposed that the efficacy of aripiprazole is mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at receptors other than D2, 5-HT1A, and 5-HT2A may explain some of the other clinical effects of aripiprazole (e.g., the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).
Pharmacodynamics: Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5- HT2A receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM). Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5- HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.
Pharmacokinetics: Aripiprazole activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady state, the pharmacokinetics of aripiprazole are dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4.
Pharmacokinetic studies showed that Aripiprazole Orally Disintegrating Tablets are bioequivalent 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.
Metabolism and Elimination: Aripiprazole is metabolized 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 catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in the systemic circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.
Approximately 8% of Caucasians lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are extensive metabolizers (EM). PMs have about an 80% increase in aripiprazole exposure and about a 30% decrease in exposure to the active metabolite compared to EMs, resulting in about a 60% higher exposure to the total active moieties from a given dose of aripiprazole compared to EMs. Coadministration of aripiprazole with known inhibitors of CYP2D6, such as quinidine or fluoxetine in EMs, approximately doubles aripiprazole plasma exposure, and dose adjustment is needed. The mean elimination 50 half-lives are about 75 hours and 146 hours for aripiprazole in EMs and PMs, respectively. Aripiprazole does not inhibit or induce the CYP2D6 pathway.
Following a single dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the dose was recovered unchanged in the feces.
It is indicated for the treatment of Schizophrenia.
Schizophrenia: Usual Dose: Adults: Aripiprazole is indicated for acute and maintenance treatment of Schizophrenia.
The recommended starting and target dose for aripiprazole tablets is 10 mg/day or 15 mg/day administered on a once-a-day schedule without regard to meals. Aripiprazole tablets have been systematically evaluated and shown to be effective in a dose range of 10 mg/day to 30 mg/day; however, doses higher than 10 mg/day or 15 mg/day were not more effective than 10 mg/day or 15 mg/day. Dosage increases should not be made before 2 weeks, the time needed to achieve steady state.
Adolescents: Aripiprazole indicated for the treatment of Schizophrenia in adolescents 13 to 17 years of age.
The recommended target dose of aripiprazole tablets is 10 mg/day. Aripiprazole was studied in pediatric patients 13 to 17 years of age with Schizophrenia at daily doses of 10 mg and 30 mg. The starting daily dose of aripiprazole tablets in these patients was 2 mg, which was titrated to 5 mg after 2 days and to the target dose of 10 mg after 2 additional days. Subsequent dose increases should be administered in 5 mg increments. The 30 mg/day dose was not shown to be more efficacious than the 10 mg/day dose. Aripiprazole tablets can be administered without regard to meals.
Maintenance Therapy: Adults: While there is no body of evidence available to answer the question of how long a patient treated with aripiprazole should remain on it, systematic evaluation of patients with Schizophrenia who had been symptomatically stable on other antipsychotic medications for periods of 3 months or longer, were discontinued from those medications, and were then administered aripiprazole tablets 15 mg/day and observed for relapse during a period of up to 26 weeks, has demonstrated a benefit of such maintenance treatment. Patients should be periodically reassessed to determine the need for maintenance treatment.
Pediatric Patients: The efficacy of aripiprazole for the maintenance treatment of Schizophrenia in the pediatric population has not been evaluated.
Or as directed by the physician.
No specific information is available on the treatment of overdose with aripiprazole. An electrocardiogram should be obtained in case of overdosage and, if QTc interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.
Charcoal: In the event of an overdose of Aripiprazole Tablets, an early charcoal administration may be useful in partially preventing the absorption of aripiprazole. Administration of 50 g of activated charcoal, one hour after a single 15-mg oral dose of aripiprazole, decreased the mean AUC and Cmax of aripiprazole by 50%.
Hemodialysis: Although there is no information on the effect of hemodialysis in treating an overdose with aripiprazole, hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins.
Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.
Use in Elderly Patients with Dementia-Related Psychosis: Increased Mortality: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis .
Cerebrovascular Adverse Events, Including Stroke: In placebo-controlled clinical studies (two flexible dose and one fixed dose study) of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in aripiprazole-treated patients (mean age: 84 years; range: 78 to 88 years). In the fixed-dose study, there was a statistically significant dose response relationship for cerebrovascular adverse events in patients treated with aripiprazole. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.
The common adverse effects are constipation, akathisia, sedation, tremor, restlessness, extrapyramidal disorder, diarrhea, toothache, upper abdominal pain, musculoskeletal stiffness, back pain, myalgia, agitation, psychotic disorder, dysmenorrhea, rash, eye disorders, vision blurred, gastrointestinal disorders nausea, vomiting, constipation, dry mouth, abdominal discomfort, salivary hypersecretion, general disorders and administration site conditions, fatigue.
Potential for Other Drugs to Affect Aripiprazole: Aripiprazole is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. Aripiprazole also does not undergo direct glucuronidation. This suggests that an interaction of aripiprazole with inhibitors or inducers of these enzymes, or other factors, like smoking, is unlikely.
Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (e.g., carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.
Potential for Aripiprazole to Affect Other Drugs: Aripiprazole is unlikely to cause clinically important pharmacokinetic interactions with drugs metabolized by cytochrome P450 enzymes. In in vivo studies, 10 mg/day to 30 mg/day doses of aripiprazole had no significant effect on metabolism by CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan) substrates. Additionally, aripiprazole and dehydroaripiprazole did not show potential for altering CYP1A2-mediated metabolism in vitro.
Alcohol: There was no significant difference between aripiprazole coadministered with ethanol and placebo coadministered with ethanol on performance of gross motor skills or stimulus response in healthy subjects. As with most psychoactive medications, patients should be advised to avoid alcohol while taking aripiprazole.
Store at temperatures not exceeding 30°C.
N05AX12 - aripiprazole ; Belongs to the class of other antipsychotics.
Bisoza 10 tab 10 mg
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