Apalife 10/Apalife 15

Apalife 10/Apalife 15

aripiprazole

Manufacturer:

Unison

Distributor:

Medispec
Full Prescribing Info
Contents
Aripiprazole.
Description
Each film coated tablet contains: Aripiprazole 10 mg.
Each film coated tablet contains: Aripiprazole 15 mg.
Action
Pharmacology: 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. Aripiprazole exhibited antagonist properties in animal models of dopaminergic hyperactivity and agonist properties in animal models of dopaminergic hypoactivity. Aripiprazole exhibited high binding affinity in vitro for dopamine D2 and D3, serotonin 5HT1a and 5HT2a receptors and moderate affinity for dopamine D4, serotonin 5HT2c and 5HT7, alpha-1 adrenergic and histamine H1 receptors. Aripiprazole also exhibited moderate binding affinity for the serotonin reuptake site and no appreciable affinity for muscarinic receptors. Interaction with receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of Aripiprazole.
Pharmacokinetics: 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 metabolized 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 catalyzed 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 metabolizers of CYP2D6 and approximately 146 hours in poor metabolizers 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 feces. Less than 1% of unchanged Aripiprazole was excreted in the urine and approximately 18% was recovered unchanged in the feces.
Indications/Uses
Indicated for the treatment of acute episodes of schizophrenia and for maintenance of clinical improvement during continuation therapy and treatment of acute manic episodes associated with Bipolar I Disorder.
Dosage/Direction for Use
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 maintenance dose for Aripiprazole is 15 mg/day. Doses in the range of 1- to 30 mg/day have been established as effective in clinical trials.
Bipolar Mania: Aripiprazole should be administered on a once-a-day schedule without regard to meals, generally starting a dose of 15 or 30 mg/day. Dose adjustments, if indicated, should occur at intervals of not less than 24 hours. Antimanic efficacy (3-12 weeks) was demonstrated in a dose range of 15 to 30 mg/day in clinical trials. The safety of doses above 30 mg/day has not been evaluated in clinical trials.
Patients taking medications metabolized by CYP2D6 of 3A4: Dosage adjustments for patients taking Aripiprazole concomitantly with potent CYP3A4 of CYP2D6 inhibitors: When concomitant administration of a potent CYP3A4 or CYP2D6 inhibitor with Aripiprazole occurs, the Aripiprazole dose should be reduced to one-half of the usual dose. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from the combination therapy, the Aripiprazole dose should then be increased.
Dosage adjustments for patients taking potent CYP3A4 inducers: When a potent CYP3A4 inducers is added to Aripiprazole therapy, the Aripiprazole dose should be doubled. Additional dose increases of Aripiprazole should be based on clinical evaluation. When the CYP3A4 inducer is withdrawn from the combination therapy, the Aripiprazole dose should be reduced. Consideration should be given to reducing the daily dose in individual patients who are on multiple concomitant medications that inhibit CYP3A4 and CYP2D6 enzymes.
Overdosage
Signs and symptoms: The potentially medically important signs and symptoms observed included lethargy, increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhea. 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: 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.
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.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Warnings
Hyperglycemia and Diabetes Mellitus: Hyperglycemia in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assessment of the relationship between atypical antipsychotics use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in general population. Given this confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with atypical antipsychotics.
Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g. obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
Pathological gambling and impulse-control problems: Patients can experience increased urges, particularly for gambling, and the inability to control these urges while taking Aripiprazole. Other urges reported include: increased sexual urges, compulsive shopping, binge or compulsive eating, and other impulsive and compulsive behaviors.
It is important for prescribers to ask patients or their caregivers specifically about the development of new or increased gambling urges, or other urges, while being treated with Aripiprazole. It should be noted that impulse-control symptoms can be associated with underlying disorder; however, in some cases urges were reported to have stopped when the dose was reduced or the medication was discontinued. Patients who are at higher risk for impulse-control problems (e.g. personal or family history of obsessive-compulsive disorder, impulse-control disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse or other addictive behaviors) would require monitoring for new or worsening of uncontrollable urges. Impulse-control problems may results in harm to the patient and others if not recognized. Consider dose reduction or stopping the medication if a patient develops such urges while taking Aripiprazole.
Special Precautions
Suicidality, Cardiovascular disorders, Conduction abnormalities, Tardive dyskinesia, Other extrapyramidal symptoms, Neuroleptic Malignant Syndrome (NMS), Seizure, Elderly patients with dementia-related psychosis (Increased mortality, Cerebrovascular adverse reactions), Hyperglycemia and diabetes mellitus, Hypersensitivity, Weight gain, Dysphagia, Pathological gambling, Lactose, Phenylketonurics, Intolerance, Patients with ADHD comorbidity.
Use In Pregnancy & Lactation
Pregnancy: Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. 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 prolonged hospitalization.
APALIFE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breastfeeding: Aripiprazole is excreted in human breast milk. Patients should be advised not to breast feed if they are taking Aripiprazole.
Adverse Reactions
Headache, fatigue, tremor, anxiety, insomnia, increased appetite, N/V, somnolence, constipation, akathisia, extrapyramidal disorder, nasopharyngitis, dizziness, restlessness, weight increase. Pathological gambling, hypersexuality, impulse-control problems.
Drug Interactions
Caution with other centrally acting drugs. Avoid with alcohol. May potentiate the effect of certain antihypertensive agents. CYP3A4 inducers (e.g. carbamazepine) may increase clearance and lower blood levels. CYP3A4 inhibitors (e.g. ketoconazole, itraconazole) or CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) may inhibit elimination and increase blood levels.
Storage
Store at temperature of not more than 30°C.
MIMS Class
ATC Classification
N05AX12 - aripiprazole ; Belongs to the class of other antipsychotics.
Presentation/Packing
FC tab 10 mg x 3 x 10's. 15 mg x 3 x 10's.
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