Abilitat - General Information
Abilitat is an atypical antipsychotic medication used for the treatment of schizophrenia. It has also recently received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder. Abilitat appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor. In addition to partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics, aripiprazole displays an antagonist profile at the 5-HT2A receptor. Abilitat has moderate affinity for histamine and alpha adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.
Pharmacology of Abilitat
Abilitat is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Abilitat is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Abilitat acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Abilitat. Abilitat's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Abilitat's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Abilitat for patients
Physicians are advised to discuss the following issues with patients for whom they prescribe ABILIFY:
Interference with Cognitive and Motor Performance
Because aripiprazole may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that aripiprazole therapy does not affect them adversely.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with ABILIFY.
Patients should be advised not to breast-feed an infant if they are taking ABILIFY.
Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.
Patients should be advised to avoid alcohol while taking ABILIFY.
Heat Exposure and Dehydration
Patients should be advised regarding appropriate care in avoiding overheating and dehydration.
Patients should be advised that each mL of ABILIFY oral solution contains 400 mg of sucrose and 200 mg of fructose.
Given the primary CNS effects of aripiprazole, caution should be used when ABILIFY is taken in combination with other centrally acting drugs and alcohol. Due to its α1- adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.
Potential for Other Drugs to Affect ABILIFYAripiprazole 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 (eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.
Ketoconazole: Coadministration of ketoconazole (200 mg/day for 14 days) with a 15-mg single dose of aripiprazole increased the AUC of aripiprazole and its active metabolite by 63% and 77%, respectively. The effect of a higher ketoconazole dose (400 mg/day) has not been studied. When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one-half of its normal dose. Other strong inhibitors of CYP3A4 (itraconazole) would be expected to have similar effects and need similar dose reductions; weaker inhibitors (erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.
Quinidine: Coadministration of a 10-mg single dose of aripiprazole with quinidine (166 mg/day for 13 days), a potent inhibitor of CYP2D6, increased the AUC of aripiprazole by 112% but decreased the AUC of its active metabolite, dehydroaripiprazole, by 35%. Aripiprazole dose should be reduced to one-half of its normal dose when concomitant administration of quinidine with aripiprazole occurs. Other significant inhibitors of CYP2D6, such as fluoxetine or paroxetine, would be expected to have similar effects and, therefore, should be accompanied by similar dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.
Carbamazepine: Coadministration of carbamazepine (200 mg BID), a potent CYP3A4 inducer, with aripiprazole (30 mg QD) resulted in an approximate 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole. When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from the combination therapy, aripiprazole dose should then be reduced.
No clinically significant effect of famotidine, valproate, or lithium was seen on the pharmacokinetics of aripiprazole (see CLINICAL PHARMACOLOGY: Drug- Drug Interactions).
Potential for ABILIFY 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- 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 ABILIFY.
ABILIFY is contraindicated in patients with a known hypersensitivity to the product.
Additional information about Abilitat
Abilitat Indication: For the treatment of schizophrenia
Mechanism Of Action: Abilitat exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5- HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors and moderate affinity for the serotonin reuptake pump. Abilitat has no appreciable affinity for cholinergic muscarinic receptors. Abilitat functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.
Drug Interactions: Carbamazepine Carbamazepine decreases the effect of aripiprazole
Itraconazole The imidazole increases the effect of aripiprazole
Ketoconazole The imidazole increases the effect of aripiprazole
Dihydroquinidine barbiturate Quinidine increases the effect and toxicity of aripiprazole
Quinidine Quinidine increases the effect and toxicity of aripiprazole
Quinidine barbiturate Quinidine increases the effect and toxicity of aripiprazole
Food Interactions: Take without regard to meals.
Food has no significant effect on absorption.
Avoid alcohol (possible additive effect to CNS).
Generic Name: Aripiprazole
Synonyms: OPC-14597; OPC 31
Drug Category: Antipsychotics
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Aripiprazole: Abilify; Abilitat;
Absorption: Not Available
Toxicity (Overdose): Not Available
Protein Binding: >99%
Half Life: 75-146 hours
Dosage Forms of Abilitat: Tablet Oral
Chemical IUPAC Name: 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one
Chemical Formula: C23H27Cl2N3O2
Aripiprazole on Wikipedia: http://en.wikipedia.org/wiki/Aripiprazole
Organisms Affected: Humans and other mammals