Brands, Medical Use, Clinical Data
Brands / Synonyms
Abilify; Abilitat; Aripiprazole [Usan]; OPC 31
For the treatment of schizophrenia
Aripiprazole is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Aripiprazole 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. Aripiprazole 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 Aripiprazole. Aripiprazole's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Aripiprazole's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Mechanism of Action
Aripiprazole 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. Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors. 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.
Biotrnasformation / Drug Metabolism
ABILIFY is contraindicated in patients with a known hypersensitivity to the product.
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
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.