Arilan Drug Interactions

Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive medicinal products.
Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is administered in combination with alcohol or other CNS medicinal products with overlapping adverse reactions such as sedation (see Adverse Reactions).
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 aripiprazole: A gastric acid blacker, 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 CY3A4 enzymes but not CYP1A enzymes. Thus, no dose adjustment is required for smokers.
Quinidine and other CYP2D6 inhibitors: In a clinical trial in healthy subjects, a potent inhibitor of CYP2D6 (quinidine) increased aripiprazole AUC by 107% while C_max was unchanged. The AUC and C_max of dehydro-aripiprazole, the active metabolite, decreased by 32% and 47%, respectively. Aripiprazole dose should be reduced to approximately one-half of its prescribed dose when concomitant administration of aripiprazole with quinidine occurs.
Other potent inhibitors of CYP2D6, such as fluoxetine and paroxetine, may be expected to have similar effects and similar dose reductions should therefore be applied.
Ketoconazole and other CYP3A4 inhibitors: In a clinical trial in healthy subjects, a potent inhibitor of CYP3A4 (ketoconazole) increased aripiprazole AUC and C_max by 63% and 37%, respectively. The AUC and C_max 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 metabolisers. When considering concomitant administration of ketoconazole or other strong CYP3A4 inhibitors with aripiprazole, potential benefits should outweigh the potential risks to the patient. When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to approximately one-half of its prescribed dose. Other strong 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 (see Dosage & Administration).
Upon discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dose of aripiprazole should be increased to the level prior to the initiation of the concomitant therapy.
When weak inhibitors of CY3A4 (e.g., diltiazem) or CYP2D6 (e.g., escitalopram) are used concomitantly with aripiprazole, modest increases in plasma aripiprazole concentrations may be expected.
Carbamazepine and other CYP3A4 inducers: Following concomitant administration of carbamazepine, a strong inducer of CYP3A4, and oral aripiprazole to patients with schizophrenia or schizoaffective disorder, the geometric means of C_max and AUC for aripiprazole were 68% and 73% lower, respectively, compared to when aripiprazole (30 mg) was administered alone. Similarly, for dehydro-aripiprazole the geometric means of C_max and AUC after carbamazepine co-administration were 69% and 71% lower, respectively, than those following treatment with aripiprazole alone. Aripiprazole dose should be double when concomitant administration of aripiprazole occurs with carbamazepine.
Concomitant administration of aripiprazole and other inducers of CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, efavirenz, nevirapine and St. John's Wort) may be expected to have similar effects and similar dose increases should therefore be applied. Upon discontinuation of potent CYP3A4 inducers, the dose of aripiprazole should be reduced to the recommended dose.
Valproate and lithium: When either valproate or lithium were administered concomitantly with aripiprazole, there was no clinically significant change in aripiprazole concentrations and therefore no dose adjustment is necessary when either valproate or lithium is administered with aripiprazole.
Potential for aripiprazole to affect other medicinal products: In clinical studies, 10-30mg/day doses of aripiprazole had no significant effect on the metabolism of substrates of CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan).
Additionally, aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2-mediated metabolism in vitro.
Thus, aripiprazole is unlikely to cause clinically important medicinal product interactions mediated by these enzymes.
When aripiprazole was administered concomitantly with either valproate, lithium or lamotrigine, there was no clinically important change in valproate, lithium or lamotrigine concentrations.
Serotonin syndrome: Case of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and symptoms for this condition can occur especially in cases of concomitant use with other serotonergic medicinal products, such as SSRI/SNRI, or with medicinal products that are known to increase aripiprazole concentrations (see Adverse Reactions).