Aripiprazole

Strong CYP3A4 inducer that decreases aripiprazole exposure. Avoid use for greater than 14 days.

Strong CYP3A4 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Strong CYP2D6 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Strong CYP3A4 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Antipsychotics, Anxiolytics and Hypnotics Lurasidone, alprazolam, oral midazolam, pimozide, triazolam aripiprazole, buspirone, haloperidol, midazolam IV, quetiapine, ramelteon, risperidone The increase in plasma concentrations of lurasidone when coadministered with ketoconazole tablets may increase the risk of serious side effects (See CONTRAINDICATIONS ). Aripiprazole: 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. When ketoconazole is given concomitantly with aripiprazole, them aripiprazole dose should be reduced to one-half of the recommended dose.

Strong CYP2D6 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Strong CYP2D6 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Strong CYP3A4 inducer decreases aripiprazole exposure. Consider increasing aripiprazole dosage.

Centrally-acting substance; caution advised when combined with aripiprazole due to CNS effects.

Benzodiazepines (e.g., lorazepam) The intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone. The orthostatic hypotension observed was greater with the combination as compared to that observed with lorazepam alone [see Warnings and Precautions (5.8)] Monitor sedation and blood pressure. 7.2 Drugs Having No Clinically Important Interactions with Aripiprazole Based on pharmacokinetic studies, no dosage adjustment of aripiprazole is required when administered concomitantly with famotidine, valproate, lithium, and lorazepam.

7 DRUG INTERACTIONS 7.1 Drugs Having Clinically Important Interactions with ARISTADA Table 10: Clinically Important Drug Interactions with ARISTADA Strong CYP3A4 Inhibitors and CYP2D6 Inhibitors Clinical Impact: The concomitant use of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of oral aripiprazole alone [see Clinical Pharmacology ( 12.3 )]. Examples: itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine Strong CYP3A4 Inducers Clinical Impact: The concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone [see Clinical Pharmacology ( 12.3 )]. Examples: carbamazepine, rifampin Antihypertensive Drugs Clinical Impact: Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.

7 DRUG INTERACTIONS Dosage adjustment due to drug interactions ( 7.1 ): Factors Dosage Adjustments for Aripiprazole Known CYP2D6 Poor Metabolizers Administer half of usual dose Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP2D6 or CYP3A4 inhibitors Administer half of usual dose Strong CYP2D6 and CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP3A4 inducers Double usual dose over 1 to 2 weeks 7.1 Drugs Having Clinically Important Interactions with Aripiprazole Table 22: Clinically Important Drug Interactions with Aripiprazole: Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) The concomitant use of aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3) ] . With concomitant use of aripiprazole with a strong CYP3A4 inhibitor or CYP2D6 inhibitor, reduce the aripiprazole dosage [see Dosage and Administration (2.7) ] . Strong CYP3A4 Inducers (e.g., carbamazepine, rifampin) The concomitant use of aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3) ] .

Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with Desvenlafaxine Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with desvenlafaxine [see Clinical Pharmacology ( 12.3 )] .

Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with desvenlafaxine Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with desvenlafaxine [see CLINICAL PHARMACOLOGY (12.3)].

Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with PRISTIQ Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with PRISTIQ [see Clinical Pharmacology (12.3) ].

aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended.

In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with aripiprazole.