Potential Drug Interactions with Aripiprazole (Abilify)
Aripiprazole (Abilify) has several important drug interactions that require dosage adjustments or monitoring, with strong CYP3A4 inhibitors/inducers and strong CYP2D6 inhibitors being the most clinically significant interactions. 1
Major Drug Interactions Requiring Dosage Adjustments
- Strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin): Increase aripiprazole exposure significantly, requiring a reduction in aripiprazole dosage 1
- Strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine): Increase aripiprazole exposure, requiring a reduction in aripiprazole dosage 1
- Strong CYP3A4 inducers (e.g., carbamazepine, rifampin): Decrease aripiprazole exposure, requiring an increase in aripiprazole dosage 1, 2
- Combination of CYP2D6 and CYP3A4 inhibitors: Can cause a 4.5-fold increase in aripiprazole exposure in extensive metabolizers of CYP2D6, requiring significant dosage reduction 1
Pharmacokinetic Considerations
- Aripiprazole is primarily metabolized through hepatic pathways involving CYP2D6 and CYP3A4 enzymes 1
- The mean elimination half-life is approximately 75 hours for aripiprazole and 94 hours for its active metabolite, dehydro-aripiprazole 1
- Poor metabolizers of CYP2D6 have a longer elimination half-life (approximately 146 hours) and may require lower initial doses 1
- Steady-state concentrations are attained within 14 days of dosing 1
Cardiovascular Interactions
- Antihypertensive medications: Aripiprazole has alpha-adrenergic antagonism properties that can enhance the effects of antihypertensive agents, requiring blood pressure monitoring 1
- QT-prolonging medications: Caution should be exercised when combining aripiprazole with other drugs that may prolong the QT interval, such as citalopram at doses exceeding 40 mg/day 2
CNS Depressant Interactions
- Benzodiazepines (e.g., lorazepam): Increased sedation and orthostatic hypotension when combined with aripiprazole; monitoring of sedation and blood pressure is recommended 1
- Other CNS depressants: Potential for additive CNS depression when aripiprazole is combined with other medications that cause sedation 3
Serotonergic Drug Interactions
- Monoamine Oxidase Inhibitors (MAOIs): Avoid combining aripiprazole with MAOIs due to increased risk of serotonin syndrome 2
- Multiple serotonergic drugs: Exercise caution when combining aripiprazole with other serotonergic medications (SSRIs, SNRIs, TCAs, opioids, dextromethorphan) due to potential risk of serotonin syndrome 2
Medications with No Clinically Important Interactions
- No dosage adjustment is necessary when aripiprazole is co-administered with famotidine, valproate, lithium, or lorazepam 1
- Aripiprazole does not significantly affect substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) 1
- No dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when co-administered with aripiprazole 1
Monitoring Recommendations
- Monitor for increased sedation, dizziness, or orthostatic hypotension when starting aripiprazole with other CNS depressants 1, 3
- Check blood pressure regularly when combining aripiprazole with antihypertensive medications 1
- Be vigilant for signs of serotonin syndrome (mental status changes, neuromuscular abnormalities, autonomic hyperactivity) when combining with other serotonergic agents 2
- Consider more frequent monitoring in elderly patients or those with renal/hepatic impairment 4
Special Considerations
- The risk of drug interactions increases with polypharmacy, which is common in psychiatric patients 5, 4
- Elderly patients are at higher risk for adverse effects from drug interactions due to age-related changes in pharmacokinetics and higher rates of polypharmacy 4
- Electronic prescribing systems can help identify potential drug interactions before they occur 4