Aripiprazole (ABILIFY) Drug Interactions

Users of the drug aripiprazole (ABILIFY) should be aware of the drug’s clinically important interactions with many other prescription medications.

Aripiprazole is one of the widely used newer atypical antipsychotic drugs. It is approved by the Food and Drug Administration (FDA) for treatment of several disorders, including schizophrenia and bipolar disorder, and for use as an adjunct to antidepressants in treating major depression.[1]

Like many drugs, aripiprazole is metabolized (broken down or chemically modified) by substances in the liver called enzymes. Two important enzymes, known as CYP3A4 and CYP2D6, metabolize aripiprazole.[2] When aripiprazole is taken with other drugs that decrease or increase the activity of these enzymes, the speed at which aripiprazole is metabolized can be affected.

If these enzymes metabolize aripiprazole too slowly, there is a risk that the blood levels of aripiprazole will become too high, leading to toxicity.[3] The most common symptoms of aripiprazole toxicity include nausea, vomiting, constipation, headache, dizziness, akathisia (inability to sit or keep still), anxiety, insomnia and restlessness.[4] The most serious adverse effects of aripiprazole include the following:

• High blood sugar levels or worsening control of diabetes
• Weight gain
• Orthostatic hypotension (a drop in blood pressure upon sitting upright or standing)
• Seizures
• Tardive dyskinesia (involuntary jerky movements of different muscles resulting in random movements of the face, lips, tongue, trunk and limbs)
• Pathologic gambling and other compulsive behaviors
• Neuroleptic malignant syndrome, a life-threatening disorder characterized by fever, muscle rigidity and altered mental status.[5]

Conversely, if the enzymes metabolize aripiprazole too quickly, the blood levels of the drug will become too low (reducing aripiprazole’s effectiveness and potentially leading to inadequate treatment).[6]

Drugs that increase aripiprazole levels

Drugs that inhibit the activity of CYP3A4 are likely to increase aripiprazole blood levels. For example, the oral form of the antifungal drug ketoconazole (available in generic only) — which Public Citizen’s Health Research Group has designated as Do Not Use — is an especially potent inhibitor of CYP3A4. This drug increases the blood levels of aripiprazole and its active metabolite (dehydroaripiprazole) by approximately 60 and 80 percent, respectively.[7]

Drugs that inhibit CYP2D6 also will increase aripiprazole blood levels. For example, the drug quinidine (available in generic only), which is used primarily to treat abnormal heart rhythms, is a particularly potent inhibitor of CYP2D6, and, on average, it more than doubles aripiprazole blood levels.[8]

See Table 1 (below) for a list of drugs that are strong inhibitors of the CYP3A4 or CYP2D6 enzymes and, thus, increase the risk of aripiprazole toxicity. The FDA-approved product labeling for aripiprazole recommends that the dosage of the drug be reduced to half the usual dose in patients concomitantly taking any one of these CYP3A4- or CYP2D6-inhibiting drugs.[9] Patients taking both a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor concomitantly with aripiprazole should take one-fourth of the usual aripiprazole dose.

Drugs that decrease aripiprazole levels

Drugs that cause CYP3A4 to metabolize drugs more rapidly (enzyme inducers) can cause aripiprazole to be metabolized too quickly, decreasing the effectiveness of the aripiprazole.[10]

For example, several studies have shown that the seizure drug carbamazepine (CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL) is a strong inducer of the CYP3A4 enzyme.[11] Concomitant use of carbamazepine markedly reduces aripiprazole blood levels, which can block the intended effect of aripiprazole.

See Table 2 (below) for a list of drugs that are strong inducers of CYP3A4 and, thus, decrease the blood levels and effectiveness of aripiprazole. The product labeling for aripiprazole recommends doubling the usual dose over one to two weeks in patients starting one of these strong CYP3A4 enzyme inducers.[12]

Other drugs that can interact with aripiprazole

If you are taking drugs for diabetes, high blood pressure or seizures, it is possible that aripiprazole therapy may affect your dosage requirements for these other drugs.[13] Notify your doctor if you have any of these conditions before starting aripiprazole.

What You Can Do

These types of potentially dangerous drug interactions reinforce the importance of bringing all of the drugs that you take each time you visit any doctor. Because many drugs, including others not listed in this article, affect the activity of the enzymes that metabolize aripiprazole, you should find out from your doctor whether any other prescribed drugs will interact with your aripiprazole treatment.

If you are taking aripiprazole and begin or end treatment with a drug that can either increase or decrease aripiprazole blood levels, speak with your doctor about whether you will need to adjust your aripiprazole dosage.

Table 1. Drugs That Strongly Inhibit CYP3A4 or CYP2D6 and Increase the Risk of Aripiprazole Toxicity

*Designated as Limited Use
**Combination drug that contains other active ingredients not listed
***Designated as Do Not Use
****Designated as Do Not Use except for serious fungal infections

Table 2. Drugs That Strongly Induce CYP3A4 and Decrease Aripiprazole’s Blood Levels and Effectiveness

*Combination drug that contains other active ingredients not listed
**Designated as Limited Use

References

[1]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[2]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[3]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[4]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[5]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[6]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[7]ARIPiprazole / CYP3A4 Inhibitors (Strong). Lexicomp Drug Interaction. UpToDate. Search date: June 15, 2018.

[8]ARIPiprazole / CYP2D6 Inhibitors (Strong). Lexicomp Drug Interaction. UpToDate. Search date: June 15, 2018.

[9]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[10]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[11]ARIPiprazole / CYP3A4 Inducers (Strong). Lexicomp Drug Interaction. UpToDate. Search date: July 5, 2018.

[12]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.

[13]Otsuka Pharmaceutical Company. Label: aripiprazole (ABILIFY). February 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021436s042,021713s033,021729s025,021866s027lbl.pdf. Accessed July 5, 2018.