Important Drug Interactions for the Stomach-Acid–Suppressing Drug Rabeprazole (ACIPHEX)

Patients taking the commonly prescribed stomach-acid–suppressing drug rabeprazole (ACIPHEX) should be aware that it has clinically important interactions with many other prescription medications. The drug belongs to the family of medications known as proton pump inhibitors, all of which Public Citizen’s Health Research Group has designated as Limited Use.

Rabeprazole is approved by the Food and Drug Administration (FDA) to treat several stomach-acid–related disorders in adults, including ulcers in the stomach and duodenum (the first part of the small intestine) and gastroesophageal reflux disease (GERD), which causes heartburn.[1] It also is approved by the FDA for short-term (up to eight weeks) treatment of symptomatic GERD in adolescents as young as 12 years of age.

Interacting drugs[2],[3]

The Table below provides examples of prescription medications that have clinically important interactions with rabeprazole. The following are some particularly notable examples of these drug interactions.

Antiviral drugs

Rabeprazole can interact with several antiviral drugs used to treat HIV infection. For most of these interacting antiviral drugs — including atazanavir (EVOTAZ, REYATAZ), nelfinavir (VIRACEPT) and rilpivirine (CABENUVA KIT, COMPLERA, EDURANT, JULUCA, ODEFSEY) — concomitant (at the same time) use with rabeprazole decreases blood levels of the antiviral drug, which may reduce the effectiveness of the antiviral drug and promote the development of HIV antiviral drug resistance. In the case of rilpivirine, the product labeling for rabeprazole warns that the drug should never be used concomitantly with rilpivirine because the interaction is so significant.

Cancer drugs

Rabeprazole also can interact with several oral cancer drugs, including erlotinib (TARCEVA), neratinib (NERLYNX) and sunitinib (SUTENT). Concomitant use of rabeprazole with these cancer drugs can reduce absorption of the latter drugs due to the reduction in stomach acidity. Such concomitant use may result in decreased blood levels of the cancer drugs, potentially decreasing their effectiveness in treating cancer.

Clopidogrel

Concomitant use of rabeprazole with the antiplatelet drug clopidogrel (PLAVIX) — which is used to prevent clot formation and reduce the risk of a new heart attack or stroke in certain patients, including those who have had a recent heart attack or stroke — may interfere with the antiplatelet effects of clopidogrel and thus increase the risk of a heart attack or stroke.

Digoxin

Concomitant use of rabeprazole with digoxin (LANOXIN) — which is used to treat heart failure and to control heart rate in patients with atrial fibrillation (a common abnormal heart rhythm characterized by an irregular and often rapid heartbeat) — can result in increased and potentially toxic blood levels of digoxin. Common symptoms of digoxin toxicity are loss of appetite, nausea, vomiting and fatigue. Digoxin toxicity also can lead to abnormal heart rhythms. If concomitant use of rabeprazole with digoxin is unavoidable, more frequent monitoring of blood digoxin levels should occur, especially during initiation and discontinuation of rabeprazole.

Methotrexate

Concomitant use of proton pump inhibitors like rabeprazole with methotrexate (JYLAMVO, OTREXUP, RASUVO, REDITREX, TREXALL, XATMEP) — which is used to treat the autoimmune diseases rheumatoid arthritis, psoriasis and several types of cancer — may increase methotrexate in the blood to toxic levels. This interaction is most likely to occur when methotrexate is administered in high doses.

Methotrexate toxicity can cause a wide range of serious and life-threatening adverse effects, including

• anemia (low red blood cell levels);
• low white blood cell levels, which can lead to serious infections;
• liver damage; and
• kidney failure.[4]

Symptoms of methotrexate toxicity may include fatigue, chills, fever, dizziness, mouth sores, nausea, vomiting, diarrhea, easy bruising and hair loss.

Warfarin

Concomitant use of rabeprazole with the oral anticoagulant (blood thinner) warfarin (JANTOVEN) can increase blood levels of warfarin, increasing the risk of bleeding complications. Patients who take warfarin should undergo more frequent monitoring of warfarin levels during therapy with rabeprazole and initially after discontinuing this proton pump inhibitor.

Examples of Medications That Have Clinically Important Interactions With Rabeprazole

†Combination drug product that contains one or more other active ingredients
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use Except For Serious Fungal Infections by Worst Pills, Best Pills News
***Designated as Do Not Use by Worst Pills, Best Pills News

What You Can Do

If you need treatment with rabeprazole, review all your other medications with your doctor to assess your risk of potentially significant drug interactions. If you are taking certain medications that interact with rabeprazole, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug, or your doctor may advise you to take a different drug for your stomach-acid condition. Be aware that other drugs not listed in this article also may have dangerous interactions with rabeprazole.
 

References

[1] Woodward Pharma Services LLC. Label: rabeprazole (ACEPHEX). March 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020973s042lbl.pdf. Accessed April 5, 2023.

[2] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “rabeprazole.” Accessed April 5, 2023.

[3] Woodward Pharma Services LLC. Label: rabeprazole (ACEPHEX). March 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020973s042lbl.pdf. Accessed April 5, 2023.

[4] Lukare Medical, LLC. Label: methotrexate oral solution (JYLAMVO). November 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212479s000lbl.pdf. Accessed April 5, 2023.