Mycophenolic Acid Drug Interactions: What to Avoid and What to Tell Your Doctor

Mycophenolic acid (Myfortic) and mycophenolate mofetil (CellCept) have significant drug interactions that every transplant patient and their caregivers should understand. Some interactions reduce the effectiveness of your immunosuppressant (increasing rejection risk), while others increase drug levels or toxicity. Here is what you need to know.

Major Drug Interactions (Most Important to Avoid)

Cholestyramine and Bile Acid Sequestrants (e.g., Welchol, Questran)

Cholestyramine and other bile acid sequestrants significantly reduce mycophenolic acid levels in the body by interrupting its enterohepatic recirculation. This can dramatically lower the amount of active drug reaching your system, reducing immunosuppression and increasing rejection risk. Do not take mycophenolate with these medications. If you must take a bile acid sequestrant, discuss timing and alternative options with your transplant physician.

Azathioprine

Both mycophenolate and azathioprine inhibit purine metabolism. Using them together does not provide additional benefit but significantly increases the risk of toxicity—including severe blood count abnormalities (myelosuppression). These drugs should never be combined; if switching from one to the other, your doctor should manage the transition carefully.

Live Vaccines

Live vaccines (such as MMR, varicella, yellow fever, intranasal flu vaccine, and Zostavax) are contraindicated while taking mycophenolate. Because your immune system is suppressed, live vaccines can cause actual infection. Killed/inactivated vaccines are generally acceptable, though their effectiveness may be reduced due to immunosuppression.

Moderate Drug Interactions (Discuss With Your Doctor)

Antacids Containing Magnesium or Aluminum (e.g., Maalox, Mylanta)

Aluminum and magnesium-containing antacids can reduce the absorption of mycophenolate mofetil (CellCept). Do not take these antacids at the same time as your mycophenolate. If you need to take antacids, separate them from your mycophenolate dose by at least 2 hours. Note: Myfortic (enteric-coated form) is less affected by antacids but should still be separated.

Sevelamer (Renvela, Renagel)

Sevelamer, a phosphate binder used in kidney disease, can decrease mycophenolic acid plasma concentrations (Cmax and AUC) by approximately 26–36%. If you take sevelamer, give your mycophenolate dose at least 2 hours after—or as directed by your physician. This is particularly relevant for transplant patients who also have chronic kidney disease.

Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir

These antiviral medications (used to treat or prevent herpes, CMV, and other viral infections) compete with mycophenolate's inactive metabolite (MPAG) for kidney excretion via tubular secretion. When taken together—especially in patients with reduced kidney function—both the antiviral and MPAG can accumulate to higher levels. This doesn't usually require stopping either medication, but your doctor should be aware and may monitor more closely.

Hormonal Contraceptives (Pills, Patches, Rings, Injections, Implants)

Mycophenolate mofetil can reduce the effectiveness of hormonal contraceptives. In one pharmacokinetic study, the levonorgestrel AUC was decreased by approximately 15% when co-administered with MMF. Since you must use two forms of reliable contraception while taking mycophenolate (per the REMS requirements), a hormonal method alone is not sufficient—you must also use a barrier method (condom, diaphragm, cervical cap with spermicide).

Cyclosporine vs. Tacrolimus

This is not a traditional drug interaction to avoid—it's an important pharmacokinetic consideration. Cyclosporine inhibits the enterohepatic recirculation of mycophenolic acid, reducing MPA exposure (AUC) compared to tacrolimus-based regimens. Patients switching from cyclosporine to tacrolimus may experience higher MPA levels at the same dose—requiring monitoring and potential dose adjustment.

Important Food and Supplement Interactions

Oral Activated Charcoal

Oral activated charcoal (sometimes taken for detoxification or poisoning) can significantly reduce mycophenolic acid levels by binding bile acids and interrupting enterohepatic recirculation. This should be avoided unless directed by your transplant physician.

Food

For mycophenolate mofetil (CellCept): Take on an empty stomach (1 hour before or 2 hours after meals) for best absorption. For Myfortic (mycophenolate sodium): Can be taken with or without food due to the enteric coating.

What to Tell Your Doctor and Pharmacist

Before starting mycophenolate and at every appointment, tell your doctor and pharmacist about:

All prescription medications, including blood pressure drugs, antibiotics, antivirals, and psychiatric medications

All over-the-counter medications, including antacids (especially those containing aluminum or magnesium), heartburn medications, and pain relievers

All dietary supplements, vitamins, and herbal products

Any new medication prescribed by a different doctor—ensure your transplant team is informed

For related information, see our guide on Mycophenolic Acid Side Effects. And if you ever have trouble filling your prescription, medfinder can help locate it near you.