8 Tacrolimus (Prograf) Interactions to Know About

Receiving an organ transplant is a life-saving and life-changing journey. And to protect the health of a newly transplanted organ after surgery, great care is taken. It’s important to prevent your body’s immune system from attacking, or rejecting, the transplanted organ over time. 

Tacrolimus (Prograf, Astagraf XL, Envarsus XR) is one medication that’s commonly prescribed after an organ transplant. It plays a vital role in maintaining the health of the newly transplanted organ by suppressing your body's immune response. But understanding its potential interactions with other medications is crucial.

Some medications can alter the effects of tacrolimus, making it either too strong or too weak. This can lead to new or worsening side effects or a less effective treatment. Other medications can cause your potassium level to get too high.

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To keep your health on top, it's important to make sure all of your medications work well together. Coming up we will dive into eight notable tacrolimus interactions. 

1. Mycophenolate

Mycophenolate (CellCept, Myfortic) is another organ transplant medication. Tacrolimus and mycophenolate are often taken together to supercharge your anti-rejection routine. However, your transplant team will monitor you closely since the combination has the potential for interactions.

Some research suggests tacrolimus increases the concentration of mycophenolate. Likewise, mycophenolate may also increase the amount of tacrolimus in the body. To complicate things further, the effects might not be the same for everyone.

This interaction likely occurs due to a decrease in the activity of specific enzymes (proteins) in the liver. These enzymes play a role in breaking down medications, influencing how long they remain active in your system. Decreasing enzyme activity can worsen the odds of experiencing side effects, such as kidney problems, infection, and higher blood pressure.

Tacrolimus is considered to have a narrow therapeutic index. This means that even slight changes in concentration can have significant health implications. Your tacrolimus dose may need to be adjusted if your mycophenolate dose is changed. Your transplant team will order regular blood tests to make sure that your medication levels stay within a healthy range.

2. Protease inhibitors, including Paxlovid

Paxlovid (nirmatrelvir / ritonavir) is a COVID-19 medication. One of its active ingredients is a protease inhibitor — an antiviral that prevents virus cells from making copies of themselves. Other protease inhibitors work similarly, including medications such as atazanavir (Reyataz).

Protease inhibitors such as these can prevent tacrolimus from being broken down by the body. They prevent certain liver enzymes (proteins) from working properly. As a result, tacrolimus levels may rise, and in turn raise the risk of side effects. This escalation can be serious in some cases.

Although Paxlovid and tacrolimus can both be life-saving, taking them together can be risky without close monitoring. Any time you notice sick symptoms such as fever, cough, or body aches — even if they only seem mild — it’s best to contact your transplant team or healthcare provider.

3. Antifungals such as fluconazole

Fluconazole (Diflucan) is an antifungal medication that treats illnesses caused by fungi. Other antifungal medications within the same family include voriconazole (Vfend) and posaconazole (Noxafil).

Antifungals like these are known to have a range of drug interactions. Similar to the above interactions, they can cause tacrolimus levels to rise to unhealthy levels.

Micafungin (Mycamine) is an antifungal that isn't thought to interact with tacrolimus. This may be a safer alternative if you’re taking tacrolimus, but it’s only available as an intravenous (IV) infusion. If a medication like fluconazole is the best option for your infection, your healthcare provider may opt to prescribe the combination with certain safeguards in place.

4. Antibiotics such as clarithromycin

Some antibiotics can affect your tacrolimus prescription, too. But their impact can vary.

Clarithromycin (Biaxin XL) and erythromycin (E.E.S, Ery-Tab, Eryc, others) are macrolide antibiotics. In a similar style as above, these antibiotics can cause tacrolimus levels to rise. 

Other antibiotics, such as rifampin, have the opposite effect. They can cause tacrolimus levels to drop.

To protect you from unsafe tacrolimus levels, your healthcare provider will try to prescribe an antibiotic that doesn’t interact with tacrolimus. But if there’s no other option available for your infection, your provider may adjust your tacrolimus dose while you’re taking the antibiotic.

5. Certain blood pressure medications

Blood pressure medications are used to lower your blood pressure. You may have started taking one before your transplant. It’s also possible to develop blood pressure issues after starting tacrolimus, with high blood pressure being a common side effect. Either way, treating high blood pressure with medication can help prevent serious conditions, such as heart attack and stroke, over time. Your transplant team will consider tacrolimus interactions when choosing a blood pressure medication for you.

Calcium channel blockers

Calcium channel blockers (CCBs) are a family of blood pressure medications that can interact with tacrolimus. Common CCBs include diltiazem (Cardizem, Cartia XT, Tiazac) and verapamil (Verelan).

CCBs can compete for the same enzymes that break down tacrolimus. This means that your body has a harder time eliminating it. The end result is a familiar story — higher tacrolimus levels. This may lead to a tacrolimus dose adjustment.

Blood pressure medications that cause high potassium levels

Tacrolimus can increase potassium levels in your blood. Some blood pressure medications might also raise potassium. Taking the two together raises the risk of developing a potentially life-threatening condition called hyperkalemia, which is caused by very high potassium levels. 

Several types of medications used to treat blood pressure can raise potassium, including: 

• Potassium-sparing diuretics (water pills) 

• Angiotensin-converting enzyme (ACE) inhibitors

• Angiotensin receptor blockers (ARBs)

Your transplant team may want you to avoid these medications. Or they may recommend monitoring your potassium level while taking one with tacrolimus.

6. Anti-seizure medications such as phenytoin

Carbamazepine (Carbatrol, Tegretol, Teril, Others), phenobarbital, and phenytoin (Dilantin, Phenytek) are common anti-seizure medications. But they can interact with tacrolimus. They lower tacrolimus levels by ramping up certain enzymes in your liver. When these enzymes are more active, more tacrolimus is eliminated.

You likely won’t be able to feel a low tacrolimus level. But without enough medication in your body, there’s a higher risk that your transplant could be rejected. 

If you take tacrolimus and an anti-seizure medication, your healthcare provider can monitor levels of both with a blood test. Make sure to report any dose changes to your transplant team.

7. Magnesium and aluminum-containing antacids

If you’re experiencing indigestion, it may be tempting to reach for over-the-counter (OTC) magnesium and aluminum-containing antacids, such as Mylanta (aluminum hydroxide / magnesium hydroxide / simethicone). But like with other medications on this list, they have the risk of interacting with your tacrolimus prescription.

Tacrolimus absorption is increased if you take your dose with antacids. This could raise your tacrolimus blood levels — and raise your risk for side effects.

It's best to avoid magnesium and aluminum-containing antacids with tacrolimus. If you’re having trouble managing your indigestion, consider trying a dietary-based solution. Change up your diet to avoid alcohol and less greasy or spicy food. You could also try to avoid lying down within 2 hours of eating.

8. Grapefruit products

Grapefruit and grapefruit juice are known to interact with a wide range of medications. Tacrolimus is no exception. Grapefruit can prompt your tacrolimus levels to rise to unsafe levels. It’s best to avoid grapefruit products while taking tacrolimus — especially in large or frequent quantities.

When should you contact your transplant specialist about tacrolimus interactions?

Tacrolimus can be a tricky medication to manage. With too little in your body, there’s a higher risk of transplant rejection. However, too much can cause harm. Possible signs or symptoms of too much tacrolimus include: 

• Headache

• Tremor

• High blood pressure

• High potassium levels

• Kidney damage

• Nerve pain

• Seizures

Your transplant provider will monitor your tacrolimus levels to catch any problem early. But if you spot symptoms like these — or simply feel “off” or unwell — contact your transplant specialist right away. For severe symptoms, get immediate medical attention. 

Keep in mind: Tacrolimus can also interact with prescription medications, OTC medications, and supplements not discussed here. It’s critically important to check with your transplant team before making any changes to the products you take.

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Written by:

Nathan Williams, PharmD, RYT

Nathan is a clinical pharmacist, certified yoga instructor, and medical content writer. His clinical practice has spanned several sub-specialties including: emergency medicine, nutrition, and pediatrics.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

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