Tacrolimus (Prograf): Newly FDA-Approved for Lung Transplant Rejection

In July 2021, the FDA approved tacrolimus (Prograf) — a medication that can be used to prevent organ transplant rejection — for a new use. It’s now the first immunosuppressant medication approved to prevent lung transplant rejection when used with other immunosuppressive medications. 

Receiving a lung transplant can be a lengthy and stressful process. Between being evaluated, getting placed on an organ waitlist, and undergoing surgery, it’s a significant health, time, and financial investment. So, after receiving a lung transplant — or any other type of organ transplant — it’s important to make sure that the body accepts the new organ. This is where tacrolimus comes in. 

Here we’ll cover what you should know about tacrolimus for lung transplant rejection — what it is, how it works, and what to expect.

What is tacrolimus?

Tacrolimus (Prograf) is an immunosuppressant medication. It can be given as a capsule, oral suspension (liquid), or an intravenous (IV) injection into the bloodstream. 

Tacrolimus is usually given twice a day, and someone’s health conditions and body weight help determine a specific dose. Oral forms are usually preferred, but it can be given into the vein if someone can’t take it by mouth. 

When tacrolimus is prescribed to someone, it’s closely monitored — through a process called therapeutic drug monitoring (TDM) — for effectiveness and tolerability. This is because even small changes to the amount of tacrolimus in the blood can lead to side effects or organ rejection.

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Tacrolimus typically shouldn’t be used by itself to prevent lung transplant rejection. Tacrolimus is often used with azathioprine (Imuran), mycophenolate mofetil (CellCept), and/or corticosteroids. These are other kinds of immunosuppressive medications. 

How does it treat lung transplant rejection?

Tacrolimus works by stopping the activity of an enzyme (protein) in the body called calcineurin. Calcineurin activates T cells — white blood cells in the immune system that target substances they don’t recognize. When an organ is placed into a new body, the new body may not recognize it as its own, and the immune system can attack it.

By stopping calcineurin, tacrolimus can make the immune system less active, so a transplant is more likely to be successful. 

What else does tacrolimus treat?

Tacrolimus was initially FDA-approved to prevent liver transplant rejection. Over time, the FDA updated this approval to also include the prevention of heart and kidney transplant rejections.  

Even though tacrolimus is now approved for lung transplant rejection, in the past it’s been used off-label for the same purpose. It also may be used off-label for conditions like myasthenia gravis — an autoimmune disease that can lead to muscle weakness — and rheumatoid arthritis.

Are there multiple types of tacrolimus?

Yes, tacrolimus immediate-release (IR) and extended-release (ER/XR/XL) versions are both available. Compared to IR medications, ER medications are released in the body more slowly over time. Prograf is an example of tacrolimus IR, and Astagraf XL and Envarsus XR are examples of tacrolimus ER. 

Tacrolimus IR is not interchangeable with tacrolimus ER. If tacrolimus IR — such as Prograf — is accidentally substituted with tacrolimus ER, serious side effects or organ rejection can occur. At this time, only tacrolimus IR — and not tacrolimus ER — is approved for lung transplant rejection. 

Another formulation of tacrolimus (Protopic) is also available as an ointment, but this is used to treat eczema — a common skin condition.

Who can use tacrolimus?

Tacrolimus is a medication that should be closely monitored, but many people can use it. Adults and children can both use tacrolimus. 

There are some health conditions and situations where someone may need a lower dose of tacrolimus than other people. Transplant specialists usually manage these dose adjustments. Some examples where tacrolimus may still be used with potential dose changes include in: 

• People with kidney problems

• People with liver problems 

• People who also take mycophenolate

• People who use other medications such as clarithromycin, voriconazole, or rifampin

There are certain situations where people shouldn’t use tacrolimus — these are discussed next. 

Who shouldn’t use tacrolimus?

Just like most other medications, some people shouldn’t use tacrolimus. 

Predictably, people who have had a serious allergic reaction to any ingredient in tacrolimus shouldn’t use it. For tacrolimus capsules, this can include ingredients like gelatin, hypromellose, or lactose. For people who receive tacrolimus by injection, this can include castor oil. Some people have had anaphylaxis — a type of severe allergic reaction — from castor oil. 

Tacrolimus can cause harm to an unborn baby if it’s given to someone who is pregnant. There haven’t been any controlled studies in humans that look at the effects of tacrolimus on a newborn baby while nursing, but animal studies show possible harm. People who are pregnant or nursing should talk to their transplant specialist about the risks and benefits of using tacrolimus. 

Separately, people with long QT syndrome — a heart complication that causes an irregular heartbeat — should typically avoid tacrolimus. People with other heart conditions may be able to take tacrolimus, but they should be monitored routinely throughout treatment. 

Certain drug interactions can also be worrisome. People who take sirolimus (Rapamune) — another immunosuppressant that can help prevent organ transplant rejection — shouldn’t use tacrolimus at the same time. Studies of people with heart or liver transplants have shown that combining sirolimus and tacrolimus can worsen health outcomes or increase the likelihood of death. 

Cyclosporine (Sandimmune) — another immunosuppressant that can help prevent organ transplant rejection — shouldn’t be used at the same time as tacrolimus because they work the same way. Combining these two medications can raise your risk of serious side effects.

It’s also recommended that people don’t drink grapefruit juice while taking tacrolimus — an interaction between the grapefruit juice and medication can raise the risks of side effects and complications. Similarly, live vaccines should generally be avoided for people with weakened immune systems. 

How effective is tacrolimus for lung transplant rejection?

One main study — whose results were recently discussed by Astellas Pharma — convinced the FDA that tacrolimus effectively prevents lung transplant rejection. This study pulled data from the U.S. Scientific Registry of Transplant Recipients (SRTR), a registry that has information about all U.S. transplant procedures. 

The study looked at records of lung transplant procedures from over 15,000 adults and 450 children between 1999 and 2017. For those that combined tacrolimus and mycophenolate mofetil, the 1-year transplant success rates were about 91% for adults and 92% for children. For those that combined tacrolimus and azathioprine, the 1-year transplant success rates were about 91% for adults and 85% for children. 

What are the side effects of tacrolimus?

Tacrolimus can effectively prevent organ transplant rejections — including lung transplant rejections — but it comes with a number of possible risks and side effects. Common side effects of tacrolimus can include:

• Constipation

• Diarrhea

• Insomnia

• Pain

• Shakiness

• Weakness

Serious side effects can also occur while taking tacrolimus. Serious tacrolimus side effects can include:

• Anemia (a low amount of red blood cells)

• Fever

• High potassium levels

• High blood pressure

• Infections

• Kidney problems 

• Symptoms of heart problems, including shortness of breath or chest pain

• Symptoms of high blood sugar, including frequent urination, higher levels of thirst than normal, and confusion — symptoms which can lead to the development of diabetes

• Nervous system issues, including confusion, seizures, or severe headaches

If you’re taking tacrolimus and you believe you’ve experienced a serious side effect, it’s recommended to seek medical attention. These are not all the possible side effects of tacrolimus — if you have any side effects that are bothersome or don’t go away, consider reaching out to your transplant specialist.

What else can be used to prevent lung transplant rejection?

Tacrolimus is the first FDA-approved medication to prevent lung transplant rejection in adults and children. But even though this is the first medication approved for this purpose, other medications are commonly used off-label to prevent lung transplant rejection. As previously mentioned, cyclosporine, mycophenolate mofetil, and azathioprine are possible options. Corticosteroids like prednisone, methylprednisolone, or dexamethasone are also used. 

According to SRTR data, the most common combination for preventing lung transplant rejection in the U.S. is tacrolimus, mycophenolate mofetil, and a corticosteroid.

Prevention aside, there are a few medications that can be used to treat active lung transplant rejections. Treating a rejected organ is a very specialized area of medicine, and specific medication choices vary on a case-by-case basis.

But, according to the American Thoracic Society, medications used to treat a rejected lung transplant can include:

• Corticosteroids

• Thymoglobulin (rabbit antithymocyte globulin)

• Alemtuzumab (Campath)

• Immunoglobulin (IVIG)

• Rituximab (Rituxan)

• Bortezomib (Velcade)

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Written 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:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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