When Tacrolimus Isn't Available or Isn't Working

Tacrolimus is the gold standard in transplant medicine — it's the most widely prescribed immunosuppressant for preventing organ rejection after kidney, liver, and heart transplants. But what happens when you can't get it? Maybe your pharmacy is out of stock, you're experiencing serious side effects, or the cost is simply too high.

Whatever the reason, it's important to know that alternatives exist. You should never stop or switch your immunosuppressant on your own — this article is meant to help you have an informed conversation with your transplant team. Let's look at what's out there.

What Is Tacrolimus and How Does It Work?

Tacrolimus (brand names Prograf, Envarsus XR, Astagraf XL) is a calcineurin inhibitor. It works by blocking an enzyme called calcineurin in your immune system's T-cells. When calcineurin is blocked, T-cells can't activate properly, which prevents them from attacking your transplanted organ.

Tacrolimus is typically taken twice daily (immediate-release) or once daily (extended-release) and requires regular blood level monitoring to make sure the dose is within a safe and effective range. It's been the backbone of transplant immunosuppression since it was first approved in 1994.

For a full breakdown of how it works, see our article on Tacrolimus mechanism of action explained.

Alternative 1: Cyclosporine (Neoral, Sandimmune, Gengraf)

Cyclosporine is the other calcineurin inhibitor — and it was actually the first one approved for transplant use, before Tacrolimus came along. It works through a similar mechanism (blocking calcineurin) but binds to a different protein called cyclophilin instead of FKBP-12.

When it might be used:

• If you can't tolerate Tacrolimus due to side effects like tremors, new-onset diabetes, or severe kidney toxicity
• If Tacrolimus is unavailable and your doctor needs an alternative calcineurin inhibitor

Key differences from Tacrolimus:

• Cyclosporine may cause more cosmetic side effects like excess hair growth (hirsutism), swollen gums (gingival hyperplasia), and coarsened facial features
• Studies generally show Tacrolimus is more effective at preventing acute rejection, which is why it replaced Cyclosporine as the preferred option
• Like Tacrolimus, Cyclosporine requires regular blood level monitoring and has significant drug interactions

Alternative 2: Sirolimus (Rapamune)

Sirolimus is an mTOR inhibitor — a completely different class of immunosuppressant from Tacrolimus. Instead of blocking calcineurin, it inhibits a protein called mTOR that's involved in cell growth and division, which suppresses the immune response through a different pathway.

When it might be used:

• When calcineurin inhibitor toxicity (especially kidney damage) is a concern
• As part of a calcineurin inhibitor-free regimen for select patients
• In combination with low-dose Tacrolimus to spare kidney function

Key things to know:

• Sirolimus does not cause the same type of kidney toxicity as Tacrolimus
• However, it has its own side effects including mouth sores, elevated cholesterol and triglycerides, delayed wound healing, and low blood counts
• It's typically not used immediately after transplant because of wound-healing concerns

Alternative 3: Everolimus (Zortress)

Everolimus is another mTOR inhibitor, closely related to Sirolimus. It's FDA-approved for preventing rejection in kidney and liver transplant recipients.

When it might be used:

• Similar situations as Sirolimus — when you need to reduce or eliminate calcineurin inhibitor exposure
• Often used in combination with reduced-dose Tacrolimus rather than as a complete replacement

Key things to know:

• Everolimus has a shorter half-life than Sirolimus, which means blood levels can be adjusted more quickly
• Side effects are similar to Sirolimus: mouth sores, high cholesterol, and increased infection risk
• Requires regular blood level monitoring, much like Tacrolimus

Alternative 4: Belatacept (Nulojix)

Belatacept is a newer option that works completely differently from both calcineurin inhibitors and mTOR inhibitors. It's a selective T-cell costimulation blocker — it prevents T-cells from becoming fully activated by blocking a key signal they need.

When it might be used:

• For kidney transplant patients who want to avoid calcineurin inhibitor-related kidney damage
• When Tacrolimus side effects (kidney toxicity, diabetes, tremors) are severe

Key things to know:

• Belatacept is given as an IV infusion, not taken orally — typically once a month after an initial loading phase. This means regular trips to an infusion center.
• It carries a boxed warning about the risk of post-transplant lymphoproliferative disorder (PTLD), especially in patients who haven't been exposed to Epstein-Barr virus (EBV)
• Studies show it may preserve kidney function better than Cyclosporine over the long term
• It's only approved for kidney transplants, not liver or heart

Important: Never Switch Medications on Your Own

This cannot be stressed enough: do not stop or switch your immunosuppressant without your transplant team's guidance. Each of these medications has different dosing, monitoring requirements, and side-effect profiles. A switch requires careful planning, dose adjustments, and close blood level monitoring to keep your transplant safe.

If you're having trouble finding Tacrolimus, your first step should be trying to locate it at another pharmacy. Use Medfinder to search for Tacrolimus availability near you, or check our guide on how to find Tacrolimus in stock.

Final Thoughts

Tacrolimus remains the most widely used immunosuppressant after organ transplant for good reason — it's effective and well-studied. But if you can't get it or can't tolerate it, there are real alternatives. Cyclosporine, Sirolimus, Everolimus, and Belatacept each have their own advantages and trade-offs.

Talk to your transplant team about which option makes the most sense for your situation. And if cost is part of the equation, don't miss our article on how to save money on Tacrolimus.

For more about Tacrolimus itself — including side effects, dosing, and drug interactions — explore our other guides:

• What Is Tacrolimus? Uses, Dosage, and What You Need to Know
• Tacrolimus Side Effects: What to Expect
• Tacrolimus Drug Interactions: What to Avoid