Does Tacrolimus Cause Diarrhea? Understanding the Link and Management

October 8, 2025 •

4 min read

In some studies, up to 72% of patients taking tacrolimus report experiencing diarrhea, making it one of the most common gastrointestinal side effects [1.3.6]. Understanding the answer to 'Does tacrolimus cause diarrhea?' is crucial for managing this challenging condition post-transplant.

Quick Summary

Tacrolimus is an essential immunosuppressant for preventing organ rejection, but it frequently causes diarrhea. This side effect can affect drug absorption and lead to complications if not properly managed with medical guidance.

Key Points

Common Side Effect: Diarrhea is a very common side effect of tacrolimus, affecting a large percentage of transplant patients [1.3.6].
Impacts Drug Levels: Diarrhea can damage the intestine, leading to increased absorption and dangerously high levels of tacrolimus in the blood [1.4.1].
Medical Supervision is Key: Never self-treat. Always contact your transplant team if you experience persistent diarrhea, as dose adjustments may be needed [1.5.3].
Other Causes: Diarrhea in transplant patients can also be caused by infections or other medications like mycophenolate mofetil (MMF) [1.2.4, 1.2.7].
Formulations Matter: Some studies suggest extended-release versions of tacrolimus may cause fewer gastrointestinal side effects than immediate-release versions [1.6.3].
Hydration is Crucial: Managing diarrhea involves staying well-hydrated and may require dietary changes to avoid irritating foods [1.3.4, 1.5.1].
Avoid Grapefruit: Consuming grapefruit or grapefruit juice is prohibited as it can dangerously increase tacrolimus blood levels [1.7.1].

What is Tacrolimus?

Tacrolimus is a powerful immunosuppressive medication primarily used to prevent organ rejection in patients who have received a kidney, liver, heart, or lung transplant [1.7.2, 1.7.1]. It belongs to a class of drugs known as calcineurin inhibitors [1.7.3]. By suppressing the body's immune system, tacrolimus prevents the immune cells from attacking and damaging the newly transplanted organ [1.7.2]. It is a critical component of post-transplant care, often used in combination with other immunosuppressants like mycophenolate mofetil (MMF), steroids, or azathioprine [1.7.2]. Tacrolimus is available in several forms, including immediate-release capsules (Prograf), extended-release capsules (Astagraf XL), and extended-release tablets (Envarsus XR) [1.7.1].

The Link Between Tacrolimus and Diarrhea

Diarrhea is a very common and well-documented side effect of tacrolimus [1.3.1, 1.3.6]. Studies and clinical data show a wide range in prevalence, with some reports indicating that up to 72% of patients may experience it [1.3.6]. In various clinical studies, diarrhea is consistently listed among the most frequent adverse events, sometimes affecting as many as 50% of participants [1.2.2].

The relationship between tacrolimus and diarrhea is complex. While tacrolimus itself can directly cause gastrointestinal upset, diarrhea can also significantly impact how the drug is absorbed and processed in the body. Severe diarrhea can damage the epithelial cells of the intestine [1.4.3]. This damage can interfere with the normal function of enzymes (like CYP3A4) and transport proteins (like P-glycoprotein) that metabolize and remove tacrolimus from the gut [1.4.1, 1.4.7]. As a result, more of the drug can be absorbed into the bloodstream, leading to elevated and potentially toxic tacrolimus levels [1.4.1, 1.4.4]. This creates a dangerous cycle where diarrhea can increase drug concentration, and high drug levels can worsen side effects. For this reason, frequent monitoring of tacrolimus blood levels is essential during and after episodes of diarrhea [1.5.1].

Tacrolimus Formulations and Gastrointestinal Side Effects

Different formulations of tacrolimus may have varying impacts on the gastrointestinal system. Some research suggests that extended-release formulations, such as LCPT (Envarsus XR), may be associated with fewer GI symptoms compared to immediate-release (IR) versions [1.6.3]. One study noted that at one month post-transplant, patients on immediate-release tacrolimus experienced a higher prevalence of symptoms like abdominal pain, excessive gas, and more frequent stools compared to those on an extended-release formula [1.6.3]. However, diarrhea remains a common side effect across all formulations, including extended-release options like Envarsus XR [1.6.1, 1.6.2].


Feature	Immediate-Release (IR) Tacrolimus (e.g., Prograf)	Extended-Release (ER/XR) Tacrolimus (e.g., Envarsus XR)
Dosing Frequency	Typically twice a day, 12 hours apart [1.7.1].	Typically once a day, in the morning [1.7.1].
GI Side Effects	Higher prevalence of some GI symptoms like gas and abdominal pain reported in some studies shortly after transplant [1.6.3].	May be associated with a lower incidence of certain GI symptoms compared to IR formulations [1.6.3].
Common Side Effects	Diarrhea, tremor, headache, nausea, constipation [1.3.4, 1.3.6].	Diarrhea, anemia, urinary tract infection, constipation [1.6.1].
Food Interaction	Can be taken with or without food, but must be consistent [1.7.1].	Should be taken on an empty stomach [1.7.1].

Managing Tacrolimus-Induced Diarrhea

Managing diarrhea while on tacrolimus is crucial for both patient comfort and preventing serious complications. It's not just a matter of discomfort; persistent diarrhea can lead to dehydration, electrolyte imbalances, and dangerous fluctuations in tacrolimus levels [1.5.1].

Medical Management

Contact Your Healthcare Provider: If you experience diarrhea for more than 24 hours, it is essential to contact your transplant team [1.5.3]. Do not attempt to self-treat without medical advice.
Dose Adjustment: Your doctor may need to adjust your tacrolimus dose. Due to the risk of increased absorption during diarrhea, levels can become dangerously high [1.5.2]. Your team will monitor your tacrolimus trough levels closely [1.5.1].
Review of Other Medications: Other immunosuppressants taken alongside tacrolimus, particularly mycophenolate mofetil (MMF), are also strongly associated with diarrhea [1.2.4]. Your doctor may consider reducing the dose of MMF [1.5.1].
Infection Testing: Diarrhea in immunosuppressed patients can be caused by infections (bacterial, viral, or parasitic) [1.2.7, 1.5.4]. Your doctor will likely request stool samples to rule out an infectious cause before attributing it solely to medication [1.5.3].
Anti-diarrheal Medications: Do not take over-the-counter anti-diarrheal medications without explicit approval from your transplant team, as they may mask a more serious issue or interact with your transplant medications.

Lifestyle and Dietary Strategies

Hydration: Staying well-hydrated is critical. Drink plenty of water or electrolyte-containing fluids.
Dietary Changes: Avoid foods known to irritate the stomach, such as spicy, acidic, or greasy foods [1.3.4]. Following a 'BRAT' diet (bananas, rice, applesauce, toast) may be helpful during acute episodes.
Food Safety: Practice good food safety to prevent foodborne illnesses, which can be more severe in transplant recipients [1.5.3].
Avoid Grapefruit: Do not eat grapefruit or drink grapefruit juice, as it can significantly increase tacrolimus levels in your blood [1.3.5, 1.7.1].

Conclusion

Tacrolimus is a cornerstone of anti-rejection therapy for organ transplant recipients, but it undeniably causes diarrhea in a significant number of patients. This side effect is more than an inconvenience; it can disrupt the drug's delicate balance in the body, potentially leading to toxicity or, if doses are over-reduced, organ rejection [1.5.1]. The mechanism is often related to the drug's impact on the gastrointestinal tract, which can alter its own absorption [1.4.7]. Close collaboration with a transplant healthcare team is essential for managing this side effect. Through careful monitoring of drug levels, potential dose adjustments, ruling out infections, and making appropriate dietary modifications, patients can effectively manage tacrolimus-induced diarrhea and maintain the health of their transplanted organ.

For more information from an authoritative source, you can visit the Mayo Clinic's page on Tacrolimus (Oral Route).

Frequently Asked Questions

Diarrhea is a very common side effect. Some studies report that up to 72% of patients taking tacrolimus experience diarrhea at some point [1.3.6].

Tacrolimus can directly irritate the gastrointestinal tract. Furthermore, severe diarrhea can damage intestinal cells, which impairs the enzymes and proteins that normally process the drug, leading to a cycle of increased drug absorption and side effects [1.4.1, 1.4.3].

Yes. Severe diarrhea can lead to dehydration, electrolyte imbalances, and, most importantly, cause a sharp increase in tacrolimus blood levels, which can lead to toxicity and kidney problems [1.4.1, 1.5.1].

You should contact your transplant doctor or coordinator, especially if the diarrhea lasts for more than 24 hours. They will likely need to check your tacrolimus levels and may adjust your medication dosage [1.5.3].

Yes, diarrhea is still a listed side effect for extended-release formulations [1.6.1]. However, some research indicates that certain GI symptoms may be less frequent compared to the immediate-release versions [1.6.3].

You should not take any over-the-counter medications for diarrhea without first consulting your transplant team. Some of these medications can mask symptoms of a more serious infection or interact with your transplant drugs [1.3.4, 1.5.3].

Yes, avoiding spicy, greasy, or acidic foods can help manage symptoms. Staying hydrated is also very important. Always remember to avoid grapefruit and grapefruit juice, as they interfere with tacrolimus metabolism [1.3.4, 1.7.1].