What is the Difference Between Tacrolimus and Sirolimus

The key difference between Tacrolimus and Sirolimus is that Tacrolimus prevents organ transplantation rejections by blocking the activity of calcineurin, while Sirolimus prevents organ transplantation rejection by inhibiting the mammalian target of rapamycin (mTOR).

Tacrolimus and Sirolimus are immunosuppressants widely used to treat transplanted organ rejection. Tacrolimus is a calcineurin inhibitor, while Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR). Tacrolimus is the first-line immunosuppressant after transplantation and is available as the formulation of capsules or liquid. In contrast, Sirolimus is a newer immunosuppressant that is often used in combination with other drugs. Nevertheless, both Tacrolimus and Sirolimus effectively prevent the rejection of transplanted organs. However, they can also cause serious side effects. Therefore, discussing the risks and benefits of these drugs with a healthcare provider before starting treatment is essential.

CONTENTS

1. Overview and Key Difference
2. What is Tacrolimus
3. What is Sirolimus
4. Similarities – Tacrolimus and Sirolimus
5.  Tacrolimus vs Sirolimus in Tabular Form
6. Summary – Tacrolimus vs Sirolimus

What is Tacrolimus?

Tacrolimus is an immunosuppressive drug for treating organ transplantation rejection and moderate to severe atopic dermatitis. It is a calcineurin inhibitor and is chemically known as macrolide. Tacrolimus binds with the immunophilin FKBP-12 to reduce the peptidyl-prolyl isomerase activity, inhibiting T-lymphocyte transduction and IL-12 transcription. Tacrolimus suppresses inflammation in a similar way to steroids with lower magnitude. Therefore, it is also used as a topical application that can be directly applied on the face to treat atopic dermatitis. Tacrolimus cures atopic dermatitis by inhibiting T-cell activation through the FKBP-12-mediated inhibition of the nuclear factor of activated T-cells (NF-AT) transcription factor.

After oral administration, Tacrolimus is incompletely absorbed from the gastrointestinal tract, while the bioavailability in healthy adults is less than 20%. Most absorbed drugs remained primarily bound with the albumin and alpha-1-acid glycoprotein. The liver primarily metabolizes Tacrolimus, and most of the drugs are incorporated in the feces and excreted. Side effects of Tacrolimus include blurred vision, liver and kidney problems, seizures, tremors, and hypertension.

What is Sirolimus?

Sirolimus, or Rapamycin, is another drug prescribed to treat transplant rejection. In addition, it is also prescribed to treat lymphangioleiomyomatosis and adults with perivascular epithelioid cell tumors. Sirolimus is a macrocyclic lactone antibiotic produced by Streptomyces hygroscopicus. It acts as an inhibitor of the mTOR, a serine/threonine protein kinase that regulates cell growth, proliferation, and survival. Sirolimus inhibits the antigens and cytokines-induced T-lymphocyte activation and proliferation through the formation of the FKBP-12 complex and the inactivation of mTOR.

Oral administration of Sirolimus into healthy individuals has been associated with approximately 14% bioavailability. The absorbed drug is then bound with plasma proteins such as albumin, α1-acid glycoprotein, and lipoproteins. Sirolimus undergoes metabolism in both the intestinal wall and liver. Most orally absorbed drugs are recovered mainly in the feces, and a lesser amount is in urine. Due to the low water solubility and higher plasma protein binding ability, the overdose of Sirolimus is not expected to be dialyzable to a significant extent.

What are the Similarities between Tacrolimus and Sirolimus?

• Tacrolimus and Sirolimus are used to prevent the rejection of transplanted organs.
• They are both given as capsules that are taken orally.
• Both drugs can potentially cause side effects, such as kidney damage, high blood pressure, and diabetes.

What is the Difference Between Tacrolimus and Sirolimus?

Tacrolimus and Sirolimus are drugs primarily used to treat organ transplantation rejections. However, there is a distinct difference between Tacrolimus and Sirolimus. Tacrolimus is a first-line immunosuppressant in many transplant protocols. Sirolimus is often used with other immunosuppressants, such as Tacrolimus or cyclosporine. Tacrolimus works by blocking the activity of calcineurin, which inhibits the activation of T cells. In contrast, Sirolimus works by inhibiting the mammalian target of rapamycin (mTOR), preventing T cell growth and division.

Below is a summary of the difference between Tacrolimus and Sirolimus in tabular form for side-by-side comparison.

Summary – Tacrolimus vs Sirolimus

Tacrolimus and Sirolimus are immunosuppressants used to prevent the rejection of transplanted organs. Tacrolimus is a calcineurin inhibitor, while Sirolimus is a mTOR inhibitor. Tacrolimus is a capsule taken orally once or twice daily, while Sirolimus is typically a capsule taken once daily. Tacrolimus is a first-line immunosuppressant in many transplant protocols, while Sirolimus is often used in combination with other immunosuppressants. Tacrolimus is associated with a higher risk of kidney damage and high blood pressure, while Sirolimus is associated with a higher risk of mouth ulcers, skin rash, and impaired wound healing. In addition, Tacrolimus is more expensive than Sirolimus. Thus, this difference between Tacrolimus and Sirolimus should be considered carefully when selecting the proper treatment for organ transplantation rejection.

Reference:

1. Scott, Lesley J, et al. “Tacrolimus.” Drugs, vol. 63, no. 12, 2003, pp. 1247–1297.
2. Kahan, Barry D. “Sirolimus: A Comprehensive Review.” Expert Opinion on Pharmacotherapy, vol. 2, no. 11, 2001, pp. 1903–1917.

Image Courtesy:

1. “Tacrolimus2DCSD” By Fuse809 (talk) – Own work (Public Domain) via Commons Wikimedia
2. “Sirolimus structure” By Vaccinationist – Own work, based on PubChem (Public Domain) via Commons Wikimedia