From the Guidelines
Bactrim (sulfamethoxazole-trimethoprim) and Prograf (tacrolimus) should be used together with caution due to potentially serious drug interactions, including possible additive neurotoxicity or nephrotoxicity, as noted in the British Thoracic Society guidelines 1. When these medications are combined, there is a risk of increased toxicity due to the potential interaction between the two drugs.
- The exact mechanism of this interaction is not fully understood, but it is thought to be related to the inhibition of the CYP3A4 enzyme that metabolizes tacrolimus, potentially leading to increased tacrolimus blood levels.
- This interaction may cause kidney damage, neurological problems, and other serious side effects, highlighting the need for close monitoring of patients taking both medications.
- If both medications must be used concurrently, tacrolimus blood levels should be monitored closely, and the tacrolimus dose may need to be adjusted to minimize the risk of toxicity.
- Patients should watch for signs of tacrolimus toxicity, including tremors, headache, confusion, high blood pressure, and worsening kidney function, and immediately report any concerning symptoms to their healthcare provider.
- Additionally, both medications can independently affect kidney function, so renal parameters should be monitored regularly to minimize the risk of adverse effects.
- It is essential to note that the information on drug interactions is not exhaustive, and healthcare providers should consult with a pharmacist to discuss potential interactions and ensure safe use of these medications 1.
From the FDA Drug Label
Cyclosporine Avoid concurrent use There have been reports of marked but reversible nephrotoxicity with coadministration of sulfamethoxazole and trimethoprim and cyclosporine in renal transplant recipients.
Although the label does not directly mention Tacrolimus, it does mention Cyclosporine, which is another calcineurin inhibitor like Tacrolimus. Given the similarity in mechanism of action between Cyclosporine and Tacrolimus, there is a potential risk of nephrotoxicity when coadministering Trimethoprim/Sulfamethoxazole with Tacrolimus. Monitoring of renal function is recommended if Trimethoprim/Sulfamethoxazole and Tacrolimus are coadministered 2.
From the Research
Potential Drug Interactions
- The potential drug interactions between Trimethoprim/Sulfamethoxazole (Bactrim) and Tacrolimus (Prograf) are not directly addressed in the provided studies.
- However, a study 3 investigated the interaction between trimethoprim-sulfamethoxazole and cyclosporine, which is another immunosuppressant like tacrolimus.
- The study found that prophylaxis with trimethoprim-sulfamethoxazole had no discernable effect on cyclosporine pharmacokinetics, and recipients of trimethoprim-sulfamethoxazole had blood levels of cyclosporine similar to those in patients in the placebo group.
- Another study 4 found that trimethoprim/sulfamethoxazole can cause acute kidney injury, which may be a concern when used with tacrolimus, as tacrolimus can also affect kidney function.
- A study 5 found that trimethoprim can affect the kinetics of creatinine, sodium, and potassium in the proximal and distal tubules in a dose-dependent manner without changing the glomerular filtration rate.
Mechanism of Interaction
- Trimethoprim inhibits the Na+ /K+ -ATPase present in the basement membrane of distal tubular epithelial cells, which can lead to hyperkalemia 5.
- Trimethoprim also inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, which can lead to reversible increases in the concentration of serum creatinine 5.
- The interaction between trimethoprim/sulfamethoxazole and tacrolimus may be related to their effects on kidney function and electrolyte balance, although this is not directly addressed in the provided studies 4, 5, 3.