| Common types of drug interactions | Examples of interacting drugs | Approach to management in the absence of appropriate noninteracting alternatives |
| Coadministration of drugs that inhibit CYP3A metabolism and/or P-gp efflux can increase immunosuppressant serum concentrations, leading to significant toxicities. | - Amiodarone
- ART-boosting agents (eg, ritonavir, cobicistat)
- Azole antifungals (eg, fluconazole, posaconazole, voriconazole)
- HIV protease inhibitors (eg, atazanavir, nelfinavir, saquinavir)
- Macrolide antibiotics
- Non-dihydropyridine calcium channel blockers
- Ombitasvir-paritaprevir-ritonavir with or without dasabuvir (an HCV, direct-acting antiviral regimen)
- Grapefruit juice
| - Closely monitor immunosuppressant concentrations and signs of toxicity (eg, tremors and headaches).
- Substantial, including preemptive, dose reduction of immunosuppressant drug may be needed (eg, on average, only 25% of the standard dose of cyclosporine is required if administered concomitantly with HIV protease inhibitors).
- Some combinations are considered contraindicated according to product labeling; refer to appropriate topic reviews for detail.
- Lists of CYP3A and P-gp inhibitors are provided as separate tables within UpToDate.
|
| Coadministration of drugs that induce CYP3A metabolism and/or P-gp efflux pumping can decrease immunosuppressant serum concentrations, increasing the risk of organ rejection. | - Antiseizure medications, enzyme inducing (eg, carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone)
- Enzalutamide
- Nafcillin
- Rifamycins (eg, rifabutin, rifampin, rifapentine)
- St. John's wort
| - Closely monitor immunosuppressant serum concentrations and signs of organ rejection.
- Significant immunosuppressant dose increases may be needed.
- Enzyme induction can require up to 2 weeks to achieve maximum effect and persists for up to 2 weeks after discontinuation of the interacting medication. Clinically significant effects can occur within hours to days of starting a CYP inducer.
- Lists of CYP3A and P-gp inducers are provided as separate tables within UpToDate.
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| Coadministration of nephrotoxic drugs with cyclosporine or tacrolimus can cause additive or synergistic kidney injury. | - Aminoglycosides
- Amphotericin B
- Colchicine
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
| - Concomitant administration of cyclosporine and tacrolimus with other potentially nephrotoxic drugs should be avoided.
- Suggested dose adjustments for use with colchicine are available in the Lexicomp monograph included within UpToDate.
|
| Coadministration of drugs that increase serum potassium with cyclosporine or tacrolimus may cause severe hyperkalemia. | - ACE inhibitors/ARBs
- Amiloride
- Spironolactone
- Triamterene
- Trimethoprim, trimethoprim-sulfamethoxazole (cotrimoxazole)
| - Closely monitor serum potassium levels.
|
| Coadministration of cyclosporine with sirolimus can increase sirolimus concentrations. | | - Separate administration of sirolimus from cyclosporine by 4 hours; give sirolimus at a consistent time with respect to cyclosporine.
- Closely monitor immunosuppressant serum concentrations.
|
| Coadministration of statin drugs with cyclosporine can increase statin levels and risk of myotoxicity. | - Atorvastatin
- Lovastatin
- Pitavastatin
- Rosuvastatin
- Simvastatin
| - Pravastatin and fluvastatin are preferred due to decreased interactions.
- Tacrolimus may be preferred over cyclosporine in patients receiving statin therapy.
- Cyclosporine and simvastatin should not be used together.
- Some combinations are considered contraindicated or statin daily dose limits are recommended in the product labeling; refer to the Lexicomp monographs included within UpToDate for detailed information.
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