OBJECT DRUGS

Immunosuppressants:

• Cyclosporine (Neoral, etc.)
• Everolimus (Afinitor)
• Sirolimus (Rapamune)
• Tacrolimus (Prograf, etc.)

PRECIPITANT DRUGS

Enzyme Inducers:

• Barbiturates
• Bosentan (Tracleer)
• Carbamazepine (Tegretol, etc.)
• Dabrafenib (Tafinlar)
• Dexamethasone (Decadron, etc.)
• Efavirenz (Sustiva)
• Etravirine (Intelence)
• Lumacaftor (Orkambi)
• Nevirapine (Viramune, etc.)
• Oxcarbazepine (Trileptal, etc.)
• Phenytoin (Dilantin, etc.)
• Primidone (Mysoline)
• Rifabutin (Mycobutin)
• Rifampin (Rifadin, etc.)
• Rifapentine (Priftin)
• St. John's wort

Comment:

Enzyme inducers have been reported to enhance the metabolism of these immunosuppressants. This effect is probably due to induction of CYP3A4 and P-glycoprotein (PGP). Preliminary evidence suggests that levothyroxine acts as a PGP inducer in the small intestine; other thyroid hormones probably act similarly. Keep in mind that cyclosporine is a strong CYP3A4 inhibitor, and may increase the plasma concentrations of enzyme inducers that are metabolized by CYP3A4, such as bosentan, carbamazepine, dabrafenib, dexamethasone, efavirenz, nevirapine, and rifabutin. The combination of bosentan and cyclosporine is listed as contraindicated in the bosentan label due to a dramatic (over 20-fold) increase in bosentan concentrations (probably due to cyclosporine-induced inhibition of both OATP and CYP3A4), along with a substantial reduction in cyclosporine concentration due to induction of CYP3A4 by bosentan.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: IUse an alternative to the enzyme inducer if possible.
• Monitor: If an enzyme inducer is necessary, monitor for altered immunosuppressant effect if an enzyme inducer is initiated, discontinued, or changed in dosage; substantial dosage adjustments of immunosuppressants may be necessary. Keep in mind that enzyme induction is usually gradual and may take days to weeks for onset and offset, depending on the specific inducer.