OBJECT DRUGS
PRECIPITANT DRUGS
P-Glycoprotein and CYP3A4 Inhibitors:
- Amiodarone (Cordarone, etc.)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Delavirdine (Rescriptor)
- Diltiazem (Cardizem, etc.)
- Dronedarone (Multaq)
- Grapefruit
- Indinavir (Crixivan)
- Lapatinib (Tykerb)
- Nefazodone
- Nelfinavir (Viracept)
- Nicardipine (Cardene, etc.)
- Propafenone (Rythmol, etc.)
- Quinidine (Quinidex)
- Ritonavir (Norvir)
- Saquinavir (Invirase)
- Tacrolimus (Prograf, etc.)
- Tamoxifen (Nolvadex)
- Telaprevir (Incivek)
- Verapamil (Isoptin, etc.)
Comment:
Colchicine is a substrate for P-glycoprotein (PGP) and concurrent use of PGP inhibitors has resulted in life-threatening colchicine toxicity. Colchicine is also a substrate for CYP3A4 and inhibitors of this enzyme may also raise its plasma concentrations. Grapefruit inhbits both CYP3A4 and PGP, and colchicine toxicity has been reported with large amounts of grapefruit juice.
Class 2: Use Only if Benefit Felt to Outweigh Risk
- Use Alternative: Given the possibility of fatal colchicine toxicity, few situations would warrant the use of a PGP or CYP3A4 inhibitor with colchicine. Select an alternative that is not known to inhibit PGP or CYP3A4, especially if the patient has renal impairment.
- Calcium Channel Blockers: Calcium channel blockers other than diltiazem, nicardipine, and verapamil appear less likely to inhibit CYP3A4, and may be less likely to inhibit P-glycoprotein. But monitor for colchicine toxicity if any calcium channel blocker is used concurrently.
- Grapefruit: Orange juice does not appear to inhibit CYP3A4.
- Monitor: If the combination must be used, monitor carefully for toxicity from colchicine including diarrhea, fever, abdominal pain, muscle pain or weakness, and paresthesias. Discontinue both drugs immediately if toxicity is suspected.