OBJECT DRUGS
PRECIPITANT DRUGS
Inhibitors of CYP3A4 and P-glycoprotein:
- Amiodarone (Cordarone, etc.)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Boceprevir (Victrelis)
- Ceritinib (Zykadia)
- Cobicistat (Stribild)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Daclatasvir (Daklinza)
- Delavirdine (Rescriptor)
- Diltiazem (Cardizem, etc.)
- Dronedarone (Multaq)
- Grapefruit
- Imatinib (Gleevec)
- Indinavir (Crixivan)
- Lapatinib (Tykerb)
- Lomitapide (Juxtapid)
- Mifepristone (Korlym)
- Nefazodone
- Nelfinavir (Viracept)
- Nicardipine (Cardene, etc.)
- Paritaprevir (Technivie)
- 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 CYP3A4 and P-glycoprotein (P-gp) and concurrent use of CYP3A4 and P-gp inhibitors has resulted in severe colchicine toxicity, including gastrointestinal toxicity, rhabdomyolysis, pancytopenia, and multi-organ failure. Colchicine toxicity is difficult to treat, and fatalities have been reported, especially if the patient has renal impairment. Most of the inhibitors listed above inhibit both CYP3A4 and P-gp, and it has not been established that drugs inhibiting only one or the other would increase colchicine plasma levels. For example, propafenone inhibits P-gp but may not have much effect on CYP3A4, so it is possible that it is less likely to interact with colchicine than drugs that inhibit both. Although grapefruit inhibits CYP3A4 and colchicine toxicity has been reported with large amounts of grapefruit juice, one study failed to find an effect of grapefruit juice on colchicine.
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.
- 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.