OBJECT DRUGS

• Irinotecan (Camptosar)

PRECIPITANT DRUGS

Enzyme Inducers:

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

Comment:

Enzyme-inducers such as carbamazepine, phenobarbital, phenytoin, and St. John's wort have reduced serum concentrations of irinotecan and its active metabolite (SN-38), probably by increasing the CYP3A4 metabolism of irinotecan and the glucuronide conjugation of SN-38. In one study, cigarette smokers had almost 40% lower exposure to the active metabolite (SN-38) than non-smokers. Medicinal cannabis (given as a tea) did not affect irinotecan metabolism in another study.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Anticonvulsants: In patients on irinotecan it would be desirable to use anticonvulsants that are not enzyme inducers, but in many cases it may not be reasonable to change the patient's anticonvulsant regimen.
• HIV Medications: Since most antiviral medications are either inducers or inhibitors, it is probably best just to monitor patients and adjust irinotecan doses as needed.
• St. John's wort: Given the questionable benefit of St. John's wort, it would be prudent to avoid giving it with irinotecan.
• Monitor: Monitor for altered irinotecan effect if enzyme inducers are initiated, discontinued, or changed in dosage. Adjustments in irinotecan dosage 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.