Pharmacokinetic drug interactions may occur at any point of the drug disposition process, including drug metabolism and elimination. The cytochrome P450 (CYP) family of enzymes is the major metabolizing enzyme system in humans, with CYP3A4 and CYP3A5 involved in the metabolism of nearly 50% of all drugs. Several antineoplastic agents undergo metabolism in part by CYP3A4, including vincristine, vinblastine, paclitaxel, and docetaxel.

Drug interactions involving CYP enzymes include inhibition and induction. Inhibition occurs when one drug interferes with the metabolism of another drug by the same CYP enzyme. In general, antineoplastic agents are administered at doses close to the maximum tolerated dose; therefore, interactions inhibiting the metabolism of an antineoplastic agent could lead to increased toxicity

Induction is the process by which one drug increases the amount of CYP enzymes present, accelerating the metabolism of a second drug. An example is the concomitant use of a strong CYP3A4 inducer such as dexamethasone with temsirolimus; this interaction could compromise the effectiveness of temsirolimus without a dose increase. 

Because many drugs used to treat cancer are metabolized by CYP enzymes, it is important to review the medication profile for drug interactions that could increase toxicity or decrease the treatment’s effectiveness.

Douglas D. Parr, PharmD, is a clinical pharmacist specialist in investigational pharmacy at Dartmouth-Hitchcock Medical Center in Lebanon, NH.