View the Inhibitors and Inducers of CYP Enzymes, P-Glycoprotein, and Other Transporters tables

View the Inhibitors and Inducers of CYP Enzymes and P-Glycoprotein table

The tables below list the drugs that induce or inhibit cytochrome P450 enzymes or P-glycoprotein.

The FDA has required the manufacturer of Plavix, an antiplatelet drug used in addition to aspirin to prevent cardiovascular events in high-risk patients,1 to add a boxed warning to the package insert about the risk of a poor response to the drug in patients with genetic polymorphisms of the cytochrome P450 enzyme CYP2C19. Clopidogrel is a prodrug and CYP2C19 is mainly responsible for its bioactivation. The Medical Letter reported last year that several studies have found higher rates of cardiovascular events, including stent thrombosis, in patients with these polymorphisms taking clopidogrel.2

At least one genetic polymorphism leading to poor metabolism of clopidogrel has been reported to occur in 15% of Caucasians, 17% of African Americans and 30% of Asians.3 Since many patients take clopidogrel to protect against life-threatening events, and some continue to do so for extended periods of time, it might be worthwhile to test for these polymorphisms. Such tests, requiring small amounts of blood or saliva, are commercially available from clinical laboratories. More directly, patients who are taking clopidogrel could have platelet aggregation assays to determine whether the drug is being activated.

However, the best course of action for patients who prove to be poor metabolizers of clopidogrel is not clear. They could be treated with higher doses of clopidogrel, but the doses that would be safe and effective in such patients have not been established. Alternatively, they could be treated with prasugrel (Effient), a similar antiplatelet drug that does not require CYP2C19 for activation, instead of clopidogrel, but prasugrel has a greater effect on platelets and may cause more bleeding.4

1. Antiplatelet and anticoagulant drugs. Treat Guidel Med Lett 2008; 6:29.
2. PPI interactions with clopidogrel revisited. Med Lett Drugs Ther 2009; 51:13.
3. Z Desta et al. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 2002; 41:913.
4. Prasugrel (Effient) vs. clopidogrel (Plavix). Med Lett Drugs Ther 2009; 51:69.

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Drugs are not the only treatment for mood disorders. Psychotherapy remains an important component in the management of these disorders, and electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective, poorly tolerated or cannot be used. Some drugs are recommended here for indications that have not been approved by the FDA.

The drugs of choice for treatment of some fungal infections are listed. Some of the indications and dosages recommended here have not been approved by the FDA. More detailed guidelines are available online from the Infectious Diseases Society of America (www.idsociety.org).

The FDA has approved prasugrel (Effient - Lilly/Daiichi Sankyo), an oral antiplatelet drug, for use with aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS) being managed with percutaneous coronary intervention (PCI). It will compete with clopidogrel (Plavix) for such use.

The FDA has approved lacosamide (Vimpat - UCB Pharma) for oral or intravenous (IV) use as add-on therapy in adults with partial-onset seizures.

The FDA has approved the proton-pump inhibitor (PPI) dexlansoprazole (Kapidex - Takeda), a delayed release formulation of the R-enantiomer of lansoprazole (Prevacid - Takeda), for treating and maintaining healing of erosive esophagitis and for treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD).

Current guidelines recommend use of a proton pump inhibitor (PPI) to decrease the risk of gastrointestinal bleeding in patients taking clopidogrel (Plavix) with aspirin. A recent issue of The Medical Letter considered whether omeprazole (Prilosec, and others) or other PPIs could interfere with the antiplatelet effect of clopidogrel. The conclusion was that patients taking both drugs should probably continue to do so until more data became available. Several new publications require reconsideration of that recommendation.

Clopidogrel (Plavix), which prevents arterial thrombosis by inhibiting platelet activation, is commonly prescribed (usually with aspirin) for months after acute coronary syndromes and stent implantation. It may also, however, increase the risk of bleeding. Therefore, a proton pump inhibitor (PPI) such as omeprazole (Prilosec, and others) is often given concurrently to decrease the risk of gastrointestinal (GI) bleeding. Some reports have suggested that omeprazole may interfere with the antiplatelet effect of clopidogrel.

Fluvoxamine maleate, a selective serotonin reuptake inhibitor (SSRI) that has been available for many years in an immediate-release formulation (Luvox, and others) for treatment of obsessive-compulsive disorder (OCD) in children and adults, has now been approved by the FDA in an extended-release formulation (Luvox CR - Jazz Pharmaceuticals) for treatment of OCD and social anxiety disorder (SAD) in adults.

Etravirine (Intelence - Tibotec), a new non-nucleoside reverse transcriptase inhibitor (NNRTI), has received fast-track FDA approval for use in combination therapy in treatment-experienced adults who have HIV-1 infection resistant to an NNRTI and other antiretroviral agents.

The FDA recently cleared the AmpliChip CYP450 Test (Roche), which analyzes blood-derived DNA to detect genetic variations in the activity of cytochrome P450 (CYP) enzymes CYP2D6 and CYP2C19 and determines the metabolizer status of the patient. The test is intended to help guide clinicians in prescribing individualized drug therapy. About 25% of all drugs, including many antidepressants and antipsychotics, are substrates of either CYP2D6 or CYP2C19. The test is being promoted initially to psychiatrists.