Why Test Your Patients?

Adverse drug reactions (ADRs) are a serious public health issue.

  • Serious ADRs occur in an estimated 6.7% of hospitalizations in the U.S. and rank as the fourth to sixth leading cause of death.1
  • Only an estimated 25%-60% of people respond in the expected way to most currently prescribed drugs.2 

All factors influencing pharmacologic response are likely under some degree of genetic control. Testing for genetic variants that are known to influence drug response will allow the clinician to select the best drug and dose from the start – avoiding some of the trial-and-error traditionally required.

Altered drug metabolism contributes significantly to drug response variability. Phase I drug metabolism is primarily performed by the cytochrome P450 enzyme family. Genetic variants in these CYP450 genes have been shown to both significantly reduce or increase enzyme activity, and therefore drug metabolism rates and response.

The CYP2C9, CYP2C19, and CYP2D6 genes are involved in metabolizing a significant percentage of currently prescribed drugs, and variants that impact their action are quite common.  Therefore, testing for a panel of genetic variants in these genes is now clinically available and allows a personalized prediction of response to a broad variety of drugs.

Enzyme% Drugs Metabolized By This Enzyme3Examples of Metabolized Drugs4
2D625%
  • Beta Blockers: S-metoprolol, propafenone, and timolol.
  • Antidepressants: many of the most commonly prescribed including paroxetine, venlafaxine, amitriptyline, duloxetine, and imipramine.
  • Antipsychotics: haloperidol, risperidone, and thioridazine.
  • Other examples: codeine, tamoxifen, dextromethorphan, and ondansetron.
2C95%
  • NSAIDs: such as celecoxib, naproxen, and ibuprofen.
  • Oral hypoglycemics: tolbutamide and glipizide.
  • Angiotensin II blockers: irbesartan and losartan.
  • Other examples: warfarin, phenytoin, fluvastatin, and sulfamethoxazole.
2C1915%
  • Proton pump inhibitors such as omeprazole, lansoprazole, pantoprazole, and rabeprazole.
  • Anticonvulsants: diazepam and phenytoin.
  • Other examples: amitriptyline, clomipramine, clopidogrel, and progesterone.
1. Lazarou J, Pomeranz B, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 1998;279:1200–1205.
2. Wijnen PA, Op den Buijsch RA, Drent M, et al. The prevalence and clinical relevance of cytochrome P450 polymorphisms. Aliment Pharmacol Ther. 2007;26 Suppl 2:211-9.
3. Blue Cross Blue Shield Association. Special Report Genotyping for CYP450 polymorphisms to determine drug metabolizer status. Technology Assessment Program. 2004;19(9).
4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table [Clinically Relevant Table]. Indiana University School of Medicine (2007). Available at: http://medicine.iupui.edu/flockhart/clinlist.htm. Accessed July 23, 2008.
this page last updated: August 29, 2008