Typically, there is substantial latitude concerning these clinical scenarios. The clinician may choose to avoid the drug combination altogether if there are suitable drug alternatives or if the disease being treated presents minimal risk to the patient. Alternatively, the clinician may choose one or several of the following options: (1) lower the drug dose—azathioprine and allopurinol, for which a 75% reduction of azathioprine dose is recommended, (2) monitor closely from a clinical standpoint—doxepin and an SSRI antidepressant such as paroxetine or fluoxetine, following the level of sedation closely, and/or (3) appropriate laboratory testing—can order an AM doxepin serum levels when the drug is administered with CYP 2D6 inhibitors such as paroxetine or fluoxetine. Concerning the doxepin/SSRI interaction described above, the clinician may choose to use an SSRI antidepressant alternative that does not inhibit the CYP 2D6 pathway (e.g., citalopram, escitalopram, or sertraline). From a proactive standpoint, baseline genetic testing of either the CYP 2D6 and CYP 2C19 polymorphisms are readily available. This genetic testing may determine in advance the rate of metabolism by the specific CYP isoform in that individual. Possibilities with genetic testing include the following (listed in descending order from the most rapid to the slowest rate of drug metabolism):
Some additional examples of the “proceed with caution” scenarios illustrating these therapeutic options are listed in Table 236-8.