Tamoxifen is metabolized by CYP2D6 to active metabolites. CPIC guidelines recommend considering aromatase inhibitors rather than tamoxifen in patients who carry two no function alleles due to the reduced effectiveness of tamoxifen in these patients.

CYP2E1 is responsible for the majority of ethanol metabolism via the CYP system. While this theoretically could impact a patient’s ability to eliminate ethanol, remember that most ethanol is metabolized via the alcohol and aldehyde dehydrogenase pathway.

Efavirenz is metabolized by CYP2B6 into its inactive metabolites. In poor metabolizing patients, efavirenz can reach higher than normal plasma concentrations, putting the patient at risk for toxicity, particularly CNS effects such as disordered sleep, psychosis, and suicidal ideation.

There are over 1500 co-dominant polymorphic alleles for HLA-B, one of which is HLA-B*57:01. The FDA recommends pre-screening all HIV-positive, abacavir-naïve patients prior to beginning abacavir therapy because of the significant predictive relationship between the presence of HLA-B*57:01 and severe hypersensitivity reactions. This allele occurs in up to 20% of people of Southwest Asian descent and up to 7% of people of European descent. It is much less common in those of African and Asian descent.

Answer: C. Higher plasma concentrations and toxicity. It is widely known that codeine is a prodrug whose active metabolite, morphine, is created through CYP2D6. CYP2D6 ultrarapid metabolizers will convert codeine into morphine at a faster rate than the average patient, which could cause morphine to accumulate in the plasma, causing toxicity.

Answer – D. Primaquine, Rasburicase, and nitrofurantoin increase the risk of hemolysis in G6PD-deficient patients.

Answer – A. Hydrocodone is metabolized via CYP2D6 into hydromorphone which has analgesic effects. Loss of function gene variant will cause a patient to be unable to metabolize the hydrocodone to hydromorphone.

Answer – A. Irinotecan is converted in the body to an active metabolite known as SN-38, which is then inactivated and detoxified by a UDP-glucuronosyltransferase (UGT) enzyme encoded by the UGT1A1 gene. The risk of irinotecan toxicity increases with genetic variants associated with reduced UGT enzyme activity, such as UGT1A1*6/*6. Irinotecan can cause diarrhea and neutropenia.

Answer – Verapamil and diltiazem can both inhibit P-glycoprotein. This can impact many medications but in particular, can raise the concentration of some of the newer anticoagulants like apixaban and rivaroxaban.

Answer – Think of omeprazole with this question. Omeprazole is well known to interact with citalopram and this happens via CYP2C19 inhibition. CYP2C19 inhibition can raise the concentrations of citalopram and increase the risk of adverse effects and QTc prolongation.