21 February 2023: Articles
Pharmacogenetic Testing in a 70-Year-Old Woman with Polypharmacy and Multiple Comorbidities: A Case Report
Unknown etiology, Adverse events of drug therapy
Jayson P. Jessop A , Joshua Russell A , Adriana DeJesus A , Chandni Bardolia A , Abeer Hanna B , Jacques Turgeon A* , Veronique Michaud A , Nishita S. Amin ADOI: 10.12659/AJCR.938850
Am J Case Rep 2023; 24:e938850
Table 2. Recommendations made by pharmacists over the course of care.
| Therapy | Recommendation | Rational | Status |
|---|---|---|---|
| Atorvastatin 20 mg | Change to pravastatin 40 mg | Increased risk of ADEs (eg, myalgia) with atorvastatin due to diltiazem-induced competitive inhibition of CYP3A4 | Accepted |
| Diltiazem 120 mg | Discontinue therapy | Therapy duplication with both carvedilol and diltiazem, resulting in increased risk of bradycardia and/or orthostatic hypotension | Rejected |
| Ezetimibe 10 mg | Discontinue therapy | Increased risk of myalgia with non-optimized statin therapy and a general concern of increased pill burden with a lack of therapeutic benefit | Accepted |
| Fluoxetine 20 mg | Change to citalopram 10 mg | Increased risk of orthostatic hypotension and/or bradycardia due to fluoxetine-induced competitive inhibition of CYP2D6 (with carvedilol) and increased risk of ADEs (eg, bone fractures, GI inflammation, and hypomagnesemia) due to noncompetitive inhibition of CYP2C19 (with lansoprazole). Additionally, greater than 8 weeks of fluoxetine therapy has not resulted in major improvements | Accepted |
| Lansoprazole 30 mg | Change time of administration to bedtime | Decreased therapeutic benefit from levothyroxine due to lansoprazole-impaired absorption. | Accepted |
| Lorazepam 0.5 mg | Discontinue therapy if used infrequently | Patients who are 65 years or older are more likely to experience significant sedative and CNS effects with benzodiazepines | Rejected |
| Therapy | Recommendation | Rational | Status |
| Carvedilol 12.5 mg | Monitor symptoms and adjust dose as necessary | Increased risk for ADEs due to the presence of a DGI (CYP2D6 intermediate metabolizer) | Accepted |
| Lansoprazole 30 mg | Discontinue therapy or switch to an H2-receptor antagonist | Increased risk of ADEs associated with long-term use of PPIs (e.g., bone loss, fractures, C. difficile infections, and gastritis). The patient is on long-term antibiotics for bacteremia/endocarditis, increasing the risk factors for C. diff infections | Rejected |
| Pravastatin 40 mg | Reduce dose to 20 mg | Increased risk for ADEs due to the presence of a DGI (SLCO1B1 decreased function). CPIC guidance notes typical myopathy risk with doses ≤40 mg and possible increased risk for myopathy with pravastatin especially with doses >40 mg. Participant is currently on 40 mg/day and noted muscle weakness and stiffness during participant counseling call | Rejected |
| Warfarin | Use frequent INR assessments to guide dose adjustments of warfarin | Increased sensitivity to warfarin and potential ADEs due to the presence of DGIs (CYP2C9 intermediate metabolizer, VKORC1 low activity, CYP4F2 reduced activity). Closely monitor for ADEs (eg, increased INR, bleeding) | Accepted |
| Additional therapy: ACEi | Start lisinopril 2.5 mg | General renal benefits in participants with type II DM | Accepted |
| ACEi – angiotensin converting enzyme inhibitor; ADE – adverse drug event; CPIC – Clinical Pharmacogenetics Implementation Consortium; CNS – central nervous system; DGI – drug–gene interaction; DM – diabetes mellitus; INR – international normalization ratio; PPI – proton pump inhibitors. | |||