Table S1.
Summary of potential drug–gene and drug–drug interactions in Case #1
| Impact | Action | Mechanism | |
|---|---|---|---|
| Drug–gene interactions | |||
| Atorvastatin calcium and CYP3A4/CYP3A5 | Major | Consider dose reduction | CYP3A4/3A5 poor metabolizer status may lead to decreased metabolism of atorvastatin |
| Fluticasone/salmeterol and CYP3A4/CYP3A5 | Major | Monitor therapy | CYP3A4/3A5 poor metabolizer status may result in decreased metabolism of fluticasone/salmeterol |
| Lidocaine/prilocaine and CYP3A4/CYP3A5 | Major | Monitor therapy | Poor metabolizer status may result in decreased metabolism of CYP3A4/CYP3A5 substrates (lidocaine) |
| Losartan/hydrochlorothiazide and CYP3A4/CYP3A5 | Moderate | Monitor therapy | Poor metabolizer status may result in decreased metabolism of CYP3A4/CYP3A5 substrates (losartan) |
| Montelukast sodium and CYP3A4/CYP3A5 | Major | Monitor therapy | CYP3A4/3A5 poor metabolizer may cause decreased metabolism of montelukast |
| Prednisone and CYP3A4/CYP3A5 | Moderate | Monitor therapy | Due to CYP3A4/3A5 poor metabolizer status, less prednisone (inactive) may be converted to prednisolone (active form) |
| Roflumilast and CYP3A4/CYP3A5 | Moderate | Monitor therapy | CYP3A4/3A5 poor metabolizer status may result in increased exposure to roflumilast |
| Drug–drug interactions based on CYP450 metabolism | |||
| Primidone and roflumilast | Major | Avoid combination | CYP3A4 inducers (primidone) may decrease the serum concentration of roflumilast |
| Atorvastatin calcium and primidone | Major | Consider modification | CYP3A4 inducers (primidone) may increase the metabolism of CYP3A4 substrates |
| Losartan/hydrochlorothiazide and primidone | Major | Consider modification | CYP3A4 inducers (primidone) may increase the metabolism of CYP3A4 substrates |
| Diclofenac potassium and primidone | Moderate | Monitor therapy | CYP2C9 inducers (primidone) may decrease the serum concentration of diclofenac |
| Prednisone and primidone | Moderate | Monitor therapy | CYP3A4 inducers (primidone) may decrease the serum concentration of prednisone |
| Non-CYP450 drug–drug interactions | |||
| Meclizine HCl and tiotropium bromide | Major | Avoid combination | Anticholinergic agents may enhance the anticholinergic effect of tiotropium |
| Nortriptyline HCl and tiotropium bromide | Major | Avoid combination | Anticholinergic agents may enhance the anticholinergic effect of tiotropium |
| Oxybutynin chloride and tiotropium bromide | Major | Avoid combination | Anticholinergic agents may enhance the anticholinergic effect of tiotropium |
| Aspirin and diclofenac potassium | Major | Consider modification | An increased risk of bleeding may be associated with use of this combination |
| Clonidine HCl and metoprolol succinate | Major | Consider modification | Alpha2-agonists may enhance the atrioventricular-blocking effect of beta-blockers. Beta-blockers may enhance the rebound hypertensive effect of alpha2-agonists |
| Clonidine HCl and nortriptyline HCl | Moderate | Consider modification | Tricyclic antidepressants may diminish the antihypertensive effect of alpha2-agonists |
| Diclofenac potassium and furosemide | Moderate | Consider modification | Nonsteroidal anti-inflammatory agents may diminish the diuretic effect of loop diuretics |
| Metoclopramide HCl and nortriptyline HCl | Major | Consider modification | Metoclopramide may enhance the adverse/toxic effect of tricyclic antidepressants |
| Prednisone and roflumilast | Major | Consider modification | Roflumilast may enhance the immunosuppressive effect of prednisone |
| Meclizine HCl and oxybutynin chloride | Moderate | Monitor therapy | Anticholinergic agents may enhance the adverse/toxic effect of other anticholinergic agents |
| Nortriptyline HCl and oxybutynin chloride | Moderate | Monitor therapy | Anticholinergic agents may enhance the adverse/toxic effect of other anticholinergic agents |