1. Trimethoprim-Sulfamethoxazole.docx

TRIMETHOPRIM-SULFAMETHOXAZOLE Session Learning Objectives Explain the mechanism of action of trimethoprim-sulfamethoxazole (TMP-SMX) Describe the spectrum of activity of TMP-SMX Discuss the PK/PD of TMP-SMX Assess uses, adverse effects, and drug interactions of TMP-SMX Apply knowledge of TMP-SMX to...

TRIMETHOPRIM-SULFAMETHOXAZOLE Session Learning Objectives Explain the mechanism of action of trimethoprim-sulfamethoxazole (TMP-SMX) Describe the spectrum of activity of TMP-SMX Discuss the PK/PD of TMP-SMX Assess uses, adverse effects, and drug interactions of TMP-SMX Apply knowledge of TMP-SMX to a patient case Mechanism of Action Spectrum of Activity TMP-SMX Uses, Adverse Effects, and Interactions TMP-SMX Uses NIT Adverse Effects GI disturbances Elevated SCr Renal injury Electrolyte derangements Bone marrow suppression Cutaneous reactions GI Disturbances Manifests as nausea and vomiting Occurs in 20 – 50% of patients receiving doses > 15 mg/kg/day Can be given with food to assist with abatement of these symptoms Elevated SCr TMP-SMX inhibits organic cation secretory transporters in the renal proximal tubule Creatinine shares this same transporter TMP-SMX competes with creatinine for excretion Results in pseudo-elevation (18%) in creatinine without compromise in renal clearance Renal Injury Sulfa can cause crystalluria, neprholithiasis, and oliguria Sulfa can also result in interstitial nephritis Typically manifests as acute kidney injury Electrolyte Derangements Bone Marrow Suppression Issues with multiple blood lines Anemia Due to folate deficiency (think MOA) Megaloblastic anemia Thrombocytopenia and neutropenia More frequent with higher dose and chronic use Risk compounded with other myelosuppressive agents Methemoglobonemia with G6PD deficiency Cutaneous Reactions Rash and pruritis Typically delayed - 7 – 14 days after treatment Hypersensitivity reactions Tumor epidermal necrosis Stevens-Johnson syndrome More common in immunocompromised (HIV) Phototoxicity Apply sunscreen when knowingly exposed Drug Interactions Potassium increasing agents ACE inhibitors and ARBs Potassium sparing diuretics Potassium supplements Warfarin May increase INR Phenytoin May increase phenytoin concentrations Cyclosporine May increase cyclosporine concentrations