What are the potential drug interactions with Levactrim (sulfamethoxazole and trimethoprim)?

Potential Drug Interactions with Levactrim (Sulfamethoxazole-Trimethoprim)

Levactrim (sulfamethoxazole-trimethoprim) has numerous significant drug interactions that can increase the risk of serious adverse events, particularly in older adults, patients with renal impairment, and those taking multiple medications. 1, 2

Major Drug Interactions

Cardiovascular Medications

• ACE inhibitors/ARBs: Increased risk of hyperkalemia, especially in patients with reduced kidney function 3
• Digoxin: Increased digoxin blood levels, particularly in elderly patients, requiring monitoring of serum digoxin levels 1, 2
• Warfarin: Increased risk of bleeding due to prolonged prothrombin time and INR; requires close monitoring 1, 2

Antiepileptic Medications

• Phenytoin: Inhibits hepatic metabolism leading to increased phenytoin half-life (39% increase) and decreased clearance (27% decrease); monitor for phenytoin toxicity 1, 2

Immunosuppressants and Chemotherapeutics

• Methotrexate: Displacement from plasma protein binding sites and competition for renal transport, leading to increased free methotrexate concentrations; concurrent use should be avoided 1, 2
• Cyclosporine: Reports of marked but reversible nephrotoxicity; concurrent use should be avoided 1, 2

Hypoglycemic Agents

• Oral hypoglycemics: Potentiates the effect of oral hypoglycemic agents metabolized by CYP2C8 (pioglitazone, repaglinide, rosiglitazone) or CYP2C9 (glipizide, glyburide); requires blood glucose monitoring 1

Diuretics

• Thiazide diuretics: Increased incidence of thrombocytopenia with purpura in elderly patients; concurrent use should be avoided 1, 2

Other Significant Interactions

• Amantadine: Risk of toxic delirium; avoid concurrent use 1, 2
• Tricyclic antidepressants: Decreased efficacy of TCAs; monitor therapeutic response 1, 2
• Indomethacin and other NSAIDs: Increased sulfamethoxazole blood levels 1, 2
• Pyrimethamine: Risk of megaloblastic anemia when pyrimethamine exceeds 25mg weekly 1, 2
• Zidovudine: Additive myelotoxicity; monitor for hematologic toxicity 1

Special Populations at Risk

Older Adults

• Beers Criteria identifies TMP-SMX as a medication requiring caution in older adults, particularly when combined with ACE inhibitors or ARBs due to hyperkalemia risk 3
• Higher incidence of severe adverse events in elderly patients 3

Patients with Renal Impairment

• Dosage adjustment required for creatinine clearance <30 mL/min 4
• Increased risk of crystalluria and nephrotoxicity; adequate fluid intake should be maintained 1, 2

Pregnant and Nursing Women

• Contraindicated in pregnant women near term, nursing mothers, and infants <2 months due to risk of kernicterus 3
• Classified as Pregnancy Category C 3

Monitoring Recommendations

• Complete blood counts: Monitor frequently to detect blood dyscrasias 1, 2
• Renal function: Perform urinalysis and renal function tests during therapy, particularly in patients with impaired renal function 1
• Electrolytes: Monitor for hyperkalemia, especially when combined with ACE inhibitors or ARBs 3
• Prothrombin time/INR: Monitor when co-administered with warfarin 1, 2
• Blood glucose: More frequent monitoring when used with oral hypoglycemic agents 1

Clinical Considerations

• TMP-SMX inhibits multiple cytochrome P450 enzymes: trimethoprim inhibits CYP2C8 and OCT2 transporter, while sulfamethoxazole inhibits CYP2C9 1
• Adequate fluid intake should be maintained to prevent crystalluria and stone formation 1, 2
• Patients should be monitored for signs of blood dyscrasias, skin reactions, and other hypersensitivity reactions 3, 1

Severe Adverse Reactions

• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis 3, 1
• Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, and other blood dyscrasias 3, 1
• Hepatic: Fulminant hepatic necrosis 3, 1
• Renal: Interstitial nephritis, toxic nephrosis 3, 1
• Metabolic: Hyperkalemia, hyponatremia 3, 1

Remember that drug interactions with Levactrim can be complex and potentially life-threatening. Always review a patient's complete medication list before prescribing and monitor appropriately during treatment.