Generally, well tolerated in patients without HIV (ADR rate: 6-8%)
In patients with HIV, ADRs are common and severe (ADR rate: 25-50%)
Gastritis (PO and IV)
- sx: nausea, vomiting, and diarrhea
- common
Skin toxicity (PO and IV)
- common sx: rash (3-7% with doses of 200mg/day) and pruritus
- uncommon sx: mucosal membrane ulceration, erythema, scaling and skin detachment
- may involve SJS, exfoliative dermatitis and toxic epidermal necrolysis
Nephrotoxicity (mainly with IV)
- uncommon
- TMP decreases tubular secretion of creatinine, leading to increase in SCr that is not reflective of a true GFR reduction
- may include renal tubular acidosis
- usually reversible
- some patients may experience prolonged recovery after discontinuation
Hyperkalemia (mainly with IV)
- caused by blockade of collecting tubule sodium channel by TMP
- more common in patients with HIV treated with high doses
- modest elevation in plasma potassium concentration can occur in patients without HIV with normal doses
- increased 7-day risk of sudden death in older patients receiving TMP-SMX and spironolactone, ACE inhibitor or ARB
Folate deficiency (mainly with IV)
- use with caution in patients with folate deficiency or at risk for complications of folate deficiency (pregnancy, chronic hemolytic anemia)
- TMP weakly inhibits human dihydrofolate reductase and reduces folate available for hematopoiesis
- may cause megaloblastic changes (macrocytic anemia, mild thrombocytopenia, leukopenia) when given over long periods or in high doses
- treatment: folic acid supplementation (except in patients with AIDS and Pneumocystis pneumonia)
Other
- hyponatremia
- hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency
- neutropenia