In this new regular series, we’ll take a closer look at some of the drugs we use frequently in the ED. We aim to capture new indications for old standbys, or risks and dosing adjustments you should know, plus some unusual facts you might enjoy.
Major indications: UTIs, skin and soft tissue infections, MRSA, PCP pneumonia, acute otitis media. Usual adult dose is 160 mg TMP/800 mg SMX 1-2 tabs BID
In the news: systematic review of adverse reactions – rare and severe (CMAJ 2011, 183;16 p1851-8)
How it works: Sulfamethoxazole and trimethoprim are both competitive antagonists of bacterial enzymes in the folic acid synthesis pathway. Bacteriostatic – it inhibits bacterial multiplication, does not kill bacteria. Excreted renally.
Cross-reactivity: The chemical moiety responsible for allergic responses is present in sulfamethoxazole and other sulfonamide antibiotics such as sulfasalazine, sulfadiazine and in anti-retrovirals amprenavir and fosamprenavir. Bactrim should be avoided in patients with allergic reactions to these medications as there is true cross-reactivity. The chemical structure of non-antibiotic sulfonamide medications such as HCTZ, furosemide and bumetanide, sulfonylureas (glipizide), celecoxib, acetazolamide, tamsulosin (Flomax), sumatriptan, sotalol— is different, and is unlikely to have cross-reactivity with Bactrim (Pharmacotherapy 2004 24;7 p856-870).
Notable History: Sulfanilamide was synthesized in 1906 and used in the dye industry. Patented in 1932. In 1930s massive manufacturing led to poisonings from dietheylene glycol additive, leading to organization of the US FDA. Controlled manufacturing allowed its use in WWII against life-threatening infections.
Dose adjustments: For renal disease use 50% of recommended dose if creatinine clearance (CrCl) is 15-30mL/min. Do not use if CrCl <15mL/min. — common cause of hyperkalemia in patients with renal insufficiency, diabetes, elderly, or HIV.
Liver disease: No change, but avoid in severe liver failure.
- Avoid with warfarin – raises INR
- Use caution with oral hypoglycemic – can cause hypoglycemia
- Use caution with NSAIDs, ARBs, Spronolactone – can cause hyperkalmia
- Pregnancy: Class D - lowers folate just when neural tube formation needs it
- Lactation: Avoid if breastfeeding infant < 1 month old and in pre-term, unhealthy, or hyperbilirubinemic infant (according to the WHO: http://www.who.int/maternal_child_adolescent/documents/55732/en/).
- Pediatrics: Avoid if ≤ 2 month old
- G-6-PD deficiency – causes dose-related hemolysis
Cost: Generic form is $4 for regular, DS tablets, or suspension at Walmart or Target, and $5-10 at Walgreens