麻豆传媒

Trimethoprim-sulfamethoxazole -- a widely used antibiotic sold as Septra, Bactrim, and others -- has a set of adverse reactions that range from minor to potentially fatal, according to a literature review.

The drug was introduced in 1968 and is popular because it's cheap, effective and familiar, according to Joanne Ho, MD, and David Juurlink, MD, PhD, both of the University of Toronto.

Although the drug is usually well tolerated, it is "associated with several potentially serious adverse reactions," Ho and Juurlink reported online in CMAJ.

"Clinicians should be cognizant of the potential consequences of prescribing trimethoprim-sulfamethoxazole, monitor patients for adverse events during therapy, or use an alternate antibiotic when appropriate," they concluded.

On the other hand, trimethoprim-sulfamethoxazole "has been an incredibly useful workhorse antibiotic for decades" and its limitations are well known, according to Brad Spellberg, MD, an expert on antibiotic issues at the University of California Los Angeles.

The compound, "is inexpensive, gets into all body tissues well, and is very effective at treating many types of infections," Spellberg told 麻豆传媒 in an email.

And the adverse events are relatively rare, he added. "I have treated many, many patients extremely safely and effectively with this drug, as have tens of thousands of physicians for many decades."

To pin down the adverse reactions, Ho and Juurlink conducted a search of medical literature from 1950 to 2011, eventually winnowing more than 900 citations down to 70 articles, including case reports, volunteer studies, observational studies, and randomized trials, that shone light on possible safety issues.

The most common adverse effects, they found, are rashes and fixed drug eruptions, drug-drug interactions, and hyperkalemia.

The rashes and fixed drug eruptions occur in about 3% of patients, the researchers reported, and are some of the most common adverse effects of the drug.

Some drug-drug interactions occur because trimethoprim-sulfamethoxazole affects two isoforms of the cytochrome P450 enzyme system, and may reduce or enhance the effects of other drugs that are metabolized by the enzymes, including oral hypoglycemic agents and warfarin.

For instance, trimethoprim-sulfamethoxazole increases levels of sulfonylureas, leading to an increased release of insulin and hypoglycemia. As well, taking the drug with warfarin leads to increased risk of gastrointestinal hemorrhage compared with other antibiotics.

Trimethoprim-sulfamethoxazole also affects renal clearance of several drugs, including methotrexate.

Excess of potassium is a "predictable and potentially fatal adverse effect of treatment with trimethoprim-sulfamethoxazole," the researchers argued, noting that in a randomized trial, 6% of patients experienced hyperkalemia -- defined as serum potassium greater than 5.5 mmol/L -- and 81.5% had an increase in serum potassium.

The hyperkalemia takes several days to build up, and risk factors include diabetes, renal insufficiency, older age, AIDS, and drugs that inhibit excretion of potassium, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, they reported.

Uncommon and rare adverse reactions include:

• Neurologic events, including aseptic meningitis, delirium, tremor, and gait disturbances
• Decreased oxygen- carrying capacity and other hematologic abnormalities, including methemoglobinemia and blood dyscrasia
• Drug hypersensitivity, with fever, rash and internal organ involvement. The fever can fool clinicians into thinking they are dealing with infection.
• Reproductive toxicity, including such effects as hyperbilirubinemia, small-for-gestational-age babies, and structural malformations
• Kidney effects, such as acute interstitial nephritis, obstructive tubulopathy, and hyponatremia

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