February 2000
WILMINGTON, Mass. - The Food and Drug Administration (FDA) recently approved trimethoprim HCI oral solution (Primsol Solution, Ascent Pediatrics) for the treatment of acute otitis media in children ages 6 months to 12 years due to susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae.
A clinical study of 262 children, the majority age 6 months to 4 years, showed no significant difference in efficacy between trimethoprim alone and the combination trimethoprim and sulfamethoxazole (90% vs. 91%) but showed a difference in the most common side effect of skin rash (1.3% vs. 6.1%). Other side effects with trimethoprim were diarrhea (4%), vomiting (2%) and abdominal pain (1%).
Trimethoprim had a clinical cure rate of 60% and clinical improvement rate of 30% after five days posttreatment. Twenty days posttreatment it showed a clinical success rate of 71%, with a cure rate of 50% and an improvement rate of 21% - clinically equivalent to the drug combination.
The dosing schedule is 10 mg/kg/day with a maximum dosage of 400 mg, in two divided doses for 10 days.
"Trimethoprim alone acts in the same way as when it's combined with a sulfa drug. It's still active against the folic acid metabolism pathways and bacteria. The majority of the activity of the combination drug is due to trimethoprim. It's clearly the more active of the two compounds," said Edward O'Rourke, MD, medical director of infection control, Children's Hospital, Boston, and assistant professor of pediatrics at Harvard University.
Sulfa side effects are more serious than typical side effects seen with penicillin, according to O'Rourke. Sulfa can produce Stevens Johnson syndrome, a potentially lethal erythema that can result in serious rashes and sloughing of the skin. "Side effects with sulfa are not so frequent that they would cause you to stop using combination trimethoprim and sulfamethoxazole, but if you have the option of using a drug with almost the identical activity and fewer side effects, it would seem a reasonable trade off," said O'Rourke, who noted trimethoprim can also be used as second-line drug to amoxicillin.
"The greatest problem in pediatric medicine is compliance," said Emmett Clemente, Ph.D., president and chairman of Ascent Pediatrics. "In this case we reduced the toxicity, maintained the efficacy and have a safer product."
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