The prescribing information for doxycycline, clindamycin and caffeine citrate has been updated to include new recommended usage and dosage for pediatric patients, according to research funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH).

The updated labeling for doxycycline, a tetracycline antibiotic, applies to the oral and intravenous (IV) formulations, with recommendations for weight-based dosing for severe or life-threatening infections (eg anthrax, Rocky Mountain spotted fever) in patients aged 2 to 8 years with no alternative options. 

The revised label is based on data from a pharmacokinetic study of doxycycline in 47 patients aged less than 21 years. The use of doxycycline in pediatric patients ≤8 years of age may be considered when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions, particularly when there are no alternative therapies.

Clindamycin is a lincosamide antibiotic indicated for the treatment of susceptible infections, including respiratory, skin and soft tissue, septicemia, intraabdominal, female pelvic or genital, and bone and joint infections. The updated labeling applies to the oral and IV formulations of clindamycin with new recommendations for weight-based dosing. 

The revised label is based on data from a prospective, open-label, pharmacokinetic study of oral and IV clindamycin in 23 patients aged 2 to <18 years with BMI ≥85th percentile for age and sex based on the Centers for Disease Control and Prevention (CDC) recommendations. Findings showed that clindamycin was well tolerated with 3 reported adverse events that were considered unrelated to the study drug. Additionally, the study determined that clindamycin dosing may be based on total body weight (max dose 2.7g/day) without adjustment based solely on obesity. 

Caffeine citrate is indicated for the short-term treatment of apnea of prematurity in infants. The updated labeling now indicates that the drug may safely be administered with a higher dose and longer duration to infants born earlier than 28 weeks. Previously, caffeine citrate was only approved for infants born 28 to less than 33 weeks gestational age, and was commonly used off-label to treat infants less than 28 weeks. 

The revised label is supported by results from a phase 3 study that compared respiratory morbidity (primary end point) with caffeine citrate to placebo in infants weighing 500 to 1250 grams with a mean gestational age of 27 weeks. Patients received caffeine citrate for a mean duration of 37 days. Results showed no increased risk of death, ultrasonographic signs of brain injury, or necrotizing enterocolitis in the caffeine citrate group vs placebo prior to discharge home. Moreover, at both 18 months and 5 years follow-up, death was not more common with caffeine citrate vs placebo, and caffeine citrate did not adversely affect neurodevelopmental outcomes. The updated labeling is also supported by data from the PROP study.

Related Articles

“Doctors routinely make off-label drug decisions when treating infants and children because many drugs do not have pediatric safety or dosage recommendations,” said Perdita Taylor-Zapata, MD, program lead for the Best Pharmaceuticals for Children Act (BPCA) at NICHD. “The BPCA program supports research to improve the information on labels so that healthcare providers have clear guidance on how to prescribe drugs for their youngest patients.”

For more information visit nih.gov.