Crushing Kaletra (lopinavir/ritonavir) tablets to make the medication easier to take by children should be avoided, according to a new paper published ahead of print by the Journal of Acquired Immune Deficiency Syndromes.

Kaletra is widely recommended as a first-line treatment option for infants, children and adolescents living with HIV.

Unfortunately, the tablet version of Kaletra—used by most adults living with HIV—is a common barrier to pediatric antiretroviral therapy. Swallowing tablets can be challenging in school-aged children and adolescents, and it may represent a choking hazard in younger pediatric patients. “Children under 7 years of age,” writes Brookie Best, PharmD, of the University of California at San Diego, and her colleagues, “are frequently unable to swallow even smaller tablets.”

A liquid version of the drug is available. However, according to the authors, “[t]he liquid formulation has an extremely unpleasant taste with a high content (42 percent) of alcohol, creating the potential for significant alcohol toxicity with overdose, especially in infants.” It must also be taken with food and requires refrigeration, which limits its use in resource-poor settings.

When the liquid formulation isn’t feasible and pill-swallowing difficulties arise, Best and her colleagues note, caregivers often consider dosing children with broken or crushed tablets.

This practice comes with risks, however. Breaking or crushing tablets may result in too little drug passing into the bloodstream, potentially increasing the risk of drug resistance and treatment failure. But until now, no studies involving human subjects have been conducted to assess this risk.

The study conducted by Best and her colleagues evaluated 12 children living with HIV, ages 10 to 16 years old, who had drug levels checked seven times during a 12-hour period after taking either a Kaletra tablet or one that had be crushed by a pharmacist. 

Among the youth who took a crushed tablet, lopinavir levels—determined using a measurement called area under the curve (AUC)—were 45 percent below those achieved using the intact tablets. Similarly, their ritonavir levels were 47 percent below what they should have been. 

The researchers noted, however, that the magnitude of the blood level reductions after taking crushed Kaletra “was highly variable and unpredictable between subjects, ranging from 5 to 75 percent reduction in AUC.”

“Increased doses and therapeutic drug monitoring are needed to ensure adequate Kaletra exposure in patients requiring crushed Kaletra tablets,” the authors conclude. “The reduced exposure with crushed Kaletra tablet dosing reinforces the need to discourage this dosing practice.”