The U.S. Food and Drug Administration announced yesterday that it had approved changes to the prescribing information for Kaletra oral solution to warn of possible toxicities in newborns and risk of overdose in newborns and young children.

The Food and Drug Administration (FDA) now recommends that Kaletra (lopinavir/ritonavir) oral solution not be given to newborns until at least 42 weeks from the date of the mother’s last period and 14 days after birth. In addition, the FDA urged medical providers to be especially careful not to overdose babies and young children due to the risk of fatal toxicity.

The FDA notes that if treating a newborn with Kaletra oral solution immediately after birth outweighs the risks, medical providers should carefully monitor the baby for increases in serum osmolality (a blood measurement that indicates the amount of chemicals dissolved in the blood) and serum creatinine (an indication of kidney function).

Babies should also be monitored for problems with the central nervous system (including coma or stupor), seizures, muscle weakness, and heart problems.

Kaletra is a protease inhibitor made by Abbott Laboratories; the oral solution form is currently considered a preferred treatment option for babies and children with HIV (see related AIDS Beacon news). Recent studies have shown that Kaletra may be more effective in children than Viramune (nevirapine), another preferred treatment (see related AIDS Beacon news).

Earlier this month, however, the FDA announced that it had placed Kaletra oral solution on a drug safety watch list due to potential safety problems in newborns (see related AIDS Beacon news). Yesterday, the FDA formally approved changes in the Kaletra oral solution prescribing information to include new safety information for children.

The changes are a result of 10 reports of life-threatening illnesses, including one death, in babies less than four weeks old who received Kaletra oral solution. The death, from severe heart damage, resulted from an overdose of 10 times the recommended dose.

The reported illnesses included severe heart problems such as an abnormally slow heartbeat or heart block, a problem with electrical signals in the heart; lactic acidosis, in which lactic acid buildup causes the blood pH to drop; kidney failure; problems with the central nervous system; and breathing problems.

Most of the problems were reported in newborns that had been born prematurely.

The FDA notes that the problems are related not just to the drug itself, but to the presence of alcohol and a chemical called propylene glycol, which make up 42.4 percent and 15.3 percent of Kaletra oral solutions, respectively.

Newborns, especially premature newborns, may not be able to metabolize propylene glycol effectively, particularly when alcohol is also present. This can lead to high amounts of propylene glycol in the system, which can be toxic.

As a result, the FDA stated that medical providers should check the total amount of these chemicals in all medications given to children 14 days to 6 months of age to avoid accidentally giving them toxic doses.

In addition, the appropriate dosage of Kaletra oral solution should be calculated individually for each child, based on body weight or body surface area.

For more information, please see the FDA website.