Dangers of Pharmacy Compounding: 1000-fold Overdose of Clonidine (CATAPRES) Used in a Child for Attention Deficit/Hyperactivity Disorder (ADHD)

Physicians at Texas Tech University’s Health Sciences Center in Lubbock reported, in the August issue of the journal Pediatrics, the case of a five-year-old boy who received a massive overdose of the high blood pressure lowering drug clonidine (CATAPRES) that was being used to treat Attention Deficit/Hyperactivity Disorder (ADHD). Thankfully, he survived.

On the day that he was admitted to the hospital, his parents had refilled his clonidine prescription. His father noted that the new refill looked and tasted different from previous prescriptions. Twenty minutes after the boy received his first dose from the new bottle he went limp and was unresponsive. He was rushed to the emergency room and was admitted to pediatric intensive care. The child was discharged 42 hours after the overdose without complications.

Clonidine is available only as tablets and transdermal patches both in dosages that are unsuitable for children. In a situation where a child cannot take a tablet, a pharmacist may make a liquid preparation from tablets or from bulk powder. This practice is known as “pharmacy compounding” and introduces an additional possibility for error.

In this case, the prescription called for a dosage of 0.05 milligrams of clonidine per 5 milliliters (approximately one teaspoon). When the new refill was analyzed, the concentration was found to be 9.78 milligrams of clonidine per milliliter or 48.9 milligrams per 5 milliliters—approximately 1000 times stronger than the prescription called for. This was clearly an inexcusable error by the pharmacist who prepared the medication.

But this was not the only important error, nor was the pharmacist the only culprit. Clonidine is approved by the Food and Drug Administration (FDA) only for the treatment of high blood pressure. The manufacturer of clonidine (Boehringer-Ingelheim Pharmaceuticals of Ridgefield, Connecticut) has not submitted FDA-required studies that prove that the drug is safe for the treatment of ADHD in children. Such an unapproved use, while not illegal, is referred to as “off-label.”

A relatively small number of drugs have been tested and subsequently approved by the FDA for use in children. Consequently, much of the prescribing for children is for uses that are off-label. However, this case is somewhat different. The child was not receiving the clonidine for a use approved for adults.

The evidence that clonidine is safe and effective for ADHD is, at best, weak. The editors of The Medical Letter on Drugs and Therapeutics, a source known for its independence and objectivity, reported in their December 6, 1996 issue that:

“Clonidine might be effective in the treatment of some children with ADHD, particularly those with sleep disturbances or tics, but controlled trials in adequate numbers of children have not been published, and its safety is worrisome.”

There is very little oversight either by the FDA or state regulatory boards over pharmacy compounding. We have frequently warned about serious problems, including quackery, that have arisen when pharmacists have engaged in the small scale manufacture of drugs under the pretense of pharmacy compounding (see the November 1998, March 2000, and August 2001 issues of Worst Pills, Best Pills News).

There are some rare circumstances when pharmacy compounding is necessary. However, even when the reason is legitimate, an additional possibility for error is introduced. And the errors, unlike those in the case of the Texas five-year-old, do not always have a happy outcome.

What You Can Do

If your child’s physician prescribes a pharmacy-compounded drug, ask if the drug is approved for the same condition in adults. Be sure the doctor explains the risks and possible benefits of using the drug in children.

You should be skeptical of pharmacists that specialize in compounding. They may pressure parents to accept a compounded drug when one is not necessary.

If a compounded prescription is required, ask that the pharmacist, and not a less well-trained technician, prepare the prescription.