Many drugs prescribed to children in general practice are either not licensed for use in children ("unlicensed") or are prescribed outside the terms of the product license ("off-label"). Most of these have never been tested on children and doctors have no way of knowing proper doses or even common side effects.

Although the medical community around the world has long known of the dangers involved in prescribing adult medications to children, three studies published in the British Medical Journal show that the practice is widespread and carries a high risk of adverse drug reactions.

In the first study, researchers in Germany found 13% of prescriptions for a group of children in primary care were off-label. The proportion of off-label prescriptions was highest for one- to two-year olds and included drugs for heart conditions, genitourinary disorders, and anti-inflammatory agents.

A second study by a team of Dutch researchers found that more than 22% of prescriptions for children up to 16 years of age were used off-label. Drug groups with the highest proportion of off-label use included oral contraceptives, and drugs for eye and skin conditions. They argue that many licensed drugs used by children in the community are poorly labeled for use in children, resulting in high rates of off-label use.

The risk of adverse drug reactions is high in these cases, since studies have never been done to determine safe doses for children, the third study indicated. The authors conclude that this situation is highly unsatisfactory, and efforts should be made to improve it.

The group of researchers from the Netherlands noted as an example the problem of long-term use of respiratory corticosteroids in children -- a treatment that results in bone demineralization and impairment of growth, problems not generally encountered by the adult population. Similarly, they noted the use of highly dosed deptropine citrate in small children can cause hallucinations, agitation, ataxia, and anxiety.

In an editorial published in the same issue, William Banner Jr, medical director of The Children's Hospital at Saint Francis in Tulsa, Oklahoma explained that "the problem being discussed is all too familiar. In the United States the Food and Drug Administration has responsibility for the licensing process for all drugs. The term 'approved' is used for a drug that has been deemed to have safety and efficacy for a particular disease process. Until recently, the drug need only to have been studied in the adult male population. Yet, once a drug is approved it may be prescribed by a physician for any population or disease state desired.

Banner also noted that the FDA Modernization Act of 1997 (FDAMA) provided that manufacturers of drugs under patent could seek a six-month patent extension for performing studies leading to labeling in children. "Although six months may seem short, the financial windfall for many of these drugs is a strong incentive," he explained.

"Some manufacturers may choose to wait until patents are about to expire to initiate these studies," said Banner. "Concerns were raised over this approach when omeprazole (Prilosec, Losec) was studied in children after its success was well established in adults and received a patent extension giving them a potential 'two billion dollar sales windfall.' This gives them more opportunity to pick drugs that are sure to be profitable to study in children." Drugs with limited potential for financial gain may never be studied, he added.

SOURCES: "Unlicensed and off-label drug use by children in the community: cross sectional study." British Medical Journal, June 1, 2002.

"Unlicensed and off-label drug use by children in the community: population based cohort study," British Medical Journal, June 1, 2002.

"Off-label prescribing to children in primary care in Germany: retrospective cohort study," British Medical Journal, June 1, 2002.