Correspondence

Unapproved and Off-Label Use of Drugs in a Children's Hospital

N Engl J Med 2000; 343:1125October 12, 2000

Article

To the Editor:

Treatment of children may be difficult because of a shortage of properly formulated or approved drugs.1 In the Netherlands and elsewhere, many drugs are not approved for use in children, and some drugs are often used outside the terms of the product's approval (off-label use). We studied the unapproved and off-label use of drugs in a children's hospital in which the hospital pharmacy, unlike pharmacies in many other European countries, is allowed to prepare “homemade” formulations and to modify commercial preparations in order to suit the needs of children.

During a five-week period, we classified the use of all drugs prescribed for children hospitalized in one medium-care and three intensive-care units as approved, not approved, or off label. The not-approved category included drugs that were not approved for use at all, were not approved or were contraindicated for use in children, or were manufactured or modified by the hospital pharmacy, as well as drugs for which there were no dosage guidelines for use in children. The off-label category included all prescriptions that differed from the approved labeling with respect to dose, frequency, dosage form (tablet, capsule, or injection), route of administration, or indication for use in children. The primary source of information used was Repertorium 98/99, 2 and the alternative source was Farmacotherapeutisch Kompas 1998. 3

During the study period, 2139 courses of drugs were prescribed for 238 children from birth to 17 years of age (median age, 20 months). Of these prescriptions, 725 (34 percent) were approved; 1024 (48 percent) were unapproved, of which 760 (36 percent of the total) were manufactured or modified by the hospital pharmacy; and 390 (18 percent) were off label (Figure 1Figure 1Frequency of the Prescription of Drugs in a Children's Hospital during a Five-Week Period, According to Whether Use of the Drug Was Unapproved, Off Label, or Approved.). Of the 238 patients, 218 (92 percent) received one or more courses of an unapproved drug.

These results indicate that many drugs that physicians consider suitable for infants and children are not officially available for their treatment. The reasons include the relatively small number of children who need drugs, which makes marketing unattractive, and the fact that pharmaceutical companies assume that research involving children is costly and complicated.4 Recent policy changes in the United States have resulted in an increased number of drug studies involving children, and similar changes are needed worldwide.

Geert W. `t Jong, M.Sc.
Arnold G. Vulto, Pharm.D., Ph.D.
Matthijs de Hoog, M.D.
Kirsten J.M. Schimmel, Pharm.D.
Dick Tibboel, M.D., Ph.D.
John N. van den Anker, M.D., Ph.D.
Erasmus Medical Center Rotterdam, 3000 CB Rotterdam, the Netherlands

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