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Letters

Unlicensed and off label drug use for paediatric patients

BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7152.204 (Published 18 July 1998) Cite this as: BMJ 1998;317:204

General practitioners prescribe SSRIs to children off label

  1. Richard M Martin, Clinical research fellow.,
  2. Lynda V Wilton, Honorary visiting lecturer.,
  3. Ronald D Mann, Senior professorial fellow. (drmann{at}dsru.u-net.com),
  4. Paul Steventon, Chairman,
  5. Sean R Hilton, Professor.
  1. Drug Safety Research Unit, Southampton SO31 1AA
  2. Faculty of Medicine, Health and Biological Sciences, University of Southampton, Southampton SO16 7PX
  3. Doctors Independent Network, Ewell, Surrey KT17 1TF
  4. Division of General Practice and Primary Care, St George's Hospital Medical School, London SW17 0RE
  5. Academic Division of Child Health, Derbyshire Children's Hospital, Derby DE22 3NE

    EDITOR—Turner et al highlight the fact that children admitted to hospital are often prescribed unlicensed drugs and drugs given outside the terms of their product licence (off label).1 The appropriateness of such prescribing is uncertain, and a high rate of adverse drug reactions has been observed in children prescribed such drugs.2 The problem is not limited to hospitals. General practitioners may be asked to prescribe unlicensed or off label drugs by specialists or may consider initiating such treatment themselves. Little information exists on the extent of such prescribing in primary care.

    We examined the prescribing of selective serotonin reuptake inhibitors to children in general practice by accessing a computerised database of 100 British general practices (349 doctors) using the AAH Meditel System 5 computer system to enter medical records (Doctors Independent Network).3We determined the number of children aged 12 and under who had at least one prescription for a selective serotonin reuptake inhibitor between January 1992 and December 1996. For each child we ascertained age at first prescription; sex; name, dose, and formulation of the drug; number of prescriptions issued during the study; and reason for prescription. To be certain that we had identified children, we included only subjects who had an immunisation record in their notes, with dates consistent with their recorded age.

    Overall we identified 25 children who met the entry criteria for the study, except that we had to exclude six because of doubt over their age. The table shows the reasons for the prescription of the drugs. The commonest antidepressant prescribed was fluoxetine capsules. The British National Formulary states that prescribing these drugs for children is not recommended.

    Prescribing of selective serotonin reuptake inhibitors in children aged 12 and under in 100 general practices in Britain

    View this table:

    These data from a small number of practices (under 1% of all British practices) suggest that nationally there are probably hundreds of children who have been prescribed off label antidepressants in general practice. Research suggests that some children are prescribed these drugs in general practice soon after their launch, when clinical experience is limited.4 We agree with Turner et al that all drugs used to treat children should be evaluated for their paediatric efficacy, safety, and quality. Doctors should have enough information to be able to discuss with parents the likely benefits and risks of using these drugs.5 Research should also assess the appropriateness of such prescribing in general practice.

    References

    Optimal dosing schedules with gentamicin are needed for premature neonates

    1. Sharon Conroy, Lecturer in paediatric clinical pharmacy.
    1. Drug Safety Research Unit, Southampton SO31 1AA
    2. Faculty of Medicine, Health and Biological Sciences, University of Southampton, Southampton SO16 7PX
    3. Doctors Independent Network, Ewell, Surrey KT17 1TF
    4. Division of General Practice and Primary Care, St George's Hospital Medical School, London SW17 0RE
    5. Academic Division of Child Health, Derbyshire Children's Hospital, Derby DE22 3NE

      EDITOR—Turner et al report unlicensed and off label drug use in the paediatric setting but do not mention off label drug use in neonatal intensive care.1

      Gentamicin is a renally excreted aminoglycoside antibiotic frequently used in neonatal intensive care units. The serum concentration achieved is critical because of its narrow therapeutic index. Renal excretion is reduced at birth and increases during the first months of life. Premature neonates are affected more than term neonates, and appreciable increases do not occur until 34 weeks of gestational age. The rate of renal maturation in neonates varies widely, and critically ill premature neonates develop more slowly than term neonates.2 Consequently the dose regimens required to achieve appropriate serum concentrations in these patients are different from those in older children and adults, whose renal function is more adequate. Examples of such regimens are found in several paediatric formularies. 34 The dose recommended ranges from 2.5 to 5.0 mg/kg/dose given at intervals of 8-36 hours, depending on the criteria used.

      Three manufacturers produce gentamicin injection. Each has a licence for the treatment of neonatal infections and recommends doses for all ages from birth onwards.5 These doses vary slightly, from 2 to 3 mg/kg/dose at intervals of 8 to 12 hours. Each recommends that doses be adjusted so that serum trough concentrations of <2 mg/l and peak concentrations of 4-10 mg/l are achieved. Blood samples are normally taken around the third or fourth dose. A premature neonate is therefore likely to receive doses more appropriate for a term neonate for two days if these recommendations are followed. Excessive and potentially toxic serum concentrations are likely to result.

      Many dosing schedules for gentamicin have been drawn up in the United Kingdom. All attempt to account for the factors influencing drug handling in premature neonates, such as gestational age, weight, postnatal age, concurrent drug treatment, and maternal drug treatment. Is it not time that the manufacturers of such widely used drugs determined the optimal dosing schedule by trials specifically designed for this population?

      References

      1. 6.
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      3. 8.
      4. 9.
      5. 10.
      View Abstract