Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials

Objectives  

To investigate the knowledge and views of a range of healthcare professionals (consultant paediatricians, general practitioners (GPs), community pharmacists and paediatric nurses) regarding the use of unlicensed/off-label medicines in children and the participation of children in clinical trials.     

Perceptions and attitudes of Jordanian paediatricians towards off-label paediatric prescribing

Objective To assess current experiences and attitudes of hospital based paediatricians towards off-label medicine prescribing. Setting Paediatric hospital wards and out-patient clinics. Design A prospective, questionnaire based study. Results A 30 item questionnaire was sent to 300 hospital based paediatricians and 250 (83%) were returned completed. Over 69% of responders were familiar with the term off-label medicines. However, only 28% were knowingly prescribing off-label medicines to children. The majority of respondents (90%) expressed concerns about the safety and efficacy of off-label medicines. Only 15% had observed Adverse Drug Reactions, and 31% a treatment failure. The vast majority of respondents (83%) did not obtain informed consent or tell parents they were prescribing off label medicines to their children. Conclusions Off-label prescribing of medicines to children is a familiar concept to the majority of paediatricians in Jordan although only a smaller number are aware that it is common in their practice. Respondents showed concern about off label prescribing, although the majority do not consider it necessary to inform parents. More comprehensive research is needed in this area in Jordan and other Middle Eastern countries.     

How well are general practice trainees prepared for paediatric prescribing?

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Children make up a significant proportion of a general practitioner's (GP's) prescribing workload.
• The realisation that children cannot be assumed to be little adults and may require specialized prescribing and therapeutic knowledge is relatively recent.
• Off-label medicines, which have been associated with an increased frequency of adverse drug reactions, are commonly prescribed by GPs to children.
WHAT THIS STUDY ADDS
• The majority of GP trainees believe that their undergraduate and postgraduate training in paediatric therapeutics is insufficient for their coming requirements in primary care.
• Approximately one-third of GP trainees do not undertake any paediatrics training prior to starting work as a GP.
• Off-label and unlicensed prescribing are the most poorly covered areas of paediatric therapeutics in universities/university hospitals.
• Those trainees who do undergo paediatric training during their vocational years report increased paediatric prescribing confidence.
AIMS AND METHODOLOGY We invited 232 General Practice Trainees to complete an on-line questionnaire to assess how they rated their training for the task of paediatric prescribing and therapeutics in the community.
RESULTS Of the 166 (71%) respondents who completed the questionnaire, 26.5% recalled specific teaching about paediatric prescribing and 59.6% covering one or more relevant topic during their undergraduate years. Undertaking a paediatric post during vocational training was associated with greater prescribing confidence ( P  < 0.001); however, 35% of respondents were not intending to undertake such a post.
CONCLUSION This study suggests that many GP trainees perceive their paediatric prescribing training as inadequate.     

Adequacy of venlafaxine dose prescribing in major depression and hospital resources implications

Venlafaxine, a dual serotonin and noradrenaline re-uptake inhibitor, has been found to be effective at doses below 375 mg daily, but for patients with major depression higher doses can be required. In this retrospective naturalistic study, we investigated the effectiveness and resource implications of prescribing higher than standard doses of venlafaxine (tablet preparation). Ninety-six outpatients fulfilling DSM-IV criteria for major depressive disorder were assigned to two demographically matched cohorts: cohort A, receiving high doses (n = 38; doses > or =375 mg/day) and cohort B, receiving standard doses (n = 58; doses <375 mg/day). Data on hospital resources, drugs and medical profiles were extracted from patients' records. Information on cohort A was also obtained before their high-dose regime, while taking standard doses. A within-group analysis of cohort A showed that patients spent fewer days in hospital (P = 0.03) and had fewer outpatients visits (P < 0.01) when on high doses than when on standard doses. A between-group analysis found that cohort A, while on higher doses, had fewer outpatient visits compared with cohort B (P < 0.01). Patients in both groups had satisfactory drug tolerability and efficacy profiles. There were no differences between cohorts with regard to baseline characteristics, a part from the more intensive use of additional medications made by cohort A. Our preliminary investigation suggests that higher doses of venlafaxine may be cost-saving in relation to selected hospital resources. However, one cannot firmly conclude that the change in service use is due to the higher-dose regime, and we recommend further research to ascertain the cost-effectiveness of adequate dose prescribing in patients with poor symptom resolution at lower doses of venlafaxine.     

Carbamazepine clearance in paediatric epilepsy patients. Influence of body mass, dose, sex and co-medication

Carbamazepine clearance was studied in Black paediatric epilepsy patients, 90 receiving monotherapy and 17 on combination therapy. For patients on monotherapy the following relationship are shown: clearance decreases with increasing body mass (r= 0.87); clearance increases with increasing dose (r = 0.70); and mean clearance for male are higher than those for females throughout the mass ranges, though the difference is not statistically significant. In the case of patients on carbamazepine plus another anticonvulsant, clearance also decreases with increasing body mass, and increases with increasing dose. Furthermore, in the mass groups which corresponded with those on monotherapy, mean carbamazepine clearance higher by a factor varying from 1.3 to 1.7; in the corresponding dosage groups, it is higher by a factor of between 1.4 and 1.7.     

Drug prescribing in hepatobiliary disease.

Liver disease in man is associated with a variety of pathophysiological processes which may influence the disposition of drugs in several ways. Interpretation of the observed pharmacokinetic changes in liver disease requires an understanding of the relationship between systemic drug clearance (Cls), volume of distribution (Vd) and the elimination half-life [t1/2(beta)], i.e. t1/2(beta) = 0.693 . Vd/Cls. Half-life will be a measure of the fluctuation in drug level one may expect with continued administration of a drug while clearance will determine the dose required to achieve a particular steady state level. Liver disease may affect clearance and volume of distribution and so produce changes in half-life; in addition, alterations in plasma binding of drugs may occur and so influence free (unbound) drug levels. It is also possible that the end organ response, particularly in the case of sedative drugs, may be affected by liver disease. Other factors such as age, nutrition, smoking, and concomitant drug therapy may also influence drug elimination in patients with liver disease. At the present time, caution should be exercised in prescribing drugs to patients with liver disease and the dose should be titrated to the clinical response. The development of liver 'function' tests using model or marker drugs may offer some help to the prescriber in the future and enable a less empirical approach.     

Drug prescribing in renal failure.

Drug prescribing for patients with renal failure should incorporate adjustment of dosage regimens in order to avoid accumulation and thus adverse effects. Drugs usually eliminated by the kidneys require the most modification. Since immediate therapeutic efficacy is of importance, the initial or loading dose is essentially unaltered for patients with renal dysfunction. Maintenance doses can be adjusted by either lengthening the interval between doses of by reducing the size of individual doses. In clinical practice, a combination of both methods is used. Serum levels should be used as guides whenever possible. In interpreting these levels, recognition of decreased plasma protein binding and prolonged elimination half-lives in renal failure is imperative. In patients requiring dialysis, consideration must be given to adjustments for drug removal by the artificial membrane. Small molecules unbound to proteins are most easily removed. Specific guidelines for therapy with common drugs prescribed for patients with renal failure are given. These include: (1) narcotics and analgesics; (2) psychotherapeutic drugs; (3) cardiovascular drugs; and (4) antimicrobial agents.