Food and Drug Administration Update for Pediatric Practitioners

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2002;8(1)

New Dosage Formulations

^®

Approved

On October 12, 2001, Shire Pharmaceuticals received approval to market an extended release preparation of Adderall^®, its widely-used amphetamine/dextroamphetamine product for the treatment of ADHD. A single morning dose is designed to provide effective symptom control throughout the entire school day. Adderall XR^® is available as 10, 20, and 30 mg capsules.^[4]

A new amoxicillin/clavulanate preparation, Augmentin ES-600^® (GlaxoSmithKline), was approved by the FDA on November 6, 2001 for children 3 months of age or older with recurrent or persistent acute otitis media. The product, an oral suspension, contains 600 mg amoxicillin and 42.9 mg clavulanate per 5 ml. It has been designed to facilitate a high-dose amoxicillin regimen (90 mg/kg/day divided into two doses) without providing excessive clavulanic acid.^[5]

An orally administered formulation of budesonide (Entocort EC^®; AstraZeneca) has been approved by the FDA for the treatment of mild to moderate active Crohn's disease. This formulation releases drug into the intestine, where it works locally to decrease inflammation. Entocort EC^® has been shown to provide the same degree of improvement in symptoms as oral prednisone or prednisolone, but with fewer systemic adverse effects. It is currently approved only for adults, but will likely also be used in younger patients in order to minimize steroid-associated growth impairment.^[6]

Dey Labs has received approval from the FDA to market their new albuterol product, AccuNeb^®, for use in children between 2 and 12 years of age. The product is available in 1.25 mg/3 ml and 0.63 mg/3 ml concentrations for nebulization without further dilution. It is a sterile, preservative-free solution and does not contain benzalkonium chloride. This is the first albuterol product designed for younger patients.^[7]

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Cite this: Food and Drug Administration Update for Pediatric Practitioners - Medscape - Jan 01, 2002.

Sidebar: Pharmacology Literature Review

Adherence with standard therapies to manage asthma symptoms is frequently poor in pediatric patients. In this retrospective study, adherence to two common treatments, oral montelukast and inhaled fluticasone, was compared. In the population sampled, 54 patients were receiving montelukast, 48 were using fluticasone, and 69 children had prescriptions for both. Based on pharmacy refill histories, adherence rates were 59% for montelukast and 44% for fluticasone. No relationship was found between adherence and age, length of monitoring, or the use of combination therapy. Sherman J, Patel P, Hutson A, et al. Adherence to oral montelukast and inhaled fluticasone in children with persistent asthma. Pharmacotherapy 2001;21:1464-7.

Thirteen children and 12 adolescents participated in this three week, open-label buspirone dose escalation study. The results obtained from these patients, all being treated for anxiety, were compared to pharmacokinetic parameters and adverse effect profiles obtained from 14 healthy adult volunteers. The authors found that peak plasma buspirone concentrations were highest in the children and the lowest in the adults. This was offset, however, by a more rapid clearance in the children. The most frequent adverse effects were lightheadedness (68%), headache (48%), and dyspepsia (20%), similar to the findings in adults. Salazar DE, Frackiewicz EJ, Dockens R, et al. Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults. J Clin Pharmacol 2001;41:1351-8.

The authors of this review discuss known drug interactions with the most commonly prescribed therapies for ADHD. In addition to methylphenidate, amphetamines, and pemoline, the article also covers antidepressants, anticonvulsants, and clonidine. Markowitz JS, Patrick KS. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet 2001;40:753-72.

Although typically administered over 30 to 60 minutes, gentamicin may also be given as an IV bolus. In this retrospective study from Children's Hospital in Columbus, Ohio, the safety and efficacy of bolus administration were evaluated in 123 patients ranging from newborns to adults. Mean peak and trough serum concentrations were within the therapeutic range for all age groups. Serum creatinine and BUN remained unchanged in all but two patients. Both were receiving other nephrotoxic drugs and had a return to normal parameters after stopping therapy. Auditory exams were normal in all neonatal patients. The authors suggest that bolus administration be considered as a means of decreasing personnel time and equipment needs as well as increasing flexibility with administration of other medications or fluids. Robinson RF, Nahata MC. Safety of intravenous bolus administration of gentamicin in pediatric patients. Ann Pharmacother 2001;35:1327-31.

In this open-label study, the authors evaluated the effectiveness of enteral methadone in preventing symptoms of withdrawal in children who had been receiving continuous infusions of fentanyl. Twenty-two children (mean age 6 years) were enrolled. The average length of previous fentanyl therapy was 17.8±8.4 days. Methadone was initiated at a dose of 0.5 mg/kg/day while the fentanyl dose was being tapered, and was then slowly weaned. The average length of methadone therapy was 18.2±11.9 days, reflecting a high degree of patient variability. Only one patient experienced withdrawal symptoms, and responded to reinstitution of fentanyl and an increase in methadone dose. This study, while small in size, supports previous work demonstrating the efficacy of methadone in preventing iatrogenic opioid withdrawal. Lugo RA, MacLaren R, Cash J, et al. Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy 2001;21:1566-73.

Single-dose midazolam pharmacokinetics were evaluated in 133 children after receiving either an oral or intravenous dose. While several other kinetic studies have been performed in children, this is the first large-scale study to evaluate the effects of the syrup formulation. Absorption of the syrup was rapid, with children less than 12 years having a faster absorption than older children. In addition, elimination half-life was shorter and production of the primary metabolite, alpha-hydroxymidazolam, was greater in the younger subjects. Overall, bioavailability of the syrup was 36% (range 9-71%). No relationship between bioavailability and age was detected. Based on their data, the authors suggest an oral midazolam dose of 0.2 to 0.3 mg/kg for procedural sedation. Reed MD, Rodarte A, Blumer JL, et al. The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration. J Clin Pharmacol 2001;41:1359-69.

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