Compounding for

Paediatric Patients Tavares, Paula

Introduction

Treating a paeditric patient presents a therapeutic challenge when the safest and most effective agent is not available

in a suitable dose or an acceptable dosage form. Most marketed products that are mostly used in adults have not

been studied in children. The market for paeditric products is small compared to the adult market because children

are generally healthy and are a smaller part of the population. A compounded medication that is formulated to meet

the unique needs of the paeditric patient and that can be quickly adjusted to more effectively address a child’s

changing medical needs can be essential to a successful therapeutic outcome. In fact paediatric compounded

preparations allow the choice of the most suitable dosage form, the adjustment of the doses to the pharmaco-therapy

of peadiatric sub-groups, the selection of excipients and the customization of the medicines to respond to some

peculiarities such as pharmacokinetic properties, biological maturity and intolerances.

Departamento de Medicamentos Manipulados

Objectives

1. Knowledge of the paediatric compounded preparations (PCP) in Portugal

2. Development and validation of oral pharmaceutical forms, establishing the galenic formula, the preparation

procedure and the term of use supported with stability studies .

3. Availability of the pharmacotherapeutic information ( package information leaflet -PIL ) for informed hand over and

suitable use of the PCP.

CONCLUSÕES

Resultados

Design & Methods

1. Inquiry targeted to Community and Hospital pharmacies asking about the active substance, dosage, dosage form,

excipients, indications for use and posology.

Evaluation of the requests settled to the PCIC (2006 – 2009) by query of a dedicated database.

The information was treated by classification of the content Question & Answer in the following items:

active substance / dosage form / dosage / disease / target group / query frequency to PCIC.

2. Edition of the Portuguese Galenic Formulary (PGF) according to the following method:

Bibliography 1 Diverse challenges in pediatric compounding, IJPC Vol14 Jan/Feb 2010 2 Lack of commercial oral drug formulations for Children, IJPC Vol12 July / Aug 2008 3 Safety of “inert additives or excipients in paediatric medicines, Arch Dis Child Fetal Neonatal, Vol 94 Nov 2009 4 Poor Formulation in published pediatrics drug trials, Pediatrics Vol116 nº4 Oct 2005 5 Inappropriate oral formulation and information in paediatric trials, Arch Dis Child, July 2010

21 st to 22nd September 2010

LEF, Instituto de Formação e Inovação em Saúde, Barcarena, Portugal;Tel(+351) 214278610; Fax (+351) 214278639; paula.tavares@anf.pt

What’s happening

in Portugal

3. The package information leaflet -PIL follow current legislation and includ the subjects:

The criteria for the PPC proposal were: a) highest frequency of use; b) therapeutic need; c) trouble in the

formulation or stability of the compound.

Auscultation needs

Target group : Paediatric

Dosage form

Route of administration

Inquiry

PCIC Data

SPP/WHO/EMA

PCP Selection

PCP proposal

Consultive Commission

approval

Pharmaceutical development

Pharmaceutical characterization

Period of use

Monograph

Preparation record

Label / PIL

FGP Evaluation

1) What ____ is and what is used for;

2) Before take ____

3) How to take ____

Disease / Dosage / range takes

4) Possible side effects

5) How to store ___

6) Further information

1. Replies to the inquiry target to community and hospital pharmacies and the analysis of the requests made to

PCIC show that, in Portugal, 30% of compounded preparations are paediatrics. 15% of PCP are dermatological,

18% are for cardiovascular diseases and 15% are anti-inflammatories.

Powder packets represent 10%, capsulas 5%, oral liquid 61%, topical liquids 10% and semisolids 14%.

2. PGF inclued 218 paediatric compounded preparations (PCP) corresponding to 90 active substances.

The cardiovascular PCP represents 17%, dermatological 21%,and anti-inflammatories 13% .

PCP adressed to the CNS, endocrine and metabolism, nutrition and gastrointestinal disorders represent 7% to

9%, each.

66% of PCP included in the PGF are oral liquid. Vehicles of different viscosities are composed of different

sweeteners (sucrose or saccharin).

AI – Drugs used in skin disorders; AII – Drugs used in otorhinolaryngological disorders; AIII –Anti-Infectives drugs; AIV – Drugs used to treat genitourinary disorders; AV – Hormones and Drugs used to treat endocrine disorders;

AVI – Drugs used to treat Central nervous system disorders; AVII - Drugs used to treat cardiovascular disorders; AVIII - Drugs used to treat gastrointestinal disorders; AIX – Correctives of blood volume and electrolytes; AX - Drugs

used to treat ocular diseases; AXI - Drugs used to treat locomotor disorders; AXIII - Drugs used to treat nutritional disorders; AXIV - Drugs used to treat blood disorders

AI AII AIII AIV AV AVI AVII AVIII AIX

Mineral Tar Boric acid Metronidazole

benzoate

Testosterona

prop

Hydrocortisone Methadone Spironolactone Triamcinolone Sodium citrate

Citric acid

Zinc Oxide Acetic acid Trimethoprim Potassium iodide Phenobarbital Propanolol Ranitidine Potassium Chloride

Iodine Sodium bicarbonate Nitrofurantoin Cortisone acetate Amitriptlyline Hydrochlorothiazide Famotidine Sodium phosphate

Hydroquinone Urea peroxide kecotonazole Dexamethasone Caffeine Captopril Cimetidine

Ictamol Ciprofloxacin Prednisolone Carbamazepine Atenolol Nitroglycerine

+Cinchocaine

Salicylic acid Dapsone Prednisone Lamotrigine Clonidine Ursodeoxycholic

Choramphenycol Griseofulvin Propylthiouracil Diltiazem Omeprazole

Boric acid Hydroxychloroquine Dipirydamole

Eosin Itraconazole Enalapril

Azelaic acid Pyrazinamide Furosemide

Glicolic acid Rifampicin Labetalol

Ditranol+ Salic. Tetracycline Minoxidil

Resorcinol + Salic Ethambutol Nifedipine

Chlorhexidine Pentoxyfilline

Fluorouracil Verapamil

Metronidazole Flecainide

Benzoyl peroxide Digoxin

Podophyllin

Tretinoin+Hydroqu

inone+Cogic ac.

AX AXI AXIII AXIV

Acetazolamide Allopurinol Riboflavin Folic acid

Indomethacin Zinz acetate Phytomenadione

Methotrexate pyridoxiune

Capsaicin Sodium benzoate

Biotin

Arginine

3. Package information leaflet is clear and simply organized. Recommendations on the dosage, posology and

indication for the therapeutic use are given for all PCP. All the information is given using patient comprehensive

language. Information included in the PIL is based inscientific literature (Taketomo CK, Hodding JH, Kraus DM.

Pediatric dosage handbook 2001 and DRUGDEX, 2006).

Pharmaceutical compounding settle clinical situations and, in fact, are extremely important since they allow the

adjustment of the medicine to the intended patient. Pharmaceutical quality and safety are underlying for a suitable use of

these medicines that obey to Good Preparation Practices’ (GPP) procedures. The identification of the pharmaceutical

compounding needs and the decision on which will be included in this category is urgent. Then, it would be appropriate

the harmonization of pharmaceutical compound in the EEA, as well as a quality system applied to the pharmaceutical

compounding characteristics that show a personalization to the patient as an added value.

In Pediatrics, it is central to comply with a judicious selection of excipients, not only for safety reasons but also for

adherence to therapy. An informative platform, managed by the different countries in concert, would minister a more safe

and efficacious use of these medicines.

Pharmacovigilance programs and efficacy monitoring should be developed and implemented.