Position paper on preferred dosage forms to be included in a Model Essential Medicines List for Children

Transcription

1 Psitin paper n preferred dsage frms t be included in a Mdel Essential Medicines List fr Children Intrductin The reprt n the 4 th Mdel List f Essential Drugs includes guidelines fr the selectin f pharmaceutical dsage frms. Under the heading f criteria fr the selectin f essential drugs, the reprt states that each selected drug must be available in a frm in which adequate quality, including biavailability, can be assured. Other issues identified were stability under anticipated cnditins f strage and use, the relative cst f different dsage frms, general utility and wide availability internatinally. Unfrtunately, the reprt states, Specific paediatric dsages and frmulatins are included in the list nly when indicated by special circumstances. The purpses f these plicy statements are t:. Identify which factrs shuld be taken int accunt when making a chice f paediatric dsage frms t be included in a Mdel Essential Medicines List fr Children. 2. Review the evidence fr the suitability f different frmulatins fr paediatric medicines, cnsidering such factrs as have been identified, including issues f dsing accuracy, palatability, stability, ease f transprt and strage. 3. Recmmend preferable frmulatins fr different age grups f children, including nenates premature & full term, yung infants and lder children. These plicy statements are primarily extraplated frm clinical practice and available published infrmatin including the Eurpean Medicine Agency Cmmittee fr medicinal prducts fr Human use, reflectin paper: Frmulatin f chice fr the paediatric ppulatin, dated 28 July Overarching statement Liquid frmulatins can ffer superir palatability t disslved slid tablets, intended fr swallwing whle, hwever the transprtatin, strage and temperature mnitring required fr liquid frmulatins render this bulky dsage frm as a ptential barrier fr their use in regins f the wrld under stress r harsh living cnditins. Plicy statement: The stability f and having access t paediatric medicines is paramunt. Whenever pssible, every effrt must be extended t ptimize their palatability f paediatric medicines. The ideal paediatric frmulatin characteristics listed belw are desirable when the chemical stability r prduct availability allws. When the stability r prduct availability des nt permit ne f the fllwing suggested characteristics, this shuld nt prevent pediatric patients frm accessing medicatins. Wrld Health Organizatin. The use f essential drugs. Secnd reprt f the WHO Expert Cmmittee. Technical Reprt Series 722, 985.

2 Plicy statement: Frmulatins shuld cntain nly excipients knwn t be safe fr all paediatric age grups. This is t ensure flexibility in medicatin supply. Oral frmulatins Plicy statement: The preferred ral frmulatin is the tablet as it is the mst easily stred and is stable ver the widest range f envirnmental cnditins. Apprpriately frmulated ral Tablets (see belw) can meet the needs f mst paediatric patients when used prperly in prviding pint f care, as patient specific slutins, suspensins r slurries can be prepared at the time f administratin. Chewing gum, capsules, ral pwder, rdispersible and rmucsal dsage frmulatins are acceptable, but require age specific dsage frms. In the absence f an ability t mdify the dse amunt fr these latter dse frms (e.g., cutting the patch frmulatin t a specific dse, etc.) these fixed dse frmulatins are nt practical when cnsidering dsing accuracy, palatability, stability, ease f transprt and strage. Factrs t cnsider in chsing a tablet frmulatin: Tablets shuld be scred s they may be easy split (with fingers) accurately accmmdate a quarter dse. Dsages shuld be standardized using increments f ne quarter tablet fr mst drugs with a wide therapeutic windw. Many dses may be adapted frm using a tablet that can be divided in fur sectins, with a quarter tablet prviding a dse fr a 0 kg child. Tablets shuld disintegrate easily in water t enable preparatin f a pint f care, patient specific slutins, suspensins r slurries at the time f administratin (e.g., disslve ne furth f a tablet in.25 t 2.5 ml f water t administer ne eighth f a tablet. This accmmdates a medicatin naïve patient t take a medicatin by simply mixing it t water prir t administratin. In applying such extempraneus pint f care dsing it is highly desirable fr calibrated measuring spns be available and used t ensure dsage accuracy f the specific slutin/suspensin/slurry at the time f administratin. Water used t suspend r dilute tablets shuld be free f cntaminants and pathgens. Excipients shuld be inert, gluten free, lactse free and free frm dyes that may cause allergic reactins r side effects such as tartrazine and red dyes. Fr patient safety, tablets shuld be identifiable by different clurs r branding imprints r markings. The use f unique imprint cde n tablet frms shuld be mandated. Chewable r rally disintegrating tablets are preferred t ral suspensins when a flavur is required t mask bad tasting medicatin. Chewable r rally disintegrating tablets shuld disintegrate in water easily t enable the preparatin f pint f care, patient specific slutins/suspensins/slurries at the time f administratin. Slw release frmulatins shuld be avided unless abslutely clinically required r that can be cut r crushed t prvide better dsing versatility. 2

3 Plicy statement: Liquid frmulatins shuld be restricted t less palatable medicatins that prevent children frm achieving a therapeutic benefit. Cst effective chewable r rally disintegrating tablets are preferred t ral suspensins/ liquids when a flavur is required t mask bad testing medicatins. Chewable r rally disintegrating tablets shuld disintegrate in water easily t enable a pint f care, patient specific slutins, suspensins r slurries at the time f administratin. Cylindrical measuring spns r ral dsing syringes shuld be prvided t ensure dsage accuracy when a liquid frmulatin is dispensed. Factrs t cnsider in chsing a liquid frmulatin: - The dse vlume shuld be (less than) 5mL fr children under 5 years and (less than) 0mL fr children 5 years r lder. - Oral slutin (ral drps) f very small dse vlumes is acceptable if the manufacturer prvides recmmendatins fr dilutin in beverage t imprve palatability. - Suspensins shuld be free f excipient(s) that may cause undesirable effects including diarrhea with srbitl r xylitl. Water used t recnstitute suspensins shuld be free f cntaminants and pathgens. - Flavurs selected shuld have been shwn t effectively mask pr taste withut risk f adverse effects. - Affrd very versatile temperature strage range fcusing n rm temperature & a temperature range that accmmdates expected envirnmental temperatures within the wrld s many temperent znes. - Dry pwder t be re cnstituted at pint f care Parenteral frmulatins Factrs that shuld be cnsidered in fr parenteral frmulatins include: - Preferably use preservative free, single dse r safe preservative avid excipient that may be harmful t paediatric patients, e.g., nenates and benzyl alchl, prpylene glycl... - preference shuld be given t latex free rubber stpper cntainers, prt f IV tubing and bags; - frmulatin shuld be available in a prtected frm light cntainers; - preferred strage at rm temperature; - tear ff label frm riginal vial t label syringes fr patient safety. Injectables Plicy statement: The intravenus and subcutaneus rutes are the preferred rutes fr parenteral administratin as are applicable t all age grups. In chsing an intravenus frmulatin the fllwing shuld be cnsidered: Manufacturers shuld prvide dilutin infrmatin t enable t have the medicatin be administered via central r peripheral vein in children. 3

4 The prduct shuld be cmpatible with glucse 5% &0%, sdium chlride 0.45% and 0.9% and a cmbinatin f glucse and saline as well as in the presence f imprtant primary electrlytes, e.g., ptassium, chlride, calcium and pssibly magnesium. The maximum rate f administratin shuld be stated in mg/kg/minute r micrgram/kg/minute. Is smtic and ph neutral preparatins are preferred t limit thse risks assciated with infiltratin txicity, thrmbphlebitis and hemlysis. In chsing a Subcutaneus frmulatin the fllwing shuld be cnsidered: The medicatin shuld be at r near physilgical ph f 7.4 The medicatin dse shuld be cntained within a small vlume. Plicy statement: Intradermal injectin shuld be restricted t medicatins r tests where there is n ther methd f administratin (e.g., tuberculin test). Plicy statement: Whenever pssible, the intramuscular rute f drug administratin shuld be avided. Althugh undesirable, intramuscular drug administratin may be apprpriate fr a ne time dse treatment r in thse patients with n venus access and n available surgical expertise fr effective line placement. Further, multiple intramuscular dses are prblematic frm a site stand pint and patient tlerability / cmpliance. In the absence f abslute necessity as nted abve, the intramuscular frmulatin is usually nt practical in sick nenates. Plicy statement: Nasal drps, sprays and pwders are acceptable dsage frm if each are nn irritating and d nt affect mucsal functin. Penetratin enhancers shuld be shwn t be safe and effective in the target ppulatin. These frmulatins may be applicable t all age grups. Plicy statement: Rectal frmulatins may be applicable in all age grups. Hwever, this mde f administratin is nt widely accepted by paediatric patients and is thus nt preferred unless it is t be used in clinical situatins where ral r intravenus administratin is nt practical (e.g., treatment f nausea and vmiting). The size f the suppsitry shuld be related t the patient s size and shuld be able t split t allw fr partial accurate dsages, if necessary. Plicy statement: Tpical agents that are cmmnly used in adults may be used in children f mst age grups. Hwever, increased skin surface area and enhanced dermal penetratin f infants and nenates must be cnsidered when selecting and dsing tpical medicatins. Transdermal patches shuld nly be used in nenates if there is age specific supprting data available. Plicy statement: Pulmnary agents can be used safely in children; nebulizers may be used in all paediatric age grups but may require specialized equipment. Metered dse inhalers with apprpriate age spacers may be used in all age grups except nenates. Dry pwder inhalers shuld be restricted t children greater than 5 years f age. 4

5 Cntributrs t this psitin paper : Regis Vaillancurt (Canada ) David Knppert (Canada), Michael Reed (US), Sandra Benavides (US), Jyce Tttn (Canada), David Hff (US), Brady Mffett (US), Kelley Nrris (US),). 20 April 2007 Bibligraphy Wrld Health Organizatin. The use f essential drugs. Secnd reprt f the WHO Expert Cmmittee. Technical Reprt Series 722, 985. British Natinal Frmulary fr Children, Guidance fr Industry General Cnsideratins fr Pediatric Pharmackinetic Studies fr Drugs and Bilgical prducts, Draft Guidance, US FDA, 0 Nvember Mdified after : Yaffe SJ and Aranda JV. Pediatric Pharmaclgy Therapeutic Principles in Practice. Saunders, Eurpean Medicines Agency. Reflectin Paper : Frmulatins f Chice fr the Paediatric Ppulatin, Lndn, 28 July Taketm CK, Hdding JH, Kraus DM. Pediatric Dsage Handbk, 3 th Editin, Lexi Cmp, Calle G, Lagmarsim E. Evaluatin f Preferred Dsage Frms in 338 Argentinian Paediatric Outpatients (persnal cmmunicatin). 8 Persnal experience 5