Can Kids Be Given Injectable Dexamethasone Orally?

Question: In the pediatric emergency room where I work, the question often arises about whether dexamethasone injection can be given orally. Is this a safe and effective method of administration? Response from Jessica C. Stovel, RPh Adjunct Assistant Professor, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada A common challenge when working with the pediatric population is administration of medication. If commercial products are unavailable, alternative measures are often undertaken, such as crushing and dissolving portions of a tablet, or extemporaneous compounding of oral products. In some cases, an extemporaneous liquid cannot be prepared easily from tablets or capsules and off-label oral use of an intravenous (IV) or intramuscular (IM) preparation is considered. Such alternative measures are being considered more commonly now that drug shortages occur frequently. How do we determine whether an IV/IM preparation is safe to administer orally? Unfortunately, there are no clearly defined guidelines in the literature to provide practitioners with guidance on this important and clinically relevant question. Thus, the clinician should consider contacting one of the following resources who often have information readily available regarding the compounding of drug formulations: •Drug information service (often provided by hospital pharmacy department); •Pharmaceutical manufacturer; or •Compounding pharmacy. In addition, a literature search should be performed in order to find pediatric studies and evidence supporting the oral use of a parenteral formulation. For example, one can find such information on methotrexate,[1] fentanyl citrate,[2] topotecan,[3] and cyclophosphamide.[4] Safe Use of IV/IM Medications for Oral Use Several important factors should be considered when assessing whether an IV/IM formulation can be safely administered orally[5-7]: •Will the solution be absorbed and bioavailable by the enteral route? •Is the pH or osmolality safe for children? •Does the injectable contain preservatives? Preservatives such as benzyl alcohol or propylene glycol, often contained in multidose vials, may have significant adverse effects in neonates, infants, and children, such as metabolic acidosis, renal failure, seizures, and central nervous system depression. •Will the volume providing the required dose be tolerated by the child based on age and medical status? •Will the formulation be palatable? •Is the resulting solution stable? The medication's stability when diluted should be confirmed with the manufacturer or other resources prior to dispensing. If an IV/IM preparation is deemed to be safe and efficacious when administered orally, it is imperative to draw up the required amount in an oral syringe that has an auxiliary label stating "For Oral Use Only." [8] In the hospital setting, several cases of serious (and sometimes fatal) medical errors have occurred in children when parenteral syringes were used to administer oral medications. Use of parenteral syringes can be problematic because they can be accidently connected to an IV line. If oral syringes are used, such an error will not occur because they cannot be readily connected to an IV line or accommodate a needle.[8] Applying Principles to Dexamethasone The question of whether an IV/IM preparation can be given to children orally commonly arises with respect to dexamethasone. The supporting evidence in the literature is limited but can be combined with the general principles discussed above. Although dexamethasone oral liquid formulations are available in the United States, some of these contain 30% alcohol or have a lower concentration than is clinically practical. In some situations, toddlers and small children can require doses over 30 mL.[9] Consequently, these commercially available products may increase the risk for adverse effects from excipients and may also lead to nonadherence in a pediatric population. In 2001, a Canadian pharmacy research team at the University of British Columbia evaluated the stability of extemporaneously prepared 0.5- and 1-mg/mL dexamethasone oral suspensions.[9] The investigators used dexamethasone sodium phosphate solution for injection and a 1:1 mixture of Ora-Sweet® and Ora-Plus®. This oral suspension was physically and chemically stable for up to 91 days with or without refrigeration. The rationale for using dexamethasone injection solution over tablets is that the drug is already dissolved, eliminating the need for crushing/grinding tablets and dissolving the powder. This method also prevents potential physical instability and microbial contamination. This formulation was used in a large pediatric randomized control trial examining the efficacy and safety of dexamethasone for the treatment of bronchiolitis,[10] and its palatability in children was evaluated and confirmed.[11] Given these studies and clinical experience, the IV preparation can be used to make an oral formulation. Other clinicians have formulated dexamethasone suspensions by adding dexamethasone phosphate injection to distilled water and cherry-flavored syrup[12] or have masked the flavor of the IV preparation by following oral administration with juice or a popsicle.[13] Conclusion When deciding whether an IV/IM preparation can be administered orally, practitioners should always carefully consider the parenteral formulation properties and conduct a literature search to determine whether evidence exists to support the efficacy and safety of administering the medication to children in this manner. Consider contacting the pharmaceutical manufacturer, a drug information service, or a compounding pharmacy.