Definitions

Adverse drug events or side effects are unintended side-effects from a medicine.

Compounding is the process where two or more ingredients are mixed (one has to be a medicine) to create a final product in an appropriate form for dosing. It can involve the alteration of the form and strength of the commercially available product and can include reformulation to allow for a new drug delivery. In this website, we do not make the distinction between compounding and extemporaneous formulations.

Excipients are substances that are formulated alongside the active ingredient of a medication. They can be included, for example, to stabilize the medicine or to aid in the manufacturing process.

Forms and Formulations: Formulations is the term denoting the combination of an active pharmaceutical ingredient (API) with other non-active constituents – termed excipients - to create a medication. Form refers to the overall physical configuration of a medication (e.g., tablet, powder, capsule, or liquid). For the purposes of simplicity, both are used interchangeably in the website and refer to both definitions.

What is Off-Label Use?

Drug approval is specific to the indication(s), age groups, route of administration, formulations, a method of manufacturing, and package labeling.

Off-label refers to a use that differs from that approved by regulatory authorities and can refer to any departure from that authorization. As such, using a medication in a different formulation than approved is considered off-label use. The lack of pediatric formulations often leaves health care providers caring for children no alternative, but to use adult medicines in a manner that has not been approved by Health Canada (manipulation of adult pharmaceutical forms).

Off-label use is a fairly common practice amongst health care provider and is not specific to Canada but widespread around the globe. It is estimated that the prevalence of off-label use in the pediatric population is approximately 45 to 60% of all medicines given to children, and up to 90% in vulnerable populations such as neonates, critically ill children, and children with cancer.

Off-label use does not necessarily imply off-evidence. It is the responsibility of the prescribing physician to evaluate whether or not the available clinical and scientific evidence supports the use of the medication in a specific patient, that beneficial patient outcomes outweigh potential risks. Patient safety should always remain the top priority of health care providers.

Off-label use is different from the use of an unauthorized medicine. It is legal for physicians to prescribe drugs as off-label medications.

What is Compounding?

Compounding is the process where two or more ingredients are mixed (one has to be a medicine) to create a final product in an appropriate form for dosing. It can involve the alteration of the form and strength of the commercially available product and can include reformulation to allow for a new route of administration.

This manipulation of dosage forms designed for adults by health care providers and parents may cause some concerns. Our goal is to increase the number of approved pediatric formulations thereby decreasing the need to compound medicines. Some of the concerns that may arise with compounding include:

  • Variation existing in the preparation of compounded medicines. As such, compounding practices may vary among hospitals and compounding pharmacies in the community, and across Canada, which can lead to significant variations in drug exposure when the child changes from one place to another, or even when a different pharmacist compounds the medication.
  • Medicines that are compounded often have a limited stability and therefore need to be prepared frequently which can translate into multiple visits for parents to the pharmacy.
  • Since compounded medicines are not approved by Health Canada’s rigorous process, we do not always know the medication’s characteristics. Therefore, it is sometimes difficult to know the exact quantity of the medicine that is absorbed.
  • Sometimes safety issues for the family may arise, in cases of toxic drugs that parents need to manipulate at home. In such examples, parents need to protect themselves, and their family members from involuntary exposure to the toxic medications, such as anti-cancer medications.
  • Pharmaceutical manufacturing practices are regulated and great care is taken to make the requested formulation; however, since these compounded materials are not made in a dedicated manufacturing facility, the standards cannot be at the same level as commercially manufactured medicines.

Other References

Improving Medicines for Children in Canada

Prescription Pharmaceuticals in Canada – Off Label Use

STEP Database Safety and Toxicity of Excipients for Paediatrics

EuPFI

Pediatric Formulations – Global research in Pediatrics (GRIP)

Paediatric formulations - European Medicines Agency - Europa EU

Pediatric Formulations - FDA

Pediatric Trials Network