Module 5
Populating the Interactions Section of a CCDS/CCSI - Handling of Information on
Drug-Laboratory Test Interferences
Labeling contains various types of information about drug-drug and drug-substance interactions. Some of this information is provided as part of the description of a product's pharmacokinetic profile. Beneficial interactions occasionally serve as the basis for a claim. However, the majority of interaction information is about those that have undesirable consequences, such as an increased likelihood of adverse reactions or the need to adjust dosage to prevent such reactions or to ensure effectiveness. Information on drug-laboratory test interferences must be differentiated from in vivo interactions and from clinical adverse effects on laboratory parameters.
The authors of local labeling and core labeling should be familiar with the criteria for including these types of information. For undesirable interactions, in particular, it is important to understand the concept of clinical relevance/significance of an interaction (as one of the threshold criteria for including an item in the Interactions section) compared with the relevance criteria that determine that an interaction should be elevated to the Warnings level. Authors also should be able to handle "trivial" or "borderline" pharmacodynamic interactions in a consistent manner, and know how to deal with situations where a mechanism is known, but not all specific interactors.
The rules for section placement of interaction information in local labeling (Clinical Pharmacology section, Interactions section, Adverse Reactions section, Warnings and Precautions section) are worldwide similar, but not necessarily stated with sufficient explicitness in labeling regulations and guidelines. Having detailed and explicit rules for core labeling helps affiliates incorporate this type of information in local labeling in a worldwide consistent manner.
Curriculum topics of this moduleinclude:
- Review of current local requirements and guidelines on the content and format of the Interactions section
- Threshold criteria for including interactions in the Interactions section
- When to elevate interactions information to the Warnings level; where to discuss precautions related to interactions; what to discuss under Pharmacokinetics
- Whether to repeat selected interactions information under Adverse Reactions
- Whether to include trivial "additive adverse effect" interactions
- What to do if the clinical relevance of pharmacokinetic effects is unclear
- Class interactions; interactions predicted based on pharmacokinetic characteristics
- Threshold criteria for and placement of information about drug-laboratory test interferences