Most third-party drug interaction services or references don’t help with determining the clinical significance of a given drug interaction. But the book Top 100 Drug Interactions by Hansten and Horn helps me determine whether an interaction is real vs theoretical, so I can guide patients and physicians safely through the complicated arena of drug interactions.
This book is my all-time favorite reference book on drug interactions, and I have purchased it every year for well over a decade. There was no edition published in 2020, so I was excited to see one that came out in 2021.
One of the best features of this book is how the authors are willing to accurately state the risk of potential drug interactions, and only include in the book interactions they feel are clinically significant. This makes Top 100 Drug Interactions a guide that can be counted on to provide practical advice for managing drug interactions, without any unnecessary recommendations for interactions that are unlikely to be clinically significant.
The book has 8 major sections:
- Operational classification of drug interactions
- Table of cytochrome p450 and transporter substrates, inhibitors, and inducers
- Top 100 drug interaction monographs
- Effects of antibiotics on warfarin
- Drug interactions that prolong the QTc interval
- Genetic polymorphisms of cytochrome p450 enzymes
- Drug interactions with herbal products
- Drug interaction probability scale
I find myself using 3 of them over and over again in my practice.
The first of these sections is the cytochrome p450 interaction table.
Not all drug interactions are known, and new drugs arrive on the market with limited drug interaction data. To allow clinicians to predict pharmacokinetic drug interactions in unstudied combinations, Hansten and Horn publish an extensive table of medications that affect and are affected by the cytochrome P450 system, as well as other transporters such as p-glycoprotein:
This table allows clinicians to identify interactions between enzyme inhibitors, inducers, and substrates. In addition, if a medication has a primary pathway of elimination, it is identified in the chart. This extra piece of information can be used to hypothesize the degree to which an interaction may be significant. For example, although amitriptyline is metabolized by 1A2, 2C19, 2D6, 3A4, and PGP, the primary pathway of elimination is 2D6. Using this information a clinician may choose to allow the use of a 3A4 inhibitor with amitriptyline with the knowledge that many other pathways for elimination exist. This table is updated with every new edition for both new data on existing medications and when new medications come to market. In 2021 for example information has been added about acyclovir being a major inhibitor of 1A2 and various new medications since the publication of the last edition.
The second section I frequently use is the top 100 drug interaction monographs.
These monographs provide practical information on how to address specific drug interactions including suggested alternatives for either drug involved in the interaction as well as actionable monitoring strategies.
The classification system for drug interactions used in the book is as follows:
Class 1 – There is no situation where the benefit outweighs the risk (such as pseudoephedrine plus a monoamine oxidase inhibitor).
Class 2 – Avoid use unless there is no alternative or the interaction is desired (such as warfarin plus aspirin).
Class 3 – An increased risk exists but monitoring may be an acceptable course of action (such as low doses of fluconazole with 3A4 substrates).
Class 4 – Minimal risk.
Class 5 – No interaction.
Although the guide contains far more than 100 potential drug interactions, the authors do a superb job focusing on only the clinically relevant interactions that are class 1, 2, or 3.
The third section I frequently use is the one for evaluating QTc interactions.
My method for evaluating QTc interactions draws strongly from Hansten and Horn’s book and I discuss it extensively in a members-only training video in the Hospital Pharmacy Academy which you can access, along with hundreds of other resources to help in your practice by going to pharmacyjoe.com/academy.
Some changes to the QTc section for 2021 include moving chloroquine from being considered to cause QTc prolongation at therapeutic concentrations to one that does so at elevated concentrations, and the addition of hydroxychloroquine to this same category.
You can order a copy of the Top 100 Drug Interactions on Amazon by clicking here.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.