*2. Major, Online, Drug Information Resources

Objectives:

1. Understand the concepts:
   • (a) adverse effects, drug interactions, IV compatibility/incompatibility
   • (b) major compendium
2. Know the unique features of Clinical Pharmacology, UpToDate LexiDrug (formerly known as LexiComp), LexiDrugs, Martindale’s, AHFS DI, and DailyMed
3. Be able to access DailyMed, Clinical Pharmacology, UpToDate LexiDrug (formerly known as LexiComp), LexiDrugs, AHFS Drug Information, and Martindale’s
4. Be able to find PPIs using Daily Med
5. Be able to generate custom Adverse Effects, drug interaction, and compatibility reports using Clinical Pharmacology and/or Lexi-­‐Comp

Pay attention to the stars ⭐

Much of the content presented from this point forward will be represented on your exam and/or on the drug resources quiz.  If we were meeting in-person, there are things that I would point out as content that would be sure to be represented on the test.  I’m going to use star symbols ⭐ to point out some of this content in the course book.   Usually, the test will require that you make a decision based on your knowledge of these pieces of content.

Objective 1 a.  Understand the concepts “adverse effects,” “drug interactions,” and “IV compatibility/incompatibility”

You will be using the major drug information resources to look up drugs’ adverse effects, interactions, and known IV compatibilities or incompatibilities so it’s important that you understand these concepts.

Adverse effects (also called adverse reactions or side effects)

⭐An adverse reaction  takes place after the drug’s administration to a patient.  It is defined as any undesired drug effect.    Adverse effects range from mild reactions like

drowsiness

or  itching

to more severe and dangerous reactions like suicidal behavior

Drug Interactions

⭐Drug interactions, like adverse effects, take place after a drug is administered to a patient.

Pharmacokinetic interactions

⭐In a pharmacokinetic interaction, a food, beverage, or second drug effects the absorption, metabolism or distribution of the first drug.

Here’s an example of a pharmacokinetic interaction:

A patient who takes felopdipine for high blood pressure decides to drink some grapefruit juice.    Grapefruit juice inhibits the action of the enzyme (CYP3A4) that degrades felodipine and the patient is exposed to much more of the active drug than he normally would be.  This could result in unexpectedly low blood pressure, fainting episodes, and worse.

The effect of grapefruit juice on the amount of active drug present at different points during felodipine absorption and distribution is shown in the table below.

The information above is shown in pictorial form in  figure 1 of https://unmc.primo.exlibrisgroup.com/view/action/uresolver.do?operation=resolveService&package_service_id=1279986780006389&institutionId=6389&customerId=6385&VE=true

Pharmacodynamic Interaction

⭐A pharmacodynamic interaction occurs when two drugs have additive or antagonistic effects.

Here’s an example of a pharmacodynamic interaction:

A patient with narcolepsy (a disorder characterized by an extreme tendency to fall asleep) is being treated with a stimulant.  The patient has  seasonal allergies and is given an over-the-counter antihistamine (with a side effect of drowsiness) by a new co-worker.  The antihistamine’s side effects diminish the positive effects of the stimulant and the patient falls asleep repeatedly all afternoon.

IV Incompatibility

⭐IV incompatibility, unlike  adverse effects or a drug interaction, occurs before drug administration to a patient.  It is the result of two drugs reacting with each other or changing the nature of the solution when  mixed.

⭐Signs of incompatibility are:

• a change in visible or electronically-­determined (even if not visible) particulates, haziness or turbidity, frank precipitation, color, or gas evolution after drug mixture.
• a loss of intact drug >10% within 24 hours when mixture constituents are assayed.

Three types of IV incompatibility

Tests are performed to see if drug mixtures are compatible or incompatible in three different types of mixing situations.   The concentrations of the drugs vary in these three situations.

1. admixture 

An example of an admixture would be two drugs and a diluent  mixed in an IV bag.

In the picture below, preparations are being made to add a drug to the IV bag.

One example of an admixture incompatibility is loss of 50% of one drug’s concentration when a mixture of two drugs sits in an IV bag overnight.

2. y-site

The diagram below shows an IV line with a y-site.

Y-cite mixtures usually involve one drug that is being delivered slowly through IV  tubing (often from a hanging IV bag) mixing in the tubing with a second drug when the second drug is administered via a syringe or second IV bag attached to the tubing’s y-site.

One example of such an interaction would be formation of a precipitate  in the tubing when the two drugs come in contact.

3. Syringe

A syringe mixture involves two drugs that are drawn into a syringe for simultaneous delivery

An example of syringe incompatibility:   Two drugs are drawn into a syringe, meet, and the previously clear solutions become milky white.

Objective 1b.  Understand the concept “major compendium”

• Compendium =  A collection of concise but detailed information about a particular subject. ·
• A drug monograph is a concise summary of the important information about a drug’s properties and therapeutic use
• Therefore, any collection of drug monographs is a drug information compendium

Objective 2.  Know the unique features of Clinical Pharmacology, UpToDate LexiDrug (formerly known as LexiComp), LexiDrugs, Martindale’s, AHFS DI, and DailyMed

Two of the drug information compendia available at UNMC, Clinical Pharmacology and DailyMed, are available through their own separate interfaces.   UNMC also licenses Lexi-Comp and its native monograph compendium Lexi-Drugs.  We pay an extra fee to UpToDate LexiDrug to obtain two additional drug compendia in the UpToDate LexiDrug interface, AHFS Drug Information (AHFS DI) and Martindale’s: The Complete Drug Reference.

The table below provides a summary of the the distinctive characteristics (in red) of these major compendia.    Below the table, you will find a more detailed discussion of the distinctive characteristics of these resources and mnemonic devices to help you begin memorizing the distinctives of these compendia.

I. Resources Published by the Manufacturer under FDA Control

DailyMed

DailyMed is a U.S. government-controlled database.  It gives the public an easy way to obtain the FDA-approved package inserts. 

• The package inserts are authored and published by the drugs’ manufacturers (DailyMed has no responsibility for their content.).   
• Package inserts are frequently called physician’s or pharmacist’s prescribing information, PPIs, FDA-approved monographs, or package labels.
• Package inserts are approved by the FDA.  They can only provide information on FDA-approved drug uses.  ⭐ 
• No uses that have not been approved by the FDA (off-label uses) will be discussed.  This does not mean that off-label uses are illegal.   Much of the totally legal drug use in the U.S. is off-label.
• The FDA must approve any changes or updates in a package insert.  FDA approval of a new label/package insert takes time.
• For the reasons listed above, DailyMed, and package inserts in general, are rarely the best resource for answering drug information questions.

When is DailyMed the best resource?

DailyMed may be the best resource when you need information that is manufacturer-specific.

• • Each manufacturer/repackager must submit its own package label/insert to the FDA for approval.
  • Different manufacturers  may use different inactive ingredients (excipients) when producing the tablets, capsules, etc. that they distribute.⭐
  • Patients are occasionally allergic to ingredients used as excipients, ingredients like lactose or dyes.
  • DailyMed can be used to find manufacturers that make a needed drug without ingredients that are a problem for a particular patient.  To find the inactive ingredients in a drug preparation:
    • Go to DailyMed
    • Search DailyMed for the drug’s generic or brand name.
    • Find one of the results that corresponds to the form of the drug that is of interest (e.g. intravenous, tablet, nasal spray, etc.) and click on the link to the PPI
    • “Expand all sections” and use Ctl-f(windows) or Command-f(mac) to open a “find” box.  Use the box to search for the word – inactive.
    • Keep looking for all instances of the word – inactive.  Some package inserts include information about multiple forms of a drug (tablet, capsule, solution for injection, etc.) so be sure you’ve seen the inactive ingredients for the drug form/preparation of interest to you.

DailyMed may also be helpful when you need a chemical structure.  Many package inserts include chemical structures.

II.  Resources NOT Published by the Manufacturer and NOT under FDA Control

The resources discussed below can cover off-­label  (off-PPI, FDA-­‐unapproved)  therapeutic uses.  Authors/Editors can change content quickly, without FDA approval.

If we were meeting in-person, I would ask the class to repeat the mnemonic devices below out-loud.   I’d suggest you  try saying these out loud and also write them down.  It’s easier to remember pieces of information if you deal with them in a variety of different ways.   The distinctive characteristics of these resources will be covered on the quiz and on the exam.  This reflects the importance of these resources in clinical pharmacy practice.

Clinical Pharmacology

• Includes drug monographs, a variety of custom report tools and more
• Unique features are:
  • Custom, consumer-level interaction reports. (both LexiComp and Clinical Pharmacology provide professional-level drug interaction reports).⭐
  • Custom, adverse reaction reports.⭐

UpToDate LexiDrug (formerly LexiComp)

• Includes a custom drug interaction tool, a custom IV compatability report tool, drug monographs, a variety of custom report tools and more
• Unique feature –unites access to diverse monograph sets in a single interface ⭐

LexiDrugs

• LexiDrugs is one of the sets of drug monographs that comes with LexiComp without having to pay an additional fee (on top of the LexiComp license fee).
• Unique features are:
  • General LexiDrugs includes a table of drugs that shouldn’t be crushed.⭐
  • General LexiDrugs monographs include prices.⭐

(The mnemonic for not crushing drugs “x” “Drugs” is not as obvious as I’d like)

Martindale:  The Complete Drug Reference via LexiComp

• UNMC pays LexiComp an extra fee to provide Martindale’s
• Unique feature:  Martindale’s provides all the drug names you need to create a very thorough keyword search.⭐

AHFS DI

• UNMC pays LexiComp an extra fee to provide the AHFS DI.
• Do not confuse the AHFS DI with AHFS essentials.

Advantages of AHFS DI -­‐-­‐

1. Online version is thoroughly referenced.
2. Extremely thorough monographs.
3. Good source for odd little pieces of info (pearls)  like information obtained from conference presentations/abstracts and personal communications with the manufacturer — Unique feature.  ⭐

The mnemonic below is a bit contrived.  Think of the letters “A” “H” “F” “S”  “D” “I” as the initials on a pearl ID bracelet.

Anticipate Weekly Resource Reviews and Resource Knowledge Assessments

The tutorial and tutorial assignment you will complete today will help you begin to become familiar with these resources.

To help you memorize the resource distinctives, I’ve added a resource review to the beginning of every week’s materials.

You will have a quiz that covers the resource distinctives

The mid-term exam will also cover this material.

Objective 3. Be able to access DailyMed, Clinical Pharmacology, LexiComp, AHFS Drug Information, and Martindale’s

Almost all drug resources available at UNMC can be reached in two ways.  Either:

1. You can go to a COP course in Canvas and click the “Library” link in the left-hand navigation column to reach the Library’s COP Research Guide with it’s list of drug resources on the homepage.

or

2.  You can start at the library’s homepage

• To reach the library’s homepage, either google – UNMC library or start at any unmc.edu homepage.
• Click on the “Library” link in the list of links at the bottom of the page.

• Click on the “Resources” menu.

• Click on “Drug Resources”
• Click on the link to the resource of interest.

Tutorial and Assignment

The tutorial and tutorial assignment will  give you a chance to practice using the compendia discussed today and will cover the session’s last two objectives:

Objective 4. Be able to find PPIs using Daily Med (MA)

Objective 5. Be able to generate custom AE, drug interaction, and compatibility reports using CP, Lexi-­‐Comp

Instructions:

1.  Complete the tutorial at https://pressbooks.nebraska.edu/modi/front-matter/introduction/
2. The tutorial contains questions and will provide feedback on your answers.
3. After considering the feedback, record your best answer to each of the questions in a document.
4. When you’ve finished the tutorial, return to Canvas and enter the best answers to the questions in the Canvas assignment/quiz entitled: “Major Online Drug Information Resources Tutorial Assignment”

Questions, Problems, Text Errors?

Before you leave, …

• Do you have any questions or do you feel that clarification of some aspect of the materials would be helpful?
• Have you noticed any errors or problems with course materials that you’d like to report?
• Do you have any other comments?

If so, you can submit questions, comments, corrections, and concerns anonymously — or with your e-mail (your choice) — through this online form .  Alternatively, you’re always welcome to contact Cindy Schmidt directly 402-650-5056, cmschmidt@unmc.edu, or by making an appointment to meet with Cindy via Zoom.

Answers to questions or requests for clarification that are submitted anonymously will be answered in Canvas on the “Discussions” page for this course.