Drug Information Notes

Learning Objectives

• Develop a consistent approach to answering drug information questions.
• Collect accurate and comprehensive drug information from appropriate sources to make informed, evidence-based, patient-specific, or population-based decisions.
• Assess the quality of the information available to answer the question.
• Use effective written and verbal communication skills to accurately respond to drug information questions.
• Recognize the types and examples of tertiary resources used by pharmacists.

Sample Questions

• What is the recommended treatment for otitis media in a $3\text{-year-old}$?
• Are there boxed warnings for isotretinoin?
• Identify a blue oval tablet, F 8 on one side, 3 on the other side
• What is the correct needle length and gauge for Shingrix?
• What is the AWP for Clomid?
• How should an unused $500\ \text{mL}$ chemotherapy infusion bag be disposed?

The First Question Is Not the Real Question

• Focus on developing detective skills to clarify and optimize the actual information need before answering.

Background Questions

• Who is asking?
• Is this for a patient?
• What is the problem?
• Why is the question being asked?
• What is the time factor?
• What are the requestor’s expectations?
• What is the history of the problem?
• What are the unique circumstances?
• What information is needed?
• What format of reply is needed?
• How will the information be used?
• How has the problem been managed so far?
• Are there alternative options to explore?

Case Study: Azithromycin for Gastroparesis

• Question: “Can you tell me the recommended dose of azithromycin for gastroparesis?”
• Azithromycin is a macrolide antibiotic similar to erythromycin; it stimulates motilin receptors leading to a prokinetic effect in the GI tract.
• Potential search strategy (without background information):
  • Treatment guidelines do not include azithromycin explicitly.
  • Use tertiary sources first.
  • Then go to secondary sources to find primary literature.
• Background info:
  • Internal medicine physician managing a patient with diabetic gastroparesis.
  • Erythromycin national shortage.
  • Patient factors:
  • Abdominal pain, nausea, vomiting, decreased appetite, flatulence.
  • Medications: metoclopramide $10\ \text{mg}$ PRN, 10 minutes after meals; insulin glargine at bedtime; insulin lispro at meals; lisinopril; HCTZ; atorvastatin; acetaminophen; multivitamin.
  • Type 2 DM for $13\text{ years}$, peripheral neuropathy for $5\text{ years}$, gastroparesis for $2\text{ years}$, HTN for $8\text{ years}$.
  • Social history: negative for alcohol, tobacco, or other drugs.
  • Labs and vitals: $ext{BP} = 151/84\ \text{mmHg}$, SCr = $1.3\ \text{mg/dL}$, A1c = $9.4\%$, LDL = $126\ \text{mg/dL}$, HDL = (not provided).
• Disease factors:
  • Gastroparesis = impaired gastric emptying due to diabetes.
  • Symptoms: nausea, vomiting, abdominal pain, fullness.
  • Management: dietary modification, prokinetics, antiemetics.
• Medication factors:
  • Erythromycin = macrolide that stimulates motilin receptors (prokinetic).
  • Azithromycin = macrolide with fewer drug interactions and longer half-life; not included in gastroparesis practice guidelines; more current tertiary sources include limited data.
  • Metoclopramide remains a first-line agent.
• Analysis and synthesis:
  • Metoclopramide is a first-line agent for gastroparesis.
  • Recommended dosing: $10\ ext{mg}$ up to $4\ ext{times daily}$ before meals and at bedtime.

Steps to Take (7 Core Steps)

1) Identify the requestor with name, role, and contact information.
2) Obtain background information.
3) Determine the ultimate question.
4) Develop a strategy and gather data to respond.
5) Analyze and synthesize information.
6) Provide a response and recommendation.
7) Follow-up and document.

Classify the Ultimate Question

• Adverse drug reactions
• Drug substitution
• IV drug compatibility and stability
• Pregnancy and lactation
• Compounding and pharmaceutics
• Geriatrics
• Medication safety
• Psychiatry
• Drug identification
• Immunizations
• Natural products
• Regulatory
• Drug interactions
• Infectious diseases
• Overdoses, poisoning, toxicology
• Therapeutics
• Drug pricing
• International drug information
• Pediatrics
• Travel medicine
• Drug shortages
• Investigational drugs
• Pharmacology

Desired Characteristics of the Response (Table 2-4)

• Timely
• Current
• Accurate
• Complete
• Concise
• Supported by the best available evidence
• Well-referenced
• Clear and logical
• Objective and balanced
• Free of bias or flaws
• Applicable and appropriate for specific circumstances
• Answers important related questions
• Addresses specific management of patients or situations

Levels of Evidence

• Meta-analysis
• Systematic review
• Randomized controlled trials (RCTs)
• Cohort and Case-control studies
• Case series and case reports
• Editorials, opinions, ideas
• Animal research
• In vitro research

Tertiary Sources

• Compiled and summarized by an author.
• Summary of a topic; information originates from other sources.
• Communication about a topic to promote accessibility for the intended audience.
• Examples: Textbooks; Review articles; Online resources such as Micromedex, Clinical Pharmacology, Lexicomp.

Secondary Sources

• Searchable databases.
• Catalog information found in other sources; scaffolding to locate information.
• Examples: PubMed, International Pharmaceutical Abstracts (IPA), EMBASE, etc.

Primary Sources

• New knowledge.
• Research reports, case reports, articles in medical journals that report new findings, data presented at meetings.

Tertiary Resources: Benefits and Limitations

• Benefits: Convenient, accessible, readable, fast.
• Limitations: Open to bias, may be out of date, errors in author interpretation.
• Choice: Match category of information needed; consider peer-review and citation of evidence; ease of use.

General Drug References

• Lexicomp
• Micromedex
• Clinical Pharmacology
• American Hospital Formulary Service (AHFS)
• Facts and Comparisons
• Index Nominum: International Drug Directory
• Martindale: The Complete Drug Reference
• Physician’s Desk Reference / Prescriber's General Reference (PDR)
• United States Pharmacopeia

Drug Monograph

• A drug monograph compiles information about a drug and cites evidence and sources.
• Follows a standard layout with categories: drug products available, dosing, indications, interactions, adverse effects, monitoring parameters, clinical studies, use in special populations, storage.
• Examples: Lexicomp, Micromedex.

Lexicomp Example: Methylphenidate (Lexi-Drugs)

• Features include: Boxed warnings, brand names (US and Canada), pharmacologic category, dosages, uses, clinical practice guidelines, administration/storage issues, medication safety issues (abuse and dependence).
• Brand Names (US): Adhansia XR; Aptensio XR; Concerta; Cotempla XR-ODT; Daytrana; Jornay PM; Metadate.
• Brand Names (Canada): ACT Methylphenidate; etc.
• Pharmacologic Category: Central Nervous System Stimulant.

Official Prescribing Information (OPI)

• Contents:
  • Boxed warning
  • Indications and usage
  • Dosage and administration
  • Dosage forms and strengths
  • Contraindications
  • Warnings and precautions
  • Adverse reactions
  • Drug interactions
  • Use in special populations
  • Drug abuse and dependence
  • Overdosage
  • Description of product
  • Clinical pharmacology
  • Toxicology
  • Clinical studies
  • References
  • How supplies/storage and handling
  • Patient counseling information
• Also called package insert, PI, product label, official labeling.
• Information approved by the FDA; available in package, on manufacturer site (Drugs@FDA, DailyMed).
• Off-label indications: Major compendia may include this information.

Classify the Ultimate Question (Revisited)

• Adverse drug reactions
• Drug substitution
• IV drug compatibility and stability
• Pregnancy and lactation
• Compounding and pharmaceutics
• Geriatrics
• Medication safety
• Psychiatry
• Drug identification
• Immunizations
• Natural products
• Regulatory
• Drug interactions
• Infectious diseases
• Overdoses, poisoning, toxicology
• Therapeutics
• Drug pricing
• International drug information
• Pediatrics
• Travel medicine
• Drug shortages
• Investigational drugs
• Pharmacology

Categories & Resources for Drug Information

• Categories for adverse effects include Meyler’s Side Effects of Drugs, FAERS, VAERS, Natural Medicines database, Drug identification resources (Ident-a-drug, Identidex, Lexi-Drug ID).
• Drug interactions references: Hansten and Horn Drug Interaction Facts; Stockley’s Drug Information; IV compatibility; Trissel’s Stability of Compounded Formulations; etc.

Lexicomp Monograph Details (Revisited)

• Lexicomp presents: Methylphenidate monograph detailing dosage, uses, and safety considerations, including BOXED WARNINGS and brand name lists.
• Emphasizes medication safety issues (abuse/dependence) and various administration considerations.

Patient Question Scenario (Pages 26–27)

• Patient Question: “Do you think Adderall is causing my headache? I can’t stop taking it, so will Tylenol PM help me get some sleep?”
• DI Question Exercise:
  • Classify the types of information needed.
  • Identify sources to use.
  • Write out relevant information.
  • Begin to formulate a response.

Notes on Notation and References

• Throughout the transcript, emphasis is on evidence-based, patient-specific, or population-based decision-making.
• When proceeding with a case like gastroparesis, prioritization of first-line agents (e.g., metoclopramide) is highlighted when guideline support exists.
• Azithromycin is discussed as an option with fewer drug interactions but lacking strong guideline support for gastroparesis due to limited data in tertiary sources.

Quick Reference Highlights (Key Takeaways)

• Always identify the requestor and context before replying.
• Use tertiary sources first, then secondary, and finally primary sources for the most robust answer.
• Understand the types of information (adverse effects, interactions, regulations, etc.) to classify the ultimate question.
• When responding, ensure the reply is timely, accurate, well-referenced, and tailored to the patient/situation.
• In cases of drug shortages or special populations, consider alternative agents and safety considerations.
• Lexicomp and other major general drug references provide monographs with standardized sections, including boxed warnings and patient education material.
• Official prescribing information constitutes a primary reference for regulatory-approved details, including boxed warnings and dosing.