Download Consumer Medication Information: A Reliable Source of Information

AUTHORS: Linh B. Van, PharmD, BCPS-AQ ID, Donna D. Huynh, PharmD, BCPS, James K. Breen, PharmD, and Nicholas J. Ratto, PharmD
Affiliations: First Databank, Inc. (FDB)
Consumer Medication Information:
A Reliable Source of Information on Grapefruit Juice Interactions?
BACKGROUND
• Grapefruit juice (GFJ) has the potential to interact with many medications due to
inhibition of intestinal cytochrome P450 3A enzymes.
• FDA recommends:
»» Manufacturers to report potential interactions with grapefruit juice in the prescribing
information (PI) of the drug product.
»» Patients to read manufacturer-authored consumer medication information such as
medication guides (MGs) and/or patient information leaflets (PILs) to determine if
a particular medication interacts with grapefruit juice.
• Due to the complexity of some MGs, their usefulness to patients has been questioned.
RESULTS
MGs/PILs with Actionable Information Regarding Grapefruit Juice Interaction
Drug Products Evaluated from the
United States and Canada
202 Drug Products Identified
from Review References and
FDB Database
Excluded Drug Products (N = 106)
• 22 no active products in US
• 3 PIs (erroneous information)
• 81 PIs without MGs/PILs
METHODS
Excluded Drug Products (N = 71)
• 58 no active products in CA
• 4 PIs not located
• 9 PIs without MGs/PIL
131 CA Drug Products Evaluated
• 61 MGs/PILs mentioned GFJ
• 70 MGs/PILs did not mention GFJ
Prescribing Information and Medication Guide/Patient Information
Leaflet Retrieval
• United States: Drugs @ FDA and National Library of Medicine’s DailyMed websites
• Canada: Health Canada Drug Product Database website
US Products
CA Products
N
Consistent—Yes (%)
Consistent — No (%)
Kappa
96
78 (81)
18 (19)
0.67
131
Data Analysis
• Kappa statistics
»» Level of agreement between a product’s PI and
MG/PIL regarding the clinical management of
grapefruit juice interaction
−− 0.81 – 0.99 as “almost perfect” agreement
−− 0.61 – 0.80 as “substantial” agreement
−− 0.41 – 0.60 as “moderate” agreement
−− 0.21 – 0.40 as “fair” agreement
−− 0.01 – 0.20 as “slight” agreement
−− Less than 0 as “less than chance” agreement
• Descriptive statistics
»» Consistency of grapefruit juice information among
MGs/PILs for specific medications with multiple formulations
»» Use of actionable information to describe the grapefruit
juice interaction in the MGs/PILs
Actionable Information
Non-actionable Information
115 (88)
16 (12)
Example of Actionable Information
from a MG
Do not drink grapefruit juice during treatment with
Cordarone Tablets. Grapefruit juice affects how
Cordarone is absorbed in the stomach.
0.78
Examples of Inconsistencies Among PI and MG/PIL Regarding Clinical Management of Grapefruit Juice Interaction
Country
Drug Product
PI
MG/PIL
Fentanyl (Abstral, Actiq, Fentora, Onsolis, Subsys)
Avoid
Did not mention
Artemether/Lumefantrine (Coartem)
Use with caution
Avoid
Triazolam
Use with caution
Did not mention
INTERACTIONS WITH THIS MEDICATION
Amlodipine/Atorvastatin (pms-Amlodipine-Atorvastatin)
Avoid
Use with caution
Etravirine (Intelence)
Avoid
Did not mention
Alfuzosin ER (Xatral)
Use with caution
No clinical significance
XATRAL is metabolized by specific enzymes in the liver. It is
not known how combined use of any drugs, herbal products
metabolized by the same enzymes or grapefruit juice may
influence the efficacy or unwanted side effects of these
drugs or herbal medicines.
Carbamazepine (Apo-Carbamazepine, Tegretol)
Use with caution
Avoid
Oxycodone (OxyNeo)
Use with caution
Did not mention
United States
Data Collection
• Data extracted from PI and MGs/PILs
»» Description of the grapefruit juice interaction
»» Recommended clinical management for the interaction
• Classification of clinical management
»» Avoid grapefruit juice
»» Use grapefruit juice with caution
»» No clinically significant interaction with grapefruit juice
»» Grapefruit juice was not mentioned
• Action required by provider or patient
»» Avoid grapefruit juice or use grapefruit juice with caution
• No action required by provider or patient
»» No clinically significant interaction or grapefruit juice interaction was not mentioned
0% 10% 20% 30% 40% 50% 60% 70% 80% 90%100%
Consistency of Grapefruit Juice Interaction Information in MG/PIL and PI from the Same Manufacturer
Drug Product Identification
• Literature review
• FDB Patient Education Monograph and Drug Food Interaction Modules
United States (N = 38)
• 38 MGs/PILs mentioned GFJ
• 58 MGs/PILs did not mention GFJ
Canada (N = 61)
OBJECTIVES
• To evaluate the consistency between manufacturer-authored MGs/PILs and PI in the
United States (US) and Canada (CA) regarding grapefruit juice interaction information
• To determine the consistency of grapefruit juice interaction information among
MGs/PILs for specific medications with multiple formulations
• To evaluate the quality of grapefruit juice interaction information in MGs/PILs based
on whether it is actionable by patients
96 US Drug Products Evaluated
Canada
Examples of Inconsistencies among MGs and PILs for the
Medications with Multiple Formulations in the United States
Drug Product
Recommendations for
Grapefruit Juice Consumption
Examples of Inconsistencies among PILs for the Medications
with Multiple Formulations in Canada
Drug Product
Recommendations for
Grapefruit Juice Consumption
Atorvastatin
Did not mention
Atorvastatin
Atorvastatin/Ezetimibe
Use with caution
Atorvastatin/Amlodipine
Use with caution
Fentanyl Lozenge (Actiq)
Did not mention
Tadalafil (Cialis)
Did not mention
Fentanyl Nasal Spray (Lazanda)
Mifepristone (Mifeprex)
Mifepristone (Korlym)
Avoid
Avoid
Tadalafil (Adcirca)
Did not mention
Avoid
No clinical significance
Example of Non-actionable Information
from a PIL
Before using any prescription, over-the-counter medicines or
herbal products, check with your doctor or your pharmacist.
CONCLUSIONS
• To minimize confusion, health regulatory agencies should ensure
manufacturers provide a consistent message regarding drugfood interactions when approving the prescribing information and
medication guide/patient information leaflet for a drug product.
• It is important to alert patients to grapefruit juice interactions to
decrease their risk for adverse drug reactions.
• MGs and PILs should convey information related to grapefruit juice
interactions in a clear, useful, and actionable manner to avoid any
ambiguity regarding administration.
© 2014 First Databank, Inc. Part of the Hearst Health network. All trademarks mentioned herein belong to their respective holders.
ACKNOWLEDGEMENTS: Authors would like to acknowledge the following employees of First Databank, Inc.: Todd Alexander and members of the
Consumer Drug Information Group.
DISCLOSURES: Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial
entities that may have a direct or indirect interest in the subject matter of this presentation: Linh B. Van: Employee, First Databank, Inc.; Donna D.
Huynh: Employee, First Databank, Inc.; James K. Breen: Employee, First Databank, Inc; Nicholas J. Ratto: Employee, First Databank, Inc.
REFERENCES: 1. Huang SM, Zhang L. Guidance for Industry Drug Interaction Studies—Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. US Department of Health and Human Services, Food and Drug Administration, Center
for Drug Evaluation and Research (CDER); February 2012. 2. Wolf MS, King J, Wilson EA, Curtis LM, Bailey SC, Duhig J, Russell A, Bergeron A, Daly A, Parker RM, Davis TC, Shrank WH, Lambert B. Usability of FDA-Approved Medication Guides. J Gen Intern
Med 2012; 27(12):1714-20. DOI: 10.1007/s11606-012-2068-7. 3. FDA. Grapefruit Juice and Medicine May Not Mix. Consumer Health Information. FDA; February 2012. http://www.fda.gov/forconsumers/consumerupdates/ucm292276.htm (accessed 1 December
2013). 4. Viera AJ, Garrett JM. Understanding Interobserver Agreement: The Kappa Statistic. Family Medicine 2005; 37(5):360-3. 5. Xatral (alfuzosin) prolonged-release tablets (package insert). Laval, Quebec, Canada: Sanofi-Aventis Canada; 2013. Available
at: http://products.sanofi.ca/en/xatral.pdf 6. Cordarone (amiodarone) tablets (package insert). Philadelphia, Pennsylvania: Pfizer Wyeth Pharmaceuticals; 2011. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018972s048lbl.pdf