Medication Safety: Medical Errors and Drug-Drug Interactions Kevin L. Zacharoff, MD PainEDU.org
Disclosures • Grant/Research Funding: Endo Pharmaceuticals, Actavis • Salary: Inflexxion
Learning Objectives • Assess the issue of medical errors in the U.S. • Assess the significance of drug-drug interactions in the management of chronic pain • Review recommendations for improved medication safety in the management of chronic pain • Describe practice points to reduce medical errors and drug-drug-related adverse events in the management of chronic pain
What is Medication Safety? • Health care provider perspective – Depends on who you ask • Medication errors – Name – Dose indication • Assessment of adherence (compliance) to regimen • Risk evaluation – Drug interactions – Adverse effect profile – Inappropriate patient selection – Co-morbid conditions – Overdose/aberrant drug-related behaviors • Conservative prescribing
What is Medication Safety? • Patient perspective – Knowledge about medications • Name • Directions – Dose – Timing – Other factors (e.g., with or without food, what about vitamins?) – Allergies – Side effects • Prior history • Awareness – Storage/Disposal
Medication Use in the United States • A Survey1 explored patterns of medication use in the US – In a given week, an average of 82% of adults in the U.S. are taking at least one medication (prescription or nonprescription drug, vitamin/mineral, herbal/natural supplement) • 29% are taking five or more – The prevalence of use of medications overall and prescription drugs has not changed materially since the Survey began in 1998 – Polypharmacy has increased since 2000, from 23% to 29% for use of five or more medications, and from 6.3% to 12% for use of at least five prescription drugs 1. The Slone Survey. Patterns of Medication Usage in the United States: 2006 A Report from the Slone Survey. 2006
Medical Errors Medication Errors
So Many Places to Make Mistakes‌‌..
Medication Errors
• The FDA defines a medication error is any preventable event that may cause or lead to inappropriate medication use or harm to a patient1 • Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use – Since 2000, the FDA has received more than 95,000 reports of medication errors – Reports come through the MedWatch program at FDA – FDA works with U.S. Pharmacopeia (USP) and the Institute of Safe Medication Practices (ISMP) to track errors in the U.S. 1. U.S. Food and Drug Administration. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048644.htm. Accessed 6/11/12.
Why do Medication Errors Occur? • A variety of reasons, including: – Miscommunication of orders • Verbal • Written – Confusion about drugs with similar names – Package design flaws – Formulations are modified (crushed) against recommendations • (e.g., Oxymorphone ER, Morphine-SR)
– Mistakes in abbreviations – Dose designations – Rarely due to carelessness or misconduct
Why do Errors Occur Commonly in Chronic Pain Management? • Lack of awareness of comorbid conditions – Wounded Warriors1,2 • PTSD • Polytrauma • Depression – General population • Stress • Depression • Anxiety • Somatization • History of physical/sexual abuse • Others 1. Clark, M.E., Scholten, J.D., Walker, R.L., & Gironda, R.J. (2009). Assessment and treatment of pain associated with combat-related polytrauma. Pain Medicine, 10(3), 456-469. 2. Lew, H.L., Otis, J.D., Tun, C., Kerns, R.D., Clark, M.E., & Cifu, D.X. (2009). Prevalence of Chronic Pain, Posttraumatic Stress Disorder and Post-concussive Symptoms in OEF/OIF Veterans: The Polytrauma Clinical Triad. Journal of Rehabilitation Research & Development, 46, 1-6
Especially Psychiatric Conditions Pain Symptoms Irritability Fatigue Tension Dysphoria Somatic focus Poor sleep
Psychiatric Symptoms Irritable
Irritability Fatigue Tension
Fatigue Irritable
Sad/depressed Fatigue
Hopeless Sad/depressed
Dysphoria
Fearful Hopeless
Somatic focus
Fearful Anergy
Poor sleep
Anergy
Concentration decreases
Appetite changes
Avoidant
Poor sleep Poor sleep
Hopelessness Hyper-vigilance Catastrophizing Decreased self care
Concentration decreases Avoidant Hopelessness
Poor concentration Poor concentration
Hyper-vigilance
Avoidant Avoidant
Catastrophizing Decreased self care Physiologic manifestations
Physiologic manifestations Increased disability Increased disability
Changes in neural networks with undertreatment
Changes in neural networks with under-treatment Suicidal
Appetite changes
Suicidal
Hopelessness
Hopelessness Hyper-vigilance
Hyper-vigilance Physiologic manifestations
Physiologic manifestations Decreased self care Decreased self care Increased disability Increased disability Changes in neural networks with under-
treatment in neural networks with under-treatment Changes Suicidal
Suicidal Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci. 2009. 11(3): 239-255.
Common Medication Errors • Chlorpheniramine/hydrocodone – Reports indicate that health care professionals have prescribed chlorpheniramine/hydrocodone for patients younger than the approved age group of 6 years old and older, more frequently than the labeled dosing interval of every 12 hours – Patients have administered the incorrect dose due to misinterpretation of the dosing directions and the use of inappropriate measuring devices • Overdose in older children, adolescents, and adults has also been associated with life-threatening and fatal respiratory events 1. U.S. Food and Drug Administration. www.fda.gov/bbs/topics/NEWS/2008/NEW01805.html. Accessed 6/11/12.
Common Medication Errors • Acetaminophen overdose – Acetaminophen is the most commonly used medication in the U.S.1 – One of the most commonly used drugs in the United States for treating pain and fever1 – In 2005, consumers purchased more than 28 billion doses of products containing acetaminophen • Acetaminophen-containing Rx narcotics represented 11 billion doses • The hydrocodone–acetaminophen combination product has been the most frequently prescribed drug since 1997 1. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002 Jan 16; 287(3) 337-44.
Acetaminophen The CDC study in 20071 also corroborated earlier data from 1998-20032 finding that a high percentage of cases of acetaminophen liver injury were related to unintentional overdose
1. Bower WA, Johns M, Margolis, HS, Williams IT, Bell B. Population-based surveillance for acute liver failure. Am J Gastroenterology. 2007;102:2459-63. 2. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Lee WM et al. Acute Liver Failure Study Group (ALFSG). Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005 Dec; 42(6):1364-72.
Acetaminophen • From 1998 to 2003, acetaminophen was the leading cause of acute liver failure in the United States1 • Unchanged in 2007 CDC survey2 • Most of the cases of severe liver injury occurred: – In patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period – Took more than one acetaminophen-containing product at the same time – Drank alcohol while taking acetaminophen products 1. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Lee WM et al. Acute Liver Failure Study Group (ALFSG). Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005 Dec; 42(6):1364-72. 2. Bower WA, Johns M, Margolis, HS, Williams IT, Bell B. Population-based surveillance for acute liver failure. Am J Gastroenterology. 2007;102:2459-63.
Medication Errors • Fentanyl Patches1
– “The directions on the product label and package insert of the fentanyl transdermal system should be followed exactly in order to avoid overdose” – “Fentanyl patches should not be used for short-term acute pain, pain that is not constant, or for pain after an operation” • “Only for moderate-to-severe chronic pain that is expected to last for any number of weeks or longer and that cannot be managed by acetaminophen-opioid combinations, nonsteroidal analgesics, or as-needed dosing with shortacting opioids” 1. U.S. Food and Drug Administration. Consumer Health Information. www.fda.gov/consumer/updates/medicationerrors031408.html. Accessed 6/11/12.
Medication Errors • Edetate Disodium vs. Edetate Calcium Disodium – Both work as chelating agents – Edetate calcium disodium was approved to treat leadpoisoning – Edetate disodium was approved to treat hypercalcemia – Fatalities have occurred when one was used instead of the other – Often mistaken for each other, both referred to as EDTA
1. U.S. Food and Drug Administration. Consumer Health Information. www.fda.gov/consumer/updates/medicationerrors031408.html. Accessed 6/11/12.
“High-Alert” Medications • The Institute for Safe Medication Practices (ISMP) has a list of high-alert medications that includes: – Adrenergic agonists – Anesthetic agents – Epidural or intrathecal medications – Opioids • Intravenous • Transdermal • Oral
Error-prone Abbreviations and Designations1 INTENDED
MISINTERPRETED
Âľg
mg
qd
qid
tiw
tid
.5
5
Inderal40
Inderal 140
1.0mg
10
100000
10,000 or 1,000,000
1. The Joint Commission
Drug Interactions
Drug Interactions • Three categories of interactions – Drug-drug – Drug-food/beverage – Drug-condition
Drug-Drug Interactions • Drug-drug interaction occurs when the effectiveness or toxicity of one medication is altered (increased or decreased) by the administration of another medicine or a substance that is administered for medical purposes • Can often be predicted but sometimes not (e.g., genetics) • Can be prevented by: – Assessment – Consideration of concomitant administration – Dose adjustments – Monitoring
Drug-Drug Interactions • Common examples – H2 Receptor antagonists and theophylline, warfarin or phenytoin – Antihistamines and sedatives or opioids – Antitussives and opioids – Opioids and sleep medications – Acetaminophen and combination opioids medications – NSAIDS and aspirin
Over-the Counter (OTC) Meds • Remember the OTCs and herbals too! – May contain the same active ingredients – Patients and healthcare providers should pay attention to the active ingredients
Drug-Food/Beverage • Drug-food interaction occurs when the effectiveness or toxicity of a medication is altered by the concomitant consumption of a food or beverage
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Drug-Food/Beverage • Other examples – Grapefruit juice – Licorice – Chocolate
U.S. Food and Drug Administration http://www.fda.gov/forconsumers/consumerupdates/ucm09 6386.htm. Accessed 6/12/12.
Drug-Condition Interactions • An existing medical condition impacts the effect of a medication, resulting in altered effectiveness or incidence of adverse effects
Drug-Condition Interactions • Examples – Hepatic Dx • Metabolism • Excretion – Renal Dx • Excretion – Lung Dx • CO2 and O2 – GI Dx • Route of administration • Complications – CNS Dx • Increased ICP
So What Can be Done?
Solutions for Drug Interactions • FDA – Off the market….. • Half of the drugs withdrawn for safety reasons from the U.S. market between 1999 and 2003 were associated with important drug interactions1,2 • Does anyone remember Terfenadine?
– Guidance for industry – FDA Interaction Work Group 1. Huang SM, Lesko LJ. Drug-drug, drug-dietary supplement, and drug-citrus fruit and other food interactions: what have we learned? Journal of Clinical Pharmacology. 2004;44:559-569. 2. Huang SM, Miller M, Toigo T, et al. Evaluation of drugs in women: regulatory perspective. In: Schwartz JLM, ed. Drug Metabolism/ Clinical Pharmacology/Principles of Gender-Specific Medicine. New York, NY: Academic Press; 2004:848-859.
Solutions for Drug Interactions • Identify the problems – Many interactions involve inhibition of metabolizing enzymes and efflux transporters – In other cases, cytochrome P450 enzymes and/or transferases and transporters are the culprits – CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A – Know what is prescribed, and who it’s being prescribed to
Can the Juice?
Patient Education about Responsibility • • • •
• • • •
Always read drug labels carefully Learn about the warnings for all drugs taken Keep medications in their original containers Ask HCP about what to avoid when prescribed a new medication – Ask about food, beverages, dietary supplements, and other drugs Check with HCP/Pharmacist before taking an OTC drug if taking any prescription medications Use one pharmacy if possible Keep all HCPs informed about everything being taken Keep records
Solutions
Tackle the Problem Areas • 24% — Communication problems (nursing, patients) • 20% — Discontinuity of care (includes referrals of existing patients and itinerant/new patients) • 19% — Lab results (logistics, timing, follow-up) • 13% — Missing values/charting • 8% — Clinical mistake (knowledge and skills) • 8% — Prescribing errors (dosage, choice, allergy or interaction) • 8% — Other
Try to Prevent Errors • Error prevention measures include – Reduced reliance on memory – Improved information access – “Error-proofing” systems – Standardization of practices – Training
Try to Prevent Errors • Examples in medical practice: – Checklists, flow sheets, tickler systems. • Handheld computers • Electronic medical records.
– Fail-safe to avoid prescribing two drugs that interact fatally – Office formularies – Guidelines synthesis – Staff inservices on prevention
Consider the Comorbidities • “Strategies for pharmacologic interventions should attempt to maximize outcomes by employing, where possible, agents that address both the pain and the comorbidities”1 • “Pharmacologic treatment should be selected based on the efficacy of the selected agent(s), potential for adverse effects, and impact on pain-associated comorbidity” 1. Nicholson B, Verma S. Comorbidities in chronic neuropathic pain. Pain Med. 2004 Mar;5 Suppl 1:S9-S27 J Am Acad Nurse Pract. 2003 Dec;15(12 Suppl):16-21; quiz 22-4. 2. McCarberg B. Managing the comorbidities of postherpetic neuralgia. J Am Acad Nurse Pract. 2003 Dec;15(12 Suppl):16-21
Consider That it’s a Mixed Bag
It Could be a Mess‌.
Rational Polypharmacy (or Not?) • Keep in mind: – That patients may have seen multiple clinicians in the course of seeking treatment for chronic pain – It is important to avoid unintentional polypharmaceutic treatment • There is the likelihood that patients may have accumulated a store of many medications.
– Educating patients about the risks of self-combining medications, and avoidance of that practice, is a critical piece of patient education and safe management – Rational polypharmacy is only safe and practical when guided by the healthcare provider. Zacharoff, K. The Role of Rational Polypharmacy in Pain Management. http://www.painedu.org/articles_timely.asp?ArticleNumber=17. PainEDU.org. Accessed 6/13/12.
EMRs • “How EMR and EHR systems can kill patients” – kevinmd.com • “I routinely see patients who are currently taking the very medications they have been electronically deemed to be allergic to. And just try to make any corrections to a patient's electronic allergy list. Lots of garbage makes its way in from many sources; very little of it can be removed without a time-consuming and frustrating effort” – Marc Gorayeb, MD
• Doctors attempting to avoid the extra hour or two per day rush through their pts. so as to get to their real work, that is, the soulcrushing computer work, and so they miss things. • I've said it before and I'll say it again. Doctoring and clerical work simply do not mix….. – PCP