The Ten Most Common Prescribing Errors

Educational Objectives

The goal of this program is to improve prescribing of medications. After hearing and assimilating this program, the clinician will be better able to:

1. Identify common mistakes made when prescribing medications.
2. Explain impact of errors made when prescribing medications.
3. Develop strategies to mitigate prescribing errors.

Summary

Mistakes when ordering medications (#10): are not necessarily errors associated with knowledge deficits, but rather physical ordering; common ordering mistakes include wrong drug, dose, time, frequency, route, or patient, provider not paying attention, or not using tools; the most frequent mistake is wrong route ordering

Dosage-form errors (#9): immunosuppressants — there are 2 forms of cyclosporin, nonmodified (Sandimmune) and modified (Neoral or Gengraf); nonmodified form (has decreased bioavailability) not interchangeable with modified form; mycophenolate — 2 dosage forms, CellCept and delayed-release form (Myfortic), not interchangeable; trimethoprim-sulfamethoxazole — eg, Bactrim; 5 to 1 ratio (sulfamethoxazole predominates); weight-based doses based on trimethoprim; when switching between intravenous (IV), liquid, and tablet forms, 1 double strength tablet is 160 mg of trimethoprim; divalproex sodium or valproic acid — Depakote; forms not interchangeable

Drug-monitoring errors (#8): misinterpreting drug levels leads to wrong doses; inappropriate timing of levels is common; examples — with digoxin (ordered IV for atrial fibrillation), check level after 6 to 8 hours after finishing of IV load (prolonged distribution period); voriconazole has long half-life so it is not recommended to check a level until patient has been on the drug 5 to 7 days; aminoglycosides uses peaks and troughs for therapeutic drug monitoring (source of confusion; consult pharmacist); there is unfamiliarity with target range, as with, eg, vancomycin, which recently changed from trough dosing to area under the curve (AUC) dosing for certain indications; drugs like phenytoin use total and free levels; free levels are more accurate and recommended; may be failure to consider clinical context; use of phenobarbital for alcohol withdrawal involves no efficacy range; get levels only if toxicity suspected

Failure to recognize drug-laboratory interactions: direct thrombin inhibitors (eg, argatroban, bivalirudin), can falsely elevate international normalized ratio

Therapeutic drug monitoring (TDM): drugs should have narrow therapeutic window, and inter- and intrapatient variability; there should be correlation among drug concentration, efficacy, and toxicity; terminology may be more relevant for some junior prescribers; analyzing where these levels fall on concentration-time curve allows better visualization; peak or maximum concentration is usually drawn ≥30 min after infusion is ended; eg, aminoglycosides use peaks to determine efficacy; AUC is total drug exposure over a percent of dosing interval (ie, total amount of drug in bloodstream over a period of time); can be calculated by getting 1 or 2 levels after dose; with, eg, vancomycin, AUC monitoring is being adopted for certain indications; trough, or minimum concentration, is drawn 30 min prior to next dose; many drugs use trough for their therapeutic drug target, so it is least variable point in dosing interval; steady state, when rate of drug administration equals rate of elimination; this takes time (usually obtained after 4 to 5 half-lives); drugs with long half-lives take long time to reach steady state

Opioid prescribing errors (#7): high-alert medications according to Institute for Safe Medication Practices (ISMP); variety of drugs and dosage forms and confusion about converting one opioid to another; some patient- and drug-specific factors to avoid; fentanyl, 100 times more potent than morphine, is dosed in μg, not mg; probably not for opioid-naive patients outside of an intensive care unit setting; 1 mg IV hydromorphone (Dilaudid) is not similar to 1 mg IV morphine (it equals ≈7 mg IV morphine); shown to cause error; events cited by Pennsylvania Safety Authority did show ≥1 mg of IV hydromorphone contributed to 70% of preventable adverse drug reaction reports

Drug-specific factors: starting dose of IV hydromorphone for an opioid-naive patient is 0.2 mg (not 1 or 2); morphine and oxycodone have concentrated liquid formulations available (potential source of error)

Errors in prescribing anticoagulation (#6): ISMP considers this high-alert medication; inappropriate dosing with direct oral anticoagulants (DOAC) common; underdosing more common than overdosing; outpatient prescriptions bigger risk factor for underdosing compared with inpatient prescriptions

Transitioning between agents: with heparin drip to DOAC, no overlap needed; DOAC can be started as soon as heparin is discontinued; from enoxaparin to DOAC, no overlap period; start apixaban or rivaroxaban at time next dose is due for enoxaparin; know what heparin protocols are available at institution

Errors related to drug allergies (#5): study found that inadvertently overlooking a patient’s drug allergy responsible for 76% of allergy mistakes; clinical decision support system (CDSS) alerts show potential reactions; classes involved are anti-infective agents, opioids, and nonopioid analgesics; failure to document an override reason or inappropriately bypassing alert typically result in a call from pharmacist; appropriately documenting an override reason in computerized provider order entry (CPOE) less likely to result in call from pharmacist

Penicillin allergy: leads to prescribing of less effective therapies (eg, vancomycin), more toxic therapies (eg, clindamycin, fluoroquinolones), use of agents that are broader (eg, carbapenems) and more costly (eg, carbapenems, aztreonam); understanding cross-reactivity important when discussing beta-lactam allergies; true cross-reactivity largely based on R1 side chain, not beta-lactam core ring; identical side chains pose highest risk for an IgE-mediated allergy cross-reactivity; cephazolin does not share a side chain with any other penicillin or cephalosporin; safe to administer in majority of cases

Mistakes related to drug-drug interactions (#4): there are medications that are substrates for cytochrome (CYP)450 enzymes for metabolism and P-glycoprotein (P-gp) for absorption; there are enzymes that induce and inhibit these entities; inhibitors increase concentration of substrate and inducers decrease concentration; DOAC drug-drug interactions are common and are overlooked; apixaban, rivaroxaban, edoxaban, and dabigatran are substrates for P-gp; apixaban and rivaroxaban are both substrates of CYP 3A4; strong inducers and inhibitors of CYP 3A4 and P-gp have potential for drug-drug interactions; recommendations — avoid both apixaban and rivaroxaban with strong inducers of CYP 3A4 and P-gp; reduce dose recommendation by 50% for apixaban if patient on 5- or 10-mg dose; if patient is on 2.5-mg BID dose, avoid apixaban with strong inhibitors; avoid strong inhibitors with rivaroxaban; manufacturer recommends a select few can be given with caution if creatinine clearance >80 mL/min; warfarin — associated with >200 drug interactions; strong CYP inducers decrease warfarin concentration; 4 main inhibitors are fluconazole (has the most CYP 2C9; other azoles also inhibitors), amiodarone, trimethoprim-sulfamethoxazole, and metronidazole (Flagyl)

Medication reconciliation (#3): one of the National Patient Safety Goals; 3 phases are listing of medication history, transitions of care, and discharge

Errors involving renal dosing (#2): inappropriate prescribing of renally clear medications is common in inpatient, outpatient, and long-term care settings; failure to adjust medications when transitioning between renal replacement modalities is common; concern in intensive care unit setting; also includes inappropriate overriding of alerts

Polypharmacy and failure to deprescribe (#1): significant issue especially for elderly patients; definition is regular use ≥5 medications; definition also includes use of multiple medications that are unnecessary, with potential to harm; reduce routine use of aspirin in patients >75 yr old

Readings

Anon. Intensive review of internal medicine palms DL. JAMA Intern Med. 2018;178(9):1267-1269; Carpenter M et al. Clinically relevant drug-drug interactions in primary care. Am Fam Physician. 2019;99(9):558-564; Grigoryan L et al. Use of antibiotics without a prescription in the U.S. population: a scoping review. Ann Intern Med. 2019;171(4):257-263; Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med. 2009;24(1):1-10; Lteif L, Eiland LS. The basics of penicillin allergy: what a clinician should know. Pharmacy (Basel). 2019;7(3):94; Patton K, Borshoff DC. Adverse drug reactions. Anaesthesia. 2018;73 Suppl 1:76-84; Wittich CM et al. Medication errors: an overview for clinicians. Mayo Clin Proc. 2014;89(8):1116-25.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Groetzinger spoke at Updates in Internal Medicine 2020: Advanced Changing Practice, presented by the University of Pittsburgh School of Medicine, Center for Continuing Education in the Health Sciences, held virtually October 22-23, 2020. For more information about this sponsor please visit https://cce.upmc.com/. The Audio Digest thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

IM680501

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.