FP Essentials™

Adverse Effects of Commonly Used Drugs, Herbal Medicines, and Dietary Supplements

Call for Authors

This edition of FP EssentialsTM will cover recent updates about the adverse effects of commonly used drugs, herbal medicines, and dietary supplements. The content should include: related general concepts; adverse effects of commonly used drugs in children and adolescents; adverse effects of commonly used drugs in adults; and adverse effects of herbal medicines and dietary supplements. The content should emphasize recent, relevant literature, rather than provide a general review of the four topics.

This edition of FP Essentials should be approximately 10,000 words in length, divided into 4 sections of approximately 2,500 words each, plus an abstract of no more than 200 words for each section, key practice recommendations, a maximum of 15 tables and figures, recommended readings, and references. This edition should focus on what is new in each topic and should answer the key questions listed for each section. Each section should begin with an illustrative case, similar to the examples provided, with modifications to emphasize key points; each case should have a conclusion that demonstrates resolution of the clinical situation. The references suggested here include information that should be considered in preparation of this FP Essentials. However, these references are only a useful starting point that should be used to identify additional information to review.

Section 1: Adverse Effects of Commonly Used Drugs: General Concepts

Example case: Emily, a 46-year-old woman, has type 2 diabetes that does not require insulin, hypertension, hyperlipidemia, morbid obesity, lumbar spinal stenosis, and gout. She presents to your office after being discharged from the hospital for treatment of acute low back pain. During the hospitalization, the hospitalist made modifications and an addition to her drug regimen. Since discharge, she reports sleepiness and dizziness. She thinks she is having an adverse reaction to the new drug.

Key questions to consider:

  • How frequently do adverse drug reactions occur? How often are they recognized (or not recognized) by health care professionals?
  • What are the best strategies to recognize and prevent adverse drug reactions in children, adolescents, and adults? What is the role of the pharmacist in recognizing or avoiding adverse drug effects?
  • To what extent does polypharmacy contribute to adverse drug effects?  Is there a threshold number of drugs above which the risk of adverse drug effects increases markedly?
  • What strategies are effective to minimize polypharmacy, and to instruct patients on recognizing potential drug-drug interactions?
  • What is the prescribing cascade?
  • What is the role of the electronic health record in mitigating polypharmacy? What strategies are useful for encouraging patients to bring all of their drugs to office visits?
  • What is the Advance Drug Reaction (ADR) Probability Scale, or Naranjo Scale, and how can it be used to assess whether or not a patient is having a true adverse reaction to a drug?
  • If you are certain that a patient’s symptoms are not due to an adverse drug effect, what are the best strategies to reassure the patient she is not having such an effect?
  • How and when should a physician report adverse drug reactions to the Food and Drug Administration? What tracking systems are available to health care professionals (eg, drug interaction software programs) to minimize adverse events?

Initial references to consider:

  • US Food and Drug Administration. Drugs. FDA adverse event reporting system (FAERS) (formerly AERS). Updated September 10, 2012. Available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm(www.fda.gov).
  • Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-245.
  • Kelly WN. Potential risks and prevention, part 1: fatal adverse drug events. Am J Health Syst Pharm. 2001;58(14):1317-1324.
  • Kelly WN. Potential risks and prevention, part 2: drug-induced permanent disabilities. Am J Health Syst Pharm. 2001;58(14):1325-1329.
  • Marcellino K, Kelly WN. Potential risk factors and prevention, part 3: drug-induced threats to life. Am J Health Syst Pharm. 2001;58(15):1399-1405.
  • Al-Tajir GK, Kelly WN. Epidemiology, comparative methods of detection, and preventability of adverse drug events. Ann Pharmacother. 2005;39(7-8):1169-1174.
  • Wessell AM, Ornstein SM, Jenkins RG, Nemeth LS, Litvin CB, Nietert PJ.  Medication safety in primary care practice: results from a PPRNet quality improvement intervention. Am J Med Qual. 2013;28(1):16-24.
  • Rollason V, Vogt N. Reduction of polypharmacy in the elderly: a systematic review of the role of the pharmacist. Drugs Aging. 2003;20(11):817-832.
  • Agency for Healthcare Research and Quality. AHRQ health literacy universal precautions toolkit. Brown bag medication review. April 2010. AHRQ Publication No. 10-0046-EF. Available at http://www.nchealthliteracy.org/toolkit/Toolkit_w_appendix.pdf(www.nchealthliteracy.org).
  • Merandi J, Morvay S, Lewe D, et al. Improvement of medication event interventions through use of an electronic database. Am J Health Syst Pharm. 2013;70(19):1708-1714.

Section 2: Adverse Effects of Commonly Used Drugs in Children and Adolescents

Example case: Lily, a 7-year-old girl, is brought to your office by her mother Augusta. Augusta reports Lily has had low-grade fever, rhinorrhea, and cough for the last few days. She has a history of seizures and takes phenobarbital and phenytoin daily. Lately, Augusta has been giving Lily over-the-counter acetaminophen, guaifenesin, and pseudoephedrine for the cold symptoms.

Key questions to consider:

  • How common are emergency department evaluations, hospital admissions, and morbidity related to adverse drug reactions in children and adolescents?
  • What are the drugs prescribed for children and adolescents by family physicians that most often result in emergency department visits, hospitalizations, and/or morbidity? (Limit the discussion to a maximum of 10 drugs).
  • What are the serious drug adverse effects that result in emergency department visits, hospitalizations, and deaths?
  • How often are prescription drugs versus over-the-counter drugs involved in serious adverse effects?
  • Are there particular drug-drug interactions in children and adolescents that predispose to serious drug adverse effects for prescription drugs and over-the-counter drugs?

Initial references to consider:

  • Top 25 medicines by dispensed prescriptions (U.S.). IMS Health National Prescription Audit. Updated March 22, 2013. Available at http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/Press%20Room/2012_U.S/Top_25_Medicines_Dispensed_Prescriptions_U.S..pdf.(www.imshealth.com)
  • Institute for Safe Medication Practices. Adverse drug events in children under age 18. Executive summary. January 16, 2014. Available at http://www.ismp.org/quarterwatch/pdfs/2013Q1-Kids-Special.pdf(www.ismp.org).
  • Schillie SF, Shehab N, Thomas KE, Budnitz DS. Medication overdoses leading to emergency department visits among children. Am J Prev Med. 2009;37(3):181-187.
  • Cohen AL, Budnitz DS, Weidenbach KN, et al. National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents. J Pediatr. 2008;152(3):416-421.
  • Zed PJ, Haughn C, Black KJ, et al. Medication-related emergency department visits and hospital admissions in pediatric patients: a qualitative systematic review. J Pediatr. 2013;163(2):477-483.
  • Kunac DL, Kennedy J, Austin N, Reith D. Incidence, preventability, and impact of adverse drug events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study. Paediatr Drugs. 2009;11(2):153-160.
  • Schaefer MK, Shehab N, Cohen AL, Budnitz DS. Adverse events from cough and cold medications in children. Pediatrics. 2008;121(4):783-787.
  • Vassilev ZP, Kabadi S, Villa R. Safety and efficacy of over-the-counter cough and cold medicines for use in children. Expert Opin Drug Saf. 2010;9(2):233-242.

Section 3: Adverse Effects of Commonly Used Drugs in Adults

Example case: Mr. Burns, a 77-year-old man presents for a routine health maintenance examination. At the beginning of the examination, you conduct a drug reconciliation and see substantial polypharmacy. The patient is currently taking 14 prescription drugs and, sometimes, 3 to 5 over-the-counter drugs/day. Mr. Burns says that he has multiple health care professionals who prescribe his drugs, and that he does not read the drug information pamphlets given to him by the pharmacist.

Key questions to consider:

  • How common are emergency department evaluations, hospital admissions, and morbidity related to adverse drug reactions in adults?
  • What are the drugs prescribed for adults by family physicians that most often result in emergency department evaluations, hospitalizations, and/or morbidity? (Limit the discussion to a maximum of 10 drugs)
  • What are the serious drug adverse effects that result in emergency department evaluations, hospitalizations, and deaths?
  • How often are prescription drugs versus over-the-counter drugs involved in those serious adverse effects?
  • What are the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, and why does the Center for Medicare and Medicaid Services require insurance plans to follow them?
  • What are the START/STOPP criteria for prescribing drugs in older adults?
  • Is polypharmacy ever appropriate in older adults?
  • Should physiologic age, rather than chronologic age, be a prescribing consideration for older adults?  If so, how can physiologic age be determined?

Initial references to consider:

  • American Geriatrics Society. AGS Beers criteria for potentially inappropriate medication use in older adults. 2012. Available at http://www.americangeriatrics.org/files/documents/beers/PrintableBeersPocketCard.pdf(www.americangeriatrics.org).
  • Salvi F, Marchetti A, D'Angelo F, Boemi M, Lattanzio F, Cherubini A. Adverse drug events as a cause of hospitalization in older adults. Drug Saf. 2012;35(Suppl 1):29-45.
  • Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012.
  • Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events. JAMA. 2006;296(15):1858-1866.
  • Wysowski DK. Surveillance of prescription drug-related mortality using death certificate data. Drug Saf. 2007;30(6):533-540.
  • Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004;329(7456):15-19.
  • Thomsen LA, Winterstein AG, Søndergaard B, Haugbølle LS, Melander A. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care. Ann Pharmacother. 2007;41(9):1411-1426.
  • Lam MP, Cheung BM. The use of STOPP/START criteria as a screening tool for assessing the appropriateness of medications in the elderly population. Expert Rev Clin Pharmacol. 2012;5(2):187-197.
  • Sox H. Tools for decision making. In: Max MD, Lynn J, eds. Symptom Research: Methods and Opportunities. Bethesda, MD: National Institute of Dental Health and Craniofacial Research, National Institutes of Health, Department of Health and Human Services; 2003. Available at http://painconsortium.nih.gov/symptomresearch/chapter_14/Part_3/sec4/chspt3s4pg1.htm(painconsortium.nih.gov).

Section 4: Adverse Effects of Common Prescription Drugs: Herbal Medicines and Dietary Supplements

Example case: Laura, a 33-year-old woman, presents to your office for a follow-up visit for migraine headache, worsening fibromyalgia, and desire to lose weight. She currently takes sumatriptan as needed for migraines, and cyclobenzaprine and tramadol up to three times daily to control the fibromyalgia pain. In addition, today she has brought a bag with more than 10 herbal medicines and dietary supplements recommended to her by a friend to reduce her pain and help with weight loss. Laura reports that she takes these sporadically, but cannot give details on exactly how often or in what quantities.

Key questions to consider:

  • How common are emergency department evaluations, hospital admissions, and morbidity related to the use of herbal medicines and dietary supplements?
  • What are the herbal medicines and dietary supplements that most often lead to emergency department evaluations, hospitalizations, and/or death? (Limit the discussion to no more than 10 medicines).
  • What are the serious adverse effects that lead to emergency department evaluations, hospitalizations, and deaths?
  • What are the common prescription drugs with which herbal medicines and dietary supplements interact? What is the nature of those interactions (eg, metabolic, excretory)? What are the most important of those interactions?
  • When and how should a family physician report adverse reactions to herbal medicines or dietary supplements? What tracking systems are available (eg, drug interaction software programs) to minimize adverse events?
  • How do electronic health records track and inform about potential interactions among herbal medicines, dietary supplements, prescription drugs, and over-the-counter drugs?
  • How should patients be counseled regarding safe use of herbal medicines and dietary supplements, and their potential interactions with prescription drugs?
  • What does it mean for an herbal medicine or dietary supplement to be USP verified? Does that verification increase safety? How does one determine if an herbal medication or dietary supplement is USP verified?

Initial references to consider:

  • Pittler MH, Schmidt K, Ernst E. Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev. 2005;6(2):93-111.
  • Posadzki P, Watson LK, Ernst E. Adverse effects of herbal medicines: an overview of systematic reviews. Clin Med. 2013;13(1):7-12.
  • Posadzki P, Watson L, Ernst E. Herb-drug interactions: an overview of systematic reviews. Br J Clin Pharmacol. 2013;75(3):603-618.
  • Chen XW, Sneed KB, Pan SY, et al.  Herb-drug interactions and mechanistic and clinical considerations. Curr Drug Metab. 2012;13(5):640-651.
  • Na DH, Ji HY, Park EJ, Kim MS, Liu KH, Lee HS. Evaluation of metabolism-mediated herb-drug interactions. Arch Pharm Res. 2011;34(11):1829-1842.
  • Chen XW, Serag ES, Sneed KB, et al.  Clinical herbal interactions with conventional drugs: from molecules to maladies. Curr Med Chem. 2011;18(31):4836-4850.
  • Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798.
  • Hussain MS. Patient counseling about herbal-drug interactions. Afr J Tradit Complement Altern Med. 2011;8(suppl 5):152-163.
  • US Pharmacopeial Convention. USP verified dietary supplements. Available at http://www.usp.org/usp-verification-services/usp-verified-dietary-supplements(www.usp.org).