Pa Patient Saf Advis 2014 Jun;11(2):61-8.
An Analysis of Reported Adverse Drug Reactions
Healthcare Executive/Administrator; Nurse; Pharmacist; Physician
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Authors

Michael O’Connor, PharmD, MS
Patient Safety Analyst

Matthew Grissinger, RPh, FISMP, FASCP
Manager, Medication Safety Analysis
Pennsylvania Patient Safety Authority

Corresponding Author
Matthew Grissinger

Abstract

Past research has shown that both the incidence and severity of adverse drug reactions (ADRs) are significant. The American Society of Health-System Pharmacists (ASHP) has published guidelines on ADR monitoring and reporting. As a part of these guidelines for pharmacists, ASHP states that any ADR program should include “evaluating, documenting, and reporting ADRs as well as intervening and providing educational feedback to prescribers, other health care professionals, and patients.” Over a 12-month period, Pennsylvania hospitals reported 4,875 reports through the Pennsylvania Patient Safety Authority’s Pennsylvania Patient Safety Reporting System describing ADRs. Nearly 30% (n = 1,365) of these reports described ADRs to contrast agents, which are considered high-alert medications by the Institute for Safe Medication Practices. Other high-alert agents that were frequently reported include opioids, taxane derivatives, platinum analogs, warfarin, and insulin. While many of the ADRs reported to the Authority could not have been prevented, there are strategies that can be utilized to reduce the incidence and severity for a portion of these ADRs. These strategies may include appropriate premedication regimens, providing clear instructions for the administration of medications with complicated infusion rate titrations, ensuring thorough patient medication and allergy histories are completed, and improving the quality of ADR reports within healthcare organizations.

Introduction

There are various published definitions for adverse drug reactions (ADRs) currently being used in practice and published in the literature. The World Health Organization defines ADRs as “any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.”1

The American Society of Health-System Pharmacists (ASHP) expands upon this definition by stating that an ADR is “any unexpected, unintended, undesired, or excessive response to a drug that requires discontinuing the drug (therapeutic or diagnostic), requires changing the drug therapy, requires modifying the dose (except for minor dosage adjustments), necessitates admission to a hospital, prolongs stay in a health care facility, necessitates supportive treatment, significantly complicates diagnosis, negatively affects prognosis, or results in temporary or permanent harm, disability, or death.”2

There are two major types of ADRs, type A and type B. Type A reactions are related to the pharmacological action of the drug and are typically predictable. Type B reactions are not related to the pharmacological action of the drug, are typically unpredictable, and are frequently classified as either immune-mediated or idiosyncratic reactions.3

Past research has shown that both the incidence and severity of ADRs are significant.3-5 A study published in 19984 sought to describe the overall incidence of ADRs and serious ADRs occurring in US hospitals by evaluating previously published literature. The overall incidence of ADRs for hospitalized patients was 15.1%. A 2005 study completed in the United Kingdom5 evaluated the incidence of ADRs on medical and surgical wards. Over a six-month time period, 14.7% of hospitalized patients experienced at least one ADR. Additionally, ADRs directly increased the length of stay for 147 patients during this same six-month time period. In order to address the significant impact that ADRs may have on patients, ASHP published guidelines on ADR monitoring and reporting in 2009.2 As a part of these guidelines for pharmacists, ASHP states that any ADR program should include “evaluating, documenting, and reporting ADRs as well as intervening and providing educational feedback to prescribers, other health care professionals, and patients.”

Analyses of ADRs reported by Pennsylvania healthcare facilities to the Pennsylvania Patient Safety Authority have identified the most common agents associated with ADRs in Pennsylvania. While many of the reported events appear to have been unpreventable, there are strategies that can be implemented to reduce the risk and severity of patient harm for several of the most common agents involved in ADRs reported to the Authority.

Methods

Authority analysts queried the Authority’s Pennsylvania Patient Safety Reporting System database for reports of ADRs submitted over a 12-month period, from November 2012 through October 2013. Pennsylvania hospitals reported 4,875 events describing ADRs during this time. Analysts manually reviewed the reported ADRs to determine the medication(s) involved in the reported event as well as other contributing factors. When the medication name field was left blank but the name of the suspected medication was provided in the event description, the medication name field was adjusted. The analysts determined, when possible, if an ADR could have been prevented. Analysts made note of ADRs involving high-alert medications, based on ISMP’s List of High-Alert Medications.6

Analysis

The Table displays the medications, or medication classes, most frequently involved in the reported ADRs. Nearly 30% (n = 1,365) of the ADRs reported to the Authority were for contrast agents. A discussion of the most frequently reported ADRs, as well as those that may be preventable, follows.

Contrast

 

Table. Predominant Medications in Adverse Drug Reaction Events Reported to the Pennsylvania Patient Safety Authority, November 2012 through October 2013 (N = 4,875) ​ ​
Medication or Medication ClassNo. of Events% of Total Events
Contrast*1,36528.0
Opioids*4168.5
Fluoroquinolones3006.1
Vancomycin2505.1
RiTUXimab*2354.8
Taxane derivatives*2194.5
Platinum analogs*1994.1
Cephalosporins1362.8
Chlorhexidine
    64
1.3
Intravenous Immune Globulin
    62
1.3
Warfarin*
    62
1.3
Insulin*
    58
1.2
Unknown
    281
5.8
* A high-alert medication
 

The majority of contrast-related reports (n = 851, 62.3%) described reactions that are consistent with product labeling for contrast agents. These reactions included headache, nausea, vomiting, itching, rash, and sensation of heat. More severe reactions included throat tightness, swelling, shortness of breath, and anaphylaxis. There were 484 instances (35.5%) of more severe reactions reported to the Authority. For 30 (2.2%) of the reports, the type of reaction could not be determined due to a lack of information. The Figure displays the specific products involved in the ADRs reported to the Authority by trade name.

Figure. Products Involved in Contrast-Related Adverse Drug Reaction Events Reported to the Pennsylvania Patient Safety Authority, November 2012 through October 2013 (N = 1,365) 


In 130 (9.5%) of the reported contrast-related reactions, the patient had a documented history of an allergy to a contrast agent. In these cases in which an allergy was present prior to administration of contrast, the use of a premedication protocol was documented in 106 (81.5%) of these cases.

Opioids

There were a total of 416 reports (8.5%) for ADRs with opioids, including reactions to the following medications: butorphanol, codeine, fentaNYL, hydrocodone-acetaminophen, HYDROmorphone, meperidine, morphine, nalbuphine, oxyCODONE, oxyCODONE-acetaminophen, and tapentadol. The event descriptions revealed a variety of reactions, ranging from generalized itching and rash to shortness of breath, excess sedation, and respiratory depression.

One trend that emerged through analysis of the opioid-related ADRs was the use of naloxone. In 136 (32.7%) of the reported ADRs with the causative agent being one or more opioids, naloxone was administered to the patient due to the level of sedation. Examples of reported ADRs that involved the administration of naloxone include the following:


Patient on fentaNYL patch, post-op from bowel resection, was found to be less responsive than last night per [registered nurse]. The patient was giving one-word or short-sentence answers to questions when stimulated. Naloxone was given with an appropriate response.
Patient was admitted for severe pain and received three doses of HYDROmorphone 2 mg [over a six-hour period]. Patient was found to be hypoxic and drowsy and received 0.04 mg of naloxone with relief.

 

Fluoroquinolones

Fluoroquinolones were cited in 300 (6.1%) of the reported ADRs. Dermatologic reactions were the most frequently reported ADRs for fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin), accounting for 268 (89.3%) of the reports.

There were four instances of documented cardiac rhythm abnormalities as detected on electrocardiogram (prolonged QT interval or ventricular tachycardia). In these instances, no other medications known to cause these changes were included in the event description or as a suspected medication. An event reported to the Authority involving prolongation of the QT interval is as follows:

Patient was admitted to the medical-surgical unit with acute bronchitis and dyspnea. Patient started on moxifloxacin 400 mg IV [intravenous] daily and received one dose in the evening and a second dose the next morning. Repeat electrocardiograms on subsequent days showed a prolonged QT interval from baseline. Moxifloxacin stopped after the second dose.

The results of a recently published case-control study indicated that there is an increased risk of hepatotoxicity associated with exposure to fluoroquinolones.7 There was one possible case of hepatotoxicity due to ciprofloxacin reported to the Authority. In this report, there were no other medications listed as a possible cause of hepatotoxicity, but there were not enough details provided in the report to definitively state that ciprofloxacin was the causative agent.

Vancomycin

Overall, 250 (5.1%) of the ADR events involved vancomycin. Infusion reactions (e.g., rash, itching, redness of the skin) accounted for 208 (83.2%) of the vancomycin-related ADRs reported to the Authority. There were several reported ADRs in which the patient’s renal function worsened during the course of vancomycin therapy (n = 14, 5.6%).

Examples of these event reports are as follows:

[There was a] likely nephrotoxic accumulation of vancomycin after following the protocol. A patient received a 2 g load then 1.5 g IV every 12 hours. The vancomycin level after four days was 100, and serum creatinine went from 0.7 to 1.8.

Patient had been on vancomycin [for 10 days before a vancomycin trough was drawn]. The patient’s serum creatinine began to climb and went from 0.9 to 1.4. On [the 10th day of therapy], the trough was drawn and the [vancomycin] level was 56.

RiTUXimab

RiTUXimab is a monoclonal antibody that is approved by the US Food and Drug Administration to treat non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, microscopic polyarteritis nodosa, and Wegener granulomatosis. RiTUXimab was involved in 235 (4.8%) of the reported ADRs. The types of reactions reported for riTUXimab were consistent with those that are reported in the prescribing information for the product.8 Infusion reactions consisted of itching, chills, rigors, hives, nausea, vomiting, and diaphoresis. The prescribing information for riTUXimab contains a boxed warning stating that severe and fatal infusion reactions may occur with riTUXimab. Serious infusion reactions reported included hypotension, chest pain, angioedema, hypoxia, and anaphylactic reactions. These reactions occurred in 94 (40.0%) of the riTUXimab-related ADR reports submitted to the Authority.

Based on the prescribing information, a premedication regimen consisting of an antihistamine and acetaminophen should be initiated prior to the infusion.8 There were examples for which the administration of premedication, as recommended in the prescribing information, was documented in the event description; however, other reports lacked this information. Examples of these event reports are as follows:

Patient having first riTUXimab infusion. Infusion started at 50 mL/hr increments. When rate increased to 150 mL/hr, the patient started to complain of feeling cold and then developed chills. Infusion stopped. Normal saline running. Physician and pharmacist were called. MethylPREDNISolone sodium succinate 100 mg IVP [IV push], meperidine 25 mg IVP, and diphenhydrAMINE 25 mg IVP were all given. Rigors stopped after approximately 10 minutes. Infusion restarted at 50 mL/hr after approximately one hour.

Patient here for first R-CHOP [riTUXimab, cyclophosphamide, DOXOrubicin, vinCRIStine, predniSONE], premedicated. RiTUXimab started. Patient complained of “itchy throat.” RiTUXimab was stopped, and additional diphenhydrAMINE 25 mg and methylPREDNISolone sodium succinate 100 mg given IVP. [Patient] returned to baseline and riTUXimab restarted [two hours later]. [Infusion] completed with no further problems.

Taxane Derivatives

Taxane derivatives are used to treat a variety of cancers. Overall, taxane derivatives were cited in 219 (4.5%) of the ADR events. The ADRs for PACLitaxel and DOCEtaxel were consistent with previously published reactions. The majority of the reports described mild reactions (e.g., rash, flushing, pruritus, fever), but several severe reactions (e.g., hypotension, angioedema, bronchospasm) were also reported.

When analyzing reactions for these medications, it is important to note that there is data to support the use of premedications to prevent and minimize hypersensitivity reactions.9,10 There were examples of cases for which premedications were listed in the event description and cases for which there was no mention of the administration of these premedications. Reports for each of these scenarios are included as follows:

[The patient] had less than ¼ of his ordered PACLitaxel dose for this date when [the patient] had complaints of back pain. [The patient] was given NSS [normal saline solution] and hydrocortisone. The patient had been pretreated with dexamethasone and diphenhydrAMINE and still reacted. CARBOplatin was able to be started as planned and was completed. The patient was able to tolerate it with no issues and was discharged after it was completed.

DOCEtaxel had been infusing for about an hour when the patient began feeling flush. Infusion was stopped and emergency medications provided. The physician was made aware and evaluated [the patient]. Once symptoms subsided, the infusion was resumed and tolerated without any further difficulty. No harm to patient.

Platinum Analogs

Analysts identified that platinum analogs were implicated in 199 (4.1%) of the reported ADRs. Platinum analogs are currently used to treat a variety of types of cancer. The reactions reported to the Authority for this group of medications (CARBOplatin, CISplatin, oxaliplatin) were consistent with those reported in previous studies. These consisted of rash, itching, hives, flushing, and shortness of breath. An example of a reaction to oxaliplatin is as follows:


Outpatient with a diagnosis of metastatic colon adenocarcinoma with metastases to lung and reproductive organs arrived to the infusion center for chemotherapy. During oxaliplatin infusion, the patient developed facial flushing. The flushing became severe. Drug [oxaliplatin] stopped and methylPREDNISolone sodium succinate 125 mg IVP, diphenhydrAMINE 25 mg IVP, and levalbuterol treatment given. Symptoms resolved. Patient rechallenged at slower rate without any further issues.

The majority of hypersensitivity reactions that occur with these agents develop after frequent treatment. Multiple studies have shown that the risk of hypersensitivity reactions increases with subsequent courses of therapy with these agents.11,12


Cephalosporins

Cephalosporins were involved in 136 (2.8%) of the ADR events. The majority of the reactions seen with cephalosporins (n = 102, 75.0%) were dermatologic in nature (e.g., rash, red skin, itching) and hives. Previous studies have shown that there is a small percentage of patients who will experience a reaction to a cephalosporin if there is a documented history of penicillin allergy.13,14 There were eight instances in which the patient had a documented penicillin allergy. The reactions for these patients were hives (five cases), redness of the skin (one case), shortness of breath (one case), and swelling of the tongue (one case).


Chlorhexidine

Chlorhexidine is a topical product that is used as a part of infection prevention practices in many hospitals and health systems. All of the reports (n = 64) submitted to the Authority for chlorhexidine described dermatologic reactions (e.g., redness, itching, rash).

Intravenous Immune Globulin

Analysts identified 62 (1.3%) ADR events that involved intravenous immune globulin (IVIG). The events reported to the Authority described ADRs that consisted of itching, flushing, chills, fever, nausea, and diaphoresis. While the majority of the reports described these mild infusion reactions, there were several that described more severe reactions following infusion of an IVIG product. An example of a severe infusion reaction is as follows:

Patient in for immune globulin infusion. Premedications given and infusion started at 25 mL/hr, with max rate calculated at 150 mL/hr. Rate increased to 50 mL/hr per protocol [with] vital signs stable. Evaluated patient prior to next rate increase, and noted change in respiratory rate. Patient reported difficulty breathing and chest tightness. Infusion stopped and the doctor evaluated the patient. Patient nebulizer activated and emergency medications given per physician. Oxygen increased to 15 L/minute. Patient received diphenhydrAMINE 25 mg IV, hydrocortisone sodium succinate 100 mg IV, and methylPREDNISolone sodium succinate 100 mg IV. Vital signs improved, and the patient [was transferred] to hospital in stable condition.

Warfarin

All of the ADR reports (n = 62) submitted to the Authority for warfarin revealed an elevated international normalized ratio (INR). There were not enough details (e.g., dose, duration of therapy) provided in the event descriptions to determine causality or contributing factors for these reports. An example of a reported ADR for warfarin is as follows:
Vitamin K administered to patient due to elevated INR levels (repeat levels drawn x1). Patient on Coumadin 1 mg to 7.5 mg.

Insulin

All of the ADR reports (n = 58) submitted to the Authority for insulin therapy described patients with low blood glucose values. There were not enough details provided in the reports (e.g., insulin product, dose, time of dose administration) to determine causality or contributing factors for these reports. An example of this type of event report is as follows:

Patient on insulin drip with titration accuchecks being done every hour. [Most recent] accucheck was 60. Patient was nonverbal with no physical symptoms noted. Physician aware, patient given ½ amp of D50 [Dextrose 50%].

Unknown

There were a total of 281 (5.8%) ADR reports in which the suspected medication, or medication class, could not be determined. In these events, multiple medications from different classes were listed as possible causative agents.

Risk Reduction Strategies


When evaluating events involving medications, it is important for organizations to focus on those that may be prevented or minimized. There are several questions that can be used to help determine whether or not an ADR could have been prevented.15 A listing of such questions can be found in “Criteria for Determining Preventability of an ADR.”

For several of the aforementioned events, there are mitigation strategies that can be utilized to reduce the incidence and severity of patient harm. In many of the ADRs reported to the Authority, there was not enough information included to determine the specific medication involved in the ADR, the type of reaction, or if the event may have been preventable.

Potential risk reduction strategies include the following:

Contrast

  • The American College of Radiology (ACR)16 offers several elective premedication regimens to be given prior to contrast for patients with a documented allergy:
    • PredniSONE 50 mg by mouth at 13 hours, 7 hours, and 1 hour before contrast media injection, plus diphenhydrAMINE 50 mg IV, intramuscularly, or by mouth 1 hour before contrast medium.
    • MethylPREDNISolone 32 mg by mouth 12 hours and 2 hours before contrast media injection. An antihistamine (e.g., diphenhydrAMINE) may also be added to this regimen.
  • When time does not allow for either of the regimens listed above, ACR offers the following for patients with a documented allergy to contrast:16
    • MethylPREDNISolone sodium succinate 40 mg or hydrocortisone sodium succinate 200 mg IV every 4 hours until contrast study is required, plus diphenhydrAMINE 50 mg IV 1 hour prior to contrast injection.
    • Omit steroids entirely and give diphenhydrAMINE 50 mg IV.
    • IV steroids have not been shown to be effective in preventing ADRs with contrast when administered less than 4 to 6 hours before contrast injection.
  • While the ADRs reported to the Authority did not reveal any incidences of contrast-induced nephropathy (CIN), this is a concern for patients with certain risk factors.16 See “Risk Factors for the Development of Contrast-Induced Nephropathy” for a list of risk factors identified by ACR. Developing and reviewing institutional guidelines for the identification and management of patients at risk for CIN can prevent or mitigate patient harm.

Vancomycin

  • Reviewing institutional guidelines for the administration and therapeutic monitoring of vancomycin.
  • Ensuring that vancomycin infusions are administered over a period of at least one hour to minimize infusion-related reactions. For larger doses (e.g., 2 g), the infusion time should be extended to 1.5 to 2 hours.17
  • Utilizing the published report “Therapeutic Monitoring of Vancomycin in Adult Patients” to guide the dosing and monitoring of vancomycin.17

RiTUXimab

  • Ensuring that protocols are in place for riTUXimab infusions that address premedication, management of infusion reactions, and infusion rates.
  • Premedicating patients before each riTUXimab infusion with an antihistamine and acetaminophen.8
  • For the first riTUXimab infusion, initiating the infusion at a rate of 50 mg/hr and then increasing the infusion rate by 50 mg/hr increments every 30 minutes (in the absence of an infusion reaction), to a maximum of 400 mg/hr.8
  • For subsequent riTUXimab infusions, initiating the infusion at a rate of 100 mg/hr and then increasing the rate by 100 mg/hr increments every 30 minutes (in the absence of an infusion reaction), to a maximum of 400 mg/hr.8

Taxane Derivatives

  • Reviewing protocols for PACLitaxel and DOCEtaxel to ensure that proper premedication regimens are included. Studies have shown that the incidence and severity of hypersensitivity reactions can be reduced by administering corticosteroids and antihistamines prior to treatment with taxane derivatives.9,10

Platinum Analogs

  • Ensuring that appropriate treatment for hypersensitivity reactions for CARBOplatin, CISplatin, and oxaliplatin is included in protocols for these agents. Consider establishing clear guidelines for the treatment of these hypersensitivity reactions (e.g., corticosteroids, antihistamines).

Intravenous Immune Globulin

Ensuring that instructions for the infusion rates are clearly defined for staff, as dosing and infusion rates vary among the different IVIG products currently on the market. Titration schedules also vary, many of which are product specific and included in the product-specific prescribing information. It is important that these are clearly defined for nurses and other healthcare practitioners.

Medication Reconciliation

  • Reviewing policies and procedures for collecting and documenting patient medications and allergy histories.
  • Ensuring that medication allergies, including the type of reaction, are documented in the patient’s medical record.

ADR Reporting Quality

  • In order to improve the ability of hospitals and health systems to utilize reported ADRs and ensure that appropriate mitigation strategies are used, there are recommendations provided by the US Food and Drug Administration to improve the quality of reported events for pharmacovigilance practices.18 If used, these recommendations can also improve the ability of an organization to utilize its internal ADR data.
  • The characteristics of a good case report include the following:18
    • Description of the event, including the time to onset of signs or symptoms
    • Suspected and concomitant product therapy details, including over-the-counter medications
    • Patient characteristics (e.g., age, race, sex), baseline condition prior to the initiation of therapy, use of concomitant medications, comorbid conditions, and presence of other risk factors
    • Clinical course of the event and patient outcomes (e.g., hospitalization, death)
    • Relevant therapeutic measures and laboratory data, if appropriate
    • Information about the response to therapy dechallenge or rechallenge

Conclusion


Although not all ADRs can be prevented, it is still important for organizations to evaluate the medications, or medication classes, suspected to be involved with ADRs. In order for organizations to see tangible benefits from ADR reporting programs, it is important to continually review reported ADRs; educate prescribers, caregivers, and patients about suspected ADRs; identify and monitor drugs most likely to cause an ADR; and implement strategies to minimize the incidence and severity of ADRs. By continually assessing the types of ADRs being reported, reviewing the mitigation strategies utilized for medications involved in these reports, and updating protocols as necessary, practitioners can likely reduce the incidence and severity of ADRs.

Notes

  1. Requirements for adverse reaction reporting. Geneva (Switzerland): World Health Organization; 1975.
  2. ASHP guidelines on adverse drug reaction monitoring and reporting. Am J Health-Syst Pharm 1995 Feb 15;52(4):417-9.
  3. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000 Oct 7;356(9237):1255-9.
  4. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998 Apr 15;279(15):1200-5.
  5. Davies EC, Green CF, Taylor S, et al. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS ONE 2009;4(2):e4439.
  6. Institute for Safe Medication Practices. ISMP’s list of high-alert medications [online]. 2012 [cited 2014 Apr 21]. http://www.ismp.org/Tools/institutional highAlert.asp
  7. Alshammari TM, Larrat EP, Morrill HJ, et al. Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study. Am J Health Syst Pharm 2014 Jan 1;71(1):37-43.
  8. Genentech, Inc. Rituxan® (rituximab) prescribing information [online]. 2013 Sep [cited 2014 Apr 21]. http://www.gene.com/download/pdf/rituxan_prescribing.pdf
  9. Trudeau ME, Eisenhauer EA, Higgins BP, et al. Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol 1996;14(2):422-8.
  10. Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 1994 Jul;5(6):495-505.
  11. Markman M, Kennedy A, Webster K, et al. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 1999 Apr;17(4):1141-5.
  12. Weiss RB. Hypersensitivity reactions. Semin Oncol 1992 Oct;19(5):458-77.
  13. Apter AJ, Kinman JL, Bilker WB, et al. Is there cross-reactivity between penicillins and cephalosporins? Am J Med 2006 Apr;119(4):354.e11-9.
  14. Blanca M, Fernandez J, Miranda A, et al. Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies. J Allergy Clin Immuno 1989 Feb;83(2 Pt 1):381-5.
  15. Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm 1992 Jun;27(6):538.
  16. American College of Radiology. ACR manual on contrast media, version 9 [online]. 2013 [cited 2014 May 6]. http://www.acr.org/quality-safety/resources/contrast-manual
  17. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009 Jan 1;66(1):82-98.
  18. US Food and Drug Administration. Guidance for industry: good pharmacovigilance practices and pharmacoepidemiologic assessment [online]. 2005 Mar [cited 2014 Jan 27]. http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126834.pdf

Criteria for Determining Preventability of an ADR


Answering “yes” to one or more of the following suggests that at an adverse drug reaction (ADR) is preventable:
  • Was the medication involved inappropriate for the patient’s clinical condition?
  • Was the dose, route, or frequency of administration of the medication inappropriate for the patient’s age, weight, or disease state?
  • Was required therapeutic drug monitoring or another necessary laboratory test not performed?
  • Was there a history of allergy or previous reactions to the medication?
  • Was a drug interaction involved in the ADR?
  • Was a toxic serum drug concentration (or laboratory monitoring test) documented?
  • Was poor adherence involved in the ADR?
Source: Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm 1992 Jun;27(6):538.

Risk Factors for the Development of Contrast-Induced Nephropathy

The American College of Radiology suggests that the presence of any of the risk factors listed below may warrant preadministration serum creatinine screening in patients ordered to receive intravascular iodinated contrast agents. Developing tools to assess patients for these risk factors can help avoid or identify contrast-induced nephropathy in order to mitigate patient harm.

  • Age greater than 60 years

  • History of renal disease, including the following:

    • Dialysis

    • Kidney transplant

    • Single kidney

    • Renal cancer

    • Renal surgery

  • History of hypertension requiring medical therapy

  • History of diabetes mellitus

  • Use of metFORMIN or metFORMIN-containing medications

Source: American College of Radiology. ACR manual on contrast media, version 9 [online]. 2013 [cited 2014 May 6]. http://www.acr.org/quality-safety/resources/contrast-manual


Self-Assessment Questions

Learning Objectives

  • Identify the medications most frequently involved in adverse drug reaction (ADR) events submitted to the Pennsylvania Patient Safety Authority.
  • Recognize ADRs that may be prevented or mitigated.
  • Identify risk reduction strategies that can be implemented as a part of an ADR monitoring program.

Questions

The following questions about this article may be useful for internal education and assessment. You may use the following examples or come up with your own questions.

    1. Which of the following medications, or medication classes, was most frequently reported to the Authority as an ADR?
      1. Heparin
      2. Opioids
      3. Warfarin
      4. Contrast
      5. Vancomycin
    2. Which of the following is not a question that may help practitioners and organizations determine the preventability of ADRs?
      1. Was required therapeutic drug monitoring or another necessary laboratory test not performed?
      2. Was a drug interaction involved in the ADR?
      3. Was poor adherence involved in the ADR?
      4. Was a nonformulary medication involved in the ADR?
      5. Was the medication involved inappropriate for the patient’s clinical condition?
    3. For which of the following medications, or medication classes, should the infusion time be extended for larger doses to reduce the risk of adverse effects?
      1. Platinum analogs
      2. RiTUXimab
      3. Vancomycin
      4. Insulin
      5. Cephalosporins
    4. Which of the following is not a risk factor for the development of contrast-induced nephropathy?
      1. History of diabetes mellitus
      2. History of liver disease
      3. Age greater than 60 years
      4. Use of metFORMIN or metFORMIN-containing medications
      5. History of hypertension requiring medical therapy
    Question 5 refers to the following case

    A patient presented for a planned, outpatient computed tomography scan of the abdomen, with contrast. Shortly after administration of the contrast agent, the patient began complaining of severe itching on both arms and legs. Hives were noted upon physical examination. The imaging procedure was temporarily stopped, and the patient was treated for an allergic reaction. After the reaction was noticed, a note was discovered in the patient’s medical record that described a previous reaction (redness of the skin, hives) to a contrast agent.
    1. Which of the following risk reduction strategies may have prevented this reaction?

      1. Conducting a thorough patient medication and allergy history

      2. Continuing with the imaging procedure as planned

      3. Administering 0.9% sodium chloride prior to the imaging procedure

      4. Considering an alternative contrast agent

      5. Administering intravenous steroids immediately prior to the imaging procedure

 

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