Safe medication use based on knowledge of information about contraindications concerning cross allergy and comprehensive clinical intervention

Figures & data

Table 1 Risk register for prevention of cross allergy

Item	Description
Risk owner	Vice dean of pharmacy and vice president in charge of medical care
Risk type	Patient care and safety
Risk description	Risk of medication errors due to cross allergy
Actual or potential risk?	Actual
Existing controls	Simple inquiry by doctors and nurses without standardized recording of drug allergies
Consequences	5
Likelihood	5
Initial risk rating	25
Risk reduction strategies and additional controls required	A pharmacist-led multidisciplinary team initiated an intervention program on cross allergy in August 2008. Clinical intervention measures were as follows:
	• Doctors must record any real or potential allergies or sensitivities in the electronic medical record which occurred prior to admission or during hospitalization.
	• Implement maintenance of pharmacy storehouse information management subsystem. For example, a warning that “Patients who are allergic to an aminoglycoside antibiotic should not receive any aminoglycosides” will appear when doctors prescribe isepamicin for patients with a history of allergy to amikacin.
	• Publish a standard operating procedure for drug allergy management and an updated list of medications associated with cross allergy in the local area network. Series of academic lectures, especially typical case analysis, arranged for medical staff.
	• Note skin test results when physicians prescribe special medications for patients. For example, a prescription of penicillamine should contain descriptions of “skin test exemption” or “skin test negative”. Otherwise, the prescription will be intercepted by auditing pharmacists.
	• Adopt a pragmatic approach to use of beta-lactams in patients with penicillin allergy.
	• Install an online database embedded in the hospital information system and electronic medical record system. The database, named the Clinical Medication Decision Support System, was developed by Elsevier Datong (http://www.clinicaldecisionsupport.com.cn), and can effectively detect contraindications related to cross allergy.
	• Software modification was implemented to overcome an information design defect, ie, the interface of the pharmacy management information system could not show the records of drug allergy (eg, allergy history, medication name, clinical manifestations) so that pharmacists could not detect severe pharmacotherapeutic issues in the dispensing process.
	• Implementation of an intrahospital pharmacovigilance system notifying all medical staff when a cross allergy occurs in the hospital.
	• Medical staff are encouraged to report any medication errors via a specific spontaneous reporting system. A Plan, Do, Check, Act cycle is built into ongoing quality improvement.^Citation10
Consequences	3
Likelihood	2
Final risk rating	6
Approximate financial resources required	$US32,000
Priority high/medium/low	High
Responsibility for action	Department of Medical Affairs, Department of Pharmacy, Office of Medical Quality Management
Due date	August 1, 2008
Completion date	December 31, 2012
Key indicator(s)	Awareness of cross allergy among doctors and nurses, cases of drug counseling about cross allergy from doctors and nurses, percentage of questions on cross allergy answered correctly first time around by pharmacists and number of medical errors
Monitoring and review	Questionnaire survey, application of the tracer methodology, analysis of all records from drug counseling, medical consultation, and online no-fault reporting system which accepts reports of adverse events and medication errors from medical staff
Communication strategy(ies)	Cooperation between Department of Information Technology, Office of Medical Quality Management, Department of Medical Affairs, Department of Pharmacy, and Division of Nursing
Contingency plan(s)	Pharmacist’s auditing should be strengthened and electronic medical record system should be installed on the pharmacy computer if modification of information system cannot be fulfilled according to the schedule. Pharmacists to review the chart for drug allergy issues

Table 2 Cross allergy descriptions in information related to contraindications concerning drugs within the same therapeutic class

Therapeutic class	Cross allergy descriptions
Antibacterials
Aminoglycosides	Contraindicated in patients who are allergic to an aminoglycoside.
Fluoroquinolones	Contraindicated in patients who are allergic to a fluoroquinolone.
Penicillins and compounds β-lactamase inhibitor formulations (eg, piperacillin-tazobactam)	Contraindicated in patients who are allergic to any of the penicillins.
Cephalosporins, cephalosporin-β-lactamase inhibitors	Contraindicated in patients who are allergic to any of the cephalosporins.
Macrolide antibiotics	Contraindicated in patients who are allergic to macrolide antibiotics.
Nitroimidazole antibiotics	Contraindicated in patients who are allergic to nitroimidazoles or drugs containing a pyrrole ring.
Glycopeptide antibiotics	Descriptions for this class are inconsistent. Vancomycin and norvancomycin are contraindicated in patients who are allergic to glycopeptide antibiotics and aminoglycosides. Contraindication information for teicoplanin does not note this issue. Precautionary information for teicoplanin notes that cross allergy possibly exists between vancomycin and teicoplanin, so should be used cautiously in patients who are allergic to vancomycin.
Cardiovascular drugs
Dihydropyridine calcium antagonists	Contraindicated in patients who are allergic to dihydropyridines.
Organic nitrates	Descriptions for this class are inconsistent. Isosorbide dinitrate tablets and 5-isosorbide mononitrate injection are contraindicated in patients who are allergic to organic nitrates or nitro compounds. However, contraindication information for nitroglycerin tablets, injection, and sustained-release 5-isosorbide mononitrate does not note warnings related to cross allergy.
Angiotensin-converting enzyme inhibitors	Descriptions for this class are inconsistent. Contraindication information for cilazapril and domestic ramipril notes “… contraindicated in patients who are allergic to other angiotensin-converting enzyme inhibitors”. Contraindication information for perindopril notes “… contraindicated in patients who have a history of angioneurotic edema disease induced by angiotensin-converting enzyme inhibitors”. Contraindication information for the original imported ramipril does not note any cross allergy issues.
Antitumor drugs
Oxaliplatin	Descriptions for this drug from different manufacturers are inconsistent. Domestic product is contraindicated in patients who are allergic to platinum derivatives whereas contraindication information for the original imported product makes no specific mention of cross allergy.
Temozolomide	Contraindicated in patients who are allergic to dacarbazine.
Topotecan	The domestic product is contraindicated in patients who are allergic to camptothecins. Contraindication information for the original imported product does not note any cross allergy issues.
Local anesthetics	Descriptions for this class are inconsistent. Lidocaine is contraindicated in patients with a history of allergy to local anesthetics. Ropivacaine is contraindicated in patients who are allergic to local anesthetic amide derivatives. Contraindication information for bupivacaine and tetracaine does not note any cross allergy issues.
Endocrine and metabolic agents
Thiourea antithyroid drugs	Thiamazole and propylthiouracil are contraindicated in patients who are allergic to thiourea homologs.
Gonadotropins	Triptorelin, goserelin, and leuprorelin acetate are contraindicated in patients who are allergic to gonadotropin-releasing hormone and its analogs.
Glucocorticoids	Contraindicated in patients who are allergic to adrenocortical hormones.
Miscellaneous
Retinoids	Descriptions for this class are inconsistent. Acitretin is contraindicated in patients who are allergic to other retinoids. Tretinoin gel is contraindicated in patients who are allergic to vitamin A derivatives.
	Contraindication information for retinoin and viaminate does not note any cross allergy issues.
Mifepristone	Contraindicated in patients who are allergic to prostaglandin analogs.
Compound ipratropium bromide solution for inhalation	Contraindicated in patients who are allergic to atropine and its derivatives.
5-HT3 receptor antagonists	Descriptions for this class are inconsistent. Tropisetron and azasetron are contraindicated in patients who are allergic to other 5-HT3 receptor antagonists. Contraindication information for ondansetron does not note any cross allergy issues.
Bisphosphonates	Descriptions for this class are inconsistent. Pamidronate and zoledronic acid are contraindicated in patients who are allergic to bisphosphonates. For alendronate sodium, information on contraindications does not note any cross allergy issues.
Ganciclovir	Contraindicated in patients who are allergic to aciclovir.

Table 3 Cross allergy involving drugs belonging to completely different pharmacological classes

Drugs	Description of cross allergy
Metoclopramide	Contraindicated in patients who are allergic to procaine and procainamide.
Penicillamine	Contraindicated in patients who are allergic to any of the penicillins.
Tacrolimus	Contraindicated in patients who are allergic to other macrolides.
Vancomycin	Contraindicated in patients who are allergic to aminoglycosides.
Cefoxitin, cefminox, latamoxef, piperacillin-tazobactam, piperacillin-sulbactam	Contraindicated in patients who are allergic to any of the cephalosporins.
Bromocriptine, dihydroergotoxine mesylate	The two drugs belong to different therapeutic classes, but the contraindication information for both drugs indicates that they are contraindicated in patients who are allergic to ergotamine.
Sulfonamide derivatives • Antimicrobial sulfonamides • Diuretics: hydrochlorothiazide, amiloride, indapamide • Hydrochlorothiazide-containing antihypertensives • COX-2 inhibitors: celecoxib, parecoxib • Hypoglycemic sulfonylureas: tolbutamide, glibenclamide, gliclazide, glipizide, gliquidone, glimepiride • Gout suppressant: probenecid	The six kinds of drugs belong to different therapeutic classes, but the contraindication information for these drugs all indicates that they are contraindicated in patients who are allergic to sulfonamides.
Lodine allergy-related drugs • Diagnostic drug: indocyanine green • Antiarrhythmics: amiodarone • Contrast agents: iodized oil injection, compound meglumine diatrizoate injection, iopromide • Cydiodine tablets • Ophthalmic drugs: prolonium iodide, iodized lecithin tablets	The five kinds of drugs belong to different therapeutic classes, but the contraindication information for these drugs all indicates that they are contraindicated in patients who have a history of iodine allergy.

Table 4 Formulation excipients and cross sensitivity

Drugs	Description of cross allergy
Amifostine, bortezomib, carboplatin, recombinant human epidermal growth factor	Contraindicated in patients who are allergic to mannitol.
Paclitaxel, teniposide, cyclosporin injection	Contraindicated in patients who are allergic to polyoxyethylene castor oil.
	Contraindication information on paclitaxel for injection (albumin-bound) does not note any cross allergy issues.
Docetaxel, mycophenolate mofetil injection	Contraindicated in patients who are allergic to Tween-80.

Table 5 Effects of intervention on prevention of cross allergy

Indices	Descriptions of outcomes
Number of drug counseling sessions about cross allergy from doctors and nurses	Decreased by 67% (an average of 60 cases monthly before August 2008 versus an average of 20 cases monthly since August 2009).
Awareness rate of special cases of cross allergy	If doctors, pharmacists, and nurses did not read the prescribing information, almost no one knew of any contraindications for use of vancomycin in patients who are allergic to aminoglycosides, use of metoclopramide in patients who are allergic to procaine, and use of piperacillin/tazobactam in patients with an allergy to cephalosporins before August 2008. Awareness of such types of cross allergy increased to 100% in August 2009.
Percentage of questions on cross allergy correctly answered first time round by pharmacists	Increased by 30% (60% before August 2008 versus 90% in August 2009).
Number of medical errors related to cross allergy	Decreased by 97% (10 cases monthly before August 2008 versus three cases yearly in 2012).
Percentage of documentation on hypersensitivity in clinical notes	About 20% before August 2008 versus 100% after introduction of a formal history sheet in May 2012.
Risk rating	Decreased significantly [initial risk rating:25(high-risk) before August 2008 versus final risk rating:6 (medium-risk) in December 2012].

Figure 1 Chemical structures of metoclopramide (A), procaine (B) and procainamide (C).

CarterJSmall-scale study using the PDCA cycleGiftRKinneyCToday’s Management Methods: A Guide for the Health Care ExecutiveNew York, NYWiley John and Sons Inc1996

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