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Clinical Observation
May 13, 2002

Using Trade Names: A Risk Factor for Accidental Drug Overdose

Author Affiliations

From the Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Drs Schwab and Eichelbaum), Robert Bosch Hospital, Center of Internal Medicine, Stuttgart (Dr Oetzel), and the Division of Clinical Pharmacology, University Hospital Tübingen, Tübingen (Drs Mörike, Jägle, Gleiter, and Eichelbaum), Germany.

Arch Intern Med. 2002;162(9):1065-1066. doi:10.1001/archinte.162.9.1065
Abstract

Medication errors due to the exclusive use of trade names of drugs may lead to life-threatening complications. We report the case of a patient with verapamil overdose as a result of this. This case illustrates that the use of trade names, omitting the international nonproprietary names of the active moiety, carries the risk of serious adverse drug events by overdose.

Report of a case

A 56-year-old woman was referred to our hospital (Robert Bosch Hospital, Stuttgart, Germany) for the insertion of a permanent cardiac pacemaker. She had acute dizziness, hypotension (blood pressure, 90/60 mm Hg), and bradycardia (pulse rate, 28/min). Her electrocardiogram (Figure 1, A) revealed third-degree atrioventricular block and left bundle branch block. Routine laboratory tests showed moderate renal dysfunction (serum creatinine level, 2.5 mg/dL [221 µmol/L]). She had a long-standing history of hypertension.

A, Electrocardiogram at patient's referral, showing third-degree atrioventricular block and left bundle branch block. B, Electrocardiogram at patient's discharge, showing regular sinus rhythm.

A, Electrocardiogram at patient's referral, showing third-degree atrioventricular block and left bundle branch block. B, Electrocardiogram at patient's discharge, showing regular sinus rhythm.

Five days prior to admission, the patient's general practitioner prescribed an 80-mg verapamil hydrochloride generic brand (Verasal) thrice daily; amlodipine besylate, 5 mg twice daily; enalapril maleate, 10 mg twice daily; and hydrochlorothiazide, 25 mg once daily. The patient continued to take a 240-mg verapamil sustained-release brand (Veramex) twice daily as prescribed at a previous stay in a different hospital. Thus, she had received 2 preparations of verapamil, adding up to a total daily dose of 720 mg.

On admission, verapamil administration was discontinued immediately. The diagnosis of verapamil overdose was confirmed by a concentration of 1128 ng/mL (verapamil therapeutic range, 120-400 ng/mL)1 and 1705 ng/mL (norverapamil) in a serum sample taken 24 hours after the last dose.2 In a second serum sample taken 24 hours later, concentrations decreased to 453 ng/mL (verapamil) and 977 ng/mL (norverapamil). On the basis of half-lives calculated from these concentrations, ie, 18.2 hours (verapamil) and 29.9 hours (norverapamil), respectively, peak concentrations of 2808 ng/mL (verapamil) and 2976 ng/mL (norverapamil) were estimated.

Within 3 days after discontinuation of verapamil, atrioventricular block and left bundle branch block resolved, and blood pressure and renal function returned to normal. Thus, the acute renal impairment was retrospectively attributed to the low blood pressure induced by verapamil use. After 5 days in the hospital, the patient was discharged symptom free, with regular sinus rhythm (Figure 1, B) and normal blood pressure, with enalapril and hydrochlorothiazide as her antihypertensive treatment.

Comment

This patient's general practitioner was apparently unaware of the active ingredients of the brands he prescribed. This case illustrates that the use of trade names, omitting the International Nonproprietary Names (INN) (or, in the United States, the US Adopted Names [USAN]) of the active moiety, carries the risk of serious adverse drug events by overdose. Table 1 gives a list of verapamil brands available in the United States and Germany.

Verapamil Brands Available in the United States and Germany, 2001
Verapamil Brands Available in the United States and Germany, 2001

Adverse drug reactions (ADRs) apparently are a major cause of morbidity and mortality in hospitalized patients. In a meta-analysis of data from hospitals in the United States,3 ADRs ranked fourth to sixth, accounting for about 106 000 deaths in 1994. Although errors in administration were excluded in this analysis, it is interesting to note that 76.2% of ADRs were type A, ie, dose-dependent4 reactions. It has been estimated that about 30% of admissions due to ADRs are avoidable,5 presumably almost exclusively type A reactions. More emphasis given to strategies in preventing ADRs and adverse drug events may have beneficial effects. In this respect, the use of INN should be strongly encouraged in education and training. In addition, using a personal list of drugs ("P drugs"), as recommended by the World Health Organization,6 may help to avoid such events. As of now, however, it is still common practice to use brand names. Rather, a significant tendency toward the use of trade names even at scientific meetings was recently demonstrated.7 This raises ethical issues in view of life-threatening complications as in our case. In addition, unnecessary cost, ie, insertion of a permanent cardiac pacemaker, may be imposed to the insurance. This case also illustrates that uncritical patient compliance may be harmful, as our patient apparently had not read or understood the package leaflets.

We conclude that the use of INN should always be encouraged. This includes educational interactions between physicians and pharmaceutical companies.

Accepted for publication September 13, 2001.

This work was supported by the Robert Bosch Foundation, Stuttgart; Federal Ministry of Science and Research, Berlin (grant 01 EC0001); and Ministry of Science and Art of Baden-Württemberg, Germany.

This work was presented in part at the 42nd Spring Meeting of the German Society of Experimental and Clinical Pharmacology and Toxicology, Mainz, Germany, March 14, 2001.

Corresponding author and reprints: Matthias Schwab, MD, Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany (e-mail: matthias.schwab@ikp-stuttgart.de).

References
1.
Scott  GNierenberg  D Pharmacokinetic data for commonly used drugs. Melmon  KLMorrelli  HFHoffman  BBNierenberg  DWeds Melmon and Morrelli's Clinical Pharmacology. 3rd ed. New York, NY McGraw-Hill1992;1029- 1072Google Scholar
2.
von Richter  OEichelbaum  MSchönberger  FHofmann  U Rapid and highly sensitive method for the determination of verapamil, [2 H7]verapamil and metabolites in biological fluids by liquid chromatography-mass spectrometry.  J Chromatogr B Biomed Sci Appl. 2000;738137- 147Google ScholarCrossref
3.
Lazarou  JPomeranz  BHCorey  PN Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.  JAMA. 1998;2791200- 1205Google ScholarCrossref
4.
Rawlins  MDThompson  JW Mechanisms of adverse drug reactions. Davies  DMed Textbook of Adverse Drug Reactions. 4th ed. Oxford, England Oxford University Press1991;18- 45Google Scholar
5.
Goettler  MSchneeweiss  SHasford  J Adverse drug reaction monitoring—cost and benefit considerations, part II: cost and preventability of adverse drug reactions leading to hospital admission.  Pharmacoepidemiol Drug Saf. 1997;6(suppl 3)S79- S90Google ScholarCrossref
6.
World Health Organization (WHO) Action Programme on Essential Drugs, Guide to Good Prescribing.  Geneva, Switzerland World Health Organization1995;Available for download at: the home page of the Department of Clinical Pharmacology, University of Groningen, the Netherlands: http://www.med.rug.nl/pharma/who-cc/ggp/homepage.htm. Accessed February 23, 2002.
7.
Bruera  ERipamonti  CBeattie-Palmer  L Use of trade names of drugs in abstracts from pain congresses.  N Engl J Med. 2000;343818Google ScholarCrossref
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