Clinical Pharmacology

"Adverse Drug Event of the month"

Case details:

We report here a case of a 42 year-old male business executive who presented with poor seizure control to the Neurology OPD of our Institute. The patient was diagnosed to have generalized tonic clonic seizures 15 years back. He was prescribed phenytoin initially (dose and duration not available) and later shifted on to carbamazepine (200 mg thrice a day) and valproic acid (500 mg once a day). His seizures were under control during this period and a therapeutic drug monitoring report done showed that his carbamazepine and valproate levels were in therapeutic range. Since the past several months he had weight gain and hence sodium valproate was discontinued and lamotrigine started. He came back to the institute with complains of increasing frequency of seizure episodes since 1 month of starting Lamotrigine. The neurologist referred him to the Therapeutic Drug Monitoring (TDM) OPD to assess the levels of carbamazepine and lamotrigine. During history taking it was seen that the patient was prescribed tablet Tegrital (CARBAMAZEPINE) 200 mg thrice a day and tablet Lamidus DT (LAMOTRIGINE) (manufactured by-Zydus) 100 mg half tablet twice a day. Patient remarked that he had increasing seizure episodes on being shifted on to Lamotrigine. On close questioning, the patient said he was very compliant with therapy which was corroborated by his wife. We examined the medications that the patient was receiving and found that he was taking tablet Lamidac (LAMIVUDINE) (manufactured by-Zydus!!) 100 mg twice a day. The patient said that the chemist dispensing the medications said that Lamidus was out of stock and in lieu of which he was substituting lamidac. The patient was on Lamidac for 4 weeks during which his seizure episodes had worsened. Therapeutic drug monitoring (TDM) showed nil levels of Lamotrigine and 9.21 µg/ml of Carbamazepine which corroborated the fact that the patient was not on Lamotrigine.

Discussion:

What is a medication error?

"A medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use"(1)

Medication errors, which are iatrogenic injuries, are a well-known, worldwide phenomenon and are common, costly and important (2,3). Approximately, 28% of adverse dug events are associated with medication errors and therefore judged preventable (4).Medication errors present a serious threat to patient welfare and a significant liability to health professionals and their insurers. Although there are many contributing factors, confusing pairs of medication names are consistently associated with errors. Look-alike and sound-alike medication names play a part in perhaps one quarter of all medication errors (5).

The implications of this case are relevant to the large proportion of patients in developing countries where medications are dispensed by pharmacies which are manned by Pharmacy trained personnel. Pharmacists are known to substitute prescriptions. The unsuspecting patient usually accepts whatever he gets without cross-checking with the doctor. If two drug names differ by just an alphabet, syllable, suffix or prefix, it becomes difficult for the patient to realize that there is a difference.

Levenshtein distance is a measure of orthographic string similarity that forms the basis for several widely used spell-checking and text-processing utilities. (6) It is the number of edit operations (e.g., substitutions, insertions, or deletions) needed to transform one word into another. The specific algorithm used to implement Levenshtein distance in these investigations was designed by Wagner and Fischer (6, 7). Consider these two brand names Lamidus and Lamidac. In order to transform the word Lamidus into the word Lamidac, one must change the U to an A, and change the S to C. Two edit operations are required; thus, the Levenshtein distance between the two names is 2, which is very significant.

Recommendations to Enhance Accuracy of Prescription Writing (8)

1. All prescription documents should be legible (doctor should write each alphabet clearly).

2. Prescription orders include a brief notation of purpose (e.g., for epilepsy), unless considered inappropriate by the prescriber. (Certain medications and disease states may warrant maintaining confidentiality - e.g. HIV/AIDS)

3. All prescription orders should be written in the metric system except for therapies that use standard units such as insulin, vitamins, etc.

4. Prescribers should include age and, when appropriate, weight of the patient on the prescription or medication order. The most common errors in dosage result in pediatric and geriatric populations.

5. Medication orders should include drug name (generic as well as brand names), exact metric weight or concentration, and dosage form. Strength should be expressed in metric amounts and concentration should be specified. Each order for a medication should be complete.

6. Prescribers should avoid the use of abbreviations including those for drug names (e.g., HCTZ for hydrochlorthiazide) and Latin directions for use (e.g. QID for four times daily).

7. Non-proprietary names should be used as far as possible in prescriptions (e.g. Lamotrigine instead of Lamidus)

8. Typed prescription and post prescription counseling are some of the standard methods to avoid unpardonable crime which can be caused by rhyme.

9. Physicians should check the drugs against the prescription. All patients should meanwhile be advised to cross-check the confusing drug with the doctor.

10. Chemists should be educated to dispense drugs carefully.


References:
1. What is a Medication Error? National Coordinating Council for Medication Error Reporting and Prevention. Online available at http://www.nccmerp.org/aboutMedErrors.html. Accessed on 18/10/2005.
2. Lesar TS, Lomaestro BM, Pohl H. Medication prescribing errors in a teaching hospital: a 9 years experience. Arch Int Med 1997;157:1569-76.
3. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients: excess length of stay, excess cost, and attributable mortality. JAMA 1997;277:301-6.
4. Bates DW, Cullen D, Laird N et al. Identifying adverse drug events and potential adverse events: implications for prevention. JAMA 1995;274:29:34.
5. Lambert BL. Predicting look alike and sound alike medication errors. Am J Health Syst Pharm1997;54:1161-71.
6. Stephen GA. String searching algorithms. River Edge, NJ: World Scientific; 1994.
7. Wagner RA, Fischer MJ. The string-to-string correction problem. Journal of Assoc. Comp. Mach 1974; 21:168-73.
8 Recommendations to Enhance Accuracy of Prescription Writing. National Coordinating Council for Medication Error Reporting and Prevention. Online available at http://www.nccmerp.org/council/council1996-09-04.html