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Rheumatology 2001; 40: 230-232
© 2001 British Society for Rheumatology
Letters to the Editor |
Methotrexate misadventure: a case for counselling
Pharmacist Intensive Care and Cardiothoracic Services and
1 Research and Cancer Services, Austin & Repatriation Medical Centre, Heidelberg 3084, Australia
SIR, Methotrexate (MTX), a broad-spectrum anti-cancer agent, is used to treat a number of autoimmune diseases, including rheumatoid arthritis and psoriasis. Oral MTX carries particular risks of serious illness through inappropriate prescribing and dispensing errors. The majority of reported medication errors have been due either to the dispensing of the wrong strength, or the patient taking the wrong strength [1–4]. The risk of misadventure is increased when a patient has supplies of both strengths, as may be needed to provide a particular dose. Counselling patients receiving low-dose oral MTX is essential at each consultation and dispensing. We report a case of MTX misadventure which might have been avoided by appropriate counselling.
A 65-yr-old woman presented to the Accident and Emergency Department (A&E) via ambulance with the provisional diagnosis of unstable angina. Her history included ischaemic heart disease (with triple coronary artery bypass 6 months previously) with two previous infarcts (1 and 10 yr previously), hypertension, hypercholesterolaemia and severe rheumatoid arthritis (first diagnosed in 1984). She presented complaining of persistent central chest pain lasting 2 h, for which she obtained some relief using sublingual isosorbide dinitrate. Intravenous morphine and glyceryl trinitrate sublingually administered in A&E relieved the pain. All tests performed, including ECG, and determination of creatine kinase and troponin I levels, were within normal limits. She was admitted for observation and her usual oral medications, which included 15 mg MTX weekly, were continued. Odynophagia and dysphagia, of which she had been complaining for the last 3 days, was also noted.
The next day the odynophagia and dysphagia persisted, although relief was obtained using antacids. The provisional diagnosis was altered to oesophagitis secondary to MTX. The weekly MTX was ceased and calcium folinate 15 mg orally four times a day was commenced. Within 24 h the odynophagia had improved and the patient was well enough to be discharged. During the admission, the patient's creatinine, electrolytes, full blood examination and liver function tests remained within normal limits. MTX serum levels were not determined and gastroscopy was not performed.
Upon preparation of the discharge prescription, the clinical pharmacist reviewing the patient's own medications discovered the MTX misadventure. A bottle labelled as ‘2.5 mg methotrexate tablets’ contained the 10 mg strength tablets. For 2 weeks, the patient had taken 60 mg (6 x 10 mg) weekly for instead of her usual 15 mg (6 x 2.5 mg) weekly dose. Further investigation revealed that the patient's general practitioner had prescribed MTX 10 mg tablets with the instructions ‘Take one and a half tablets weekly’. Her local pharmacy dispensed the 10 mg tablets and labelled the bottle correctly. Upon arrival home the patient, out of habit, emptied the contents of the new prescription into an old bottle of MTX tablets which bore the label ‘Methotrexate 2.5 mg tablets. Take 6 tablets weekly’. The patient was unaware of the change in tablet strength and directions, and was subsequently taking the incorrect dose.
Methotrexate misadventure is not a new problem [1–4]. The major risk outlined in these reports relates to frequency of dosing. The dose of MTX used for the treatment of different diseases varies significantly. In the treatment of rheumatoid arthritis and psoriasis, the dose is often once each week, either as a single or divided dose. There have been instances where this weekly dose has, in error, been taken either daily or on several days each week, resulting in severe unwanted effects, including neutropenia, hepatotoxicity and bone marrow suppression [1–4].
The other reported risk in MTX misadventures is due to the availability of two tablet strengths [5–7]. Errors have arisen when a different strength of MTX has been dispensed and there has been inadequate counselling from the medical practitioner, the pharmacist or both [8]. These cases have resulted in calls for clearer identification between tablet strengths or the abolition of the 10 mg tablet altogether.
Our case highlights the continued need for the counselling of patients receiving low-dose MTX. The general practitioner may have had good intentions in changing the prescription. The new prescription was convenient as the patient had a reduced number of tablets to be taken at each dose. Also, the new prescription allowed a greater supply of medication as a pharmaceutical benefit item at no extra cost to the patient. The failure to communicate this change appropriately resulted in the medication misadventure.
There have been numerous efforts to establish measures to prevent future MTX misadventures [6]. These recommendations must now include mandatory counselling of every patient receiving low-dose oral MTX, including repeat prescriptions. These recommendations can be summarized as:
- MTX for oral use should not be prescribed by a general practitioner without a specific written request, with full dosing particulars, from the treating specialist.
- No prescription for oral MTX should call for an amount greater than 1 month's supply.
- A prescriber's directions for oral MTX taken weekly must nominate a specific day of the week.
- Prescribers should involve a district nurse in dose administration in circumstances where patients inadvertently take the medication incorrectly.
- Manufacturers of oral dose forms of MTX should ensure the ready availability of patient information, and such information should be passed on to patients at the time of dispensing.
- Pharmacists dispensing medications with instructions for weekly doses of potent medication should append to the container an easily noticeable, prominently displayed sticker highlighting this feature.
- There should be mandatory counselling of every patient receiving low-dose oral MTX, including repeat prescriptions. Such counselling must come from both the prescriber and the pharmacist.
- Manufacturers of oral dose forms of MTX should consider either increasing the size of the 10 mg tablet, altering its shape or colour, or abolishing it altogether.
- Clear information regarding the weekly dosing of MTX should be available in published medication guides.
- There should be computer software prompts to check the validity, dose and frequency of MTX prescriptions.
Whenever MTX tablets are prescribed or dispensed, it is essential that there be no doubt that the patient understands the strength of tablets being supplied, any changes in the strength of tablets, and when the tablets are to be taken.
Notes
Correspondence to: J. Siderov, Pharmacy Department, Austin & Repatriation Centre, Studley Road, Heidelberg 3084, Australia. 
References
- Brown MA, Corrigan AB. Pancytopenia after accidental overdose of methotrexate. Med J Aust1991;155:493–4.[Medline]
- Lomaestro BM, Lesar TS, Hager TP. Errors in prescribing methotrexate [letter]. J Am Med Assoc1992;268:2031–2.[ISI][Medline]
- Isdale AH, Hordon LD, Daly M. Methotrexate mishap [letter]. Br J Rheumatol1994;33:503–4.
[Free Full Text] - Adverse Drug Reactions Advisory Committee. Low dose methotrexate therapy—toxic if not taken correctly. Med J Aust1994; 161:152.[ISI][Medline]
- Davies J. Potential problems with methotrexate prescribing [letter]. Br J Rheumatol1994;33:991.
[Free Full Text] - Klaber M. Methotrexate tablet confusion [letter]. Lancet1992; 339:683.[Medline]
- Dwyer P. The legal note. Aust Pharm1996;15:205–6.
- Adverse Drug Reactions Advisory Committee. Methotrexate misadventures—a need for care and counselling. ADRAC Bull1999;18:14.
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