was purely due to lack of proper understanding of the drug information given to the patients and incorrect packing of doses. Older people are found to be more prone to accidental overdosing of the drug due to memory loss and eye problems.
‘Accidental daily dosing of the drug methotrexate leads to severe toxic effects and life-threatening conditions. Older people are at high risk for medication errors associated with methotrexate in Australia.’
Methotrexate - Folate Antagonist
Methotrexate is a
synthetic folic acid analogue and an
immune modulator which mainly acts by inhibiting the action of dihydrofolate
reductase enzyme and DNA synthesis. It has the ability to inhibit the growth of
tumor cells and possess anticancerous properties.
Methotrexate is an effective drug which is widely used in the treatment of rheumatoid arthritis
, psoriasis and cancers. It helps to reduce the pain and swelling thereby reducing the progression of arthritis. The drug should be used only in appropriate quantity as an accidental overdose of methotrexate may be lethal and can lead to mucosal ulceration in the gastrointestinal tract, suppression of the bone marrow, liver toxicity, sepsis
due to infections and finally death.
Retrospective Review of Methotrexate Dosing Errors
The study based on the medication errors reported to National Coronial Information System
(NCIS), Therapeutic Goods Administration Database of Adverse Event Notification
and Australian Poisons Information Centres (PICs) were investigated for a decade. The study was mainly done on
patients who took methotrexate for more than three days consecutively in a week.
Medication error is the
inappropriate use of medicines that may harm the patient. These type of errors
can occur anytime of the medication process. It can be done by a doctor while
prescribing the dose, by a pharmacist while dispensing the drug or by the patient
while taking the drug.
National Coronial Information System (NCIS)
The National Coronial
Information System (NCIS) managed by the Victorian Department of Justice is
a data storage and retrieval system
that gives information on coronial cases that were recorded in Australia and
New Zealand to prevent injury related deaths. The study was based on the number
of deaths recorded from the year 2000-2014 in Australia.
Data collected from NCIS
on July 2015 was mainly done to identify deaths that were linked to accidental
overdosing of the drug methotrexate and deaths due to antineoplastic
(anticancer) agents from July 2000 to 2014 for all states in Australia except
Queensland for which the data was available only from the year 2001. The
reports stated that about 22 deaths were recorded due to medication error of
methotrexate out of which 12 were due to severe bone marrow suppression. Five
men and two women of the total seven cases were documented of abnormal blood
cell counts and died due to daily dosing errors of methotrexate.
Therapeutic Goods Administration (TGA)
Administration Database of Adverse Event Notification TGA DAEN is a regulatory authority for therapeutic
goods in Australia which looks to assess and monitor activities to set acceptable standards for therapeutic
goods. The regulatory body receives adverse event reports from public and
healthcare professionals. The database of adverse events notification (DAEN)
provides complete information on medicines, vaccines and their adverse events.
The data collected from
January 2004 to December 2014 from TGA DAEN on medication error or accidental
overdose of methotrexate reported ten cases including two deaths aged between
Poison Information Centers in Australia (PICs)
centers (PIC) provide immediate, free medical assistance and advice on
treatment of various poisons. The study was reviewed based on the information
from New South Wales, Victorian, Western Australian and Queensland PIC
databases. About 92 cases were recorded due to methotrexate overdosing. An
average of four to nine cases were documented every year from 2005 to 2013.
This rate increased for the year 2014-2015, and it was found to be more in the aged population who are at a
high risk of memory loss, confusions and decline in visual acuity.
Preventive Measures of Methotrexate Overdose
The ongoing medication errors due to
methotrexate overdosing may be fatal. Therefore proper preventive measures have
to be initiated by the manufacturers, TGA and healthcare professionals to lower the risk and reduce the adverse effects.
- The pack size of methotrexate in Australia can exceed a year' s
supply and should be reduced to decrease the number of dosing errors.
- Methotrexate being a
folate antagonist is co-prescribed with
folate and must be packed
together as that of oral contraceptives and sugar pills in order to avoid
- Formulation of methotrexate should be done in a distinct color
to lower the risk of medication errors.
- Specific warning on how to take the medication must be given to
the patients. It should be strictly taken weekly and not on a daily basis.
- Proper patient counseling and education about the drug
information and its dose must be provided to the patient.
- Warnings and alerts related
to methotrexate dosing should be included in prescribing and dispensing
software to reduce the number of medication errors.
error may further increase in
Australia and therefore,
proper measures have to be initiated to prevent these errors.
The study was on Accidental daily dosing of weekly drug
linked to deaths taken from the Medical Journal of Australia
which is a publication of Australia Medical
- Incorrect drug dosage linked to deaths
- Methotrexate: Managing Side Effects
- National Coronial Information System (NCIS)
- Database of Adverse Event Notifications (DAEN)