Accidental methotrexate overdoses have recently been reported to the College through the complaints process. While these cases have been resolved, it was suggested that it would be valuable to bring this to the attention of pharmacy professionals across the province.
Methotrexate is a cytotoxic drug which is typically taken once a week orally or intramuscularly up to a maximum of 30 mg, although it may be taken in 3 divided doses over a 12 hour interval. Methotrexate peak serum levels are reached in one to four hours following oral administration and 30 to 60 minutes following intramuscular injection.
Methotrexate has the potential for serious toxicity which may be related to dose and administration frequency and can happen at any time during therapy. Overdose symptoms may include those reported at pharmacologic doses (e.g. nausea and vomiting) yet it may also be asymptomatic. Monitoring blood cell counts and liver and kidney functions should be ordered at regular intervals during methotrexate therapy. It is important to follow up with patients who are on methotrexate as many adverse reactions are reversible if detected early. When methotrexate is dosed correctly and monitored appropriately, its toxic effects can be minimized.
In a recent case, a patient experienced an accidental fatal overdose of methotrexate after it was discovered that they received more than double the prescribed amount of methotrexate over a one-year period as recorded on the patient’s PharmaNet record. The patient received the original prescription and all refills from a single pharmacy.
There are three issues with this particular circumstance: the initial prescription indicated “Take as Directed”, the pharmacists involved did not meet minimum practice standards in dispensing, and the pharmacists did not fulfill the minimum counselling requirements.
“Take as Directed” (or “Take as needed”) is not an acceptable instruction for methotrexate. It does not meet the dosage instructions requirement. In this instance, a consultation with the prescriber should have taken place to clarify the correct dosage instructions.
Methotrexate fatal toxicities may be associated with overdoses related to inadvertent daily rather than weekly dosing. For oral administration, it should be emphasized to the patient that the recommended dose is taken once weekly for rheumatoid arthritis and psoriasis.
Under the Health Professions Act, Bylaws, Schedule F, Part I – Community Pharmacy Standards of Practice, Section 11(4), pharmacists are required to review PharmaNet to ensure that the patient’s drug therapy needs are being met. This includes taking the appropriate action with respect to:
(a) appropriateness of drug therapy,
(b) drug interactions, noteably with those drugs that increase methotrexate levels;
(c) allergies, adverse drug reactions and intolerances,
(d) therapeutic duplication,
(e) correct dosage, route, frequency and duration of administration and dosage form,
(f) contraindicated drugs,
(g) degree of compliance, and
(h) any other potential drug related problems.
Patient counselling is an essential step to ensure patient understanding and compliance. It will help identify any dosage instructions issues, as the patient may offer his or her interpretation of any instructions they were given by the prescriber. In this case, the patient’s lack of understanding would have, at the very least, signalled to the pharmacist that a consultation with the prescriber was necessary.
When counselling patients on methotrexate, pharmacists should consider the following additional points:
- Remind patient of the importance of regular laboratory tests;
- Inform patient of the early signs and symptoms of toxicity, and the need to see their physician promptly if they occur.
Safeguards such as checking a patient’s PharmaNet profile, consulting with practitioners, and patient counselling exist to identify and prevent errors and must be done for each prescription. It is the responsibility of the pharmacist to use his or her clinical assessment for each patient medication and take appropriate action if needed – this is particularly critical if it is concerning a drug with significant toxicities such as methotrexate.
Methotrexate is an extremely valuable and effective medication. Given its significant toxicities, pharmacists need to be especially vigilant of its appropriate use.