A 72-year-old female patient with multiple co-morbidities suffered from rheumatoid arthritis (RA). Her rheumatologist treated the condition with methotrexate injections, supplied in 2 mL vials (25 mg/mL). In addition to RA, her health history included congestive heart failure (CHF), coronary artery disease (CAD) with placement of three stents, hypertension (HTN), hyperlipidemia, seizures, and a cerebrovascular accident (CVA) that resulted in residual left-side weakness three years prior to the incident.
Despite the patient’s significant medical history, her health had been stable enough to allow her to live with family members. Three adult children and their spouses shared caregiver responsibilities.
The incident occurred soon after a family member with whom the patient was living picked up the patient’s renewed prescription for methotrexate injections. Based on the claim investigation findings, the patient received two weekly doses of the medication before she was due to move to the home of another family member for a few months. Soon after the move, the patient began to exhibit slurred speech and an increasingly unstable gait, leaning toward her weaker left side more than in the recent past. Fearing the patient had suffered a new CVA, the family sought care at their local hospital’s emergency department (ED).
After initial assessment, the patient was admitted for a possible CVA. However, computed tomography (CT) and magnetic resonance imaging (MRI) were both negative, exhibiting no evidence of acute intracranial infarction/bleeding or head trauma. The patient improved with supportive care, and she was discharged to the care of her family, supported by home healthcare services.
Unfortunately, the patient was transported to the ED of another hospital just over a week after her discharge. The findings included confusion, fever, tachycardia, leg edema, and shortness of breath. She complained of mouth pain, and examination revealed bleeding ulcerations. ED records indicated that the initial medical impression was sepsis. Further testing showed severe pancytopenia and an unremarkable CT. Furthermore, a urinary tract infection (UTI) was diagnosed soon after admission to the intensive care unit (ICU) of the hospital and antibiotic therapy began. Given the patient’s medical history, symptoms, and test results, the neurologist’s differential diagnosis included methotrexate toxicity.
The patient’s RA methotrexate therapy seemed appropriate. The recent prescription history indicated a weekly injection of 0.8 mL for a 20 mg/week dose. This was within the typical treatment range of 7.5 mg to 25 mg per week for RA therapy. However, when family members produced the current medication vials, the labeling indicated 8 mL per week, for a dose of 200 mg, ten times the prescribed dose. As a result, leucovorin therapy was initiated to counteract the methotrexate overdose. Antibiotic therapy continued, along with fluid management and supportive care.
The patient’s condition deteriorated over several days, followed by slow improvement. She was on a ventilator for two days and suffered two asystole events during this time. As her condition stabilized and improved, she required aggressive physical therapy and ongoing supportive care before discharge could be considered. Given the complex medical issues and persistent weakness, discharge to a skilled nursing facility was necessary.
Resolution
Approximately three months after hospital discharge, the family filed a lawsuit alleging negligence, naming the insured pharmacy and the dispensing pharmacist. Although minor improvements continued for a time after discharge from the hospital, the patient did not return to her pre-incident health status.
The pharmacy’s investigation pointed to human error. The rheumatologist’s prescription was written as intended for 0.8 mL (20 mg) injected weekly. However, the instructions entered into the pharmacy’s electronic medication system — and subsequently printed on the medication label — directed that 8 mL be administered weekly. The investigation further uncovered that the family caregiver who picked up the renewed prescription was familiar with the medication and administered the correct dosage. Apparently, they had not consulted the (incorrect) prescription label. When the patient moved to another family member’s home, the instructions were reviewed and followed, resulting in the overdose and hospitalizations.
Given the investigation results and facts of the case, the defense team determined that it would be in the insured’s best interest to pursue an early settlement. Finding expert support and building an effective defense seemed unlikely, if not impossible. Working with the co-defendant pharmacist’s defense team, settlement discussions began immediately after securing consent to settle. The primary defense position involved the patient’s significant and pre-existing co-morbidities and health concerns. Although this position proved effective to a degree, an error did occur, and the patient suffered a significant health decline. Within the time frame of the legal proceedings, she continued to require skilled nursing care.
Effective negotiations with the co-defendant’s team in advance of mediation resulted in a 30/70 split for indemnity if the case settled, in favor of the insured pharmacy. The initial mediation was unsuccessful. However, the plaintiffs agreed to a second mediation which came to a successful conclusion. With an original demand of nearly $2,000,000, the defense team was pleased with a $300,000 payment on behalf of the insured pharmacy.
Risk Management Comments
Methotrexate is categorized as one of several “high-alert” medications. High-alert medications present a significant risk of causing severe harm when used in error. As a result, pharmacies and pharmacy team members must heighten risk awareness, assess their practices and implement preventive measures to minimize the potential for patient harm associated with such medications.
This incident began with human error upon entry of the prescription into the pharmacy’s electronic medication system. Even though the prescription was double-checked by the pharmacist on duty before dispensing, the error was not caught and corrected. While human error may never be eliminated, the potential for patient harm may be reduced significantly by integrating multiple processes designed to prevent and/or discover errors before dispensing.
Risk Management Considerations
Along with methotrexate for non-oncologic use, examples of other high-alert medication categories include anticoagulants, insulin products, opioids, and chemotherapeutic agents. Errors associated with high-alert medications continue to result in significant patient injuries and professional liability claims.
For the community pharmacy setting, consider downloading a recently updated resource, ISMP’s Targeted Medication Safety Best Practices for Community Pharmacy, 2026-2026. Although Best Practice 3 in this document focuses on oral methotrexate for non-oncologic use, the principles and methods also apply to the injectable dosage form described in this case study for the treatment of RA. A link for this and several other helpful documents appears below under the Resources header.
Preventive measures to mitigate the risk of high-alert medication errors include, but are not limited to, the following bulleted items. Readers are strongly encouraged to explore more detailed information in the bulleted items under Resources.
Methotrexate for non-oncologic use:
- Set a weekly dose regimen as the electronic medication system default for oral/non-oncologic methotrexate prescription orders.
- Require a system hard-stop verification or clarify/confirm all daily methotrexate prescription orders before dispensing if there is no documented oncologic diagnosis.
- For manual systems or electronic systems that do allow a hard stop, require pharmacists to clarify any daily order for non-oncologic use and/or weekly dosages that exceed the typical non-oncologic use range.
- Provide the patient or caregiver with counseling on oral methotrexate and confirm understanding of the dose schedule and medication risks.
General actions:
- Consider a secondary labeling system and unique automated warnings for high-alert medications.
- Enter a minimum of five letters into the electronic medication system to mitigate the risk of selection errors.
- If possible, include both the brand and generic names in electronic medication system menus and search options.
- As much as possible, limit access to high-alert medications to appropriately trained staff.
- Use electronic hard stops at the point of sale to require patient counseling and education before dispensing high-alert medications.
- Ensure that pharmacy computer systems incorporate critical alerts for narrow therapeutic index and high-alert medications. Establish a protocol to confirm routine system updates.
- Utilize pharmacy computer systems that are designed to perform dose range checks and that warn staff regarding potentially dangerous doses for narrow therapeutic index and high-alert medications.
- Provide education to pharmacy staff on strategies to avoid errors with high-alert medications, narrow therapeutic index medications, and other error-prone medications or devices at least annually.
- Incorporate medication safety discussions into team meetings. Review near misses, successful safety process improvements and corrective actions, as well as medication safety resources.
By following these and other medication safety practices, pharmacy professionals can significantly reduce the risk of dispensing errors and enhance patient safety.
Resources
Disclaimer
The information, examples and suggestions presented in this material have been developed from sources believed to be reliable, but they should not be construed as legal or other professional advice. CNA accepts no responsibility for the accuracy or completeness of this material and recommends the consultation with competent legal counsel and/or other professional advisors before applying this material in any particular factual situations. This material is for illustrative purposes and is not intended to constitute a contract. Please remember that only the relevant insurance policy can provide the actual terms, coverages, amounts, conditions and exclusions for an insured. All products and services may not be available in all states and may be subject to change without notice. Certain coverages may be provided by a surplus lines insurer. Surplus lines insurers do not generally participate in state guaranty funds, and insureds are therefore not protected by such funds. The claims examples are hypothetical situations based on actual matters. Settlement amounts are approximations. Certain facts and identifying characteristics were changed to protect confidentiality and privacy. “CNA” is a registered trademark of CNA Financial Corporation. Certain CNA Financial Corporation subsidiaries use the “CNA” trademark in connection with insurance underwriting and claims activities. Copyright © 2025 CNA. All rights reserved.