Legal Review & Commentary

Improper prescribing leads to toxicity and death: $2.2 million settlement in Missouri

By Jan J. Gorrie, Esq., and Blake J. Delaney, Summer Associate
Buchanan Ingersoll Professional Group, Tampa, FL

News: An elderly man diagnosed with rheumatoid arthritis was prescribed methotrexate by his doctor. Although he immediately began to experience symptoms of methotrexate toxicity, the doctor failed to take his patient’s complaints seriously and refilled the prescription for another month. The man continued to experience the same symptoms and, two weeks later, he was rushed to an emergency department (ED) for treatment. The ED physicians, however, were unable to prevent the man’s death, which they attributed to methotrexate toxicity. After the man’s widow filed suit against the doctor and the pharmacy, the parties settled for $2.2 million.

Background: An 80-year-old man experiencing pain in his joints visited his doctor for treatment. The doctor diagnosed the man’s condition as rheumatoid arthritis, an abnormality in his immune system that caused inflammation of the lining in his joints and internal organs. The doctor prescribed methotrexate. The patient filled the prescription at a regional pharmacy and he took daily doses as prescribed. After a few days, the man developed inflammation in his mouth and trouble swallowing.

After his prescription ran out, the patient revisited his doctor to complain of the symptoms. The physician told him not to worry and prescribed a refill of methotrexate. The man continued to take the drug. Two weeks later, the inflammation of his mouth and his difficulty in swallowing became too severe for him to bear and he went to a hospital emergency department. The ED’s physician team recognized the man’s symptoms to be indicative of methotrexate toxicity and gave him folic acid as an antidote. The man’s condition began to improve, but it was too late and he died shortly thereafter.

The decedent’s widow filed a wrongful death action against the prescribing physician and the regional pharmacy for their prescription of methotrexate. One of the plaintiff’s experts said the doctor never should have prescribed methotrexate because the decedent did not have rheumatoid arthritis. A second expert witness testified that the drug, which had immunosuppressant effects, should have been administered in a single large dose on a weekly basis rather than in a series of small daily doses to give the man’s body time to recover from the side effects. The second witness also concluded that the pharmacy had acted negligently because the doctor’s prescriptions exceeded the maximum recommended daily dosage.

In his defense, the doctor argued that the drug did not cause any injuries to the man. He claimed that the patient’s age and pre-existing health condition were the principal contributing factors to the death. The pharmacy, on the other hand, maintained that it acted properly for two reasons. First, the prescription did not exceed the maximum recommended dosage that could be taken on a weekly basis. Second, because the pharmacist was not permitted to substitute his or her judgment for that of the physician, the pharmacy should not be held accountable for the treating physician’s negligence.

Before the matter proceeded to trial, the two defendants settled with the plaintiff for $2.2 million.

What this means to you: "Several readily available medication safety tools were apparently not used in this case leading to the tragic death of this elderly man," notes Marva West Tan, RN, ARM, FASHRM, health care consultant in Marietta, GA. "Clinicians unfamiliar with the correct dosing or possible side effects of methotrexate can easily consult print or on-line drug guides, pharmacists should have a policy and procedure for contacting physicians regarding any medication orders that raise questions and physicians should both instruct patients about potential medication side effects as well as listen carefully to patients’ complaints. Using any one of these safe practices might have prevented this fatal error.

"Current medication error research and reporting systems have identified certain groups of drugs more likely to be involved in serious medication errors," says Tan. "Physicians, whether prescribing in an office or inpatient setting, should take special care in prescribing high-alert medications, those drugs that the Institute for Safe Medication Practices (ISMP.org) have found carry a heightened risk of causing significant patient harm when they are used in error.’ The ISMP lists oral and parenteral chemotherapeutic agents as a high-alert class of medications and oral methotrexate, used in nononcologic treatment, as a specific high-alert drug," adds Tan.

"Fatality related to incorrect methotrexate dosing as identified in this claim is not an isolated problem," states Tan. "The ISMP notes dozens of reported fatalities in patients receiving oral methotrexate. Common errors include incorrect prescribing by physicians, incorrect transcription of correct orders, and patient misunderstanding of correct dosing and labeling. In most of these errors, the patient took the medication daily rather than weekly as recommended. The ISMP further points out that methotrexate’s once-a-week dosing schedule is used in relatively few medications, which could be a contributing cause of error on the part of physicians and patients more familiar with daily dosing of medications.

"Confusion about the correct dosing schedule for oral methotrexate presents a large pool for potential medication errors, due to the large numbers of patients with rheumatoid arthritis, asthma, psoriasis, inflammatory bowel disease, myasthenia gravis and inflammatory myositis who may be prescribed methotrexate for immune modulation or suppression. The Arthritis Foundation (www.arthritis.org) estimates that 2.1 million Americans now have rheumatoid arthritis, a disease that is more common in women in their 40s or 50s although it can strike either gender at any age. Although methotrexate used to be reserved for patients in the latter stages of rheumatoid arthritis, the current therapeutic approach favors early use of methotrexate or one of the other disease-modifying antirheumatic drugs (DMARDs) to retard progression of rheumatoid arthritis before joint destruction and disability occur. Other DMARDs include intramuscular and oral gold, hydroxychloroquine, sulfasalazine and azathioprine with new drugs emerging in this group. Methotrexate is one of the most frequently used DMARDs and often is combined with hydroxychloroquine and one of the nonsteroidal anti-inflammatory drugs, e.g., ibuprofen or naproxen, in multidrug therapy," continues Tan.

"The usual dose of methotrexate is 7.5 to 20 mg, given orally as a single dose weekly," she reminds. "Because methotrexate use can be associated with liver damage, baseline liver function tests should be performed before methotrexate is started and periodically, usually monthly, while treatment continues. Red cell, white cell, and platelet production may also be monitored. Physicians should remind patients that monthly blood tests will be needed for ongoing monitoring, schedule the next laboratory test date at each office visit and enter the patient’s name into an office tickler system for callback if laboratory test dates are missed. Folic acid is often prescribed along with methotrexate and alcohol use should be minimal to prevent liver damage. Patients should also be informed that they are at risk for opportunistic infections while on methotrexate and should call the physician if any infections, mouth ulcers or stomach problems develop while they are taking the medication. The physician may recommend that methotrexate use temporarily be suspended until the patient recovers from the infection. Long term methotrexate use may increase a patient’s risks of certain types of cancer but this risk must be balanced against the risks of prednisone, a powerful alternative with many serious side effects. Since rheumatoid arthritis is a chronic disease currently requiring lifelong treatment, patients should be encouraged to get involved in self-management, which may reduce errors as well as improve outcomes," notes Tan.

"Pharmacists and nurses daily provide a marvelous safety net to catch problematic drug orders before any medication error occurs," states Tan. "Physicians should welcome pharmacists and nurses’ questions about their drug orders because catching incorrect orders early benefits both the patient and the physician from the devastation of a medication error, poor outcome, and possible malpractice claim. Pharmacists and nurses have an independent professional responsibility for correct medication use and must contact a physician if they have questions or concerns about an order. Fear of an angry response from a physician is no excuse to avoid a call. Patient safety must come first. Inappropriate physician responses can be reported later up the chain of command. Hopefully in the new culture of safety, there will be less hesitation to question unsafe orders. As part of the organizational patient safety program, clinicians in many health care settings are making an effort to report saves’ or near misses’ as well as actual medication errors. Capturing and recording near misses in order to be able to analyze potential root causes currently is an elusive task as no easy process has been identified. One approach is to discuss daily "saves" at shift change."

In conclusion, Tan notes that one of the ISMP’s Medication Safety Alerts contains a list of safe practice recommendations for methotrexate prescribing. "These safe practices include general recommendations applicable to all medications, such as use of electronic prescribing systems with built in alerts," says Tan, "as well as methotrexate-specific recommendations such as naming a specific day of the week on the label instructions to reinforce the weekly dosing schedule. ISMP further recommends that Monday’ not be selected as the dose day as a patient might confuse it with morning.’ Fatal medication errors with high-alert medications such as methotrexate can be prevented if physicians, pharmacists and patients all take responsibility to inform themselves about the medications they prescribe, dispense and use, and to ask questions if they have concerns."

Reference

Estate of Anonymous v. Anonymous Doctor & Anonymous Pharmacy, St. Louis City (MO) Circuit Court.