Physicians Urged to Write Indications on Drug Scripts as Methotrexate Users Face New Barriers Under Roe v Wade Decision

Jennifer Lubell

July 12, 2022

A commonly prescribed cancer and arthritis drug that is sometimes used as an oral abortifacient is facing prescription roadblocks in the wake of the Supreme Court's overturning of Roe v Wade.

The Court's 5-4 decision in Dobbs v Jackson Women's Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.

"It's happening all over," Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University in Fargo, said in an interview. "Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they're afraid of going to jail."

Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician's office stopped prescribing the drug because it is considered an abortifacient. "I had care that made my disabled life easier, and they [Supreme Court] took that from me," Schwartz wrote.

Prior to the Supreme Court's ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that's a teratogen, said Miller.

MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine – Phoenix. It's a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.

Texas Pharmacies Target Two Drugs

MTX denials have caught the attention of healthcare organizations. "Uncertainty in financial and criminal liability for healthcare professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications," warned the American Pharmacists Association (APhA) in a statement to Medscape Medical News.

The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.

The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation's website.

In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, "Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled."

MTX, approved by the FDA in 1985, "is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug," said John Reveille, MD, vice-chair for the Department of Medicine at the University of Texas McGovern School of Medicine, and a member of the Arthritis Foundation expert panel, in an interview.

"While it's true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective." he said.

"If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It's surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone," added Dr Reveille.

The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the Department of Lymphoma and Myeloma.

"We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the healthcare team," he said in an interview.

Conflicting Laws Pose Challenges for Physicians

In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. "Lots of confusion can result when people pass laws against abortion. There's sometimes no insight into the ramifications of those laws," said Miller.

North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe v Wade. However, another law that regulates abortion conflicts with the trigger law. "Some of the language will need clarification in the next legislative session," he said.

APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.

Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother's life is the only exception for abortion, said Dr Young.

Denials Aren't Widespread

Not all doctors are seeing MTX denials, but they're worried about the future. "To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care," said Dr Westin.

Dr Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.

It's a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr Reveille. "In Texas, we're a bit ahead of the tidal wave."

Access problems also haven't shown up at the university clinic where Dr Young practices. "In Arizona, it's unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient," she said.

Specificity Is Key in Writing Rx Scripts

Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Miller.

Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, "patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren't using it to terminate pregnancies," said Dr Zahabi.

She further noted that if the diagnosis is already indicated on the script, pharmacies generally won't give patients a hard time.

Patients can also ask their physicians for a letter of medical necessity that confirms a drug's use for a specific medical condition.

Mail order is another option if a local pharmacy won't fill a prescription, said Miller. "This is legal unless a state makes it illegal to send an abortifacient across state lines," he added.

Many medications used in rheumatic diseases are harmful in pregnancy, and it's important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.

Actions at the Federal, State Level

President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.

In a statement on Twitter, the American College of Rheumatology (ACR) said that it was "…following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate, or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn't allowed where they practice."

ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.

The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.

"We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication, and what this means for specific patients," said Schultz. Through a survey, the foundation hopes to get a better idea of what's going on in the states at a macro level.

This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Schultz.

Being involved in local advocacy is more important than ever, stressed Dr Young. "Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues."

Rheumatologists have a unique voice in this discussion, she added. "We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary."

Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr Westin. This situation with Roe v Wade is no different, he added. "We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care — and to help our patients overcome barriers that may interfere."

Dr Reveille participated on an advisory board with Eli Lilly in October 2021.

Jennifer Lubell is a freelance medical writer in the Washington Metropolitan Area.

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