July 14, 2022 -- A commonly prescribed cancer and arthritis drug that is sometimes used for medical abortions is facing prescription roadblocks in the wake of the Supreme Court's overturning of Roe v Wade.

The court's decision, which halted abortion procedures in many states, also appears to be affecting the use of certain prescription drugs. Reports have emerged that pharmacies are denying access to methotrexate, a drug often used in patients with arthritis or cancer. In very high doses, 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, says. "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 methotrexate for lupus, recently tweeted that her doctor’s office stopped prescribing the drug because it is considered an abortion drug. "I had care that made my disabled life easier, and they [Supreme Court] took that from me," Schwartz wrote.

Even before the Supreme Court's ruling, doctors were concerned about the impact an overturning of Roe would have on patient access to methotrexate and other prescription medications with abortion properties. Miller says doctors in general are becoming afraid of prescribing anything that's known as a teratogen, which are drugs that are known to cause damage to an embryo. Certain ACE inhibitors, which include some of the most common blood pressure medications, are examples of teratogens.  

Methotrexate is used far more often for autoimmune disease than it is for abortions, says 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 abortion drugs, she added. Specifically, this will have a significant impact on patients with rheumatic disease.

Texas Pharmacies Target Two Drugs

Methotrexate denials have caught the attention of health care organizations. "Uncertainty in financial and criminal liability for health care 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.

The group said it is monitoring the  situation to assess the effect on patients and pharmacists.

The Arthritis Foundation was made aware of challenges from patients in accessing their prescription to manage their arthritis and shared a statement on the the organization’s website.

In Texas, pharmacists can refuse to fill scripts for misoprostol and methotrexate, 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."

Methotrexate, approved by the FDA in 1985, "is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug," 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, says 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 says.

" 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," Reveille says.

The court’s ruling in Roe could also affect the ability of oncologists to provide lifesaving cancer care, says Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center.

"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 health care team," he says.

Conflicting Laws Pose Challenges for Physicians

In North Dakota, inconsistencies in several laws are making it difficult for doctors 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," says 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 Miller says.

The American Pharmacists Association 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, says Miller. State pharmacy associations in North Dakota are working with lawmakers to clarify any exceptions in the law, he says.

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

Denials Aren't Widespread

Not all doctors are seeing methotrexate denials, but they're worried about the future.

Westin, the oncologist in Texas, says they have not had difficulty getting the drug, but they are “concerned that this could occur and result in dangerous delays in care."

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 says.

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

Access problems also haven't shown up at the university clinic where 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 says.

Specificity Is Key in Writing Rx Scripts

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

Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, says Fehmida Zahabi, MD, president of the Society of Texas Association of Rheumatology. For methotrexate 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," Zahabi says.

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

Patients can also ask their doctors 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, says Miller. "This is legal unless a state makes it illegal to send an [abortion drug] across state lines.” .

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, Young says. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she says.

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 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, says Steven Schultz, director of state legislative affairs.

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, says Schultz.