The REMS Program And Abortion Laws – What Every Physician Needs To Know

If you or the doctors at your hospital prescribe any of these 11 drugs and live in states that have abortion laws, you need to take action IMMEDIATELY. The medical malpractice implications of teratogenic drugs (those that can cause embryofetal damage) are changing and physicians who prescribe these drugs need to protect their women patients from fetal damage and to protect themselves against future lawsuits.

The FDA created the REMS program (Risk Evaluation and Mitigation Strategy) in 2007 as a way to be sure that physicians take appropriate precautions when prescribing certain high-risk drugs. Typically, the REMS program will recommend physicians to have specific training and certification before being allowed to prescribe these drugs. The problem is that hospitals and pharmacies rarely verify that a physician has been certified for drugs on the REMS list and as a consequence, many physicians prescribe them without having the proper certification. Currently, the FDA lists 60 such drugs on the REMS website. I am most familiar with the REMS drug, mycophenolate mofetil. During my career, I have prescribed mycophenolate… a lot of mycophenolate… typically as an immunosuppressant for various lung diseases.

Mycophenolate, a REMS medication

Mycophenolate mofetil is often sold under the brand names CellCept or Myfortic. It is commonly used in patients who have undergone organ transplant to prevent rejection of those organs. It is also commonly used as an immunosuppressant drug to treat various autoimmune diseases. When used properly, it can be life-saving and is considerably safer than older immunosuppressant drugs, such as cyclophosphamide. In many patients, it is also safer than corticosteroids such as prednisone. The biggest problem with mycophenolate is that it is highly teratogenic. Overall, about half of women who become pregnant while taking mycophenolate will have a miscarriage and 1 out of every 4 live births have serious congenital malformations. Because of the very high risk of embryofetal damage, mycophenolate was added to the FDA’s REMS drug list in 2012.

The mycophenolate REMS requirements are:

1. Physicians need to apply to the mycophenolate REMS website and undergo an on-line training program before prescribing mycophenolate.
2. Once certified to prescribe mycophenolate, physicians must educate patients about the risk of miscarriage and fetal harm.
3. Physicians must insure that women of childbearing potential use adequate contraception – preferably either vasectomy, tubal ligation, or an intrauterine device. In the absence of any of these 3 methods, women must use 2 forms of other approved contraception (for example, birth control pills + condoms).
4. Women should have a pregnancy test at every office visit.
5. Woman should be counseled about emergency contraception (Plan B) in the event of intercourse without adequate contraception.
6. Women must be given the printed REMS information about mycophenolate precautions.
7. Women should sign an agreement form acknowledging that they understand the risks of mycophenolate and agree to the requirements of the REMS program (note: this requirement was discontinued in January 2021).

All too often, I would see women of child-bearing potential in my office who had been started on mycophenolate by other physicians and who had never been informed about the REMS program. Frequently, these women were not using adequate contraception and were not undergoing regular pregnancy testing. Until last month in Ohio, if a woman became pregnant while taking mycophenolate, we could recommend pregnancy termination. Now, that is no longer an option if it is more than 6 weeks after her last menstrual period and the Ohio legislature has signaled that later this year, it intends to make pregnancy termination illegal in all pregnancies from the time of conception.

The heightened risk of malpractice lawsuits

The implication of anti-abortion laws, such as Ohio’s, is that if a woman becomes pregnant while taking mycophenolate, then there is a 25% chance that her baby will have severe congenital deformities. Children with these deformities can require life-long care and can be very expensive for families. Women taking mycophenolate because they have had an organ transplant or because they have chronic diseases such as lupus are generally not in a good position to provide care for the life of a child with serious birth defects and usually do not have the financial resources necessary for that care. This is especially true for my patients who have undergone lung transplant – the life expectancy after transplant averages about 6 years so these women will not be alive to care for a child with severe deformities.

We live in a litigious society. When faced with the birth of a child who will never grow up to be a normal adult and will incur large healthcare costs, women (or their widower spouses) will seek financial compensation to pay for these costs. Every personal injury attorney in the country knows that the person to name in a lawsuit is the person who has the most money. Hospitals and physicians are the ones with the most money. If a physician prescribed mycophenolate without having REMS certification to prescribe it or if there is no documentation that a woman was educated about pregnancy risks with mycophenolate, then that physician will be highly vulnerable in a malpractice suit.

The best defense for physicians is to get REMS certification before prescribing mycophenolate and adhere to the REMS requirements when prescribing it to any woman with child-bearing potential. The best defense for hospitals is to ensure that every physician prescribing mycophenolate has REMS certification. Electronic medical records make it easy for hospitals to determine which of their physicians are prescribing mycophenolate or other REMS drugs.

What other drugs are on the REMS list?

There are a variety of reasons that the FDA may put a drug on the REMS list. Some are on because of a high risk of anaphylaxis (Palforzia). Some are on because of a high risk of neurological toxicity (Abecma). Some are on the list because of risk of neutropenia (clozapine). Others are on the list because of a risk of over-sedation or addiction (buprenorphine). Of the 60 drugs on the REMS list, 11 are on the list because of the risk of embryofetal toxicity. The following is a list of these 11 drugs and what physician specialties are likely to be prescribing them.

A recent article in the American Journal of Obstetrics & Gynecology lists 141 drugs that are definite teratogens and 65 drugs that are considered to be potentially teratogenic. Of these 206 drugs, only 11 are included on the REMS list. However, the risk of embryofetal toxicity exists with all of these drugs and therefore the risk of medical malpractice lawsuits exists should a woman become pregnant while taking any medication known to be teratogenic and then develops fetal abnormalities.

Currently, 3% of all abortions performed in the United States are because of fetal abnormalities. This works out to about 28,000 per year. In states that ban abortion, these fetuses will go on to be infants with severe birth defects. The implication is that in the future, there will be potentially thousands of new malpractice suits filed each year against physicians who will be blamed for these birth defects because they prescribed a teratogenic drug to a woman who could not legally have her pregnancy terminated.

What physicians need to do right now

In medicine, doctors recognize that prevention is the best cure. The same goes for malpractice lawsuits. The best time to prevent a malpractice suit about a birth defect is before the woman becomes pregnant. To that end, there are measures that all physicians practicing in abortion-ban states should take now:

• Know which drugs are teratogenic. The recent list from the American Journal of Obstetrics & Gynecology is a good starting point.
• If you prescribe one of the 11 teratogenic drugs on the FDA’s REMS list, get your REMS certification and follow the REMS requirements.
• If you prescribe a teratogenic drug that is not on the REMS list, develop a process for educating women of child-bearing potential about the risks of the drug.
• Document, document, document. Include information in your office notes documenting patient discussions about drug teratogenicity, about contraception advice, and about any printed information that you gave them. 
• Consider signed acknowledgement forms. In the past, this was a requirement of the mycophenolate REMS program. Even though it is no longer required by REMS, a signed form scanned into the electronic medical record is still a good practice since it can provide very strong malpractice defense.
• Get comfortable recommending contraception. I have become at ease discussing contraception with my patients and their partners. If the woman is done having children, vasectomy is usually the safest and most effective option. For other women, I am a proponent of IUDs and although I do not place them myself, I know who to refer women to in order to get one. 
• Educate women about Plan B. The “morning after pill” is available at pharmacies over the counter without a prescription and is effective up to 3 days after unprotected intercourse. Include information about Plan B in the educational materials you give patients when prescribing any teratogenic drug.
• Understand your state’s abortion laws. In some states, it is (or will be) illegal for a physician to even discuss abortion with a woman or to advise her to travel to another state where abortion is legal. Be very careful what you write in the chart. A note in the electronic medical record stating: “She is 6 weeks pregnant while taking mycophenolate so I recommended she go to the Acme Abortion Clinic across the state line” could be your invitation for a prison sentence and revocation of your medical license. 
• Do a malpractice insurance check-up. For physicians in Ohio who care for adults, there is a 1-year statute of limitations for filing a malpractice lawsuit. But for cases involving children, that statute of limitation extends to 1-year after the child’s eighteenth birthday. In other words, a physician who prescribed a teratogenic drug to a pregnant woman can be sued by the child 19 years later. Be sure that you either have a comprehensive claims-made policy or a tail coverage policy that will provide coverage long after you retire or leave your practice.
• For hospital medical directors and administrators, use your electronic medical record’s prescribing database to identify physicians who prescribe REMS drugs and require that those physicians be REMS-certified.
• For medical schools, education during pharmacology courses about teratogenicity and about the REMS programs has suddenly become considerably more urgent.

Abortion prohibitionists have long set their sights on laws to criminalize abortion. There are a myriad of unintended consequences of banning abortion and many of the the socioeconomic consequences will not be fully recognized for several years. For physicians, waiting several years to protect against medical malpractice suits for prescribing a teratogenic drug will be too late. The time for physicians and hospitals to protect their patients and themselves is right now.

July 16, 2022