Arthritis Medications During Pregnancy

Updated Nov. 21, 2022

If you have a rheumatic disease, the chances are good that you can have a healthy pregnancy and baby, but you’ll also encounter challenges pregnant people without disease don’t face. One key problem is a shortage of data about the effects of arthritis drugs on fertility and pregnancy, mainly because lactating and pregnant women are usually excluded from clinical trials. There is even less evidence about the effect of arthritis drugs on prospective fathers and on people of different races and ethnicities.

If you’re considering pregnancy or you become pregnant, your rheumatologist should work closely with your OB/GYN. Yet this kind of coordination isn’t an option for everyone, and most rheumatologists aren’t trained in this field. That’s why it’s important to know the basics, do your own research and know the right questions to ask.  

Drugs to Avoid Before Conception and During Pregnancy

Some of the most prescribed arthritis medications aren’t safe when you’re pregnant or trying to conceive. Newer drugs that haven’t yet been studied in pregnant people are also off-limits. If you wish to become pregnant, talk to your doctor. It’s important to stop taking the following medications when you’re still in the planning stages:

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin), aspirin and naproxen (Aleve). Study results are mixed on whether NSAIDs are safe in the first and early second trimesters. If your doctor OKs an NSAID earlier in pregnancy, you’ll need to stop it at 20 weeks, according to recent warnings by the Food and Drug Administration (FDA) about an association with low amniotic fluid. NSAIDs have long been held in the third trimester, when it can cause lung and heart problems in a developing fetus. NSAIDs can also prolong labor and increase blood loss during delivery. Because less is known about the COX-2 inhibitor celecoxib (Celebrex), it’s not recommended when you’re pregnant.  Men planning to father a child can safely continue NSAIDs, including celecoxib. If you’re having trouble conceiving and take an NSAID regularly, try stopping it for several months because NSAIDs can affect ovulation. Low-dose aspirin may actually have the opposite effect, increasing your chance of becoming pregnant.

Acetaminophen (Tylenol). Although small doses of acetaminophen were once thought safe during pregnancy, a growing body of new research shows that the drug may cause developmental problems, such as reproductive tract and urogenital disorders, in infants and developmental problems, like attention-deficit/hyperactivity disorder and autism, later in life. There aren’t many good alternatives to acetaminophen, and some experts have pushed back against these findings, pointing out that fever and pain – conditions acetaminophen treats – can also pose dangers to a developing fetus. If you need acetaminophen for medical reasons, use the lowest dose you can for the shortest time.

Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), including methotrexate, mycophenolate mofetil (Cellcept), cyclophosphamide (Cytoxan) and thalidomide (Thalomid). These medications are used to treat a variety of rheumatic diseases, although methotrexate, a cornerstone therapy for rheumatoid arthritis, is prescribed most often. All four drugs can cause severe birth defects and should be stopped about three months before you try to conceive. Your physician may suggest substituting an alternative medicine that is considered low risk for pregnancy. Men planning to father a child should also discontinue thalidomide and cyclophosphamide one to three months before trying to conceive, though evidence suggests it’s safe for them to continue mycophenolate and methotrexate. Cyclophosphamide can cause irreversible infertility in both men and women. Some men taking the drug choose to freeze their sperm, and women may receive hormone treatment to suppress their ovaries while receiving the drug, which seems to reduce risk of ovary damage.

Leflunomide (Arava): This drug should be stopped and all traces removed from your blood before you try to conceive. Doctors often use a medication called cholestyramine to wash it out quickly; otherwise, the drug can stay in your system for up to two years. If you become pregnant while taking leflunomide, let your doctor know right away. You’re more likely to have a positive outcome if it’s washed out with cholestyramine early in pregnancy. And if you think you want to become pregnant in the future, talk to your doctor about using a different drug to begin with.

Biologics, including rituximab (Rituxan), belimumab (Benlysta), anakinra (Kineret), abatacept (Orencia), tocilizumab (Actemra), secukinumab (Cosentyx) and ustekinumab (Stelara). These are complex molecules made from living cells and they’re increasingly used to treat rheumatic diseases. But those listed should be stopped as soon as you know you’re pregnant because of inadequate information about their safety throughout pregnancy. Rituximab, anakinra and belimumab are safe for men trying to conceive or whose partner is pregnant.   

Janus kinase (JAK) inhibitors, including baricitinib (Olumiant), tofacitinib (Xeljanz) and upadacitinib (Rinvoq). These medications belong to a newer drug class called targeted synthetic DMARDs (tsDMARDs), or small-molecule inhibitors. In animal studies, they were associated with an increased risk of birth defects. There’s not much data about their safety in humans, but it’s likely they cross the placenta and aren’t recommended in pregnancy. All three JAK inhibitors also carry warnings for an increased risk of heart attack, stroke, blood clots and cancer in adults.

Apremilast (Otezla), a phosphodiesterase 4 (PDE4) inhibitor, is used to treat psoriasis and psoriatic arthritis. There are no studies of apremilast in pregnancy, but the drug’s manufacturer recommends against its use in pregnant people.

Corticosteroids, such as prednisone and prednisolone. According to the American College of Rheumatology (ACR), less than 10 mg a day of prednisone may be safe in pregnancy. Higher doses should be tapered to 20 mg or less when possible, sometimes with the addition of a pregnancy-safe medication to prevent flares. Prednisone and prednisolone don’t cross the placenta to a significant degree at low doses, and the most recent studies suggest there is no increased risk of birth defects. Higher doses may lead to ruptured membranes and infants who are smaller than normal at birth as well as to a greater risk of high blood pressure and gestational diabetes in pregnant people.

Safer Drugs in Pregnancy

If you’re trying to become pregnant or just thinking about it, be sure to talk to your doctor about getting your disease under tight control and switching to safer drugs early on, watching for several months to assure your disease stays stable on the newly substituted medications.

Certain csDMARDs, including sulfasalazine (Azulfadine, Sulfazine), colchinine (Colcrys), azathioprine (Imuran), 6-mercaptopurine (Purinethol), cyclosporin (Gengraf, Neoral) and hydroxychloroquine (Plaquenil) are safe to take or continue taking when you’re pregnant. If you have lupus and don’t already take hydroxychloroquine, pregnancy is a good time to start, as it has been shown to improve maternal and pregnancy outcomes. The safety of tacrolimus (Prograf, Protopic) isn’t as clear, although it is increasingly used. It can cross the placenta, and while not associated with birth defects, it may increase the risk of preterm birth and worsen high blood pressure in pregnant people. It’s usually only tried when a safer drug like azathioprine hasn’t worked well enough. Men planning to conceive can continue using all of these drugs, including tacrolimus, based on its relative safety in pregnancy.

Tumor necrosis factor (TNF) inhibitors, including etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi) and their biosimilars. These biologics are frequently used to treat inflammation in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis – conditions in which TNF plays a major role. TNF-inhibitors have been around longer than other biologics. The FDA approved the first, etanercept, in 1998, yet there are few published studies about their effects on pregnancy. They are considered relatively safe through conception and the first two trimesters. They should be stopped in the third trimester, if possible, when higher amounts of medication pass through the placenta. This can potentially suppress a newborn’s immune system. The exception is certolizumab, which is considered safe throughout pregnancy and after because there is little transfer through the placenta or through breast milk.
 

Safer Drugs With Breastfeeding

Breastfeeding has all kinds of benefits for a newborn, including high-quality nutrition, enhanced immunity, better gastrointestinal (GI) function and a lower risk of diabetes, heart disease and cancer later in life. The American Academy of Pediatrics recommends exclusive breastfeeding for the first six months of life and continued breastfeeding until an infant is at least a year old.

The problem for people with rheumatic diseases is that symptoms often flare after delivery and medications may be needed to control them. This means new parents and their doctors must weigh the possible harm of medications for an infant against the damage caused by untreated disease in the mom. Some medications pass easily into breast milk and may be absorbed at a higher rate by premature infants whose GI tracts aren’t fully developed.

If you breastfeed, these drugs are safe to use:

• Hydroxychloroquine
• Colchicine
• Sulfasalazine
• TNF inhibitors
• Prednisone at a strength of less than 20 mg daily

Drugs that are probably safe include:

• Azathioprine
• 6-mercaptopurine
• Ibuprofen
• Non-TNF biologics such as anakinra, rituximab, belimumab, abatacept, tocilizumab, secukinumab and ustekinumab

Drugs that are not safe during breastfeeding are the same ones that are dangerous during pregnancy:

• Cyclophosphamide
• Leflunomide
• Methotrexate
• Mycophenolate mofetil
• Thalidomide

For people with a rheumatic disease, pregnancy and breastfeeding are balancing acts. Your doctor should explain the pros and cons of all your options so you can make the best decision possible to maintain your own health and the development of the baby.