Can I Take This Drug While Pregnant?

In the last week of September 2021, a group of more than 90 doctors and researchers published a call to action, cautioning against the liberal use of Tylenol (acetaminophen) during pregnancy. The studies suggested that exposure to the drug could increase the risk of a baby having neurodevelopmental, reproductive and urogenital disorders.

The authors added, however, that Tylenol has long been considered one of the few safer options to treat pain in pregnancy, since Advil (ibuprofen) and opioids are considered riskier. They pointed out that, in some cases, a woman’s condition (fever and pain, for example) could be worse for her fetus than exposure to Tylenol. Until the research is more clear, talk to your doctor before taking Tylenol while pregnant and take the lowest possible dose for the shortest time period.

Definitive advice on the use of medications during pregnancy is hard to come by. Researchers generally won’t enroll pregnant people in clinical trials because, as Lauren Demosthenes, MD, an OB-GYN with Babyscripts, says, “When a drug comes out, they’re not going to say, ‘’Let’s experiment with this on pregnant women all the time.’” Physicians and patients must piece together information from animal and pharmacological studies and data gathered after the drug is approved.

For years, the Food and Drug Administration (FDA) supported a simple categorization strategy. It labeled each drug A, B, C, D or X, based on how safe it was thought to be, in descending order, for a fetus. Over time, doctors noted that while the system was easy-to-use, its simplicity could at times be misleading. Rankings often had more to do with how long a drug has been on the market than how safe it was during pregnancy. 

In 2014, the FDA rolled out a new strategy. Now each drug’s label is required to list findings (or lack thereof) from clinical trials, animal studies and more in a specialized format, allowing doctors and patients to weigh the information together for themselves. Physicians say that while the new strategy can’t be interpreted as quickly as the previous letter-based categories, it better supports the doctor-patient shared decision-making process.

“Even though there used to be categories, the process has always been the same. So even if a drug was in one of the in-between categories, it’s still required that you just sit down and have a conversation about it,” says Demosthenes.

Nicole Derish, MD, who runs a private psychiatry practice specializing in working with perinatal, child and adolescent patients, explains that the decision is more complicated than avoiding any drug that can raise the risk to a fetus. “You have the risk of being exposed to the medication versus the risk of being exposed to [an] untreated illness. Just because a medication has some risk doesn’t mean it’s not the safest option for a pregnant woman and their baby,” she says. “Every woman I’ve ever treated – every single one – says, ‘Well, I don’t care. It’s nine months. I can white-knuckle it. I just want what’s best for my baby. I don’t care if my life is miserable.’ I have to say, ‘No, no. I hear you, but this is what’s good for the baby. What’s good for you is good for the baby.”

History of Drugs in Pregnancy

Pregnant people have good reason to be wary of using medications in pregnancy. In the 1950s, thalidomide was prescribed to expecting mothers for a variety of ailments, from morning sickness to pneumonia. About five years later, researchers made the connection between fetal exposure to the drug and birth defects that left about 10,000 babies with deformities in limbs, ears and other organs. The FDA never approved thalidomide despite incredible pressures from manufacturers (and the fact that most European countries were using it widely).  As a result, very few babies were harmed in America. Even so,  his tragedy led to increased scrutiny on drug approvals, and thalidomide is still the classic example of why a strong, independent FDA is crucial for everyone’s safety.

Thalidomide Is not the only regulatory catastrophe for drugs in pregnancy. DES (diethylstilbestrol), which was developed before thalidomide and used in pregnancy for years after, resulted in less visible but more insidious effects on growing fetuses. DES, which was prescribed until 1971 to prevent preterm births, is now known to have caused elevated risks of cancer, infertility and more, not only to one generation, but even to their children and grandchildren. (See our sister website and member organization, DES Action, for more information.)

Even though the FDA removed DES’s approval for use in pregnancy, similar drugs have taken its place. (See our article on Makena.)

New Labeling Guidelines

The FDA gradually phased out the letter-naming program,which ended in June 2020. Drug labels now must list available information under several consistent headings.

Pregnancy Risks Label

Under Section 8.1 of the drug label, the drug must have four headings.

The first is Pregnancy Exposure Register: Here, the drugmaker lists whether there is a registry where doctors must report outcomes in pregnant patients using the drug, and where to find it. Derish says, “You have to report any potential adverse reaction, even if you think it’s still unrelated, like, [for instance, if] somebody starts the medication and they start to get more mosquito bites. That goes on the registry. So one of the ways that these medications collect data is just by being on the market.”    

The next section is Risk Summary. This is the crux of the label’s information. Here, the manufacturer lists what’s known about whether the drug can cross the placental barrier and if animal studies or human studies have identified any risks to the fetus. If data is unavailable, the company states this explicitly. This section also contains background information, such as how likely a baby is to be born with a birth defect in the general population and how likely they are to be born with a birth defect if the disease the drug addresses goes untreated during their mother’s pregnancy. 

For example, if “the baseline rate [for a particular birth defect] is 1% of the general population, [research on a drug may indicate that using it in pregnancy] might raise the rate to 2%. And that is a big increase, right? From 1 to 2[%],” says Derish. “But even with that medication, 98% of the time, your baby’s going to be fine.”

The third section is Clinical Considerations, which lists information about dose adjustments during pregnancy or breastfeeding, and risks to the mother and the fetus.

The final section is Data, which lists more detailed information about the studies supporting the clinical guidelines.

Common Medicines: What’s Known

According to the Centers for Disease Control and Prevention (CDC), 70% of women say they take at least one prescription drug while pregnant.  

There are some drugs, explains Demosthenes, like the acne drug Accutane (isotretinoin), that are known to be dangerous to a fetus. “There are certain medicines that even [have] requirements. You are asked to sign a form to say you understand the risk and you commit to being on birth control and [will] do everything you can not to get pregnant,” she says. “If you’re a teenager and you [are prescribed] Accutane, they will want you to be on some kind of contraception if sexually active.”  

Some other drugs that are contraindicated before and during pregnancy in most instances are:

Methotrexate (Trexall): This rheumatoid arthritis drug blocks the action of folic acid, a crucial component to a fetus’ development.

Leflunomide (Arava): This is an immunosuppressant used to treat rheumatoid arthritis. It takes some time to leave your system, so physicians suggest getting a blood test first and stopping about a month before trying to conceive. Studies have shown an increased risk of miscarriage, and mixed results on birth defects.

Non-steroidal anti-inflammatory drugs (NSAIDS): The FDA recommended using Tylenol instead of non-steroidal anti-inflammatory drugs (NSAIDS), because NSAIDs, like Advil, can cause kidney problems in the fetus.

Most drugs fall into gray areas. Some of the most common questions, according to both doctors, are about psychiatric medications.

Stimulants in Pregnancy

Heather has been taking the attention deficit hyperactivity disorder (ADHD) medication Adderall since her late 20s. She’s now 36 and pregnant. When her physician said she needed to stop taking the drug during pregnancy, she was offered an alternative, but decided to forgo it. It’s been a struggle, she says, to get through her day and her work, but she’s managing with the help of counseling and meditation. The CDC states that stimulants used to treat ADHD may increase the risk of certain birth defects of the limbs and digestive system, though the organization maintains that the risk remains small.

SSRIs (selective serotonin reuptake inhibitors) in Pregnancy

“We actually have a ton of data on SSRIs (selective serotonin reuptake inhibitors) and pregnancy, the most common antidepressant, in pregnancy. And it’s very robust,” says Derish. “They’re very safe. They’re very well-tolerated.”

Untreated mental illness can be dangerous. Health Affairs published a study in October 2021 showing that women with mental health disorders had more expensive deliveries ($458 higher) and were 50% more likely to experience severe complications while giving birth, than others. Those with stress or trauma-related disorders had the most expensive deliveries. Those with untreated depression are more likely to experience preterm birth and have babies with low birth weights. This risk is especially high among Black women.

Pregnancy comes with a lot of stress and physical changes. If she diagnoses a mother with new depression during her pregnancy, “I try as hard as I can to try a nonpharmacological intervention. Protecting sleep is a very big one,” Derish says. But sometimes an SSRI makes more sense. For some, medications are more effective. For others, lifestyle changes during pregnancy aren’t practical. “I can recommend yoga. If I have a single mom who has three other kids, it’s not that yoga hasn’t occurred to her, it’s just [that] it’s not going to happen for her because she’s already so taxed.”

Benzodiazepines in Pregnancy

“Benzodiazepines are a little bit more iffy [than SSRIs],” explains Derish, because they’re more likely to cross the placental barrier, meaning that your baby can be exposed to and hurt by them. She adds that, in many cases, untreated anxiety is a bigger risk to the fetus. “We have a lot of data showing that women that have very high levels of anxiety have more complications of pregnancy and poorer outcomes.” Untreated anxiety during pregnancy has been linked to increased risk of preterm birth, for example.

Derish explains that that’s one of the benefits of the new labeling system. It allows for doctors and physicians to weigh the risks of untreated conditions versus those of exposures to their treatments, rather than just identifying some drugs as safe and others as dangerous.

MotherToBaby.com offers a series of factsheets on commonly used medications like ACE (angiotensin-converting-enzyme) inhibitors, proton pump inhibitors and statins in pregnancy. The FDA also maintains a searchable database with drug labels and  pregnancy information.

Supplements

In addition to talking with your physician about any medications you’re prescribed, you should also tell your doctor about any supplements or herbal remedies you’re using . Many of these are safe during pregnancy, but some do come with the risk of complications. For example, ginger may interact with other medicines you’re taking to increase the risk of bleeding.

Most herbal supplements have not been well-studied in pregnancy. Additionally, many supplements contain different combinations of ingredients that make it difficult to compare one brand to another. Bring any herbal supplements you use with you to the doctor to review the ingredients.

“Just because it’s ‘natural’ and it’s over-the-counter doesn’t necessarily mean that it would be advised to take in pregnancy,” says Demosthenes.

You should always discuss the risks and benefits of your medications and supplements with your healthcare provider, but during pregnancy is an especially important time to do so. The new labeling system ensures that you’re able to have an open conversation regarding what is and isn’t known about anything you may expose yourself or your fetus to. 

“Everybody has an opinion of what pregnant women should do… So you really need to believe, at the end of the day, you can make good choices and you have to surround yourself with a team that you trust and that trusts you,” says Derish. “That way, when a relative or friend says, ‘You shouldn’t be taking that in pregnancy,’ you can definitively say, ‘My OB-GYN says I should, and I’m going to listen to them because they’re my doctor.’ ”

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Dance and movement therapy holds promise for treating anxiety and depression, as well as deeper psychological wounds

A few years ago, framed by the skyline of Detroit, a group of about 15 children resettled as refugees from the Middle East and Africa leapt and twirled around, waving blue, pink and white streamers through the air.

The captivating scene was powerfully symbolic. Each streamer held a negative thought, feeling or memory that the children had written down on the streamers. On cue and in unison, the children released their streamers into the air, then sat down nearby. Then they gathered up the fallen streamers, which carried their collective struggles and hardships, threw them in a trash can and waved goodbye.

The children were participating in a dance therapy activity as part of our team’s research program exploring body-based approaches to mental health treatment in people resettled as refugees.

In 2017, our lab – the Stress, Trauma and Anxiety Research Clinic – began piloting movement therapies to help address trauma in refugee families. We are learning that movement may not only provide a way to express oneself, but also offer a path toward healing and lifelong strategies for managing stress.

Dance and movement therapy offers a self-empowering mind-body approach to mental health treatment.
David Dalton, CC BY-ND

On average, every year about 60,000 children are resettled as refugees in Western nations. Now, the refugee crisis resulting from the U.S. withdrawal from Afghanistan is bringing renewed attention to their needs. The UN Refugee Agency estimates that 6 million Afghans have been displaced over the past 40 years, and a new wave of tens of thousands are now fleeing from Taliban rule.

I am a neuroscientist who specializes in understanding how trauma reshapes the nervous system of developing youth. I use this information to explore creative arts and movement-based therapies to treat stress and anxiety. The instinct to move the body in expressive ways is as old as humanity. But movement-based strategies such as dance therapy have only recently been given much attention in mental health treatment circles.

As a dancer myself, I always found the nonverbal emotional expression offered through movement to be incredibly therapeutic – especially when I was experiencing significant anxiety and depression in high school and college. Now, through my neuroscience research, I am joining a growing number of scholars working to bolster the evidence base supporting movement-based interventions.

One mind and body

During the COVID-19 pandemic, the incidence of anxiety and depression doubled in youth. As a result, many people are searching for new ways to cope with and handle emotional turmoil.

On top of the pandemic, conflicts around the world, as well as climate change and natural disasters, have contributed to the growing global refugee crisis. This demands resources for resettlement, education and occupation, physical health and – importantly – mental health.

Interventions that offer physical activity and creativity components at a time when children and people of all ages are likely to be sedentary and with reduced environmental enrichment can be beneficial during the pandemic and beyond. Creative arts and movement-based interventions may be well-suited to address not just the emotional but also the physical aspects of mental illness, such as pain and fatigue. These factors often contribute to the significant distress and dysfunction that drive individuals to seek care.

With outstretched arms, neuroscientist Lana Ruvolo Grasser performs a tension-and-release exercise with her study participants.
David Dalton, CC BY-ND

Why dance and movement therapy?

Body movement in and of itself is known to have a multitude of benefits – including reducing perceived stress, lowering inflammation in the body and even promoting brain health. In fact, researchers understand that the majority of our daily communication is nonverbal, and traumatic memories are encoded, or stored, in nonverbal parts of the brain. We also know that stress and trauma live in the body. So it makes sense that, through guided practices, movement can be leveraged to tell stories, embody and release emotions and help people “move” forward.

Dance and movement therapy sessions place an emphasis on fostering creativity and adaptability in order to help people develop greater cognitive flexibility, self-regulation and self-direction. This is especially important because research shows that early-life experiences and how children learn to cope with them can have a lasting impact on their health into adulthood.

According to the Child Mind Institute Children’s Mental Health Report, 80% of children with anxiety disorders are not receiving the treatment they require. This might be due to barriers such as clinician availability and cultural literacy, cost and accessibility, and stigma surrounding mental health conditions and treatment.

In this ice-breaker exercise, study participants created a dream catcher by tossing strings of yarn to one another, introducing themselves and then tossing the string to another child across the room.
David Dalton, CC BY-ND

We are finding that dance and movement therapy and other group behavioral health programs can help fill important gaps. For instance, these strategies can be used in combination with services people are already receiving. And they can provide an accessible and affordable option in school and community settings. Dance and movement therapy can also instill coping skills and relaxation techniques that, once learned, can last a lifetime.

But does it work?

Our research and that of others are showing that dance and movement therapy can build up children’s sense of self-worth, improve their ability to regulate their emotions and reactions and empower them to overcome obstacles.

Much like yoga and meditation, dance and movement therapy has, at the root of its practice, a focus on deep breathing through the diaphragm. This intentional breathing movement physically pushes on and activates the vagus nerve, which is a large nerve that coordinates a number of biological processes in the body. When I work with kids, I call this form of breathing and nerve activation their “superpower.” Whenever they need to calm down, they can take a deep breath, and by engaging their vagus nerve, they can bring their bodies to a more restful and less reactive state.

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An analysis of 23 clinical research studies indicated that dance and movement therapy may be an effective and appropriate method for child, adult and elderly patients experiencing a wide array of symptoms – including psychiatric patients and those with developmental disorders. And for both healthy individuals and patients, the authors concluded that dance and movement therapy was most effective for reducing the severity of anxiety compared with other symptoms. Research from our team has also shown promise for the benefits of dance and movement therapy in reducing symptoms of post-traumatic stress disorder and anxiety in youth who resettle as refugees.

We have scaled up these programs and brought them into the virtual classroom for six schools throughout the metro Detroit region during the pandemic.

Perhaps the most promising evidence for dance and movement therapy isn’t, as the saying goes, what the eyes cannot see. In this case, it is what the eyes can see: children releasing their streamers, their negative emotions and memories, waving goodbye to them and looking ahead to a new day.

Lana Ruvolo Grasser, Ph.D. Candidate and Graduate Research Fellow, Wayne State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Pregnant or worried about infertility? Get vaccinated against COVID-19

As the delta variant of SARS-CoV-2 surges across the U.S., almost 1 in 5 Americans continue to resist getting shots that are widely available, safe and effective – particularly for preventing the most severe outcomes of the virus.

While people have many different justifications for not getting the shot, one particularly insidious bit of pseudoscience has surfaced. It is routinely invoked in the contentious debate over vaccine policy in the U.S. and continues to stir confusion and skepticism toward vaccines in young women across the globe.

This misinformed argument reasons that the coronavirus vaccines could affect fertility in women by mistakenly triggering the creation of antibodies that react with an important placental protein called syncytin-1. This protein contains minor similarities to the coronavirus spike protein used in all current COVID-19 vaccines. Thus, the false narrative goes, the immune system will not be able to differentiate between the two and will create antibodies that interfere with proper development of the placenta.

This argument lacks understanding of how the immune system does its job.

As an immunologist who studies COVID-19 infection and the ways it can cause the immune system to turn against itself, this misunderstanding comes up frequently in my conversations with friends, family members and even medical workers who are legitimately concerned about their health and their future ability to have children.

It is completely understandable to have questions about how a new vaccine might affect reproductive health. But the science is clear that getting vaccinated does not put women at risk for infertility. It protects women, their unborn children and their families from a serious disease that, ironically, could in fact affect fertility in men.

Antibodies rarely make mistakes

The immune system is an immensely complicated network of cells, tissues and proteins that interact with one another – and the outside world. It works to maintain a balanced, healthy environment so the rest of the cells in the body can do their jobs. Among other things, the immune system helps direct fetal development, oversees and manages the microbes that aid in digestion and, of course, fights off infection.

One of the immune system’s most critical jobs is to differentiate between the body’s own cells and those of outside invaders to prevent accidental attacks on itself. In immunology, this careful selection of responses is called “immune tolerance.” People whose immune systems fail to maintain this tolerance and instead attack their own cells and tissues are diagnosed with autoimmune disorders. These can range in symptoms and severity depending on the tissue being attacked. An example is rheumatoid arthritis – a misdirected antibody attack on soft tissue in the joints.

This depiction of antibodies attacking neurons illustrates what happens in some individuals with autoimmune disorders.
Kateryna Kon/Science Photo Library via Getty Images

The immune system has a series of checks and balances that are intended to prevent such autoimmune attacks. When B-cells – the cells in the immune system that produce antibodies – are first “born,” they carefully screen themselves to make sure that they won’t target the body’s own organs. That self-screening continues as B-cells patrol the body looking for an infection to fight; if they find something potentially threatening, like a vaccine, they engage in a highly orchestrated dance with other immune cells. Through that weeks-long process, only B-cells that produce antibodies against the outside invader survive. B-cells with self-destructive potential are killed.

Importantly, in parts of the body where it is absolutely critical that the immune system not mistakenly turn on its own cells – such as a developing placenta or in the brain – the entire region is immunosuppressive. This means that the threshold for activating the body’s immune response in those areas is set at an even higher bar.

This is not emerging science. These are well-established concepts among immunology experts. and have been for almost a half-century. As a result, it was not particularly noteworthy that a new preliminary study of women with fully developed immune responses against coronavirus showed no activity against the placental protein syncytin-1. Another study unsurprisingly demonstrated that the vaccine does not damage the placenta.

COVID-19 is the real threat to the immune system

It is important to remember that the COVID-19 vaccines authorized – and in the case of Pfizer-BioNTech, fully approved – in the U.S. carry the instructions to make the same spike protein that the virus uses to force its way into cells. Regardless of whether a person is infected with COVID-19 or receives a vaccine that emulates part of the virus, the immune system will respond aggressively to the spike protein that the body sees as foreign. Study after study confirm that in people who contract the virus, the majority of the immune response is directed at the spike protein.

However, there is one critical difference between vaccination and infection.

When you get vaccinated, your immune system has the time to respond under relatively low-risk circumstances. In other words, the immune system senses a threat and begins to build up its arsenal without rushing. But when it is confronted with a severe infection, the immune system recruits every weapon it has, as quickly as possible, to fend off severe infection or death.

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This is important because we now know that under the severe stress of fighting COVID-19, the immune system fires up an emergency response pathway and begins producing antibodies that are not well selected. Many of these antibodies will target the virus, but our work now under review and others’ published findings confirm that in more than half of severe patients, a large number of antibodies also target their own cells.

Simply put: The danger of this kind of “auto-reactivity” in COVID-19 doesn’t come from responding against the spike protein in a vaccine – it occurs when the body has to fight a real COVID-19 infection.

Getting vaccinated protects unborn children

Getting vaccinated costs people a couple of days of not feeling 100%. In return, it provides protection from contracting a serious disease with the potential to cause serious illness or death. Being vaccinated also gives crossover protection to an unborn child.

COVID-19 infection, on the other hand, puts pregnant women at risk of severe disease, pregnancy complications and death. It may also affect a couple’s ability to have children by decreasing a man’s sperm counts and causing erectile dysfunction.

The science is clear, but for me this is also deeply personal. My wife was vaccinated in March, and we are expecting a baby in December. We are both deeply grateful for a vaccine that has given us the confidence to support a healthy pregnancy in the midst of a pandemic.

Matthew Woodruff, Instructor of Human Immunology, Emory University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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FDA’s Black Box Warning for Xeljanz Leaves Patients, Doctors Scratching Their Heads

If you watch television, you’ve likely seen the commercials for the JAK (Janus kinase) inhibitors Xeljanz and Rinvoq that make bold claims.

Those ads depict men and women ziplining, moving large amounts of heavy soil, hauling furniture and riding ATVs. “The [misleading] message is that you don’t have to be limited in any way,” explains Terry Graedon, PhD, a medical anthropologist and co-host of The People’s Pharmacy. “I would say that the likelihood [is pretty slim] that this is a realistic goal for most people, much less women with rheumatoid arthritis,  especially if they are people whose condition has not responded to other treatments [that the Food and Drug Administration (FDA) recommends trying before JAK inhibitors].”

On September 1, 2021, the FDA issued a newly updated black box warning, the most serious of the agency’s safety advisories, on three JAK inhibitors — Xeljanz (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib). The warning states that these drugs, used to treat several inflammatory diseases like ulcerative colitis and rheumatoid arthritis, are associated with a heightened risk of heart disease, blood clots, cancer and death. Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), which doctors prescribe for certain blood disorders, were not included in the warning.

After the FDA first approved Xeljanz in 2012, research suggested that the drugs could raise health risks. Because of that possibility, the FDA asked its manufacturer, Pfizer, to conduct a post-market Phase IV clinical trial to assess safety. Interim results showed that at higher doses, the drug could increase the risk of blood clots. As a result, the FDA issued a boxed warning back in 2019. Later, the finished trial demonstrated more risks at all doses.

With the September announcement, the FDA added that the drugs should only be prescribed to patients who have not experienced relief from tumor necrosis factor (TNF) inhibitors after taking Enbrel and Humira.

Still, the FDA statement included little data. The clinical trial conducted by Pfizer only assessed Xeljanz, not the similar drugs, Olumiant or Rinvoq, and the results are not public. 

In the Q&A, below, two members of MedShadow’s Medical Advisory Board, Terry Graedon and Joe Graedon, MS, a pharmacologist and co-host of The People’s Pharmacy, help us make sense of the FDA advisory.

MedShadow: What did we know about the safety of Xeljanz before this warning?

Joe Graedon: We’ve known for almost a decade that there were some [safety] issues. As a class, the Janus kinase inhibitors are messing around with basic biological systems at a very fundamental and early stage, which is why they were effective as anti-inflammatories.

Pretty early on in the Xeljanz story, there were concerns about a variety of potential adverse reactions, not the least of which was cardiovascular, because it has a negative impact on lipids and, in particular, [on] LDL cholesterol.

Terry Graedon: Even more than five years ago, there were some signals that this drug is not benign.

MedShadow: Xeljanz was approved in 2012 by the FDA. Why are we hearing this warning just now?

J. Graedon: When there are safety concerns, the FDA says, “Well, you need to do a Phase IV clinical trial [a trial conducted after the drug has already been FDA- approved].” But a lot of times, those companies just never do them. It’s not like the FDA can require a Phase IV trial, but they could encourage it. So that’s what they did. The Phase IV trial for Xeljanz didn’t start until 2014.

MedShadow: What did the trial tell us?

J. Graedon: The results of that clinical trial were not released. [The FDA] just gave us a sort of overview. We now know, nine years later, that this drug in particular, Xeljanz, increases the risk for some pretty serious consequences, not the least of which are heart-related events. Then they also say, “Oh yeah, and cancer and blood clots.”

MedShadow: Will this new, serious warning  from the FDA change how the drugs are used?

J. Graedon: There were some caveats before this phase for trial was complete. Now that the Phase IV trial has been completed, it’s pretty clear that the FDA is saying, “No, no, doctor, you cannot prescribe or should not prescribe a JAK inhibitor, unless you’ve tried one of the TNS blockers [first]. You’ll have to go with Humira [the leading TNS blocker]. You’ll have to go with one of those other expensive drugs. And when they fail or when patients can’t tolerate them, and you’ve already tried, presumably, methotrexate, and whatever else you have in your toolkit, well, now you can prescribe a JAK inhibitor. But you better be careful, because there are a lot of side effects.”

MedShadow: What should patients ask their doctors about, if they’ve been prescribed these drugs?

T. Graedon: I don’t think we’re in a position to say, “Don’t take these drugs,” because, for some people, they’re going to be very useful.

J. Graedon: How do we assess risk [before]we see the data? How do we know the risk for heart attack, stroke, cancer? What are the risks? It’s absolutely impossible for a physician even to be able to say, “Oh, well, we’re increasing the risk of, fill in the blank, lymphoma by an absolute risk of 4%”

T. Graedon: We don’t have those numbers. If you were [prior to taking the drugs] at risk for a stroke or a heart attack, I would think you might want to ask the doctor about an alternative to the JAK inhibitors. And in terms of trying to lower your risk, I trust that most people are doing what they can to lower their risk of heart disease and stroke anyway, by trying to make sure that they get some physical activity, by trying to make sure that they’re following something like a Mediterranean diet. But those things, although they’re pretty powerful if you apply them over a lifetime, on a short-term basis, they’re not very powerful.

J. Graedon: Here’s the problem. We don’t completely understand what the mechanism of the increase is. That information is missing. How are [the drugs] increasing the risk for blood clots? What about cancer? How are they affecting cancer susceptibility?

Until we have some actual quantitative data, we’re sort of shooting blind. But the FDA is just [issuing] the black box warning that says, “Watch out. These are all your worst fears: cancer, heart disease and early or premature death.” It really leaves the patient without any details, and ditto for doctors.

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Five Sunscreens Voluntarily Recalled; Many More Also Contain Carcinogen

October 4 Update: Five more sunscreen sprays recalled for benzene contamination. The new group is from Coppertone and includes: 

• Coppertone Pure & Simple SPF 50 (5 oz aerosol  spray)
• Coppertone Pure & Simple Kids SPF 50 (5 oz aerosol spray)
• Coppertone Pure & Simple Baby SPF 50 (5 oz aerosol spray)
• Coppertone Sport Minteral SPF 50 (5 oz aerosol spray)
• Travel-size Coppertone Sport Spray SPF 50 (1.6 oz aerosol spray)

You can find photos of the products and information about specific lot # and refunds here.

Continuing a recent trend, Johnson & Johnson recalled five sunscreens that were shown to contain unsafe levels of benzene, a known carcinogen. The recalled sunscreens are:

• NEUTROGENA® Beach Defense® aerosol sunscreen,
• NEUTROGENA® Cool Dry Sport aerosol sunscreen,
• NEUTROGENA® Invisible Daily™ defense aerosol sunscreen,
• NEUTROGENA® Ultra Sheer® aerosol sunscreen, and
• AVEENO® Protect + Refresh aerosol sunscreen.

Back in May, an independent company, Valisure, announced that it had detected benzene in 78 different sunscreens. 

The chemical is considered a contaminant, meaning it is not supposed to be in the sunscreen to begin with. The company does not yet know how benzene found its way into the sprays.

Several scientists told the Washington Post that the benzene is unlikely to harm users, as it evaporates very quickly after the sunscreen is sprayed. Benzene is also present in the air we breathe daily, but if you ingest or inhale too much, you may become dizzy, disoriented, experience a rapid heart beat or even die. Long term exposure can cause anemia, irregular menstruation and certain cancers.

Just in case, Ranella Hirsh, MD, a dermatologist, posted a list of the products that were tested and found to be free of benzene contamination on Instagram, along with a caption encouraging people to continue using sunscreen to prevent skin cancer.

 

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If you have used any of these sunscreens and experienced an adverse event, you can report it using FDA’s MedWatch system.

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New Chemo Drug Rylaze Offers Treatment for Children’s Leukemia

A new chemotherapy drug promises to treat some patients with pediatric acute lymphoblastic leukemia (ALL) who have been unable to take the other two other chemo medicines because one can cause allergic reactions and the other is frequently in short supply. 

This summer, the Food and Drug Administration (FDA) fast-tracked the approval of Rylaze, a newer version of the chemo drug Erwinaze to treat ALL, made by Jazz Pharmaceuticals, which was previously a distributor of Erwinaze. The agency approved the drug based on an ongoing Phase 2/3 trial of about 102 patients, with an average age of 10. 

The rare disease ALL affects fewer than 6,000 people a year in the US, half of whom are children. Doctors have attempted to treat patients with Oncaspar, also known as pegaspargase. However, Oncaspar has been found to cause serious allergic incidents in about 20% of patients, which can lead to discomfort and a blunting of the drug’s effectiveness. While Erwinaze doesn’t trigger allergies, since 2016, it has been plagued by production shortages making the drug difficult to obtain. 

Haneen Abdella, MD, an oncologist with Nicklaus Children’s Hospital, describes securing enough Erwinaze as a lottery-style system in which drug companies announce that it’s available, and hospital pharmacists rush to claim doses before the company runs out. “It’s like trying to buy concert tickets in a certain amount of time,” she says.

Out of necessity, doctors have found that, in some cases, they can treat patients with anti-allergy medications before administering Oncaspar to thwart the allergic reaction. “This was really essential in the last two years,” says Abdella, “in light of the Erwinia shortage.” But it didn’t work for everyone. Some still needed to wait for Erwinaze to become available.

It was the allergic reactions to Onscapar that led scientists to develop the alternative treatment Erwinaze (Erwinia chrysanthemi) in 2011. Though Erwinaze works the same way as Oncaspar, it is produced differently, which means that those who are allergic to Oncaspar can usually take Erwinaze without developing the same reactions. 

An allergy occurs when your immune system reacts to an outside substance – like pollen or medicine – as if it were an infection. You mount an immune response, creating antibodies to neutralize the invader. “An allergic reaction means you have an antibody against [the drug]. If you have an antibody, not only are you having an allergic reaction, but the asparaginase is also not working properly because you’re neutralizing it with an antibody,” says Ziad Khatib, a hematologist and oncologist with KIDZ Medical Services.

For the patients who can get the chemotherapy, the results can be stunning. “We expect anywhere between 80% to 90% of children [with ALL] to be cured. But they do have to go through the treatment, which is two and a half years of [Oncaspar],” adds Khatib. Oncaspar is “very important in treating childhood leukemia and lymphoma.” If the child is being treated with Erwinaze and the treatment is interrupted by a shortage in supply, their cancer is more likely to recur.

All three drugs — Oncaspar, Erwinaze and Rylaze — use the same active ingredient, asparaginase, to kill cancer cells. The difference is in the manufacturing process. Oncaspar uses the E. coli bacteria, Erwinaze is derived from Erwinia chrysanthemi and Rylaze is produced using other easily sourced bacteria that have been genetically altered to hold the Erwinia chrysanthemi DNA.  

What Are the Side Effects?

Rylaze’s clinical trial isn’t completed yet, but, so far, it has shown similar side effects to Erwinaze and Oncaspar. “You pretty much expect the same spectrum of side effects, which are significant, but Rylaze is not specifically different,” says Khatib. Chemotherapy is notorious for causing myriad challenging side effects, but Khatib and Abdella say that the three most consequential are pancreatitis, clotting issues and an increased risk of diabetes and obesity.

Pancreatitis: Pancreatitis is an inflammation of the pancreas leading to nausea, abdominal pain and vomiting. The condition usually requires hospitalization. Abdella says there isn’t much you can do to prevent this condition, and doctors are unable to predict who will experience it.

Clotting issues: The drugs can cause the blood to either clot too much or too little. “One thing that we have to be very cognizant of is clotting risk,” says Abdella. If your child’s blood isn’t clotting, she may receive blood transfusions that replenish clotting factors. If it’s clotting too much, doctors may treat the condition with anticoagulants (blood thinners.)  

Diabetes and obesity: Children who are treated for cancer have a higher risk of becoming obese as they get older. During treatment, they may quickly develop high blood sugar and diabetes. Doctors can recommend a balanced, low-carb diet and frequent monitoring to help prevent these outcomes.

How Do I Know If My Child Is Allergic to Oncaspar?

If your child is allergic to Oncaspear, Abdella says, the medical team will usually notice symptoms in the hospital during the infusion, such as nausea and vomiting. However, in some cases, the symptoms don’t arise until a few hours after treatment, explains Abdella.

The symptoms of an allergic reaction are similar to those of an infusion reaction, a common side effect that isn’t dangerous. If a doctor suspects the child is having an allergic reaction, she or he may conduct a blood test to rule out an infusion reaction.

Does the Treatment Plan Change?

One reason that physicians use Oncaspar as the frontline treatment instead of Erwinaze or Rylaze is that it’s easier to administer. Each dose of Oncaspar is long-lasting, one dose covers a two-week course of chemotherapy. However, patients being treated with Rylaze (or Erwinaze) will need to return to the hospital six times over the course of two weeks for repeated infusions for each course of therapy.

 

 

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V-Safe: How Everyday People Help the CDC Track Covid Vaccine Safety With Their Phones

Of the 203 million people who have received at least one dose of a covid-19 vaccine, more than 9 million have enrolled in a program to share information about their health since getting the shot.

The initiative was created for the covid-19 vaccines to complement the Centers for Disease Control and Prevention’s vaccine safety monitoring system. Known as v-safe, the registry lets inoculated people report their experiences, including serious suspected side effects, directly to the CDC through smartphones, adding to the data gathered from clinical trials and other safety monitoring systems.

So how does v-safe strengthen the nation’s existing safety checks and how well is it working?

Going in, some public health experts expressed doubts about its effectiveness. But since the tool’s Dec. 13 release, reviews have mostly been positive.

“It’s a really good way to make everybody part of the process,” said Dr. Kathryn Edwards, founder of the Vanderbilt Vaccine Research Program and principal investigator for the CDC-funded Clinical Immunization Safety Assessment Network.

“There never has been so much scrutiny of vaccines and so much reporting and so much tailored information,” she added.

How Is Vaccine Safety Traditionally Monitored?

The federal government has various systems to monitor the safety of vaccines as well as other pharmaceutical products once they reach the marketplace. For starters, the Vaccine Adverse Event Reporting System, jointly run by the CDC and the Food and Drug Administration, since 1990 has served as a repository for reports on health problems that may be side effects of vaccines. Health care providers are required by federal law to report certain adverse events, but patients, their family members or caregivers can also submit a report online.

VAERS receives tens of thousands of reports each year, which are stripped of personal identifiers and publicly shared in an online database. These reports, which frequently lack details and sometimes contain errors, are not enough to establish a causal relationship between the vaccine and an adverse event, but they offer the agencies, along with scientists and researchers, a chance to identify and investigate unusual patterns.

VAERS helped spot unexpected cases of rare blood clots in several people who received the Johnson & Johnson vaccine. After studying the VAERS reports, the CDC listed what experts later identified as thrombosis with thrombocytopenia syndrome as a serious but rare health problem associated with the J&J vaccine.

Then there’s the Vaccine Safety Datalink, which uses electronic health data from nine large health care organizations across the country, including various Kaiser Permanente systems on the West Coast and Harvard Pilgrim Health Care in Massachusetts. According to Minnesota-based HealthPartners, another participating organization, the VSD network looks at data for 3% of the U.S. population, or roughly 12 million people — everything from medical and pharmacy claims to vital records. National Geographic reported that analyses are done weekly so signals of adverse events are quickly noted.

What Does V-Safe Add to the Mix?

Launched the day before covid vaccines were first available to the public, v-safe allows the CDC to track people over time to see how they fare.

Some vaccine safety experts have criticized the U.S. for leaning too heavily on a “passive” system that relies on people reporting issues that may or may not be related to the shots as opposed to “active” surveillance that scans large volumes of electronic health data and compares adverse events in people who receive the vaccine to those who didn’t.

V-safe requires individuals to opt in, with no control group for comparison. But some still view the tool as a step forward.

“It is a little bit more of a proactive monitoring system,” said Andrea Carcelén, an assistant scientist at the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health.

Here’s how it works: People register with the v-safe program on their smartphone or computer after receiving their first vaccine dose. The CDC then sends them daily text messages the first week, and weekly ones for six weeks after that. Additional follow-up texts are sent at the three-, six- and 12-month marks.

Every message includes a brief health survey, always asking: “How are you feeling today?” The first week, participants are asked whether they have experienced symptoms — chills, headache, joint pain or something not listed. They are also asked if they were unable to work or attend school or perform “normal daily activities,” or if they sought a physician’s care.

Over time, the check-ins focus on new or worsening symptoms or health conditions and compare participants’ health before and after vaccination. Participants are also asked whether they have tested positive for covid since the previous survey.

CDC scientists then study responses, looking for patterns of problems that go beyond what the clinical trials predicted. And the data may provide a fuller snapshot of vaccine outcomes because it reflects not only reports of side effects but also of people who had no complaints, said Carcelén.

Even as these investigations proceed, people who reported a problem may not ever hear directly from the CDC, and v-safe is not intended to offer medical advice. The CDC requests and reviews medical records, death certificates and autopsy reports only for serious adverse events, said Martha Sharan, a CDC spokesperson. “If a report is a hoax, it is quickly caught,” she said.

And what has v-safe shown so far? “The findings in normal, regular people that got the vaccine were pretty reflective of what you saw in the clinical trials,” said Vanderbilt’s Edwards. Edwards also served on an independent safety data monitoring committee for the Pfizer-BioNTech vaccine, now branded as Comirnaty.

How Is the V-Safe Data Used?

Unlike VAERS, v-safe data is not published without context. Meaning, no one can just sort through the database and interpret the numbers as they please, as many do with VAERS data. It is, however, publicly shared through CDC studies and presentations given during meetings held by the CDC’s independent panel of experts, the Advisory Committee on Immunization Practices.

And like VAERS reports, v-safe data is susceptible to misinterpretation. One post that circulated on social media inaccurately said “3,150 persons were paralyzed” based on an ACIP presentation slide. Reuters debunked the post, saying it is a “misinterpretation of the CDC health events.”

Information gleaned from v-safe has been used in several safety analyses, including one focused on adolescents. That analysis, published Aug. 6, found that serious adverse events are rare among adolescents, partly based on v-safe surveys from tens of thousands of people ages 12 to 17. The analysis also found that a minority reported being unable to perform “normal daily activities” the day after receiving a second dose.

V-safe has perhaps been most helpful at providing real-world evidence that the covid-19 vaccines are safe during pregnancy. This is important because there was little information on how the vaccines affected pregnancy when they were first authorized, said Dr. Dana Meaney-Delman, a member of the CDC’s vaccine task force, in a recent call with clinicians.

Pregnant women were excluded from the initial clinical trials that led to the emergency use authorization of the Pfizer, Moderna and J&J vaccines, and misinformation was rampant.

Because pregnant health care workers got vaccinated and enrolled in v-safe, Meaney-Delman said, there is more evidence that indicates the benefits of getting vaccinated during pregnancy outweigh any potential risks. Following the publication of an analysis that leaned on v-safe’s vaccine pregnancy registry, the CDC recommended on Aug. 11 that people who are pregnant, lactating or trying to become pregnant get vaccinated against covid.

Currently, uptake is low — as of mid-August, 23% of pregnant people ages 18 to 49 are at least partially vaccinated.

Who Is Participating in V-Safe?

More than 9.2 million people have enrolled in v-safe as of Aug. 9, or roughly 5% of the U.S. population who received at least one dose of a covid vaccine. This seemingly low participation rate is often linked to weak advertising and public education programs about v-safe. Also, a segment of the vaccinated public likely considered it tedious or had privacy concerns. The number also excludes people who do not have smartphones.

Dr. Matthew Laurens, a vaccine researcher at the University of Maryland School of Medicine, considers this an important gap in reporting. Roughly a quarter of adults who earn below $30,000 per year — or an estimated 16% of U.S. households — say they do not own a smartphone.

People who line up for an additional vaccine dose — often referred to as a booster but representing the same formula as previously administered — will have another opportunity to sign up for v-safe.

Meanwhile, as nationwide vaccination efforts continue, some v-safe participants said they joined the effort because they wanted to help.

John Beeler, 44, of Atlanta, considered it a “public good.” He reported experiencing tinnitus — a condition that was part of his medical history — after receiving his first Moderna dose. He was never contacted but hopes his report proved helpful. Still, he appreciated being checked on, even via automation.

“Dr. Fauci is not reading my response. But the feeling is there,” said Beeler.

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