ondansetron during pregnancy

• How to Weigh Risks versus Benefits

• Action Steps to Ease Fears and Make Confident Decisions

 

Pregnancy is often depicted as a time of glowing health and joy for women, but for those suffering from hyperemesis gravidarum (HG), it can be a harrowing experience. HG is a severe form of nausea and vomiting during pregnancy that can lead to malnutrition and dehydration, posing serious risks to both mother and baby. Despite life-threatening risks and potential long term risks for both mom and baby, many women are hesitant to or completely resist the idea of taking medications. These fears stem from societal pressures along with having roots in historical tragedies. The exclusion of pregnant women from clinical trials validates the fear of using medications while pregnant. Following is advice to address these fears and provide guidance on how to make informed decisions about medication use during pregnancy.

The Paradox of Modern Medication

We live in an era where more medications are available than ever before in history, with many of these medications being taken by women of childbearing age, yet pregnant women often find themselves without clear guidance on their use. The fear of causing harm to the baby, ranging from malformations to miscarriage or stillbirth, is compounded by societal perceptions that women should “glow” during pregnancy and that relying on medication is a sign of weakness or will cause harm to the baby. For women suffering from HG, these fears can lead to severe consequences, including malnutrition and dehydration. According to research by Dr. Marlena Fejzo published in Trends in Molecular Medicine, “Recent large studies reveal that exposure to hyperemesis gravidarum (HG) in utero is associated with not only adverse maternal/fetal outcomes but also increased risk for adverse child outcomes, including abnormal brain growth, neurodevelopmental delay, autism spectrum disorder, childhood cancer, and respiratory disorders.” With many options, albeit none directly treating the cause, the risk of not taking medications can have profound consequences.

Historical Context: The Thalidomide Disaster

The thalidomide disaster of the late 1950s and early 1960s left a lasting scar on the medical community and public perception of medication use during pregnancy. Thalidomide was initially marketed as a safe treatment for morning sickness and other ailments. However, it caused severe birth defects in thousands of babies, leading to its withdrawal from the market and a reevaluation of drug safety protocols. This tragic event still haunts the collective memory and contributes to the fear of taking any medication during pregnancy. Today, it’s well understood how thalidomide stops certain processes in the developing fetus, but this disaster set the tone for what is, unfortunately, possible when modern medicine interferes with natural processes without fully understanding the mechanisms. Today, we have a deep understanding of medication safety with tried and true options available to ease symptoms, so put those fears to rest.

Exclusion from Clinical Trials

One of the significant challenges in prescribing medications to pregnant women is the lack of clinical trial data. Ethical concerns prevent the inclusion of pregnant women in most drug trials, leaving a gap in our understanding of the safety and efficacy of medications during pregnancy. This exclusion stems from the necessity to avoid any potential harm to the fetus, making it almost impossible to determine which medications are safe and effective.

Understand the Risks and Benefits

When considering medication support for HG, it’s crucial to weigh the risks and benefits. Malnutrition and dehydration pose significant dangers to both mother and baby, potentially outweighing the risks associated with medication use. Here are some steps to help overcome the fear of taking medication during pregnancy and make informed decisions:

Determine your need for medication support

Where does your nausea and vomiting land on a spectrum from normal to life-threatening?

• Use scales like the HER Foundation’s comparison of Morning Sickness to Hyperemesis Gravidarum, their HELP score or the PUKE score created by Dr. Gideon Koren and colleagues at the Motherisk Program at The Hospital for Sick Children, which has been used in clinical studies.
• Consider the changes in your quality of life. For example, are you able to complete activities of daily living like taking a shower, going to work or spending time with your significant other.
• Review your lab values to include your electrolytes (sodium, magnesium potassium), iron levels which may decrease in the 2nd and 3rd trimesters, and thyroid levels.

Then, use these results to discuss treatment options with your healthcare providers. When it comes to Hyperemesis Gravidarum, the sooner you get on a medication regimen, the more chances you have of preventing your disease from escalating. Treating HG takes a combination of medications, so it’s important to not only look at each medication individually but also the possible synergistic or adverse effects of the combinations.

Review Studies on Medication Use in Pregnancy

Look for multiple clinical studies and peer-reviewed publications on the use of specific medications during pregnancy. Google Scholar and PubMed are two places to start your research. While many studies may be conflicting, there is often enough information to make an informed decision. Consider how many patients were in the study, the design of the study, and the locations of the study. For example, the results of a meta-analysis with 1000s of women from multiple sites around the world will carry more weight than a small, single-centered analysis.

The biggest controversy has to do with ondansetron (Zofran). While there are flaws in many studies, the one in Europe prevented thousands of women from accessing the medication, leaving them to suffer unnecessarily. As this class of medications is one of the few for HG that does not cause drowsiness, If this is one of the medications you are considering, read the HER Foundation’s statement on ondansetron here:

Understand the Drug Approval Process

In the U.S., the Food and Drug Administration (FDA) regulates medication safety. Medications go through rigorous testing and evaluation from the manufacturer before they are approved for use. This data is then presented to the FDA for approval. Understanding this process can help provide reassurance.

Understand Safety Ratings

The Pregnancy and Lactation Labeling Rule (PLLR), which replaced the older A to X rating system, provides detailed information on the risks and benefits of medication use during pregnancy. The FDA’s PLLR provides comprehensive information on medication safety, including sections on pregnancy exposure, risk summary, clinical considerations, and data.

Reviewing these sections can help you understand the potential risks and benefits of a medication. Read the manufacturer’s label, with pregnancy information always found in section 8.1 of each patient package insert. This can be found with the medication or by a quick online search. As the guidance has changed over time, know that older medications have been “grandfathered in” and will not have any ratings.

Check multiple drug resources. 

You’ll find that many drug resources will have different and/or conflicting information. If you’re not sure what to believe or have any concerns, ask the manufacturer. Drug manufacturers have departments called medical information, whose sole job is to share this information, and pharmacovigilance, which monitors adverse outcomes. In the US, Medwatch is another

Know who you can trust. 

Do NOT take advice from:

• A Google search
• Social media platforms

• Friends or family. Just because a medication helped during their pregnancy or someone they supported, remember that what works for one person may or may not be the right medication for another.

• Lawyers advertising online!
• Some online or local social groups may be a lifeline for emotional support, but when it comes to medication efficacy and safety, unless those members are also licensed clinicians or researchers, their advice is just their experience or possibly hearsay.

Do come to conclusions from:

• Your medical team
• Clinical researchers
• The manufacturer of the medication

Join a pregnancy medication registry. 

As the numbers of medications taken during pregnancy continue to grow, the FDA is working hard to monitor outcomes, done in the form of a registry. Take a look at the current registries for more information.

Practical steps for deciding on medication use

When suffering from HG, a regimen of multiple medications is likely to be necessary, here are some practical steps to support safety and efficacy:

• • Prioritize Nutrition and Hydration: This includes intravenous therapy for vitamins and electrolytes to address dehydration and malnutrition. IV nutrition can provide a foundation of nutritional support to prevent the disease from escalating, before or while simultaneously adding medications.

• Suggestions for creating a medication plan: 
• • Work with your healthcare providers to select first-, second-, and third-choice medications. This should be different for each patient, not based on exactly what various guidelines may say are first, second and third.
  • Choose medications that have different mechanisms of action (MOA) For example, if the first medication used is an antihistamine, then do not add another antihistamine. The MOA can be found in the pharmacology section of each drug resource. Keep in mind that medications may have multiple MOAs and therefore fall in more than one category. For example, Medscape says that phenergan is a “Phenothiazine derivative with antidopaminergic effect: Blocker of mesolimbic dopamine receptors and alpha-adrenergic receptors in brain and Antihistaminic effect: H1-receptor blocker.” Because of the antihistaminic effect, it would be best not to combine phenergan with another antihistamine like doxylamine or diphenhydramine…) but to choose a medication like ondansetron which is a “Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally.”
  • Ask for different routes of therapy. For example, some medications are topicals, like patches and creams, others are dissolvable or disintegrating, and yet others come as intravenous or subcutaneous. Multiple medications and pathways may increase the likelihood of symptom relief.
  • Be sure to include a de-escalation plan. If medications are not easing your symptoms, then do not continue taking them, as the cost and adverse effects outweigh the benefits.
  • Know when medications are safest. Some may be in the first trimester, so the medication is out of your system before delivery, Some are safest in the second trimester, after the heart and palate are formed. Others are safest in the third trimester, to prepare for a safe delivery.
• Address Side Effects for mom and baby:
  • While the medications prescribed by your provider are known to not be teratogenic, most will have some adverse effects on the mother. These adverse effects range from headache and constipation to changes in the heartwave, called QT prolongation, or extrapyramidal effects, like twitching muscles. Some may present right away, while others have increased risks with prolonged therapy. Know what to look for so that the benefits continue to outweigh the risks.
• Create a complete treatment regimen: Consider intermittent medications to manage side effects like acid reflux and constipation. This holistic approach can improve overall well-being.
• Consult a pharmacist: Have all medications reviewed by a pharmacist to check for safety, drug-drug interactions, and drug-disease interactions. This step is crucial to prevent adverse effects on both mom and baby.
• Discuss concerns with providers: Maintain open communication with your healthcare providers about your concerns and treatment options. Their expertise can guide you in making informed decisions.
• Ask for pharmacogenetic testing: For more precise decision-making, ask your provider about pharmacogenetic testing. This can help tailor medications to your genetic profile, potentially improving efficacy and safety. If your medication is not working, knowing the reason is in your DNA offers proof.

Navigating the use of medications during pregnancy, especially for conditions like hyperemesis gravidarum, requires a careful balancing of risks and benefits. While the historical legacy of the thalidomide disaster and the exclusion of pregnant women from clinical trials contribute to the fear of medication, understanding the drug approval process and reviewing available data can provide reassurance. By prioritizing nutrition and hydration, choosing medications carefully, and consulting with healthcare professionals, women with HG can make informed decisions that improve their quality of life and the health of their baby.

Remember, the decision to use medication is a personal one, and it should be made in partnership with your healthcare team. By weighing the risks and benefits, and understanding the safety profiles of medications, you can take confident steps towards a healthier pregnancy. With diseases like Hyperemesis Gravidarum, when the alternative is to starve, taking a regimen of medications is often the way to have the healthiest pregnancy with optimal outcomes, and the earlier the start may prevent the disease from escalating out of control.

The exciting news is that research is in progress for a targeted treatment for HG. Until then, it is risk versus benefit. Know that being left malnourished is not the only option. Follow these steps to take the medications prescribed by your healthcare providers with confidence that the benefits outweigh the risks for best clinical outcomes.