Antihistamines - Cyclizine and Promethazine

By using either cyclizine or promethazine in combination with pyridoxine (Vitamin B6) it is very similar to the medication Xonvea which is licensed in the UK. This is the basic first line treatment in the UK.

Safety information - A wide body of evidence suggests that these antihistamines cause no harmful defects in the foetus. Data from 7 randomised controlled trials indicate that these antihistamines are effective in the treatment of nausea and vomiting in pregnancy. These antihistamines can cause drowsiness and should not be taken without medical advice, although they are available over the counter. It can take a couple of weeks to become accustomed to the drowsy effect.

Prochlorperazine

Safety information - Prochlorperazine is one of a number of drugs called phenothiazine. Prospective and retrospective cohort studies, case-control, and record linkage studies of patients with exposure to various and multiple phenothiazines have failed to demonstrate any increased risk of major malformations. It was found to be effective for nausea and vomiting in pregnancy in 3 randomised controlled trials in severe nausea and vomiting in pregnancy (hyperemesis gravidarum). Side effects include drowsiness, restlessness and occasional extra pyramidal effects (Such as tremor, slurred speech, anxiety, distress and others). These are prescription only medications.

Chlorpromazine

Currently rarely prescribed, other first line medications are tried first then often people are moved up the treatment ladder to try a second line medication in combination with the other first line medications.

Xonvea

Xonvea is the brand name of a prescription medicine that has recently been licensed in the UK to treat symptoms of nausea and vomiting of pregnancy (NVP). It is one of the few licensed drugs in pregnancy; studies have shown there is no increased risk to major malformations. It is the same medication that has been licensed for many years in Canada called Diclectin and in America for the last few years as Diclegis.

Xonvea comes in a slow-release tablet form. It contains two active medicinal ingredients:

1. Doxylamine succinate which belongs to a group of medicines called antihistamines and
2. Pyridoxine hydrochloride which is another name for Vitamin B6.

Safety information - Like all medicines, Xonvea can cause side effects although not everybody gets them. It is very common to feel very tired when taking Xonvea and you might also experience dizziness or dry mouth. Do not take Xonvea if you are allergic to any of the ingredients in this medicine or other antihistamines (such as diphenhydramine), or, if you are taking medicines for depression called ‘monoamine oxidase inhibitors’ (MAOIs).

Further information - It is currently a postcode lottery as to whether you can get prescribed Xonvea in your area. There have been distribution issues in the UK. If you would like further information you or your GP/Midwife can contact the Medical Information team at Exeltis uk.medinfo@exeltis.com for more information.

Information from the Pregnancy Sickness Support Medical Advisory Board:

Taking cyclizine/ promethazine/ prochlorperazine in the third trimester/ during labour can mean the baby is drowsy/ agitated when it is born. The baby will need monitoring just as they would if pethidine, which is a commonly used pain reliever, was given in labour. The risks are incredibly rare, and you need to weigh up the potential risk of this to the benefits of being able to eat, drink and function. If you are concerned, you can ask to be switched to ondansetron which does not have this potential risk associated with taking it.

Metoclopromide

Safety information - There is only limited information on its safety in pregnancy, although the little that has been published is reassuring. Side effects include drowsiness, restlessness and occasionally extra pyramidal effects (such as tremor, slurred speech, anxiety, distress and others). This is a prescription only medication.

In 2015 the European Medicines Agency recommended that metoclopramide should only be given for 5 days. This is because it is felt that longer courses are more likely to produce side effects in the person taking this therapy, although this mostly relates to children and older patients. Specifically, there is concern that beyond 5 days there is more chance of facial and skeletal muscle spasms and dizziness devloping. Though, if you haven’t developed these particular side effects in the first 5 days of treatment, it is very unlikely you will get these side affects. In the BNF under the “Important Safety Information”, at the end of the paragraph around restricted use, including the 5 day ruling, it does state that “This advice does not apply to unlicensed uses of metoclopramide”. As it is unlicensed to be used to treat pregnancy sickness, this means that the 5 day ruling should not be applied in this instance.

Please note, there is no new concerns about foetal problems this recommendation refers only to side effects for the mother.

Ondansetron

Safety Information - If your nausea and vomiting is so severe that first line medications aren't helping enough then your GP may prescribe Ondansetron. It was originally used to treat nausea and vomiting caused by chemotherapy for cancer patients but is increasingly used for hyperemesis gravidarum and you are likely to read about it on internet forums and websites.

Research regarding the safety of this drug is increasing. A well conducted, study by Huybrechts et al (2018) looked at 88,467 pregnancies in which ondansetron was used in the first trimester. It found there is no link to heart defects and an extremely minimal 'associated risk' (not direct cause) to cleft lip/palate when taken in the first 10 weeks of pregnancy (the face is fully formed past this point.) In a regular pregnancy, with no medication use, the baseline risk of cleft lip/palate is 11 in every 10,000 babies. With ondansetron use there was an extra 3 babies in every 10,000, so it is a very tiny risk. Taking into consideration that a person being so sick they need to take ondansetron would also not be able to keep down their folic acid supplements and are likely to be dehydrated and possibly malnourished, which could all be contributing factors. Realistically, if ondansetron was the cause of cleft palate development, then the number of babies born with cleft palate in the group that took ondansetron would most likely be significantly higher.

Some healthcare professionals have misinterpreted this positive study and may refuse to prescribe before 12 weeks, but you are within your rights to request for this to be issued, as the GPs are only advised to not issue within the first trimester due to the research. You can quote the following, which is from the BNF, which all GPs have to refer to for medication:

“Healthcare professionals are advised that if there is a clinical need for ondansetron in pregnancy, patients should be counselled on the potential benefits and risks, and the final decision made jointly.”

It is a prescription only medication and side effects include constipation and headaches. We suggest asking for bowel care medication to help with the constipation at the same time as you are prescribed ondansetron. It can be taken orally, as an injection, as a suppository (inside your rectum) or as an 'oro-dispersal' tablet (melted on the tongue). 

Recent updates: The BNF has unfortunately recently been updated to say only 5 days’ worth of ondansetron can be issued, however this is only related to cancer treatment. The NICE guidelines also state that “the dose is based on that used for chemotherapy, so is for guidance only.” Please reiterate this to your GP if you are experiencing issues of obtaining more than five days, as the five day rule is for guidance for chemotherapy patients only and not related to the use of ondansetron in pregnancy sickness.

Domperidone

Domperidone works by speeding up the passage of food through the stomach into the intestine, which then helps prevent nausea and vomiting. It also prevents food from flowing the wrong way through the stomach and so can prevent reflux. Domperidone blocks dopamine receptors found in an area of the brain known as the chemoreceptor trigger zone (CTZ). The CTZ is activated by nerve messages from the stomach when an irritant is present or when certain chemicals are in the blood stream, such as pregnancy hormones. Once activated, messages are sent to the vomiting centre which sends messages to the gut and triggers vomiting. By blocking the dopamine receptors in the CTZ, domperidone prevents nausea messages from being sent to the vomiting centre and in turn reduces the nausea and vomiting.

Safety information - As with many of the treatments mentioned here, the safety of domperidone has not been established in proper medical trials. It has, however, been used for a number of years in pregnancy and as yet no adverse effect on the foetus has been reported. As with all these treatments, their use should be restricted to cases where first line treatment has failed to suppress symptoms and the benefits of further treatment would outweigh the risks to the foetus.

Like with metoclopramide, domperidone may only be suitable for short term use due to European Medicines Agency guidance regarding prolonged use and an association with heart problems, however this advice mostly relates to people over 60, those already taking certain heart medications, and with increased doses of more than 30mg.

Domperidone is a prescription only medication and can be given as a suppository (in your rectum) which some people may find easier then swallowing tablets. 

Steroids are often successful for treating HG in many people where all other measures have failed. Most people will be able to stop steroids by 18–20 weeks but around 1 in 5 people will need to continue them at a low dose for the rest of their pregnancy. We don’t entirely understand how steroids work for HG, but it is thought that one action is by having a boosting effect on other medications, so you shouldn’t stop your other anti-sickness medications but add in the steroids to hopefully get symptoms under control.

If your hyperemesis is so severe that you are considering termination of the pregnancy, then your doctor should be willing to try steroids first.

Steroids have been widely used for many decades in pregnancy and, while it’s important to use them sparingly at the lowest dose for the shortest time possible to reduce side effects it is generally considered that the benefits outweigh the risks in cases of severe HG which hasn’t responded to other treatment. There are some side effects that you should be aware of.

Only a tiny amount of the steroids used to treat HG passes from you to your baby and they are generally considered safe for use in pregnancy (steroids are used for many other reasons during pregnancy also such as Crohn’s disease, ulcerative colitis, asthma etc). It is also important to remember that if hyperemesis gravidarum is not treated, it may cause more harm to the baby than any possible effects of a medicine, including steroids.

Potential side effects on the baby:

• If taken very early in pregnancy there is a possible small increase in risk of cleft lip, although the evidence for this is limited and additional risk factors for oral cleft are malnutrition and folic acid deficiency. Therefore, if taking a steroid also enables you to take folic acid and to eat food then the balance of risk is altered. The base line risk for oral cleft in the general population is around 11 in 10,000. There is not much evidence for how much taking a steroid before 10 weeks increases this, but it is thought to be by around 3 in 10,000. So, in babies exposed to steroids in early pregnancy you might see around 14 in 10,000 oral clefts.
• Another study has suggested babies may be born with slightly lower birth weight and again, this is also a risk of poorly managed HG, particularly where symptoms are ongoing in the second or third trimester. If taking steroids enables symptom control, the balance of risk is again altered.
• Chronic exposure to high dose steroids in pregnancy may cause fetal/neonatal adrenal suppression. The baby should be monitored after delivery. However, if you still have severe uncontrolled HG at delivery then the baby would need monitoring also.

If you are still taking steroids at delivery, you will require special monitoring in labour and an increase in dose of steroids until after delivery.

Potential side effects for the pregnant person with long-term steroid use:

• Developing gestational diabetes – blood sugar monitoring should be performed if taking steroids long term (>4 weeks)
• Increased risk of infection e.g., urinary tract infections
• Adrenal suppression which may, very rarely, be irreversible requiring long term replacement and close monitoring as over-replacement and under-replacement carry their own risks too.

What other options are there?

If you would prefer not to take steroids, then you could discuss with your doctor if you are on the maximum doses and combinations of other medication and you could consider trying other novel options such as mirtazapine. If you are able to access regular outpatient IV fluid rehydration, then that may also help you to manage symptoms without the use of steroids. If you are malnourished and unable to eat sufficiently you could also consider a nasogastric tube to receive adequate nutrition.

You can read more about the use of systemic corticosteroids in pregnancy here.

Intravenous (IV, meaning directly into the vein) fluids are given to correct dehydration, and medication can be given through the IV port when oral medication is unable to be kept down.

Unfortunately, many doctors and hospitals rely on assessing ketones in urine to decide the need for IV fluids, but this not best practice or evidence based and can often lead to a barrier for treatment. In fact, there is evidence to the contrary. Signs and symptoms of dehydration should be assessed as they would for any non-pregnant or pregnant patient with any other condition. It is illogical to demand a dehydrated person to produce a urine sample.

Some clinical indictors of dehydration are:

• Darker urine
• Not urinating as often
• Passing less urine when you do go
• Dry mouth 
• Dry lips
• Headaches
• Dizziness
• Weakness
• Confusion

Those with HG who are showing signs of dehydration are unlikely to be able to rehydrate themselves sufficiently due to the ongoing and constant nature of the condition, therefore the threshold requirement for IV fluid rehydration should be low.

The main risk associated with IV therapy lies at the site of cannulation. Blood and fluids can leak in to surrounding tissues causing damage and pain. Repeated cannulations can lead to destruction of the vein by scar tissue making future cannulations impossible. Infection is a risk, and in the days of antibiotic-resistant strains of bacteria such as MRSA, treating infection can be difficult. Therefore, those who require IV rehydration should also be treated with appropriate anti sickness medication to reduce the need for repeated IVs.

However, IV fluid replacement does remain an effective treatment for dehydration. People often feel a temporary but effective relief from several bags of IV fluids, in this window of relief it is important to take anti sickness medication and ensure the treatment plan is effective.

In inner city areas there is an increasing move towards IV day clinics where hyperemesis patients can be rapidly rehydrated during the day and go home in the evening. The areas this is available is limited but the future hope is that all those who have HG can have access to IV fluid treatment either at a day clinic or at their home.

At Pregnancy Sickness Support we believe making an informed decision based on research. There is no evidence to show that anti-sickness medications cause harm. As with all medication use, not just in pregnancy, but throughout life, decisions must be based on the balance of risks and benefits.

There are medications you may be prescribed which have been extensively researched and used for many years (some over 50). Some medications can cause side effects e.g. – cyclizine is an antihistamine and can cause drowsiness, but so can pethidine which is prescribed as pain relief in labour.

The research into the effects to baby from dehydration and malnutrition when symptoms are not managed well with medication show significant long-term effects, which can continue into adulthood. The research suggests that the risk of untreated HG outweighs the risk of potential side effects from medication that can be prescribed to treat the symptoms of HG.

There is no shame in taking prescription medication whilst pregnant. Some people have life threatening conditions which are managed by medication, when they become pregnant, they can't just stop taking them as it could put their own life at significant risk. Have a discussion with your GP about the benefit vs risk of anti-sickness medication and be prepared to learn about treatment for NVP or HG together as many doctors aren’t well informed about the condition.

The medications they prescribe will be used off licence which means you will see on the packet it says to not take whilst pregnant or to consult your GP. Truth is there are very few licenced medications in pregnancy, even self-administering medications such as paracetamol and aspirin have no licence. This isn't to say that they aren't safe. Pharmaceutical companies usually exclude pregnant people from drug trials, and this is not likely to change in the future. It doesn’t mean they are unsafe; it just means no clinical trials have been carried out during pregnancy.

With all the correct information you can make an informed decision which best suits you. If you have any medication queries at all, please contact our support team.

If you are currently breastfeeding and suffering with NVP / HG please read more information on safe medications you can take. This information is provided by Wendy Jones, PhD MRPharmS, Breastfeeding and Medication.

The risk of a baby being born with a congenital abnormality - the difference between relative and absolute risk

You may have read medication information that says, “Taking drug X to help manage severe pregnancy sickness symptoms increases the risk of your baby having a congenital abnormality by 50%.” It is important to understand this is an increase in “relative" risk and that a 50% relative risk increase in a small absolute risk, is still a small “absolute" risk.

The risk of a baby being born with ANY congenital abnormality is quoted as being around 5% or 50 per 1000 births Some of these abnormalities are minor, such as skin blemishes, abnormalities of fingers and toes etc. Major congenital abnormality rates are quoted as 2-3% or 20 – 30 per 1000 births. Medications taken after 12 weeks cannot usually cause major congenital abnormalities in any major organ system because these are already fully developed at this stage.

The quoted rates for severe congenital abnormalities are around:-

• Heart problems 6 per 1000
• Limb defects 4 per 1000
• Central Nervous system (CNS) problems 2 per 1000
• Cleft lip & palate 2 per 1000

Let us compare these 1000 people taking drug X compared with 1000 people not taking drug X where they are saying there is a 50% increased risk of having a baby born with cleft lip and palate.

Issue	Taking Drug X	Not Taking Drug X
Babies born with heart problems	6	6
Limb defects	4	4
CNS Problems	2	2
Cleft Lip & Palate	3	2

 

So, drug X which is thought to cause a 50% increased risk of cleft lip and palate would result in 1 extra baby to be born with a cleft for every 1000 people taking it to control their severe pregnancy sickness symptoms before 12 weeks of pregnancy. If drug X does help to manage their symptoms, we might expect to prevent a number of people from having to terminate the pregnancy as well as making the pregnancies of many, much more manageable. Additionally, because severe NVP and HG are not without their own risks, where people are extremely malnourished or dehydrated in pregnancy, or exposed to high levels of stress, the risks of taking drug X must be balanced with the risks of being seriously unwell. 

Some people want to try alternative therapies first; whilst they can help with some mild symtpoms of NVP and HG it is likely that you will still need to try some medication if your symptoms persist.

If you decide not to take medication, then your healthcare team need to ensure that you have access to IV fluids to manage your dehydration and malnutrition. Should you need them – they can arrange this with the early pregnancy unit team and let you know what the procedure will be. The protocols from area to area do vary so contact your usual GP to organise.

Accupressure

Stimulation of the P6 point, located three fingers breadth above the wrist, has been used for many years to treat nausea from a variety of causes. Trials of a non-blinded randomised nature have shown a decrease of persisting nausea by at least 50%. Bands worn at the wrist (e.g., Sea Bands) that apply pressure may be a simple way of stimulating the P6 point. There are no theoretical concerns about the safety of acupressure in pregnancy. Long term use throughout pregnancy may cause minor markings on the wrists.

Acupuncture or hypnotherapy

Some people seem to find help by alternative medicine, particularly hypnotherapy and acupuncture but success varies between individual patients, and it tends to be expensive. These remedies are worth a try if you can afford it but have a back-up plan and seek medical advice. 

Ginger

Ginger is commonly suggested to those suffering with sickness, one small study even suggested that it may be effective for nausea and vomiting in pregnancy. However, the small number of patients in these studies allocated to receive ginger (303) may have been insufficient to properly test the safety of ginger with regards to pregnancy outcome. Ginger is a non-regulated food product and most preparations available are of variable purity and composition, so dose is uncertain. 

Survey work conducted via our charity of over 500 women's experience of being offered and taking ginger for hyperemesis gravidarum found that it was ineffective and could cause harm. Not only did ginger produce unpleasant side effects, which could exacerbate symptoms but the psychological impact of being told to take ginger repeatedly was very detrimental to well-being. Where healthcare professionals recommended ginger to people with HG their trust and confidence in the professional was eroded and they were left feeling dismissed and not believed.

Some healthcare providers may have limited knowledge about pregnancy sickness due to the curriculum of their training and lack of experience in dealing with the condition. Because of this, there is a tendency for them to leave people who have NVP and HG until they are dehydrated and/or lost weight to offer treatment and IV fluids. This is not considered to be best practice. Mild and moderate HG can be managed so that no in-patient treatment is required if treated soon enough. Weight loss and the need of IV fluid therapy should not be a requirement for either diagnosis of HG or to get treatment. Your treatment plan should be based on your presenting symptoms and the amount of food and fluid you have been able to keep down.

Unfortunately, many GPs in the UK are unaware of modern treatment protocols for the management of HG. If your GP is unwilling to give you medication and you want to pursue with a treatment plan then please understand that you have the right to medication; you may benefit from speaking to a member of our support team to talk this through. 

The NICE guidelines update (August 2021) highlights the importance of informed shared decision making, stating that pregnant people should be listened to, and healthcare professionals should be responsive to their needs and preferences. The risks, benefits and implications of any assessment, intervention or procedure should be discussed with the person when offered, and their decisions on their care should be respected even if they differ to the view of the health professional.

If you are struggling to get through to your surgery, you can contact 111 to speak to a clinician (but you may have to do this out of hours as they may direct you straight back to your GP). You can also follow this link to download the LIVI app and speak to a GP online, which is provided by the NHS. Most GP practices use an online service which enable you to book appointments online and order repeat medication, which you can register with on your GP’s website and then continue to access through the Patient Access app or the NHS app (separate from the NHS COVID app). You can also submit an online form through most GP practice websites via eConsult or AskFirst. Ultimately, there will be a way to reach a GP, having someone who can advocate for you may be beneficial if you are struggling.

In subsequent pregnancies healthcare providers can create a pre-emptive care and treatment plan, the risk of having HG again is approximately 89%. Read more about planning for a HG pregnancy here. 

Over 50% of people diagnosed with HG have considered a termination. Research suggests between 5-10% terminate a very much wanted baby due to hyperemesis. Often this is due to inadequate treatment of symptoms and a lack of support and understanding from healthcare professionals, employers, and their support network. If you are considering termination as an option but would like to explore all treatment options first then get in touch with our support team. Equally, if your decision is made and you are going to go through with a termination contact us for support so we can help you through this challenging time.

There are a number of people in our support network who have themselves terminated due to hyperemesis and there is also a section on our Community Space to help those who have lost babies to hyperemesis gravidarum.

There are charities who can support you in making a decision aswell as after termination. ARC - Antenatal Results & Care are HG Friendly and understand the impact HG has on the mother leading to them considering termination.

In partnership with the British Pregnancy Advisory Service (BPAS) Pregnancy Sickness Support examined the main drivers for terminations in pregnancies complicated by HG to examine what more can be done to improve care for people in this situation and better support for their choice.

• Download research
• Download the report

We recommend BPAS for termination services.. They can also make sure you have the treatment you need between now and your termination.

For further information and to book an appointment you can call 03457 30 40 30