All first line medications listed in the guidelines for medications to treat NVP and HG  are antihistamines.

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.

Crucially, Xonvea has now been included in the new RCOG Greentop Guidelines. It was licensed after the 2016 guidelines were published so it has taken until 2024 for them to be included. If you are struggling to access Xonvea, download the guidelines and show your prescriber that they are very much available to hyperemesis sufferers.

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 – also known as Stematil and Buccastem

Prochlorperazine can help stop you feeling or being sick (nausea or vomiting). It comes as tablets that you swallow and tablets that dissolve in your mouth. It can also be given as an injection, but this is usually done in hospital.

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. 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.

Safety Information:

The scientific information currently available so far does not show that this medicine is harmful to a developing baby.

Metoclopramide

Metoclopramide is an anti-sickness medicine (known as an antiemetic). It’s used to help stop you from feeling or being sick (nausea or vomiting) including:

• after radiotherapy or chemotherapy (treatment for cancer)
• sickness you may get with a migraine
• if you’ve had an operation

It is also prescribed for pregnancy sickness and HG.

Metoclopramide comes as tablets or a liquid that you swallow. It can also be given as an injection, but this is usually given in a hospital or by a member of a care team visiting you at home.

It’s only available on prescription.

Safety Information: In 2015, the European Medicines Agency advised limiting metoclopramide use to 5 days due an increased risk of extrapyramidal symptoms (such as muscle twitching, spasms, tremors and dizziness). You would generally know quite quickly if you were going to be affected by these symptoms and if they haven’t appeared in the first 5 days it’s unlikely that they will develop later. The risk is also higher (but still rare) when receiving metoclopramide via IV rather than in tablet form. If you haven’t experienced any negative side effects during the first 5 days, and the medication is helping, you can continue to take it for longer. The BNF Notes that the 5-day rule restriction does not apply to unlicensed uses (such as treating pregnancy sickness). The side effects mentioned are in the mother, not the foetus.

The new RCOG Guidelines 2024 also expressly state its safety in pregnancy. 

Ondansetron

Ondansetron (also known as Zofran) is a medication that was originally used to treat nausea and vomiting caused by chemotherapy for cancer patients. It is now widely used to treat nausea and vomiting in pregnancy, and you are likely to read about it on internet forums and websites.

Safety Information: There is some reluctance to prescribe Ondansetron in the first trimester, however, an ondansetron research paper found that 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 found to be an extra 3 babies in every 10,000 so it is a very tiny risk – however to get to the point of ondansetron use then a person would have likely been at the point of dehydration and possibly malnutrition, these could also be a factor in causing the extra 3 babies. 

Ondansetron is prescription only.

The new RCOG Guidelines 2024 also expressly state its safety in pregnancy and that it should be offered to women who are not having success with first-line treatments.

Domperidone

Domperidone, primarily used to prevent nausea and vomiting, accelerates food movement from the stomach to the intestine and prevents reflux. It blocks dopamine receptors in the brain’s chemoreceptor trigger zone (CTZ), inhibiting nausea signals to the vomiting center.

It has been widely used in pregnancy without reported foetal harm, however, its safety hasn’t been conclusively established in trials. Its use is recommended when first-line treatments fail, balancing benefits against foetal risks.

Safety Information: The European Medicines Agency advises caution with prolonged use, but this is specifically for people over 60 or on certain heart medications, due to potential heart risks.

Domperidone, is a prescription-only medication, is available as a suppository, offering an alternative to oral tablets.

Steroids

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.

In 2024, the Royal College of Obstetricians & Gynaecologists NVP and Hyperemesis Gravidarum Guidelines were published WITHOUT ketones included as a diagnosis tool for dehydration, after research and concerns from the medical community, demonstrated how 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).

Actual 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.

IV fluid remains 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.

PSS welcomes the removal of ketones from diagnosis, however we understand that this information may take some time to diseminate to all healthcare professionals who treat women with hyperemesis, therefore if you are stuggling to receive IV fluids because you have no or low ketones in your urine please contact our support team.

You can also read more about this in our blog.

Over 50% of people diagnosed with HG have considered a termination.

Research suggests between 5-10% terminate a pregnancy 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 charities who can support you in making a decision as well 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

If you have recently terminated a pregnancy please do visit our HG & Loss page for more support.