Medications & treatments
This information is intended to inform and to raise awareness so that treatment options can be discussed with qualified health care professionals. The responsibility for any medical treatment rests with the prescriber.
Are anti-emetics safe to prescribe in pregnancy?
The most important feature of any treatment for nausea and vomiting in pregnancy are:-
- Does it work (efficacy)?
- Does it do any harm to the developing foetus (safety)?
- Does it have significant side effects on the mother to be?
The RCOG Guidelines provide information about the efficacy and safety of medications so clinicians can feel confident that these guidelines are based on the best available evidence at the moment.
Early recognition and management of NVP could have a profound effect on women’s health and quality of life during pregnancy, as well as a financial impact on the healthcare system.
What is the definition of HG?
Two systematic reviews on treatments for NVP and HG (O’Donnell et al, 2016 and Boelig et al, 2016) both concluded that further research is required and research to date has been hampered by a lack of international definition and consensus on outcomes.
But did you know in 2021 an international definition of hyperemesis gravidarum was proposed and agreed to? It is called the Windsor Definition.
This definition will help clinical studies to achieve more uniformity, and ultimately increasing the value of evidence to inform patient care.
Ginger and pregnancy sickness
Survey work conducted via our charity of over 500 women’s experience of being offered and taking ginger for hyperemesis gravidarum found that Ginger is ineffective for hyperemesis gravidarum, and causes 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 women with HG trust and confidence in the professional was eroded and women were left feeling dismissed and not believed.
The Aetiology of Hyperemesis Gravidarum
What medications and treatments can be prescribed?
Hyperemesis Gravidarum is a serious complication of pregnancy and it is essential that sufferers are offered timely and effective treatment. The RCOG Greentop Guidelines include a treatment ladder that outlines the various medications that are recommended for use in HG pregnancies alongside intravenous fluid therapy and PPIs.
Currently, there is only one anti-emetic licenced for use in pregnancy in the UK which is called Xonvea. It is not available everywhere and as it’s only available in oral form, it is a first-line medication and may not be sufficient alone to treat HG in all patients.
PSS are campaigning for Xonvea to be included on all formulary to avoid the current postcode lottery. If you want support to add this to your formulary please contact us.
Alongside IV Fluids, 3 lines of anti-emetic medications are outlined in the RCOG Guidelines for use during an HG pregnancy. They are often most effective when used in combination and can vary from patient to patient in terms of effectiveness.
The Principles of treatment of HG are: Rehydrate – Balance electrolytes – Maintain with antiemetics – Manage expectations
Any information provided here is based on RCOG Guidelines 2024 and, as with all clinical decisions, medications should be considered on a risks v benefits basis and in partnership with the patient.
More detailed information about treatments and medications can be found below.
FIRST LINE MEDICATIONS
All first line medications listed in the guidelines for medications to treat NVP and HG Xonvea are antihistimines.
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:
- Doxylamine succinate which belongs to a group of medicines called antihistamines and
- Pyridoxine hydrochloride which is another name for Vitamin B6.
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.
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.
SECOND LINE MEDICATIONS
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 to 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 RCOG Greentop Guidelines 2024 state Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics.
Ondansetron (also know 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.
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 base line 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, so these could also be a factor in causing the extra 3 babies. Please read our blog here if you wish to find out more.
Ondansetron is prescription only.
The RCOG Greentop Guidelines 2024 state Ondansetron is safe and effective, Its use as a second-line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. is safe and effective and can be used alone or in combination with other antiemetics.
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.
THIRD LINE MEDICATIONS
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 alongside anti-emetics when oral medications cannot be tolerated.
Signs and symptoms of dehydration should be assessed when considering the need for IV fluids rather than outdated Ketone analysis which has been rejected as a diagnostic tool for HG and already discussed on this page.
Although IV therapy is common and some doctors would prefer to repeatedly prescribe IV fluids rather than medication for pregnant women, they are not without risk. 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, women who require IV rehydration should also be treated with appropriate anti sickness medication to reduce the need for repeated IVs.
However, IV fluid replacement remains an effective treatment for dehydration, which actually can cause nausea and vomiting. Women often feel temporary but effective relief from a few bags of IV fluids.
TERMINATION FOR MEDICAL REASONS (TFMR)
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.
In the above research women who choose to terminate their pregnancies have often reported feeling that their healthcare professionals (HCPs) lack compassion, with such sentiments being three times more common among them than among those who did not terminate. Additionally, numerous accounts highlighting a distressing dilemma where they felt their only options were either abortion or suicide.
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.
PSS advocate for all options to be explored before a termination is offered. Of course the need to balance the woman’s request is needed, as not all women will want to terminate solely because of the diagnosis of Hyperemesis. Please do sign post your patients to us if they want extra support and a listening ear or to be part of our Peer Support programme.
If you have a patient that has terminated a pregnancy please signpost them to our HG & Loss page for more support.
UNDERSTANDING SAFETY AND CONFIDENCE TO PRESCRIBE
At Pregnancy Sickness Support we believe in 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 that you can prescribe 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.
It’s also important to consider the effects to mother and baby from unmanaged dehydration and malnutrition. The risk to mother and baby of untreated HG is something that women should be made aware of to enable them to make an informed decision on medications and treatments and undertake a risk benefit analysis.
The medications that can be prescribed are often off-license, the truth is there are very few licenced medications in pregnancy, even self-administering medications such as paracetamol and aspirin have no licence.
Pregnancy Sickness Support’s mantra is that with all medications health care professionals should always discuss any safety information about prescription drugs and perform a risk benefit analysis with the patient and feel empowered to prescribe.
Please do contact out support team if you want to discuss any of the information on this page or need advice about a patients care.
ADVOCATING FOR PATIENTS IN YOUR CARE
Sufferers often report that along the many touchpoints with healthcare professionals during their pregnancy, some professionals gave excellent advice and were supportive with managing and treating their symptoms.
Sadly, at other touchpoints the care given can have a detrimental effect whereby they are misadvised or told that they shouldn’t have been prescribed medication in the first place.
Whilst it is difficult to advocate for your patients if you are unaware of them being treated by or discussing their experience with another professionals, it can be helpful to preempt it.
If they know they have a safe space to come to and are made aware that if they receive poor care at any point that they can discuss this with you and you can then advocate on their behalf – this would be a huge catalyst for change in HG pathways and care.
Also, if you have found Pregnancy Sickness Support and are treating women and birthing people with hyperemesis gravidarum, please let them know about us. Ou fantastic Peer Support programme can be a non-clinical life line for sufferers and our support pages can also ease any worries and concerns and offer support with coping strategies. Please spread the word!
“Measuring for ketones would have indicated that I was not unwell even when I was extremely dehydrated. Thankfully I was generally assessed and given appropriate treatment.”