NVP Medication Introduction
Dietary changes and lifestyle modifications are the recommended first steps in the management of NVP. However, these steps are very often not enough for even mild NVP symptoms. If NVP is having a significant effect on a woman’s quality of life – to include her physical, mental, and emotional health – there are numerous additional options available.
Antacids/proton pump inhibitors (Pepcid®)
Vitamin supplementation (B6)
Antihistamines (Unisom®, Dramamine®, Phenergen®, Tigan®)
Phenothiazines/Dopamine antagonists (Reglan®, Phenergen®, Compazine®, Thorazine®)
Serotonin 5-HT3 antagonists (Zofran®)
Nausea and vomiting are very complex physiological processes, involving the central nervous system, autonomic nervous system, gastrointestinal (GI) tract, and the endocrine (hormones) system; but in general, the underlying mechanisms involved in nausea are not completely understood.
Current anti-nausea medications generally fall into two categories, and some medications have properties of both categories:
Agents directed at suppressing nausea and preventing vomiting (antiemetics) which typically act on the brain and central nervous system, and
Agents directed at regulating the digestive tract (prokinetics)
Similar to general nausea and vomiting, the primary causes of NVP are also not known, and the factors that do play a role likely vary significantly among women; this is largely why no single most effective medication has been identified.
As such, women are often prescribed numerous different types, which have different mechanisms of action on the body. Therefore, without knowing why a woman's symptoms are so severe, or what contributing factors she may be experiencing, women are continuing to have dramatically different and inconsistent results with these various medications.
*Although some of the above/below-described medications are available over-the-counter (OTC), women should never attempt to treat themselves, or take any OTC medication without talking to their HCP, including multivitamins.
The chemoreceptor trigger zone (CTZ), or “vomiting center” is located in the brain. The CTZ contains receptors that detect agents in the blood that cause nausea/vomiting. This information is then relayed to the vomiting center, which induces vomiting.
Stimuli that lead to nausea and/or vomiting are regulated, in part, by the serotonin/dopamine and histamine receptors in the CTZ; blocking these receptors serves as the main function of different anti-nausea medications.
Other sites in the body that relay information to the vomiting center include the GI tract and the vestibular system (inner ear – i.e. motion sickness).
Receptors of the CTZ that have been identified to induce vomiting include dopamine-type 2 (D2), histamine-2 (H2), and serotonin-type 3 (5-HT3).
Phenothiazines/Dopamine antagonists block dopamine receptors in the brain to reduce vomiting stimuli; they are also known to stimulate gastrointestinal motility, which encourages the transit of food through the stomach.
Brand names: Reglan® (metoclopramide), Inapsine® (droperidol), Phenergen® (promethazine), Compazine® (prochlorperazine), Thorazine® (chlorpromazine)
Serotonin 5-HT3 antagonists are known to be very effective in post-operative and chemotherapy-related nausea and vomiting; they block 5-HT3 receptors in the brain, as well as vagal and spinal afferent nerves, which can also detect nausea-inducing stimuli.
Brand names: Zofran® (ondansetron)
Antihistamines block histamine (H1 receptor) effects, as well as increased stimulation of the vestibular system (i.e. balance/motion sickness) that can trigger the vomiting center.
Brand names: Dramamine® (dimenhydrinate), Benadryl® (diphenhydramine), Unisom® (doxylamine), Tigan® (trimethobenzamide)
The exact mechanism for how pyridoxine (Vitamin B6) relieves nausea is not known, but most of B6’s primary effects are on the central nervous system; doxylamine succinate (Unisom®) an antihistamine, is commonly used in combination with B6.
Antacids, histamine-2 receptor antagonists, and proton pump inhibitors can also be used safely during pregnancy to reduce acid reflux, heartburn, and nausea. H2 receptors are similar to H1 receptors, and are located in the brain and stomach.
Women have numerous options for the pharmacological management of NVP, based on risks and benefits conversations with their HCP. These discussions are important, as well as an overall assessment of the woman’s physical symptoms, her perception of her symptoms, and how her symptoms are affecting her quality of life. Medication regimens are therefore individualized to each woman.
Additionally, since various medications have different mechanisms of action, some women may need to be given a combination of different agents to more effectively manage their symptoms.
Further, some women may also need to take certain medications "around the clock" rather than "as needed", even if they feel better. This is due to the assessment that management should be one step ahead of symptoms, so symptoms do not spin out of control.
Evidence-based information and recommendations regarding medication for NVP focuses on two factors: the effectiveness of the medication and safety of the medication. However, most of this current data comes from non-pregnant individuals, as well as numerous studies comparing different medications during pregnancy, almost none of which take into account a woman's individualized factors.
Due to this lack of data, several health organizations have a recommended hierarchy – or algorithm – to guide HCPs in determining proper management (see Resources).
Doxylamine/vitamin B6, dimenhydrinate, metoclopramide, promethazine, prochlorperazine, chlorpromazine, ondansetron, meclizine, and droperidol-diphenhydramine are commonly used medications to treat and manage NVP.
As of 2016, antihistamines were regarded as a first-line treatment in North American and Europe, including the United Kingdom. However, antacids and ondansetron were more frequently prescribed in the U.S. It has also been reported that Canada uses mostly antihistamines, while Australia had the highest use of metoclopramide.
In their updated guidelines for NVP, published in January 2018, the American College of Obstetricians and Gynecologists (ACOG) recommended* the following, if dietary and lifestyle modifications have no effect on symptoms:
Vitamin B6 at 10 to 25 milligrams (mg) orally three to four times/day with or without 12.5 mg of doxylamine 3 to 4 times/day (usually OTC tablet cut in half; women should never take OTC medication without talking to their HCP first)
Second-line agents (variable dosing):
Third-line (no dehydration present):
Third-line: (dehydration is present)
Various intravenous antiemetics to include metoclopramide, ondansetron, or promethazine
Fourth-line: (usually intractable vomiting)
Corticosteroids as well as possible intravenous nutrition/thiamine
*These are recommendations, and ACOG indicates a woman’s perception of her NVP is important to consider when assessing management options. Women who do not see their HCP often in early pregnancy, or who begin with very severe NVP may have to skip first- or even second-line therapies depending on severity of symptoms.
This is also why treatment of NVP as soon as possible is vital in preventing severe and unmanageable NVP in pregnant women.
Women should never attempt to treat themselves using OTC medication, supplements, or taking more medication than prescribed without talking to their HCP. Further, their HCP may find it necessary to stray from the recommendations above.
Read more detailed information on each of the medications described above.
Based on current research regarding NVP symptom peak, NVP generally progresses in severity until about week 9 or 10, and may not go away fully until 18 to 22 weeks of pregnancy. Therefore, pregnant women suffering with NVP early in pregnancy (5 to 6 weeks) should call their HCP to determine a plan forward should symptoms get worse, even if symptoms are currently manageable.
Women may save valuable time this way, by either implementing what was already discussed, or calling for a quick follow up appointment or prescription, based on their prior discussion with their HCP.
Women should not have to guess what they should do next. With the right support, women can combat their NVP with a combination of lifestyle modifications, dietary changes, non-pharmacological options, and prescription medications, if necessary. Women should also consider aspects of their mental and emotional heath as well.
Women should also consider sharing their NVP experience below, especially if their experience included taking any form of medication for their symptoms. This can help other women talk to their HCP and gain additional perspectives on this condition when diet and lifestyle changes have failed to work.
It is not uncommon for partners to feel helpless once a woman's NVP symptoms start spiraling.
However, partners and other family members of pregnant women can help women keep track of their vitamins, supplements, and various medications, as well as doses and time each dose was taken.
It may be difficult for some women to accurately keep track of time/dose when they are not feeling well or are falling in and out of sleep. Partners should also attend prenatal appointments and learn the NVP management plan as well.
Algorithm for Treatment of NVP (page 18; Association of Professors of Gynecology and Obstetrics; 2011)
The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum (algorithm page 25 and 26; U.K. Royal College of Obstetricians and Gynaecologists)
Nausea and Vomiting of Pregnancy (Gastroenterol Clin North Am. 2011 Jun)
Nausea and Vomiting of Pregnancy-What’s New? (Auton Neurosci. 2017 Jan)
Morning Sickness: Nausea and Vomiting of Pregnancy (American College of Obstetricians and Gynecologists)
Nausea and Vomiting of Pregnancy: Committee Opinion 189; January 2018 (American College of Obstetricians and Gynecologists)