Rx

A New Pharmacologic Treatment

for Nausea and Vomiting
of Pregnancy
N
Nausea and vomiting of pregnancy (NVP) is
a common condition that can affect up to 80
percent of all pregnant women. Symptoms
can range from mild nausea alone to nausea
with vomiting that is unrelenting (Lacroix,
Eason, & Melzack, 2000). The most severe
HEIDI COLLINS FANTASIA

weight loss and electrolyte imbalance that can

form, hyperemesis gravadarum, affects a
smaller proportion of women and can lead to
serious complications including dehydration,
require hospitalization (Davis, 2004). Women
with NVP report higher levels of discomfort,
lower quality of life and lost time from work
(Kramer, Bowen, Stewart, & Muhajarine,
2013; Munch, Korst, Hernandez, Romero, &
Goodwin, 2011).

Abstract Nausea and vomiting of pregnancy (NVP) affects up to 80 percent of pregnant women. This condition is usually
self-limiting, but the symptoms can be distressing and interfere with work, social activities and sleep. Symptoms can often
be managed by diet and lifestyle changes, but these interventions may not be successful for everyone. In April 2013, the U.S.
Food and Drug Administration approved doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg (Diclegis®) as the
first medication to specifically treat NVP in more than 30 years. This article reviews the indications, dosage and nursing
interventions associated with using doxylamine succinate/pyridoxine to treat NVP. DOI: 10.1111/1751-486X.12096
Keywords morning sickness | nausea | vomiting | NVP | pregnancy

http://nwh.awhonn.org © 2014, AWHONN 73


Rx
levels of discomfort, lower quality
Heidi Collins Fantasia,
PhD, RN, WHNP-BC,
is an assistant professor
in the School of Nursing,
College of Health Sciences,
at the University of
Massachusetts in Lowell,
MA, and a women’s
health nurse practitioner
at Health Quarters
in Beverly, MA. The
author discloses that
she is currently serving
on a women’s health
advisory board for Actavis
Pharmaceuticals, for
which she receives
financial consideration.
Address correspondence to
Heidi_Fantasia@uml.edu.
74 Nursing for Women’s Health
Etiology of NVP
The exact etiology of NVP is unknown,
although rising levels of human chorionic
gonadotropin and other endocrine factors, such
as fluctuating levels of estrogen, progesterone
and thyroid-stimulating hormone, have been
implicated in the development of NVP (Lee
& Saha, 2011; Niebyl, 2010). Other possible
contributing factors include slowed peristalsis of
Women with NVP report higher
of life and lost time from work
the gastrointestinal tract from mechanical and
hormonal factors and changes in carbohydrate
metabolism (Cibulka & Barron, 2013).
Controlling NVP
Women with NVP are educated about the
typical course of symptoms and strategies to
alleviate these symptoms, and are encouraged
to avoid potential triggers such as odors, foods
and situations that may increase the likelihood
of nausea and/or vomiting. Women’s and
health care providers’ concerns about possible
teratogenic effects of medications during
pregnancy, especially during the first trimester,
has led to many health care providers being
cautious about prescribing pharmacologic
treatments for NVP (Davis, 2004; Matthews,
Dowswell, Haas, Doyle, & O’Mathuna, 2010).
Therefore, medications that are safe and
effective are often underutilized, and women
who may benefit from treatment are not able to
fully explore this option.
A New Option
In April 2013, the U.S. Food and Drug
Administration (FDA) approved doxylamine
succinate 10 mg and pyridoxine hydrochloride
10 mg (brand name Diclegis®) for the treatment
of NVP. This is the first drug approved
specifically for NVP in more than 30 years
(FDA, 2013). The drug is a new version of
Bendectin®, which was originally manufactured
by Merrill Dow but was voluntarily removed
from the market by the manufacturer in the
early 1980s because of concerns over birth
defects and costs associated with malpractice
litigation (Brent, 2002). Subsequent evidence-
based reviews and meta-analyses did not
demonstrate an increased risk of birth defects
(Magee, Mazzotta, & Koren, 2002; McKeigue,
Lamm, Linn, & Kutcher, 1994), and the FDA
concluded that there were no reproductive
risks to the developing fetus associated with
the use of doxylamine succinate/pyridoxine
hydrochloride in pregnancy (Brent, 2002).
Medication Overview
Doxylamine succinate 10 mg and pyridoxine
hydrochloride 10 mg is a combination drug
consisting of an antihistamine (doxylamine) and
a vitamin B6 analog (pyridoxine) (Duchesnay,
Inc., 2013). This delayed-release oral medica-
tion is indicated for NVP that has not respond-
ed to other treatment modalities, such as dietary
modification and lifestyle management.
Mechanism of Action
The specific mechanism of action for how
the combination of doxylamine succinate/
pyridoxine hydrochloride works to alleviate
NVP is not entirely known. The vomiting
center in the medulla of the brain receives
signals from the cerebral cortex, the inner
ear and the sensory organs through multi-
ple neurotransmitters, including histamine.
When the pathway of the neurotransmitters is
interrupted, the vomiting reflex is decreased or
eliminated. Doxylamine, an antihistamine, may
interrupt the histamine pathway and reduce
vomiting (Davis, 2004). Vitamin B6 alone and
combined with other medications (such as
doxylamine) has shown to be effective in some
clinical trials to reduce nausea, although the
therapeutic mechanism is unclear (Matthews
et al., 2010). Although the mechanism of action
is not clear, the combination of doxylamine and
pyridoxine has been shown to be effective over
placebo in clinical trials (Koren et al., 2010).
Dosage and Administration
The dose amount and schedule are determined
by response to the medication. The initial
starting dose is two tablets at bedtime. If
symptoms are relieved, the next day this dosing
schedule can be maintained. If symptoms
persist, the dose can be increased to one tablet
in the morning and two tablets at bedtime. If
adequate relief still isn’t obtained, the dose can
Volume 18 Issue 1
be increased a final time to one tablet Implications for Nurses assessment will help identify women
in the morning, one in mid-afternoon NVP, although often mild and self- who may need more aggressive
and two at bedtime. Four tablets is the limiting, can be very distressing to treatment. Refractory cases of NVP,
maximum dose that can be taken each women and can interfere with work, especially when associated with
day (Duchesnay, Inc., 2013). sleep, relationships and social activities weight loss and clinical symptoms
(Cibulka & Barron, 2013). It may even of dehydration, may require
Adverse Reactions
increase anxiety about pregnancy and hospitalization, tube feedings and/or
The most frequently reported side is associated with depressive symptoms parenteral nutrition (Niebyl, 2010).
effects of doxylamine succinate 10 (Kramer et al., 2013). For women with mild to moderate
mg/pyridoxine hydrochloride 10 mg Nurses who care for pregnant NVP who are clinically stable, nurses
are related to the sedating effects of women should screen for NVP, suggest dietary and behavioral changes
antihistamines, and include drowsiness, including severity and associated that may help alleviate or lessen NVP
sleepiness and somnolence. Use of symptoms. NVP is different from (see Box 1). Although many of these
other central nervous system (CNS) hyperemesis gravadarum, the more interventions have not been supported
depressants such as alcohol, narcotics, severe form of NVP, and careful through randomized, clinical trials,
antianxiety medications and sleep aids
will potentiate this effect and increase
For women with mild to moderate NVP who are
the risk for accidents and falls. Women
who are taking doxylamine succinate/ clinically stable, nurses suggest dietary and behavioral
pyridoxine hydrochloride should not changes that may help alleviate or lessen NVP
use these medications. Monoamine
oxidase inhibitors prolong the CNS
effects of doxylamine succinate/
pyridoxine hydrochloride and should
not be combined. Additionally,
the doxylamine component has
anticholinergic properties and should
be used with caution in women who
have a history of asthma and urinary
retention (Duchesnay, Inc., 2013).

Special Populations
Doxylamine succinate/pyridoxine
hydrochloride is intended for use by
pregnant women, as its main indication
is to relieve nausea and vomiting
specifically caused by pregnancy. It
is considered a category A drug in
pregnancy, indicating that no well-
controlled studies have demonstrated
a risk to the fetus in the first trimester
and subsequent trimesters. This drug
is not recommended for women who
are breastfeeding. Both doxylamine
and pyridoxine are excreted in breast
milk and irritability and sedation have
been documented in infants exposed
to doxylamine via breastfeeding.
Safety and efficacy have not been
established in women under the age of
18 (Duchesnay, Inc., 2013).

February | March 2014 Nursing for Women’s Health 75

 they are not associated with maternal or fetal
Rx harm and may provide some level of relief.
Individual results will vary, and women may
need to try different combinations of dietary and
behavioral interventions prior to experiencing
symptom improvement. Additionally, NVP may
persist into the second trimester. Anticipatory
guidance should be provided about the expected
duration of symptoms to decrease anxiety
related to prolonged symptoms.
Women who are considering taking
doxylamine succinate/pyridoxine hydrochloride
should be informed of the dosing structure and
side effects. This is a delayed-release medication
and should not be crushed or chewed. Food may
Box 1.
Dietary and Behavioral Interventions for NVP
Dietary Interventions
• Eat small, frequent meals to avoid
gastric distention
• Avoid foods with strong odors/tastes
• Increase protein and decrease high-fat
foods
• Eat dry carbohydrates upon awakening
• Decrease or avoid spicy foods
• Try ginger, raspberry and peppermint
teas
affect absorption, so to increase the likelihood
of maximum benefit tablets are best taken on an
76 Nursing for Women’s Health
empty stomach. Because the primary potential
side effects are drowsiness and somnolence,
women should be cautioned to avoid activities
that require attention and concentration, such as
driving, until they know how they will react to
the medication. Excessive drowsiness can lead
to falls and, therefore, women should be aware
of their surroundings and use caution on stairs,
slippery and/or uneven surfaces, area rugs and
in decreased lighting until they know how they
will react to the medication.
In addition to providing education about
how to take the medication and about its
potential side effects, nurses who care for
pregnant women may need to dispel myths
Behavioral Interventions
• Acupuncture
• Acupressure wrist bands (P6 on the
wrist)
• Decrease or eliminate cigarette smoking
• Brushing teeth after eating
• Avoid lying supine for 2 hours after
eating
• Consider chewable prenatal vitamins
• Straight posture to decrease stomach
compression
Volume 18 Issue 1
about safety and provide reassurance to women
who may be concerned about medication use
during pregnancy. Some women may have
received information from family members
or friends that is incorrect. Nurses have the
responsibility to promote evidence-based
practice and provide current and clinically
accurate information based on the best available
evidence. Even so, women may still be reluctant
to take medication during pregnancy.
Conclusion
NVP is a common condition most often
associated with the first trimester of pregnancy.
Up to 80 percent of pregnant women may report
some form of NVP that can range from mild,
intermittent nausea to unrelenting vomiting.
The majority of cases of NVP are self-limiting
and can be managed with lifestyle and dietary
modifications. But for women who are still
experiencing symptoms despite these behavioral
changes, the FDA has approved doxylamine
succinate 10 mg/pyridoxine hydrochloride
10 mg as the first drug to treat NVP in 30 years.
This delayed-release medication is a combination
of an antihistamine and a vitamin B6 analog and
can titrated up or down based on the severity
of symptoms. This represents an additional
option for women who are experiencing
NVP and reporting inadequate relief with
nonpharmacologic treatments. NWH
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Rx
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Nursing for Women’s Health 77