A New Pharmacologic Treatment for Nausea and Vomiting of Pregnancy

Transcription

1 A New Pharmacologic Treatment for Nausea and Vomiting of Pregnancy NNausea 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 form, hyperemesis gravadarum, affects a smaller proportion of women and can lead to serious complications including dehydration, HEIDI COLLINS FANTASIA weight loss and electrolyte imbalance that can 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: / X Keywords morning sickness nausea vomiting NVP pregnancy , AWHONN 73

2 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 litigation (Brent, 2002). Subsequent evidencebased 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). 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. Women with NVP report higher levels of discomfort, lower quality 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 Medication Overview Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg is a combination drug consisting of an antihistamine (doxylamine) and a vitamin B 6 analog (pyridoxine) (Duchesnay, Inc., 2013). This delayed-release oral medication is indicated for NVP that has not responded 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 multiple 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 B 6 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 74 Nursing for Women s Health Volume 18 Issue 1

3 be increased a final time to one tablet in the morning, one in mid-afternoon and two at bedtime. Four tablets is the maximum dose that can be taken each day (Duchesnay, Inc., 2013). Adverse Reactions The most frequently reported side effects of doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg are related to the sedating effects of antihistamines, and include drowsiness, sleepiness and somnolence. Use of other central nervous system (CNS) depressants such as alcohol, narcotics, antianxiety medications and sleep aids will potentiate this effect and increase the risk for accidents and falls. Women who are taking doxylamine succinate/ pyridoxine hydrochloride should not 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). Implications for Nurses NVP, although often mild and selflimiting, can be very distressing to women and can interfere with work, sleep, relationships and social activities (Cibulka & Barron, 2013). It may even increase anxiety about pregnancy and is associated with depressive symptoms (Kramer et al., 2013). Nurses who care for pregnant women should screen for NVP, including severity and associated symptoms. NVP is different from hyperemesis gravadarum, the more severe form of NVP, and careful assessment will help identify women who may need more aggressive treatment. Refractory cases of NVP, especially when associated with weight loss and clinical symptoms of dehydration, may require hospitalization, tube feedings and/or parenteral nutrition (Niebyl, 2010). For women with mild to moderate NVP who are clinically stable, nurses suggest dietary and behavioral changes that may help alleviate or lessen NVP (see Box 1). Although many of these interventions have not been supported through randomized, clinical trials, For women with mild to moderate NVP who are clinically stable, nurses suggest dietary and behavioral changes that may help alleviate or lessen NVP 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 wellcontrolled 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

4 they are not associated with maternal or fetal 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 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 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 Behavioral Interventions Acupuncture Acupressure wrist bands (P 6 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 affect absorption, so to increase the likelihood of maximum benefit tablets are best taken on an 76 Nursing for Women s Health Volume 18 Issue 1

5 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 B 6 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 References Brent, R. (2002). Medical, social, and legal implications of treating nausea and vomiting of pregnancy. American Journal of Obstetrics and Gynecology, 186, S262 S268. doi: / mob Cibulka, N. J., & Barron, M. L. (2013). Guidelines of nurse practitioners in ambulatory obstetric settings. New York: Springer Publishing Company. Davis, M. (2004). Nausea and vomiting of pregnancy: An evidence based review. Journal of Perinatal and Neonatal Nursing, 18(4), Duchesnay, Inc. (2013). Diclegis full prescribing information. Retrieved from pdf/diclegis_full_prescribing_information.pdf Food and Drug Administration (FDA). (2013). FDA approves Diclegis for pregnant women experiencing nausea and vomiting. Retrieved from PressAnnouncements/ucm htm Koren, G., Clark, S., Hankins, G. D. V., Caritis, S. N., Miodovnik, M., Umans, J. G., & Mattison, D. R. (2010). Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: A randomized placebo controlled trial. American Journal of Obstetrics and Gynecology, 203, e1 e7. doi: /j. ajog Kramer, J., Bowen, A., Stewart, N., & Muhajarine, N. (2013). Nausea and vomiting of pregnancy: Prevalence, severity, and relation to psychosocial health. MCN Journal of Maternal Child Nursing, 23(1), doi: / NMC.0b013e Lacroix, R., Eason, E., & Melzack, R. (2000). Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change. American Journal of Obstetrics and Gynecology, 182, doi: /mob Lee, N. M., & Saha, S. (2011). Nausea and vomiting of pregnancy. Gastroenterology Clinics of North America, 40(2), doi: /j. qtc Magee, L. A., Mazzotta, P., & Koren, G. (2002). Evidence-based review of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). American Journal of Obstetrics and Gynecology, 186, S256 S261. doi: /mob Matthews, A., Dowswell, T., Haas, D. M., Doyle, M., & O Mathuna, D. P. (2010). Interventions for nausea and vomiting in early pregnancy. Cochrane Database of Systematic Reviews, 9, CD doi: / cd pub2 McKeigue, P. M., Lamm, S. H., Linn, S., & Kutcher, J. S. (1994). Bendectin and birth defects: 1. A meta-analysis of the epidemiologic studies. Teratology, 50(1), Munch, S., Korst, L. M., Hernandez, G. D., Romero, R., & Goodwin, T. M. (2011). Journal of Perinatology, 31, doi: /jp Niebyl, J. R. (2010). Nausea and vomiting of pregnancy. New England Journal of Medicine, 363, doi: /nejmcp Rx February March 2014 Nursing for Women s Health 77