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Home , Drugs in pregnancy, Melasma, Oligohydramnios, Pregnancy category

2.0 ANCC Contact Hours Angela Y. Stanley, DNP, APRN-BC, PHCNS-BC, NEA-BC, RNC-OB, C-EFM, Catherine O. Durham, DNP, FNP-BC, James J. Sterrett, PharmD, BCPS, CDE, and Jerrol B. Wallace, DNP, MSN, CRNA SAFETY OF Over-the-Counter MEDICATIONS IN Abstract Approximately 90% of pregnant women use medications while they are pregnant including both over-the-counter (OTC) and prescription medications. Some medica- tions can pose a threat to the pregnant woman and with 10% of all birth defects directly linked to medications taken during pregnancy. Many medications have docu- mented safety for use during pregnancy, but research is limited due to ethical concerns of exposing the fetus to potential risks. Much of the information gleaned about safety in pregnancy is collected from registries, case studies and reports, animal studies, and outcomes management of pregnant women. Common OTC categories of readily accessible medications include antipyretics, analgesics, nonsteroidal anti- infl ammatory drugs, nasal topicals, , decongestants, expectorants, antacids, antidiar- rheal, and topical dermatological medications. We review the safety categories for medications related to pregnancy and provide an overview of OTC medications a pregnant woman may consider for management of common conditions. Key words: Pharmacology; Pregnancy; Safety; Self-medication. Shutterstock

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. he increased prevalence of pregnant women identifi ed risks in animal-reproduction studies or completed taking medications, including over-the-counter animal studies show no harm. The assignment of Category (OTC) medications presents a challenge to C has two indications; (1) limited or no research has been nurses providing care to women of childbear- conducted about use in pregnancy, and (2) animal studies ing age. Approximately 90% of women take identifi ed adverse fetal risks (Brucker & King, 2017). The Tat least one medication and 50% take at least four dual indications have resulted in the majority (60–70%) medications during some point in pregnancy (Schonfeld, of US FDA-approved drugs being assigned to this catego- Schmid, Brown, Amoura, & Gordon, 2013). Whether ry (Brucker & King). Category D indicates fetal risks are a healthcare provider prescribes a medication, or it is evident in human studies. Use of these medications may be OTC, medications can pose a threat not only to the preg- necessary for the pregnant woman despite the risk to the fe- nant woman, but also to the fetus due to potential tera- tus. Category X indicates there is evidence based on human togenicity. At least 10% of birth defects were noted to experience showing fetal harm or animal and human stud- be a result of maternal drug exposure and thus a catalyst ies demonstrated fetal abnormalities. The risk of use clearly for establishing pregnancy risk categories (Black & Hill, outweighs any medicinal benefi ts and therefore, the drug 2003; Wilson, 1977). More than 50% of is contraindicated (Wilmer, Chai, & Kroumpouzos, 2016). are unplanned and inadvertent administration of certain Although these categories were the standard over the medications can jeopardize the outcome of an unborn past 30-plus years, concerns still exist with the ambiguity child before a woman realizes that she is pregnant (Pa- of some of the categories. In response to concerns identi- risi, Spong, Zajicek, & Guttmacher, 2011). fi ed by the Society Public Affairs Committee, Although some medications are well documented to be the US FDA made major changes in the way healthcare safe for the pregnant woman, more studies need to be con- should manage medication administration in the preg- ducted to generate a robust list of safe and effective medi- nant population (Public Affairs Committee of the Tera- cations for the woman and fetus. The lack of safety data tology Society, 2007). The challenge has always been how to inform appropriate prescribing of medications during healthcare providers interpret the pregnancy categories pregnancy is related to safety, fi nancial incentives, and eth- when counseling pregnant women on benefi ts versus spe- ics (Sheffi eld et al., 2014). Safety is the primary concern cifi c risks. In December 2014, the US FDA developed the addressed by researchers and pharmaceutical companies Pregnancy and Lactation Labeling Rule that replaces the for conducting pharmacokinetic and pharmacodynamic letter categories with a narrative-based labeling require- studies in pregnant women (Sheffi eld et al.). These con- ment (US FDA, 2016). The new label consists of three cerns are shared by institutional review boards and are subsections—pregnancy (including labor and delivery), the basis for ethical arguments (Sheffi eld et al.). The lack lactation (including nursing ), and females and of a federal mandate does not impose a fi nancial incentive males of reproductive potential (US FDA, 2014b). The (Sheffi eld et al.). Most information gleaned about the ef- pregnancy subsection includes a risk summary, clinical fects of medications on pregnant mothers and the fetus has considerations, and available safety-related information been obtained from pregnancy registries, case studies, case obtained from pregnancy exposure registries (US FDA, reports, animal studies, extensive discussions with moth- 2014b). The lactation subsection includes details about ers during and after pregnancies, and children and the amount of drug transferred into breastmilk and the with birth defects (Addis, Sharabi, & Bonati, 2000; Schae- potential for adverse effects on the fer, Peters, & Miller, 2007; Schonfeld et al., 2013). (US FDA, 2014b). The newest category, females and males Informed nurses who understand the maternal-fetal of reproductive potential, includes “relevant information risk with medications, classifi cation and safety of OTC when pregnancy testing or contraception is required or drugs, and limitation in research can help to decrease recommended before, during, or after drug therapy or risk and improve patient education. We outline the safety when there are human or animal data that suggest drug- categories for medications related to pregnancy, review associated fertility effects” (US FDA, 2014b, p. 3). common OTC medications that a pregnant woman may The Pregnancy and Lactation Labeling Rule ensures that consider, and address therapeutic guidance for the nurses prescription drugs include the following subcategories: the who assist in the care of the pregnant population. pregnancy exposure registry, risk summary, clinical consid- erations, and data (US FDA, 2016). All four sections of the Background Pregnancy and Lactation Labeling Rule allow healthcare In 1979, the United States Food and Drug Administra- providers and patients to obtain a global view of medica- tion (US FDA, 1979) developed a classifi cation system for tions. The new labeling format was effective June 30, 2015 pregnant women to categorize the level of safety associ- (US FDA, 2014a). A phased approach will be used for drugs ated with medications and their effects on fetal develop- approved on or after June 30, 2001 (US FDA, 2014a). Drugs ment and outcomes. There are fi ve categories that were approved prior to June 30, 2001 are not required to use the created and still used in most healthcare settings. The cat- Pregnancy and Lactation Labeling Rule; however, must re- egories are A, B, C, D, and X (US FDA, 1979). move the “old” by June 29, 2018 (US Category A shows no risk to the fetus based on the result FDA, 2017). The Pregnancy and Lactation Labeling Rule of human studies. Category B indicates no evidence of fe- does not apply to OTC medication; only prescription medi- tal risk in humans. There are no human studies to confi rm cations (US FDA, 2014a).

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Informed nurses who understand the increased fetal risk associated with how the physiologic changes of pregnancy affects the pharmacoki- netics of over-the- counter medications can help to decrease risk and improve patient education. iStock

Medication safety in pregnancy has a few unique chal- Chang). See Table 1. The timing of taking acetaminophen, lenges. “The physiology of pregnancy affects the pharma- whether during the fi rst or second trimester, has limited cokinetics of medications used and certain medications evidence to possible defects, little is known about the can reach the fetus and cause harm” (Sachdeva, Patel, & impact of consumption on the fetus during the third tri- Patel, 2009, p. 1). Preexisting medical conditions prompt mester (Servey & Chang). Ongoing studies evaluating the a thorough evaluation to determine the most appropriate potential impact of frequent maternal use of acetamino- medical management during pregnancy. In many instanc- phen and risk of subsequent wheezing and asthma in the es, the management plan may remain the same. However, infant have demonstrated a potential relationship (Per- the associated fetal risk may prompt a management plan zanowski et al., 2010). Recent cohort studies evaluating change or closer surveillance of fetal growth. The “safety the relationship between consumption of acetaminophen profi le of some medications may change according to the and risk of attention-defi cit hyperactivity and other kinetic of the fetus” (Black & Hill, 2003, p. 2517). disorders seem to demonstrate some risk. Stergiakouli, Use of OTC medications is a common concern among Thapar, and Davey Smith (2016) reviewed data from a pregnant women; therefore, it is important for nurses to prospective birth cohort of 7,796 mothers and found an recognize their role in patient counseling and medica- association of prenatal exposure of acetaminophen to an tion safety. Accessibility, affordability, and convenience increased risk of multiple behavioral diffi culties. Parker et of OTC medications warrant discussion of common al. (2017) suggest a possible relationship between oxida- categories queried and used by pregnant women—anti- tive stress, infl ammation, and acetaminophen exposure af- pyretics and analgesics, nonsteroidal anti-infl ammatory ter birth to the development of autism. They recommend drugs (NSAIDs), nasal topicals and antihistamines, de- an “acetaminophen withdrawal study” as a viable option congestants and expectorants, antacids and antidiarrhe- to explore (Parker et al.). Therefore, recommend use of als, and topicals (dermatological). acetaminophen with caution and when medically neces- sary such as with fever (Andrade, 2016; Servey & Chang).

Antipyretics & Analgesics Nonsteroidal Anti-Infl ammatory Drugs Acetaminophen The risks of NSAIDs (, Motrin, Advil) are depen- Over-the-counter use of acetaminophen (Tylenol), wheth- dent upon the medication, dosage, gestational age, and er taken alone or in readily available combination drugs, duration of treatment. Currently, the US FDA (2016) rec- is common during pregnancy (Servey & Chang, 2014). ommends a risk–benefi t analysis using prescribed NSAIDs The National Births Defects Prevention Study found no due to the increased risk of in the fi rst half increased risk of birth defects with in-utero exposure to of pregnancy. Antonucci et al. (2012) associated NSAID acetaminophen during the fi rst trimester and it may be use in early pregnancy to increased risks of miscarriage protective against birth defects if taken by the and birth defects, but they did not defi ne the term “early for febrile illness (Feldkamp, Meyer, Krikov, & Botto, pregnancy” by gestational age. However, “exposure to 2010). When taken for febrile management, a protective NSAIDs after 30 weeks’ gestation is associated with an in- factor has been demonstrated, as untreated febrile illness creased risk of premature closure of the fetal ductus arte- can lead to various cranial and facial defects (Servey & riosus and ” (Antonucci et al., p. 474).

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. TABLE 1. Antipyretics & Analgesics in Pregnancy Old FDA Categorya Drug/Drug Current Pregnancy and Category Lactation Labeling Rule Labelingb Risks/Side Effects Acetaminophen B/B/B • Skin , anaphylaxis Acetaminophen (; Tylenol; FeverAll, etc.) Crosses the No increased risk for teratogenic effects observed Not associated with increased risk of miscarriage or spontaneous Frequent use during pregnancy may be related to wheezing or asthma in early childhood Nonsteroidal B/B/D • Elevated pressure, anti-infl ammatory Crosses the placenta; Class impact: dependent on dose, gesta- headache, dizziness, medication drugs tional age, duration allergy, gastrointestinal distress, renal insuffi ciency (Voltaren): avoid use starting at 30-weeks’ gestation • Increased risk of acute kidney injury, HELLP syndrome, Birth defects have been noted after exposure to some NSAIDs; anemia, etc. however, data confl icting Premature closure of ductus arteriosus in the fetus Nonteratogenic effects: review pregnancy considerations for data Mild rheumatoid arthritis: may be ok for early fl airs; avoid late usage Avoid third trimester: premature closure patent arteriosus in the fetus

Migraine: other treatments preferred • , elevated blood pressure, dizziness, drowsiness, allergic (Aleve, Naprosyn): avoid use starting at 30-weeks’ reaction, gastrointestinal distress, gestation renal insuffi ciency, elevated liver Data confl icting on teratogenic effects enzymes Nonteratogenic effects: review pregnancy considerations for data • Edema, dizziness, headache, rash, allergic reaction, fl uid retention, (Advil, Motrin): gastrointestinal distress Ibuprofen: may be associated with low birthweight and increased asthma risk of fetus

Diclofenac/Naproxen: crosses placenta; may increase risk of early spontaneous abortion aX/X/X indicates pregnancy trimester as per FDA drug classifi cations bPregnancy and Lactation Labeling Rule available recommendations Source: Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online (2018).

Several sources, including the US FDA (2015), advise there was an association of ibuprofen use in the second use with caution in the fi rst and second trimester, and trimester with low birthweight and an association of ibu- to avoid in the third trimester (Antonucci et al., 2012; profen use in the second and third trimester with asthma Bloor & Paech, 2013). Bloor and Paech estimate preva- in 18-month-old children (Nezvalová-Henriksen et al.). lence of use from preconception through the fi rst trimes- Maternal use of diclofenac in the second trimester was as- ter, as 2.9% to 18%. The ability of medications, such sociated with low birthweight. Use of diclofenac (Cambia) as diclofenac and naproxen, to cross the placenta in the in the third trimester was signifi cantly associated with ma- fi rst trimester highlights the potential for increased risk ternal vaginal bleeding (Nezvalová-Henriksen et al.). of spontaneous abortion. Case-control and cohort stud- Nonsteroidal infl ammatory drugs were identifi ed as ies have demonstrated an increased risk of spontaneous a causative factor for acute kidney injury in pregnancy abortion associated with NSAID use during early preg- (Wiles & Banerjee, 2016). The development of acute nancy (Bloor & Paech). kidney injury in pregnancy is a serious complication and Nezvalová-Henriksen, Spigset, and Nordeng (2013) requires early identifi cation and timely intervention to were unable to associate NSAID use with infant survival, minimize perinatal complications. The best safety pro- congenital malformation, or structural defects among fi le has been associated with ibuprofen [Motrin, Advil] a study population of 6,500 pregnant women. However, (Wiles & Banerjee). However, management of medical

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. complaints that warrant ibuprofen use at the lowest ef- the reason behind adoption of second-generation antihis- fective dose and discontinuation at the earliest opportu- tamines as a reasonable choice (Kar, Krishnan, Preetha, & nity are recommended (Wiles & Banerjee). In the pres- Mohankar, 2012). According to recent studies, there is, ence of preeclampsia, volume depletion, acute kidney however, no signifi cant risk to fetal malformations with injury, and chronic kidney disease, NSAIDs are not rec- fi rst-generation antihistamines and they are considered ommended (Wiles & Banerjee). safe in pregnancy. For example, chlorpheniramine (Chlor- Tabs) is recommended as the of choice for pregnant women (American College of Obstetricians and Nasal Topicals and Antihistamines Gynecologists [ACOG] & American College of Allergy, Hormonal changes cause vascular engorgement and in- Asthma and Immunology [ACAAI], 2000). creased mucous production in the nose; especially, in the Second-generation antihistamines such as third trimester when plasma volume and fl uid shifts cause (Claritin) and (Zyrtec) are considered the second- more nasal discharge and nasal blockage (Shiny Sherlie & generation drugs of choice OTC. Extensive studies have not Varghese, 2014). The complaint of nasal congestion often identifi ed any teratogenic effects to date (ACOG & ACAAI, interferes with sleep and appetite. Patients may be advised 2000). Kar et al. (2012) recommend avoidance of second- to raise the head of the bed at least 30 degrees and par- generation drugs in early pregnancy during organogenesis. ticipate in light physical activity to increase nostril patency (Allegra), a second-generation antihistamine (Pray & Pray, 2014). Saline lavage using an isotonic saline has been associated with early pregnancy loss in animal stud- product (Simply Saline Nasal Relief Spray) and external ies, but this has not been found in humans (Servey & Chang, nasal dilators (Breathe Right Nasal Strips) are additional 2014). Fexofenadine is a metabolite of terfenadine that was treatment options to facilitate air movement (Pray & Pray). removed from the market in 1998 due to cardiotoxicity; how- Pharmacologic options may include topical intranasal ever, there was no evidence of congenital malformations on decongestants (Afrin, NasalCrom), intranasal corticoste- safety of terfenadine in human pregnancy (Servey & Chang). roids (Nasacort Allergy 24HR), and intranasal anticholin- ergics [Atrovent] (Namazy & Schatz, 2014). See Table 2. Topical intranasal decongestants containing oxymetazo- Oral Decongestants and line (Afrin) are strongly discouraged due to the poten- Expectorants tial complication of rhinitis medicamentosa (Namazy & “Nearly one in four pregnant women seek relief of nasal Schatz). Oxymetazoline and xylometazoline are well ab- congestion caused by upper respiratory infection, allergic sorbed from the nasal mucosa to produce systemic effects; rhinitis, or pregnancy rhinitis” (Servey & Chang, 2014, however, there is no knowledge regarding fetal effects. Yau, p. 549). (Sudafed) and Mitchell, Lin, Werler, and Hernández-Díaz (2013) con- (Sudafed PE) are the most common oral decongestants in ducted the fi rst study exploring the risks associated with OTC medications. The overall safety of oral and intrana- fi rst-trimester intranasal decongestants. The risk of pyloric sal decongestants has not been established. Decongestant stenosis and tracheoesophageal fi stula was associated with use in the fi rst trimester has been associated with gastros- fi rst-trimester intranasal decongestants; oxymetazoline or chisis, small intestinal atresia, and hemifacial macrosomia. xylometazoline (Yau et al.). There was an association be- Pseudoephedrine, guaifenesin (Mucinex), and dextro- tween second-trimester exposure to oxymetazoline and methorphan (Robitussin, Delsym) are the most commonly renal collecting system anomalies (Yau et al.). used cold medications taken during pregnancy (Black & The only OTC option for an intranasal corticosteroid is Hill, 2003). “Among the cold, allergy, and cough medica- Nasacort Allergy 24HR. There have been no studies on its tions, pseudoephedrine and guaifenesin use increased from use among pregnant women; thus, a risk–benefi t analysis pre-pregnancy to the second trimester, then decreased in the should be conducted by the individual healthcare provider. third trimester” (Werler, Mitchell, Hernandez-Diaz, Honein, Likewise, there are no adequate or well-controlled stud- & the National Birth Defects Prevention Study, 2005). De- ies regarding intranasal (Atrovent) among congestants have not been shown to improve nasal itching, pregnant women; and, healthcare providers should decide sneezing, or rhinorrhea. Yawn and Knudtson, (2007, p. 296) the treatment plan on an individualized basis. reported short-term benefi ts using intranasal decongestants Use of antihistamines for the management of allergic “for nasal congestion that interferes with sleep, but pregnant rhinitis and nausea is common in pregnant women and women should reserve their use until after the fi rst trimes- readily available as OTC preparations (Servey & Chang, ter and avoid them during labor.” Inhaled decongestants, 2014). Oral or systemic absorption of antihistamines is such as xylometazoline (Otrivin) and oxymetazoline (Af- generally considered safe with both fi rst- and second- rin, Zicam), are available OTC. The extent of systematic generation antihistamines and are readily available and absorption is unknown, and the nurse should be prepared inexpensive. Oral ingestion may be less effective than top- to discuss the limitations in research and recommenda- ical in addressing the nasal symptoms and women should tions on these drugs in effi cacy and safety. be educated to start with second-generation options due There is little research on use of expectorants during to side effect profi le (Servey & Chang). Side effects of fi rst- pregnancy. Guaifenesin was weakly associated with neu- generation antihistamines include sedation, performance ral tube defects and inguinal hernias. Dextromethorphan, impairment, and effects and is generally a cough suppressant, is associated with teratogenic effects

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. TABLE 2. Nasal Topicals & Antihistamines Old FDA Categorya Current Pregnancy and Drug Category Lactation Labeling Rule Labelingb Class Risks/Side Effects Nasal topicals B/B/B Cromolyn (NasalCrom) • Topical skin irritation most fre- Topicals generally considered safe, fi rst-line quent reported side effect Cromolyn (NasalCrom): considered safe for topical use

C/C/C • Short-term use only; dependence Glucocorticoid Nasal Topical Fluticasone propionate (Flonase and rebound congestion with OTC): adverse events seen in animal studies (limited data on prolonged use intranasal use)

Intranasal Decongestant: Oxymetazoline (Claritin Allergic De- congestant, Dristan Nasal, Drixoral Nasal): adverse events noted in fi rst trimester with high doses; not preferred for treatment of rhinitis in pregnancy Antihistamines B/B/B • First-generation antihistamines First-Generation Antihistamines: generally considered safe—see are generally avoided due to side class risks and side effects. Chlorpheniramine (Aller-Chlor, Allergy effects of class; sedation, perfor- Relief OTC, Chlor-Trimeton) mance impairment, dizziness, excitability, urinary retention, headache, for example B/B/B Second-Generation Antihistamines Loratadine (Claritin, Alavert): no associated risk of fetal malformations. Generally considered • Sedation, headache, drowsiness, safe. and fatigue potential side effects for both Loratadine and Cetirizine Cetirizine (Zyrtec): no associated risk of fetal malformations. Gen- erally considered safe. • Headache, drowsiness, fatigue, diarrhea, dyspepsia C/C/C Fexofenadine (Allegra): limited information available, animal studies indicate early pregnancy loss. Fexofenadine: metabolite of terbinafi ne, removed from the market due to cardiotoxicity. Providers may want to discourage use in pregnant women. aX/X/X indicates pregnancy trimester as per FDA drug classifi cations bPregnancy and Lactation Labeling Rule available recommendations Source: Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online (2018). in chicken embryos; however, a human epidemiological OTC management with antacids containing calcium and study did not demonstrate an increased risk of congenital magnesium (Tums, Mylanta) may be considered fi rst-line malformation again further highlighting the need to rec- and safe in pregnancy. Antacids with aluminum taken at ommend with caution and use for the shortest necessary high dose can lead to neurotoxicity and recommenda- timeframe (Servey & Chang, 2014). tions for nurses include education to read labels and daily dosages (Mahadevan & Kane, 2006; Servey & Chang). Second-line management may include sucralfate, Antacids and Antidiarrheals available OTC as sucralfate (Carafate). This is not In pregnant women, almost 80% experienced some readily absorbed and does not appear to have any ad- symptoms of gastrointestinal distress by the end of the verse effects in utero during the fi rst trimester (Kahri- third trimester (Kahrilas, 2018; Servey & Chang, 2014). las, 2018; Mahadevan & Kane, 2006). It is important First-line management of refl ux type symptoms includes for nurses to know this medication works by protect- avoidance and prevention. Nurses should encourage ing the gastric mucosa. If fi rst-line options of avoid- pregnant women to avoid food and drinks most likely ance fail in conjunction with sucralfate, then women to trigger symptoms such as high acid foods, fried and may opt to try other options for acid-reducing therapy spicy foods, avoid lying fl at after eating, and elevation of and symptom management, such as histamine recep- the head of the bed and dietary management (Kahrilas). tor antagonist (H2RAs), ranitidine [Zantac] (Kahrilas; If fi rst-line management fails to resolve symptoms, then Mahadevan & Kane). Histamine receptor antagonist

July/August 2019 MCN 201

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. blockers have been used safely in all trimesters of preg- Topical steroids are the most common medication nancy and there are no known teratogenic effects (Kah- used to treat skin conditions; however, little clarity ex- rilas; Servey & Chang, 2014). Proton pump inhibitors ists about safety or potential harm they may pose during (PPIs) such as omeprazole (Prilosec), lansoprazole pregnancy. A systematic review of 14 observational stud- (Prevacid), or pantoprazole (Protonix) are also consid- ies to examine the safety of topical steroids in pregnancy ered a safe second-line option, have been widely used concluded no association between maternal use of topi- in pregnancy, and have generally good short-term use cal steroids of any potency and birth mode with congeni- safety profi les (Katz, Gerson, & Vela, 2013; Kahrilas; tal malformations, preterm births, or low Apgar scores Servey & Chang). However, the majority of studies de- (Chi, Wang, & Kirtschig, 2016). Nurses should provide termining safety of PPI therapy for the management of adequate education and ensure appropriate diagnosis refl ux symptoms in pregnant women involve the fi rst and management for skin conditions that may require available PPI; omeprazole. this treatment. Loperamide (Imodium) is a readily available OTC Antifungal agents, such as (Desenex), mi- drug that is commonly used for noninfectious diarrhea. conazole (Monistat 3), and tioconazole (Vagistat-1), are The goal of managing diarrheal episodes in a pregnant the most common medications available OTC. One of woman is to identify the etiology, restore or maintain the largest population-based, case-control studies explor- hydration status, and avoid a food-based response from ing the teratogenicity of clotrimazole did not conclude a nursing perspective (Mahadevan & Kane, 2006). A an association with congenital malformations (Black medical condition of infectious diarrhea during preg- & Hill, 2003). The authors recommend clotrimazole as nancy should be managed by a healthcare provider. The “probably” safe in the fi rst trimester and safe in the sec- nurse may provide education on strategies to maintain ond and third trimesters (Black & Hill). “Several small adequate hydration. Although loperamide is an OTC trials have indicated butoconazole and miconazole are medication, the decision to use is based upon the presence likely to be safe during the second and third trimesters” of debilitating symptoms and with provider recommenda- (Black & Hill, p. 2522). There are no suffi cient data on tion (Kallen, Nilsson, & Otterblad Olausson, 2008; Ma- the safety of tioconazole in pregnancy. Based on this lim- hadevan & Kane). ited data, the nurse should educate the woman to ensure For pregnant women with constipation, it is recom- appropriate diagnosis, risk and benefi t of treatment, and mended to avoid OTC medications that contain bismuth, appropriate referrals as needed. mineral oil, and castor oil (Servey & Chang, 2014). Poly- ethylene glycol 3350, commonly marketed as Miralax®, Insect Repellents is considered a safe and readily available alterative for The Zika Virus and other mosquito-borne diseases the management of constipation (Mahadevan & Kane, sparked concern and raised questions about the safe and 2006). This medication is minimally absorbed, and there effective use of insect repellents during pregnancy and is little research on this drug related to in-utero effects lactation. The Centers for Disease Control and Preven- (Mahadevan & Kane; Servey & Chang). The nurse can tion (CDC, 2018b) recommends several Environmen- assist with preventive management of constipation in edu- tal Protection Agency (EPA)-registered insect repellents cating on hydration needs, dietary sources of fi ber, and to prevent mosquito bites, including diethyltoluamide preventative measures. (DEET [Off!]), picaridin (Repel), and IR3535 (Avon Skin-So-Soft Bug Guard Plus Towelettes). Since 1950, DEET has been marketed worldwide as an insect re- Antifungals and Topicals pellent (Wylie, Hauptman, Woolf, & Goldman, 2016). Common skin conditions during pregnancy can be preex- There are limited data on the effects of DEET in pregnant isting, hormone-related, and pregnancy-specifi c. Preexist- women. To date, no studies have been conducted among ing (i.e., , , and fungal infections) women in the fi rst trimester when most birth defects oc- and pregnancy-specifi c conditions (i.e., pruritic urticarial cur. Safe use of DEET is recommended at concentrations and plaques of pregnancy, prurigo of pregnancy, of 30% or less, during pregnancy or lactation (Wylie et and intrahepatic cholestasis of pregnancy) require a medi- al.). Newer products, Picaridin and IR3535, have been cal evaluation for diagnosis and appropriate treatment deemed safe for use among pregnant women. Effi cacy and the nurse can assist with ensuring appropriate evalua- studies have demonstrated no signifi cant difference when tion, diagnosis, and management. picaridin or IR3535 was compared with DEET (Environ- , also known as “the mask of pregnancy” mental Working Group, 2018). Oil of lemon eucalyptus, occurs in up to 50% of pregnant women (Ogbechie- or para-menthane-diol, is the only plant-based repellent Godec & Elbuluk, 2017). Exposure to sunlight and oth- recommended by the CDC with comparable effectiveness er ultraviolet radiation causes the condition to worsen; to DEET. Para-menthane- diol is a synthesized version of therefore, recommendations to prevent development oil of lemon eucalyptus. It is important to note “pure” or exacerbation include high-potency broad-spectrum oil of lemon eucalyptus has not been evaluated for safety sunscreens and avoiding excessive exposure to sunlight and effi cacy, and is not an EPA-registered insect repel- is an appropriate nursing intervention (Tunzi & Gray, lent. Pregnant women should be cautioned that no repel- 2007). lent is 100% effective; therefore, additional precautions

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. TABLE 3. Recommendations for Repellent encouraged to use reliable resources, such as the National Use for Pregnant Women Institutes of Health’s Label Data- base (www.dsld.nlm.nih.gov) and the Natural Medicines Percent Comprehensive Database (www.naturaldatabase.com) to Indication Product Concentration obtain current safety-related information when natural Zika virus DEET 20–30% supplements are used in pregnant or lactating women. Picaridin 20% Sunscreens Lyme disease DEET 20–30% Hormonal changes during pregnancy may increase the Picaridin 20% skin’s sensitivity to ultraviolet (UV) rays. The effects of IR3535 20% increased sun exposure are well known—skin cancer, pre- West Nile virus DEET 7–30% mature aging, and (US FDA, 2018). Sunscreens are an effective OTC skin care product to pre- Picaridin 10–20% vent and minimize the damaging effects of UV rays (US IR3535 20% FDA). During pregnancy, sunscreens with zinc oxide and Outdoor activities DEET 7–10% titanium dioxide block damaging UV rays; they have been deemed safe and are the preferred agents (Krause et al., (Short time) Picaridin 5–10% 2012; Ruszkiewicz et al., 2017). Advise pregnant women All-day bug protection DEET 7–10% to avoid OTC products with oxybenzone and retinyl pal- Picaridin 5–10% mitate. Oxybenzone has been linked to allergies, disrup- tion of hormones, and cell damage; and, retinyl palmitate Sensitive skin Picaridin 5–10% or allergies is a vitamin A derivative (Krause et al.). Oral versions of vitamin A derivatives () have been dem- Source: Environmental Working Group (2018). onstrated to be teratogenic (Krause et al.). It is less clear Note. Products should always be used as directed. whether retinol topical products can have negative effects; and therefore, should be avoided as well (Krause et al.). are recommended. Table 3 lists product recommenda- tions for use of insect repellents among pregnant women Clinical Implications (Environmental Working Group). The decision to prescribe or recommend a medication for a pregnant woman is an everyday challenge for many Natural Supplements healthcare providers and it is important for nurses to be Herbal and dietary supplements in the United States are aware of risks, benefi ts, and limitations of current lit- not regulated by the US FDA; therefore, do not have the erature. “Numerous medications have been used safely same safety and effi cacy standards as pharmaceutical and effectively in pregnancy with minimal risk to the fe- products. Despite the lack of data on safety of use during tus and mother, although the decision to use them is not pregnancy, natural supplements are used by a signifi cant without apprehension” (Pernia & DeMaagd, 2016, p. portion of the US population for common primary care 713). The purpose or intent of the Pregnancy and Lacta- complaints or to simply maintain a healthy state (Gray tion Labeling Rule is to provide the healthcare provider, & Rutledge, 2013). Studies have found that up to 6% of whether physician, pharmacist, or nurse, with relevant mothers use natural products during pregnancy (Louik, data for critical decision-making when treating pregnant Gardiner, Kelley, & Mitchell, 2010). Use appears to in- or lactating women, recommending medications, and crease with age and is also affected by geographic regions, offering accurate information. The new labeling allows most likely refl ecting cultural acceptance of natural medi- for a more complete statement of the known risks based cine use among particular populations (Louik et al.). upon available data, including considerations of medical/ In a multinational, cross-sectional study, the largest disease factors, animal data put into context of human group of contraindicated herbal supplement users were exposure, human data (upon availability), and explicitly from the United States (Kennedy, Lupattelli, Koren, & states if no data are available. High use of OTC medi- Nordeng, 2016). Researchers were able to associate the cations and the transition to the new prescription drug following maternal factors with the use of contraindicat- labeling highlight the critical need for nurses to be fa- ed herbal supplements during pregnancy; housewife, uni- miliar with indications, risks, and benefi ts of all OTC versity education, not using folic acid, and con- and other medications administered during pregnancy. sumption (Kennedy et al.). Study participants indicated Limited data on OTC medications present challenges in use of an herbal supplement was classifi ed as safe for use providing accurate and timely advice to pregnant women in pregnancy; and, in many instances, the supplement was and those of childbearing age about medication safety recommended by a healthcare provider (Kennedy et al.). and potential risks. ✜ “The paucity of human studies on herbal medicines safety in pregnancy stands in stark contrast to the widespread Angela Y. Stanley is an Instructor, College of Nursing, use of these products among pregnant women” (Kennedy Medical University of South Carolina, Charleston, SC. The et al., p. 8). Nurses and other healthcare professionals are author can be reached via e-mail at [email protected]

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Clinical Implications Table Chi, C. C., Wang, S. H., & Kirtschig, G. (2016). Safety of topical corti- costeroids in pregnancy. JAMA , 152(8), 934–935. doi:10.1001/jamadermatol.2016.1009 Over-the-counter (OTC) medications are widely used dur- Environmental Working Group. (2018). EWG’s 2018 guide to bug repel- ing pregnancy; approximately 9 out 10 pregnant women lents: Repellent chemicals. Retrieved from https://www.ewg.org/ take at least one OTC medication. research/ewgs-guide-bug-repellents/repellent-chemicals Feldkamp, M. L., Meyer, R. E., Krikov, S., & Botto, L. D. (2010). Acet- aminophen use in pregnancy and risk of birth defects: Findings Nurses caring for pregnant women will likely be asked from the national birth defects prevention study. and about safety of these types of drugs during pregnancy and Gynecology, 115 (1), 109–115. doi:10.1097/AOG.0b013e3181c52616 should be able to provide current information and direct Gray, D. C., & Rutledge, C. M. (2013). Herbal supplements in primary care: Patient perceptions, motivations, and effects on use. Holistic them to additional resources. Nursing Practice, 27(1), 6–12. doi:10.1097/HNP.0b013e318276fb32 Kahrilas, P. J. (2018). Medical management of gastroesophageal refl ux dis- The information we offer here can be used as a source to ease in adults. In Talley, N. J. & Grover, S. (Eds.), UpToDate. Retrieved from https://www.uptodate.com/contents/medical-management-of-gastroeso seek more data on specifi c medications. phageal-reflux-disease-in-adults?search=Medical%20manage- ment%20of%20gastroesophageal%20reflux%20disease%20in%20 The CDC provides information about OTC medications adults&source=search_result&selectedTitle=1~150&usage_type=default &display_rank=1 during pregnancy and breastfeeding. Women can be Kallen, B., Nilsson, E., & Otterblad Olausson, P. (2008). Maternal use of referred to these CDC resources at this site: https://www. loperamide in early pregnancy and delivery outcome. Acta Paediat- cdc.gov/pregnancy/meds/treatingfortwo/index.html rica, 97(5), 541–545. doi:10.1111/j.1651-2227.2008.00718.x Kar, S., Krishnan, A., Preetha, K., & Mohankar, A. (2012). A review of antihistamines used during pregnancy. Journal of Pharmacology & Pharmacotherapeutics, 3(2), 105–108. doi:10.4103/0976-500X.95503 Catherine O. Durham is Doctor of Nursing Practice Katz, P. O., Gerson, L. B., & Vela, M. F. (2013). Guidelines for the diagnosis Program Director, College of Nursing, Medical Univer- and management of gastroesophageal refl ux disease. The American Journal of Gastroenterology, 108(3), 308–328. doi:10.1038/ajg.2012.444 sity of South Carolina, Charleston, SC. Kennedy, D. A., Lupattelli, A., Koren, G., & Nordeng, H. (2016). Safety James J. Sterrett is an Assistant Professor, College classifi cation of herbal medicines used in pregnancy in a multina- of Pharmacy, Medical University of South Carolina, tional study. BMC Complementary and Alternative Medicine, 16, 102. doi:10.1186/s12906-016-1079-z Charleston, SC. Krause, M., Klit, A., Blomberg Jensen, M., Søeborg, T., Frederiksen, H., Jerrol B. Wallace is Program Director, Nurse Anes- Schlumpf, M., …, Drzewiecki, K. T. (2012). Sunscreens: Are they benefi cial for health? An overview of endocrine disrupting properties of UV-fi lters. thesia Program, Uniformed Services University of the International Journal of Andrology, 35(3), 424–436. doi:10.1111/j.1365- Health Sciences, Bethesda, MD. 2605.2012.01280.x The authors declare no confl icts of interest. Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online. (2018). Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc. Louik, C., Gardiner, P., Kelley, K., & Mitchell, A. A. (2010). Use of herbal Copyright © 2019 Wolters Kluwer Health, Inc. All rights treatments in pregnancy. American Journal of Obstetrics and Gy- reserved. necology, 202(5), 439.e1–439.e10. doi:10.1016/j.ajog.2010.01.055 Mahadevan, U., & Kane, S. (2006). American gastroenterological as- sociation institute medical statement on the use of gas- DOI:10.1097/NMC.0000000000000537 trointestinal medications in pregnancy. Gastroenterology, 131(1), 278–282. doi:10.1053/j.gastro.2006.04.048 References Namazy, J. A., & Schatz, M. (2014). Diagnosing rhinitis during preg- Addis, A., Sharabi, S., & Bonati, M. (2000). Risk classifi cation systems for nancy. Current Allergy and Asthma Reports, 14(9), 458. doi:10.1007/ drug use during pregnancy: Are they a reliable source of information? s11882-014-0458-0 Drug Safety, 23(3), 245–253. doi:10.2165/00002018-200023030-00006 Nezvalová-Henriksen, K., Spigset, O., & Nordeng, H. (2013). Effects of American College of Obstetricians and Gynecologists & American Col- ibuprofen, diclofenac, naproxen, and piroxicam on the course of lege of Allergy, Asthma and Immunology. (2000). The use of newer pregnancy and pregnancy outcome: A prospective cohort study. asthma and allergy medications during pregnancy. Annals of Al- BJOG: An International Journal of Obstetrics and Gynaecology, lergy, Asthma & Immunology: Offi cial Publication of the Ameri- 120(8), 948–959. doi:10.1111/1471-0528.12192 can College of Allergy, Asthma, & Immunology, 84(5), 475–480. Ogbechie-Godec, O. A., & Elbuluk, N. 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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Ruszkiewicz, J. A., Pinkas, A., Ferrer, B., Peres, T. V., Tsatsakis, A., & United States Food & Drug Administration. (2015). FDA drug safety Aschner, M. (2017). Neurotoxic effect of active ingredients in sun- communication: FDA has reviewed possible risks of pain medicine screen products, a contemporary review. Toxicology Reports, 4, use during pregnancy. Retrieved from https://www.fda.gov/Drugs/ 245–259. doi:10.1016/j.toxrep.2017.05.006 DrugSafety/ucm429117.htm Sachdeva, P., Patel, B. G., & Patel, B. K. (2009). Drug use in pregnancy; A United States Food & Drug Administration. (2016). Pregnancy and lac- point to ponder! Indian Journal of Pharmaceutical Sciences, 71(1), tation labeling (drugs) fi nal rule. Retrieved from https://www.fda. 1–7. doi:10.4103/0250-474X.51941 gov/Drugs/DevelopmentApprovalProcess/ DevelopmentResourc- Schaefer, C., Peters, P., & Miller, R. K. (2007). Drugs during pregnancy and es/Labeling/ucm093307.htm lactation: Treatment options and risk assessment (2nd ed.). London, United States Food & Drug Administration. (2017). Two years of PLLR UK: Elsevier Academic Press. implementation. Retrieved from https://www.fda.gov/downloads/ Schonfeld, T., Schmid, K. K., Brown, J. S., Amoura, N. J., & Gordon, B. Drugs/GuidanceComplianceRegulatoryInformation/LawsActsan- (2013). A pregnancy testing policy for women enrolled in clinical dRules/UCM598986.pdf trials. Ethics and Human Research, 35(6), 9–15. United States Food & Drug Administration. (2018). Tips to stay safe Servey, J., & Chang, J. (2014). Over-the-counter medications in preg- in the sun: From sunscreen to sunglasses. Retrieved from https:// nancy. American Family Physician, 90(8), 548–555. www.fda.gov/ForConsumers/ConsumerUpdates/ucm049090.htm Sheffi eld, J. S., Siegel, D., Mirochnick, M., Heine, R. P., Nguyen, C., Berg- Werler, M. M., Mitchell, A. A., Hernandez-Diaz, S., Honein, M. A., & man, K. L., …, Nesin, M. (2014). Designing drug trials: Considerations the National Birth Defects Prevention Study. (2005). Use of over- for pregnant women. Clinical Infectious Diseases: An Offi cial Publication the-counter medications during pregnancy. American Journal of the Infectious Diseases Society of America, 59(Suppl. 7), S437–S444. of Obstetrics & Gynecology, 193(3 Pt 1), 771–777. doi:10.1016/j. doi:10.1093/cid/ciu709 ajog.2005.02.100 Shiny Sherlie, V., & Varghese, A. (2014). ENT changes of pregnancy and Wiles, K., & Banerjee, A. (2016). Acute kidney injury in pregnancy and its management. Indian Journal of Otolaryngology and Head and the use of non-steroidal anti-infl ammatory drugs. The Obstetrician Neck Surgery, 66(Suppl. 1), 6–9. doi:10.1007/s12070-011-0376-6 & Gynaecologist, 18, 127–135. doi:10.1111/tog.12257 Stergiakouli, E., Thapar, A., & Davey Smith, G. (2016). Association of Wilmer, E., Chai, S., & Kroumpouzos, G. (2016). Drug safety: Pregnancy acetaminophen use during pregnancy with behavioral problems rating classifi cations and controversies. Clinics in Dermatology, in childhood: Evidence against confounding. JAMA , 34(3), 401–409. doi:10.1016/j.clindermatol.2016.02.013 170(10), 964–970. doi:10.1001/jamapediatrics.2016.1775 Wilson, J. G. (1977). Current status of teratology. In J. G. Wilson, & F. Tunzi, M., & Gray, G. R. (2007). Common skin conditions during preg- C. Fraser (Eds.), Handbook of teratology (pp. 47–74). New York, NY: nancy. American Family Physician, 75(2), 211–218. United States Plenum. Food & Drug Administration. (1979). Federal register. Retrieved Wylie, B. J., Hauptman, M., Woolf, A. D., & Goldman, R. H. (2016). from http://cdn.loc.gov/service/ll/fedreg/fr044/fr044124/fr044124.pdf Insect repellants during pregnancy in the era of the Zika Vi- United States Food & Drug Administration. (2014a). Questions and answers rus. Obstetrics and Gynecology, 128(5), 1111–1115. doi:10.1097/ on the pregnancy and lactation labeling rule. Retrieved from https:// AOG.0000000000001685 www.fda.gov/drugs/developmentapprovalprocess/development Yau, W. P., Mitchell, A. A., Lin, K. J., Werler, M. M., & Hernández-Díaz, resources/labeling/ucm093311.htm S. (2013). Use of decongestants during pregnancy and the risk of United States Food & Drug Administration. (2014b). Content and format of label- birth defects. American Journal of Epidemiology, 178(2), 198–208. ing for human prescription drug and biological products; Requirements for doi:10.1093/aje/kws427 pregnancy and lactation labeling. Retrieved from https://www.federalregis- Yawn, B., & Knudtson, M. (2007). Treating asthma and comorbid aller- ter.gov/documents/2014/12/04/2014-28241/content-and-format-of-labeling- gic rhinitis in pregnancy. Journal of the American Board of Family for-human-prescription-drug-and-biological-products-requirements-for Medicine, 20(3), 289–298. doi:10.3122/jabfm.2007.03.060144

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Instructions for Taking the CE Test Online Safety of Over-the-Counter Medications in Pregnancy

• Read the article. The test for this CE activity can be Provider Accreditation: taken online at www.nursingcenter.com/ce/MCN. LPD will award 2.0 contact hours for this continuing Tests can no longer be mailed or faxed. nursing education activity. • You will need to create a free login to your personal LPD is accredited as a provider of continuing nursing CE Planner account before taking online tests. Your education by the American Nurses Credentialing Cen- planner will keep track of all your Lippincott Profes- terʼs Commission on Accreditation. sional Development (LPD) online CE activities for you. This activity is also provider approved by the California • There is only one correct answer for each question. A Board of Registered Nursing, Provider Number CEP passing score for this test is 25 correct answers. If you 11749 for 2.0 contact hours. LPD is also an approved pass, you can print your certifi cate of earned contact provider of continuing nursing education by the District of hours and the answer key. If you fail, you have the Columbia, Georgia, and Florida CE Broker #50-1223. option of taking the test again at no additional cost. Payment: • For questions, contact LPD: 1-800-787-8985. • The registration fee for this test is $21.95. Registration Deadline: June 4, 2021. Disclosure Statement: The authors and planners have disclosed no other potential confl icts of interest, fi nancial or otherwise.

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