Prescribing guidelines for ENT medications during pregnancy.Abstract
Profound physiologic changes occur during pregnancy, and they can alter the pharmacodynamics of an administered drug. Almost 85% of women take at least one prescription medication during a pregnancy. Nearly every drug administered to a mother crosses the placenta, and fetal drug levels can reach 50 to 100% of maternal serum concentrations. Because many otolaryngologic conditions are associated with pregnancy, it is essential that otolaryngologists who care for gravid gravid /grav·id/ (grav´id) pregnant.
Carrying eggs or developing young.
gra·vid patients know which drugs are safe and avoid unnecessary, prescriptions so that the best care can be delivered to the pregnant patient without harming her unborn child. In this article, we discuss the relative safety and efficacy of various types of drugs frequently prescribed for pregnant women by otolaryngologists.
Nearly 85% of women will take at least one prescription medication during the course of a pregnancy. (1) According to a large survey conducted by the National Institutes of Health (NIH "Not invented here." See digispeak.
NIH - The United States National Institutes of Health. ), the average pregnant woman takes three or four different drugs, excluding vitamins and mineral supplements. (2) Moreover, 40% of women in the NIH survey took medication during the critical first-trimester period of fetal development.
Many otolaryngologic conditions are associated with pregnancy. Therefore, when caring for gravid patients, otolaryngologists must be aware of maternal and fetal side effects of the medications commonly prescribed in otolaryngology.
Profound physiologic changes occur during pregnancy, and they can alter the pharmacodynamics of an administered drug. Most notable are the changes in maternal blood volume, serum albumin levels, renal excretion, and hepatic metabolism.
During pregnancy, maternal blood volume (i.e., distribution volume) increases by approximately 50% and thus lowers the serum concentrations of drugs. The gravid state results in a gradual decrease in maternal serum albumin, which leads to less protein-drug binding and more free circulating drug, which is the only fraction of a drug that can cross the placenta.
There is a gradual increase in renal function during pregnancy, which results in an augmented clearance rate of those agents that are eliminated primarily by the kidney (e.g., ampicillin and gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, ). (3,4) The changes in hepatic elimination patterns during pregnancy are less consistent. Whether there is an increase or decrease in hepatic metabolism appears to vary from one class of drug to another. (5) Finally, the fetal liver and the placenta have been shown to demonstrate drug metabolism, although they contribute only marginally to the total elimination capacity of drugs by the maternal system.
The capability of producing fetal malformation.
Nearly every drug administered to the mother crosses the placenta, and fetal drug levels can reach 50 to 100% of maternal serum concentrations. (6) When considering the teratogenicity of compounds, the two most important factors are total fetal exposure to a drug and the gestational age of the fetus at first exposure. Teratogenic ter·a·to·gen·ic
Of, relating to, or causing malformations of an embryo or a fetus.
pertaining to or emanating from teratogen. drug exposure around the time of conception and/or implantation (i.e., the first 2 weeks) is likely to result in spontaneous abortion. Teratogen teratogen /ter·a·to·gen/ (ter´ah-to-jen) any agent or factor that induces or increases the incidence of abnormal prenatal development.teratogen´ic
n. exposure during weeks 3 through 10 can result in impaired organogenesis. If the exposure occurs during the early embryo stage (5 weeks), cardiac and central nervous system defects are more likely. Nearer the end of the embryo stage (10 weeks), defects in the palate and ears are more common. After the 10th week, physiologic defects and growth delay are the most common adverse effects, especially when exposure takes place over a sustained period rather than as a single or short-term insult.
Food and Drug Administration
n.pr See Food and Drug Administration.
n.pr the abbreviation for the Food and Drug Administration. risk categories
In response to the thalidomide-induced birth defects that occurred in the early 1960s, the United States government generally prohibited women of child-bearing age from enrolling in most research studies. Although many of these restrictions were eased by most federal research agencies in the 1990s, the NIH and many hospital review boards continue to bar most pregnant women from research protocols. (6) Most drug safety data that apply to pregnancy are based on pregnancy registries, which are maintained by researchers or drug manufacturers, and on research on pregnant animals. Although experiments with animals have provided considerable information regarding the teratogenic effects of drugs, it is not always possible to extrapolate experimental findings from animals to humans.
In 1979, the federal Food and Drug Administration (FDA) introduced regulations that were intended to improve labeling for the use of medications during pregnancy. The FDA created five risk categories that address potential adverse fetal effects, including congenital abnormalities (table 1). The FDA recognizes that the utility of this classification scheme is limited, and it has charged a Pregnancy Labeling Task Force with developing a narrative format that will better assist clinicians in prescribing drugs to pregnant women and in counseling them about fetal risks. All classifications noted in this manuscript are derived from the prescribing information sheets for each particular medication. (7) More up-to-date information can be obtained through the online REPRORISK[R] system from Micromedex (www.micromedex.com/products/reprorisk/), which contains four databases with information on reproductive risk. Additional prescribing guidelines and patient counseling services can be obtained on two other Web sites (www.motherisk.org and www.otispregnancy.org).
Bacterial infections of the head and neck are common during pregnancy, and they often require treatment with antimicrobials. Virtually all antimicrobial agents readily cross the placenta. Thus, there exists the potential for adverse effects on the fetus. Unfortunately, there are few scientific data regarding the use and safety of various antibiotics during pregnancy.
Nevertheless, many of these agents have been used in pregnant women for many years without apparent adverse effects and can, therefore, be prescribed with a great degree of comfort when indicated. These include the penicillins (including those combined with clavulanic acid and sulbactam), the cephalosporins, clindamycin, and certain macrolides (e.g., azithromycin and erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). ), all of which the FDA classifies as category B agents (table 2). Another macrolide, clarithromycin, has been associated with adverse outcomes in animal experiments, and it is listed as a category C drug by its manufacturer.
Other antibiotics that are specifically known to have caused abnormalities in human and/or animal studies, and therefore should be avoided in pregnant patients, include the following agents, which are listed in either category C or D: the aminoglycosides, the quinolones, the sulfonamides Sulfonamides Definition
Sulfonamides are medicines that prevent the growth of bacteria in the body.
Sulfonamides are used to treat many kinds of infections caused by bacteria and certain other microorganisms. , the tetracycline derivatives, chloramphenicol chloramphenicol (klōr'ămfĕn`əkŏl'), antibiotic effective against a wide range of gram-negative and gram-positive bacteria (see Gram's stain). It was originally isolated from a species of Streptomyces bacteria. , and vancomycin.
During pregnancy, elevated cortisol levels place the patient in a relatively immunosuppressed state that can allow for the reactivation of latent viral infections. Antiherpetic formulations (e.g., acyclovir, famciclovir, and valacyclovir) have exhibited no teratogenic effects in animal or human pregnancies, and they are listed in category B.
Both acetaminophen and aspirin are believed to be safe for use during the first two trimesters. However, the use of aspirin (category C) closer to term may result in excessive bleeding in both the mother and fetus. (8) Acetaminophen, which lacks antiplatelet an·ti·plate·let
Acting against or destroying blood platelets.
directed against or destructive to blood platelets; inhibiting platelet function. activity, is a category B drug and has become the antipyretic antipyretic /an·ti·py·ret·ic/ (-pi-ret´ik)
1. relieving or reducing fever.
2. an agent that so acts.
An agent that reduces or prevents fever. and analgesic of choice during pregnancy. Of course, ingestion of large doses of acetaminophen or the protracted pro·tract
tr.v. pro·tract·ed, pro·tract·ing, pro·tracts
1. To draw out or lengthen in time; prolong: disputants who needlessly protracted the negotiations.
2. use of this drug may result in renal and hepatic toxicity in the adult and, at least theoretically, could cause the same complications in the fetus.
Ibuprofen and naproxen, two common nonsteroidal anti-inflammatory drugs Nonsteroidal Anti-Inflammatory Drugs Definition
Nonsteroidal anti-inflammatory drugs are medicines that relieve pain, swelling, stiffness, and inflammation. , have not been associated with an increased risk of congenital malformations, although ibuprofen has been reported to be associated with decreased amniotic fluid volume. (9) Moreover, because they are both prostaglandin synthetase synthetase /syn·the·tase/ (-the-tas) a term used in the names of some of the ligases, no longer favored because of its similarity to synthase and its emphasis on reaction products.
n. inhibitors, ibuprofen and naproxen could, in theory, cause premature closure of the ductus arteriosus. Therefore, they should be avoided after 34 weeks of gestation. They are both listed in category B. The newer cyclo-oxygenase-2 inhibitors (e.g., celecoxib and rofecoxib) fall into category C and should be avoided.
Narcotic analgesics (category C) should be reserved for those patients whose pain is refractory to more conservative approaches. Codeine codeine (kō`dēn), alkaloid found in opium. It is a narcotic whose effects, though less potent, resemble those of morphine. An effective cough suppressant, it is mainly used in cough medicines. Like other narcotics, codeine is addictive. , hydrocodone, oxycodone oxycodone /oxy·co·done/ (-ko´don) an opioid analgesic derived from morphine; used in the form of the hydrochloride and terephthalate salts.
n. , and morphine may be used, but they carry the potential to cause dependence and withdrawal symptoms in the fetus and newborn if they are abused or even used regularly. (8) Fetal respiratory depression is another potential complication of narcotics if they are used around the time of delivery.
Corticosteroids cross the placenta, and animal studies have suggested that these compounds are teratogenic when they are administered systemically, especially during the first two trimesters. Therefore, all glucocorticoid glucocorticoid /glu·co·cor·ti·coid/ (-kor´ti-koid)
1. any of the group of corticosteroids predominantly involved in carbohydrate metabolism, and also in fat and protein metabolism and many other activities (e.g. formulations are listed in category C. Nonetheless, corticosteroids are often prescribed during premature labor to stimulate fetal lung maturation. (10) To date, no evidence of any apparent adverse fetal effects has been noted. Most experts agree that corticosteroids can be taken safely during the third trimester when medically indicated for conditions such as Bell's palsy, laryngeal edema, or sudden sensorineural hearing loss Sensorineural hearing loss
Hearing loss caused by damage to the nerves or parts of the inner ear governing the sense of hearing.
Mentioned in: Tinnitus
sensorineural hearing loss .
Prednisone is regarded as the oral steroid of choice, while dexamethasone dexamethasone /dex·a·meth·a·sone/ (dek?sah-meth´ah-son) a synthetic glucocorticoid used primarily as an antiinflammatory in various conditions, including collagen diseases and allergic states; it is the basis of a screening test in the is a commonly used intravenous formulation. Hilsinger et al reported that two-thirds of pregnant women with Bell's palsy received steroids during their third trimester, and in no case were there any fetal side effects. (11) In that study, the authors recommended using up to 60 mg of prednisone for 5 days and then tapering the dosage over the following 5 days.
Decongestants Decongestants Definition
Decongestants are medicines used to relieve nasal congestion (stuffy nose).
A congested or stuffy nose is a common symptom of colds and allergies.
Upper respiratory infections, sinusitis, rhinitis, and nasal congestion are relatively common during pregnancy. Decongestants may be administered either topically or systemically to provide symptomatic relief. According to their manufacturers, systemic decongestants carry a theoretical risk for decreasing uterine blood flow, but no data to confirm this have been published. Nonetheless, the use of systemic vasoconstrictors should be avoided in the gravid patient with suspected placental insufficiency and in the presence of pregnancy-related hypertension.
Although pseudoephedrine pseudoephedrine /pseu·do·ephed·rine/ (-e-fed´rin) one of the optical isomers of ephedrine; used as the hydrochloride or sulfate salt as a nasal decongestant.
n. is in category C, it has been recommended as the oral decongestant decongestant /de·con·ges·tant/ (de?kon-jes´tint)
1. tending to reduce congestion or swelling.
2. an agent that so acts.
n. of choice in a position statement released in 2000 by the American College of Obstetrics and Gynecology obstetrics and gynecology
Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system. and the American College of Allergy, Asthma, and Immunology. (12) Epidemiologic studies of more than 1,000 first-trimester human pregnancies exposed to pseudoephedrine indicate that it is not associated with congenital anomalies. (13) Topical sympathomimetic sympathomimetic /sym·pa·tho·mi·met·ic/ (-mi-met´ik)
1. mimicking the effects of impulses conveyed by adrenergic postganglionic fibers of the sympathetic nervous system.
2. an agent that produces such an effect. sprays (e.g., oxymetazoline oxymetazoline /oxy·met·az·o·line/ (-met-az´o-len) an adrenergic used as the hydrochloride salt as a vasoconstrictor to reduce nasal or conjunctival congestion.
n. and phenylephrine phenylephrine /phen·yl·eph·rine/ (-ef´rin) an adrenergic used as the hydrochloride salt for its potent vasoconstrictor properties.
n. ) may also be used for relief of nasal congestion, but they carry a risk of causing rebound rhinitis medicamentosa.
Antihistamines Antihistamines Definition
Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H1 and allergy medications
Allergic rhinitis may develop or worsen during pregnancy. The treatment of pregnancy-associated allergic rhinitis begins with environmental control. Chlorpheniramine (category B) is generally the antihistamine antihistamine (ăn'tĭhĭs`təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine. of choice for use during pregnancy (table 3). (14) If sedation becomes an issue, cetirizine and loratadine (both category B) are approved for use in pregnant women, but ideally only after the first trimester. (14) Fexofenadine and azelastine are in category C and should be avoided.
Leukotriene inhibitors (e.g., montelukast montelukast /mon·te·lu·kast/ (mon?te-loo´kast) a leukotriene antagonist used as the sodium salt in prophylaxis and chronic treatment of asthma.
n. and zafirlukast zafirlukast /za·fir·lu·kast/ (zah-fir´loo-kast) a leukotriene receptor antagonist used as an antiasthmatic agent.
n. ) are in category B. Manufacturers of leukotriene inhibitors maintain active registries to monitor the pregnancy outcomes of women who are exposed to these relatively new medications.
Patients with chronic allergic symptoms can safely us intranasal cromolyn (category B) and topical intranasal steroid preparations, which, although they are in category C, should not reach plasma levels high enough to affect the growing fetus. Of the topical intranasal steroids, mometasone is essentially free of systemic absorption (0.1% bioavailability) and is quantitatively the safest of these preparations during pregnancy. (15) Finally, patients who are undergoing immunotherapy for allergy hyposensitization hyposensitization
decreasing the hypersensitivity response to allergens by exposure, usually as intradermal injections, to minute but increasing doses of the allergens. A treatment modality for atopic dermatitis, most commonly in dogs, cats and horses. Called also desensitization. can be continued on these injections during pregnancy. (16) However, allergy testing during pregnancy should not be undertaken because of the potential risk of an anaphylactic response. (17)
Gastroesophageal reflux occurs with a much higher frequency during pregnancy, and it is most prevalent during the third trimester. (18) The [H.sub.2] receptor antagonists cimetidine, famotidine, and ranitidine are all category B agents and are preferred over nizatidine, which is listed in category C (table 4).
The proton-pump inhibitors esomeprazole, lansoprazole, pantoprazole, and rabeprazole are all in category B. Omeprazole is the only member of this class that carries a category C listing.
Antivertigo and antinausea agents
Isolated episodes of vertigo and exacerbations of preexisting pre·ex·ist or pre-ex·ist
v. pre·ex·ist·ed, pre·ex·ist·ing, pre·ex·ists
To exist before (something); precede: Dinosaurs preexisted humans.
v.intr. Meniere's disease are common during pregnancy. Conservative management with antiemetics and vestibular suppressants is the treatment of choice during pregnancy. Dimenhydrinate dimenhydrinate /di·men·hy·dri·nate/ (di?men-hi´dri-nat) an antihistamine used as an antiemetic, particularly in the treatment of motion sickness.
n. and meclizine meclizine /mec·li·zine/ (mek´li-zen) an antihistamine used as the hydrochloride salt as an antinauseant in motion sickness and to manage vertigo associated with disease affecting the vestibular system. are category B drugs and are especially safe when administered in the smaller doses required to control vertigo and the accompanying nausea. Both ondansetron and metaclopramide (category B) are safe and effective antinausea medications, and they should be used instead of prochlorperazine prochlorperazine /pro·chlor·per·a·zine/ (pro?klor-per´ah-zen) a phenothiazine derivative, used as the base or the edisylate or maleate salts as an antiemetic and antipsychotic.
n. (category C) and diazepam diazepam /di·az·e·pam/ (di-az´e-pam) a benzodiazepine used as an antianxiety agent, sedative, antipanic agent, antitremor agent, skeletal muscle relaxant, anticonvulsant, and in the management of alcohol withdrawal symptoms. (category D). Diazepam carries an increased risk of congenital malformations when used during the first trimester.
Table 1. FDA labeling categories for medication use during pregnancy Category Risk A Controlled human studies have failed to demonstrate a risk to the fetus. B Either animal studies have not demonstrated a fetal risk but there have been no controlled human studies, or animal studies have shown an adverse effect that has not been confirmed in controlled human studies. C Either animal studies have revealed adverse effects and there have been no controlled human studies, or studies in women or animals are not available. Use only if the potential benefit outweighs the potential risk to the fetus. D There is positive evidence of human fetal risk. Use only in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective. X They use of such a drug during pregnancy is contraindicated. Table 2. FDA classification of selected antimicrobials Category Drug B Azithromycin Cephalosporins Clindamycin Erthromycin Penicillins (including amoxicillin/ clavulanic acid and ampicillin/ sulbactam) C/D Aminoglycosides Chloramphenicol Clarithromycin Quinolones Sulfonamides Tetraycyclines derivatives Vancomycin Table 3. FDA classification of selected antihistamines Category Drug B Azatadine Cetirizine Chlorpheniramine Clemastine Dimenhydrinate Diphenhydramine Loratadine C Azelastine Brompheniramine Fexofenadine Hydroxyzine Promethazine Table 4. FDA classification of selected gastrointestinal agents Category Drugs B Cimetidine Esomeprazole Famotidine Lansoprazole Pantoprazole Rebeprazole Ranitidine C Nizadine Omeprazole
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From the Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University It began as Jefferson Medical College in 1824. On July 1, 1969 the institution officially became Thomas Jefferson University.
The university is made up of three colleges:
Reprint requests: Edmund A. Pribitkin, MD, Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, 925 Chestnut St., Sixth Floor, Philadelphia, PA 19107. Phone: (215) 955-6784; fax: (267) 200-0820; e-mail: Edmund.Pribitkin@jefferson.edu
Originally presented at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery; Sept. 9-12, 2001; Denver.