Drugs And Pregnancy Part 28

Isotretinoin (Accutane) and etretinate (Tegison) are oral preparations, and tretinoin (Retin-A) is a topical agent.

Isotretinoin Except for thalidomide, isotretinoin is the drug with greatest teratogenic potential of all the medications to which pregnant woman may be exposed in the first trimester. The 'retinoic acid embryopathy' is a distinct pattern of anomalies that has been described in several reports encompa.s.sing over 80 offspring of women exposed to this agent during Vitamin A derivatives Vitamin A derivatives 241.

Box 13.1 Characteristic anomalies in offspring of mothers exposed to isotretinoin (accutane) exposed to isotretinoin (accutane) Anotia Cleft palate Microtia Cardiovascular defects Eye anomalies Thymic abnormalities Central nervous system Limb reduction anomalies Micrognathia the first trimester of pregnancy (Coberly et al et al., 1996; Lammer, 1985, 1987; Medical Letter, 1983; MMWR, 1984; Rizzo et al et al., 1991; Rosa, 1983, Rosa et al et al., 1986; Thompson and Cordero, 1989). Among 94 infants who were born to women who used isotretinoin in early pregnancy, 28 percent had major congenital anomalies (Chen et al et al., 1990; Dai et al et al., 1992). In this series, 18 percent of the pregnancies resulted in spontaneous abortions. The constellation of anomalies is called retinoic acid embryopathy (Box 13.1). Postnatal intellectual development of infants apparently unaffected (without major or minor congenital anomalies) at birth was subnormal at 5 years of age (IQ less than 85) in 47 percent of 31 (Adams and Lammer, 1993; Adams et al et al., 1991, 1992).

Clinicians are concerned about the risks a.s.sociated with pregnancy among patients who recently discontinued taking isotretinoin. This agent has a short half-life of 1012 h, and the risk of congenital anomalies is not increased in the offspring of women who discontinued this medication within days of conception (Dai et al et al., 1989). The terminal elimination half-life of isotretinoin is 96 h.

Major and minor anomalies were found in animal teratology studies with isotretinoin, similar to the pattern of malformations seen in human retinoic acid embryopathy (Agnish et al et al., 1984; Kamm, 1982; Kochhar and Penner, 1987; Kochhar et al et al., 1984; Webster et al et al., 1986).

Etretinate Etretinate is an oral retinoid used to treat psoriasis. A significant complication of use of this medication in women of reproductive age is that it may be detected in serum at therapeutic levels for at least 2 years after cessation of therapy (DiGiovanna et al et al., 1984).

The manufacturer reports that etretinate is detected at near-therapeutic levels for 37 years following cessation of therapy (Hoffman-LaRoche, personal communication). No epidemiological studies have been published of etretinate use by pregnant women. Of 43 pregnancies exposed to etretinate, there were 14 pregnancy terminations and five had malformations similar to retinoid embryopathy. Twenty-nine live-born infants were reported, of whom six had major congenital anomalies (Geiger et al et al., 1994). Case reports are published of neural tube, other central nervous system, and limb reduction defects in the offspring of mothers exposed to this drug during embryogenesis (Happle et al et al., 1984; Lammer, 1988; Rosa et al et al., 1986; Verloes et al et al., 1990). In one published case report, a fetus with a hypoplastic leg was born to a mother who conceived several months after discontinuing etretinate (Grote et al et al., 1985).

Conceptions after etretinate exposure may pose serious risks of birth defects because the drug has an indeterminate half-life. although the elimination half-life is published as 242 242 Use of dermatologics during pregnancy 100 to 120 days for etretinate, therapeutic levels of the drug have been detected as long as 2 years after discontinuation. The manufacturer has offered pro bono testing for etretinate in women of reproductive age who used this drug. In the ideal situation, this should be done preconceptually.

Animal teratology studies have produced teratogenic effects with etretinate similar to those observed in the retinoic acid embryopathy, such as limb, genitourinary, neural tube, and cloacal defects (Mesrobian et al et al., 1994). The implication of this with regard to human teratogenicity is unknown. Obviously, this drug should not be used for psoriasis during pregnancy.

Acitretin Acitretin is an active metabolite of etretinate. It has an elimination half-life of approximately 60 h, as opposed to 100120 days for etretinate. Eight cases of acitretin exposure during pregnancy have been published, and there was one infant with multiple congenital anomalies that were consistent with the retinoic acid embryopathy, and one case of congenital hearing deficit (Geiger et al et al., 1994). One case report of an infant born with features of the retinoic acid embryopathy was published. At 18 months' follow-up, the infants had microcephaly and significant neurodevelopmental delay (Barbero et al et al., 2004). Notably, the dose of acitretin that the mother took from conception to the 10th week of pregnancy was low (10 mg/day) compared to other reports (e.g., Geiger et al et al., 1994). Among 52 pregnancies where exposure to acitretin occurred after 6 weeks postconception, no congenital anomalies were observed (Geiger et al et al., 1994). Animal models of acitretin teratogenicity have produced anomalies consistent with the retinoic acid embryopathy (Lofberg et al et al., 1990; Turton et al et al., 1992).

Caution: Acitretin can be metabolized back to etretinate through re-esterification.

Therefore, it would be prudent to test serum for etretinate in addition to acitretin (Almond-Roesler and Orfanos, 1996).

Tretinoin Tretinoin (Retin-A) or retinoic acid is prepared as a liquid, gel, or cream for local application in the treatment of acne vulgaris. Minimal amounts of this topical agent are absorbed systemically, and the theoretical teratogenic risk of tretinoin appears quite low (Kligman, 1988). The drug is poorly absorbed topically, and skin is capable of metabolizing this agent, resulting in none to minimal amounts acc.u.mulating in maternal serum (DeWals et al et al., 1991; Kalivas, 1992; Nau, 1993; Nau et al et al., 1994).

Major congenital anomalies occurred among 2 percent of 212 pregnancies exposed to tretinoin during the first trimester, compared to 3 percent of controls (Jick et al et al., 1993). In another study of 112 infants born to women who received prescriptions for tretinoin, there was no increased frequency of major anomalies (Rosa, personal communication, cited in Briggs et al et al., 2005). In contrast, Johnson and colleagues (1994) reported 45 pregnancies in which tretinoin was used, and one infant had features of the retinoid embryopathy.

However, the mother of the affected infant had also taken Accutane during pregnancy.

Major structural malformations in 106 infants and minor anomalies in a subset of 62 infants were examined by an experienced dysmorphologist to test the hypothesis that Antibiotics Antibiotics 243.

topical tretinoin during the first trimester might pose a risk for birth defects similar to those a.s.sociated with the retinoic acid embryopathy. No differences in major or minor anomaly frequencies between the tretinoin and control groups were found (Loureiro et et al al., 2005), offering rea.s.surance for patients exposed to the drug during the first trimester.

Tretinoin administered to pregnant animals during embryogenesis in doses up to 50 times those used in humans was not a.s.sociated with congenital anomalies or adverse fetal effects. In summary, tretinoin does not appear to be a.s.sociated with an increased risk of congenital anomalies in infants born to women who used the drug as directed as directed during pregnancy. ('As directed' is inserted here because we have encountered patients who ate took orally tretinoin cream.) during pregnancy. ('As directed' is inserted here because we have encountered patients who ate took orally tretinoin cream.) ANTIBIOTICS.

Topical antibiotics are adjunct therapy for acne and for other skin infections (Box 13.2) and include: clindamycin, erythromycin, meclocycline, tetracycline, sulfa-drug creams, and lotions. It is unlikely that absorption of topical antibiotics through the skin results in significant serum concentration, or would be a.s.sociated with an increased risk of congenital anomalies. Unlike oral or parenteral tetracycline, topical preparations are not a.s.sociated with yellow-brown discoloration of the teeth.

Other topical antimicrobial agents are used to treat minor skin infections and include neomycin (usually in combination with polymixin B, bacitracin, gramicidin, and/or hydrocortisone). Some combinations of these agents are used to treat ophthalmic infections. No adequate human reproduction studies of polymixin B are available. The frequency of congenital anomalies was not increased among 30 or 61 infants whose mothers took neomycin or gramicidin, respectively, during early pregnancy (Heinonen et al et al., 1977).

Other topical antimicrobials used to treat local skin infections include chloramphenicol, gentamicin, and metronidazole. When applied topically, physiologically significant amounts of these agents are not likely to be absorbed systemically. These agents are discussed in other chapters, and do not increase the risk of congenital anomalies.

Mupirocin (Bactroban) is a topical antibacterial used to treat skin infections and fol-liculitis. Mupirocin was not teratogenic in several animal studies, but no human studies of this drug have been published.

Box 13.2 Topical antibacterial agents to treat of acne and minor skin infections skin infections Chloramphenicol Mupirocin Clindamycin Neomycin Clioquinol Neomycin plus polymixin B, bacitracin, Erythromycin gramicidin, and hydrocortisone Gentamicin Silver sulfadiazine Meclocycline Sulfur Metronidazole Tetracycline 244.

Use of dermatologics during pregnancy Clioquinol is an antibacterial and antifungal agent. No studies are published of the use of this drug during human or animal pregnancy.

Mafenide (Sulfamylon) and silver sulfadiazine (Silvadene, Thermazene, Flint SSD, Sildimac) are topical antibacterial and antifungal agents used to treat infections secondary to skin burns. No human studies have been published on mafenide or silver sulfadiazine. No animal teratology studies of mafenide are available. According to its manufacturer, silver sulfadiazine was not teratogenic in animal studies (unpublished).

ANTIFUNGALS.

Several topical antifungal agents are used to treat vaginitis (butoconazole, clotrimazole, econazole, miconazole, nystatin, and terconazole). Some systemic preparations are also used for vaginitis: amphotericin B, griseofulvin, and ketoconazole. These agents are discussed in Chapter 2. Systemic antifungals are not a.s.sociated with an increased risk of birth defects, except for griseofulvin (conjoined twinning is hypothesized with griseofulvin; see Chapter 2). Topical application of these agents on parts of the body is not a.s.sociated with an increased frequency of congenital anomalies or other medical complications.

Ciclopirox, haloprogin, naftifine, and tolnaftate are antifungals used to treat tinea corpus, cruris, pedis, and versicolor. No human studies of these drugs during pregnancy have been published, but their manufacturers report that these antifungal agents were not teratogenic in several animal studies.

Tolnaftate (Aftate, Genaspore, NP27, Tinactin, Ting, Zeasorb-AF) is another topical antifungal, available as a powder, aerosol solution, spray solution, gel, or cream.

Applied topically, it is used to treat tinea captis, corporis, cruris, versicolor, pedis, and barbae. No human or animal reproduction studies are available.

ANTIPARASITICS.

Topical antiparasitics are discussed in detail in Chapter 2.

KERATOLYTICS, ASTRINGENTS, AND DEFATTING AGENTS.

Nearly all of the large number of agents in this category may be purchased over the counter and are used to treat acne and related dermatologic conditions (Box 13.3). No human reproduction studies for any of these agents have been published and the same is true for animal data. Benzoyl peroxide, resorcinol, and salicylic acid have significant potential for systemic absorption, but no cases of adverse fetal effects are doc.u.mented related to the topical route of delivery. Salicylates are discussed in detail in Chapter 8, a.n.a.lgesics during pregnancy. Manufacturer data on salicylic acid was reported to be teratogenic in animals when used in large doses, several times that used in humans.

ANTISEBORRHEIC AGENTS.

Antiseborrheic agents are used primarily in the treatment of dandruff or seborrheic dermat.i.tis (Box 13.4). The mechanism of action is unknown. No animal or human repro-Adrenocorticosteroids 245.

Box 13.3 Ketatolytic, defatting, and astringent agents Alcohol and sulfur (Liquimat, Transact, Xerac) Alcohol and sulfur (Liquimat, Transact, Xerac) Alcohol and acetone (Seba-Nil, Tyrosum) Benzoyl peroxide (Clearasil, Oxy-10, Acne-10, Benoxyl, Del-Aqua, Desquam, Dry & Clear, Fostex, Neutrogena, Acne Mask, Zeroxin-10) Resorcinol (RA) Resorcinol and sulfur (Acnomel, Clearsil, Rezamid, Sulforcin) Salicylic acid (numerous brand names) Salicylic acid and sulfur (numerous brand names) Salicylic acid, sulfur and coal tar (Sebex-T, Sebutone, Vanseb-T) Box 13.4 Antiseborrheic agents Box 13.4 Antiseborrheic agents Chloroxine (Capitrol) Coal tar (numerous brands) Pyrithione (Danex, Head & Shoulders, Sebex, Sebulon, Zinolon) Salicylic acid (numerous brands) Selenium sulfide (Episel, Exsel, Glo-Sel, Selsun) duction studies have been published. It is very unlikely that these agents have any effect on prenatal development because they are not absorbed systemically. Coal tar and salicylic acid are often used in combination with other agents, such as sulfa, and in combination with one another to treat seborrhea and seborrheic dermat.i.tis.

ADRENOCORTICOSTEROIDS.

Numerous topical adrenocorticosteroids are used to treat dermatologic disorders (Box 13.5) and are usually used to treat localized dermat.i.tis with a.s.sociated inflammation and pruritis.

No studies in pregnant women using topical steroids have been published. According to the manufacturer, however, several of these agents may be teratogenic in laboratory animals. Topical steroids are very unlikely to be a.s.sociated with significant risk to the human fetus, except triamcinolone (see below).

Systemic adrenocorticosteroids are sometimes indicated to treat dermatologic diseases and there is a small collection of these agents (Box 13.6). Prednisone and prednisolone Box 13.5 Topical adrenocorticoids for dermatological conditions Box 13.5 Topical adrenocorticoids for dermatological conditions Alclometasone Alclometasone Desoximetasone Flurandrenolide Amcinonide Dexamethasone Halcinonide Betamethasone Diflurasone Hydrocortisone Clobetasol Flumethasone Methylprednisolone Clocortolone Fluocinolone Mometasone Desonide Fluocionide Triamcinolone 246.

Use of dermatologics during pregnancy Box 13.6 Commonly used systemic adrenocorticoids Betamethasone Methylprednisolone Cortisone Prednisone Dexamethasone Prednisolone Hydrocortisone Triamcinolone are the two most commonly used systemically of this drug cla.s.s. The frequency of congenital anomalies was not increased among 43 infants born to women who took prednisone during early pregnancy (Heinonen et al et al., 1977). Perinatal deaths were increased in frequency among infants born to women who took this steroid throughout pregnancy, but the disease being treated (e.g., lupus) may in itself be etiologic, rather than prednisone per se per se (Warrell and Taylor, 1968). Fetal growth r.e.t.a.r.dation was a.s.sociated with prednisone use during gestation by one research group (Reinisch (Warrell and Taylor, 1968). Fetal growth r.e.t.a.r.dation was a.s.sociated with prednisone use during gestation by one research group (Reinisch et al et al., 1978), but not several others (Lee et al et al., 1982; Walsh and Clark, 1967).

Prednisone and prednisolone Prednisone and prednisolone are active adrenoglucocorticoids. Prednisolone is an active metabolite of prednisone. Numerous animal studies reported an increase in the frequency of cleft palate with prednisolone (as well as other steroids) when given in large doses (e.g., Ballard et al et al., 1977; Pinsky and DiGeorge, 1965; Shah and Killistoff, 1976; Walker, 1967).

The a.s.sociation between oral clefts and prednisone exposure was a.s.sessed among humans using data from well-regarded casecontrol studies (Carmichael and Shaw, 1999; Rodriguez-Pinilla and Martinez-Frias, 1998) and it was concluded that the risk of nonsyndromic cleft palate may be a.s.sociated with prednisone/prednisolone and other glucocorticoid exposure during embryogenesis. However, if such a risk exists it is less than 1 percent (Shepard et al et al., 2002). Note that most oral clefts can be surgically corrected and this isolated defect is not a.s.sociated with other physical or mental abnormalities.

Hydrocortisone Hydrocortisone, another glucocorticoid, is the main steroid produced by the adrenal glands. The frequency of congenital anomalies was not increased among infants whose mothers took hydrocortisone during early pregnancy, including the first trimester (Heinonen et al et al., 1977). As with prednisone/prednisolone, an increased frequency of cleft palate was found among the offspring of experimental animals whose mothers were given hydrocortisone during embryogenesis (Chaudhry and Shah, 1973; Harris et al et al., 1980). This is similar to experimental findings with other glucocorticoids. It is possible that a small risk for cleft palate in humans exists with hydrocortisone use during embryogenesis, but it is likely that the risk is small at less than 1 percent (Shepard et al et al., 2002).

Adrenocorticosteroids 247.

Dexamethasone and betamethasone These agents (dexamethasone and betamethasone) are glucocorticoids that are closely related to prednisone (see Prednisone and prednisolone above). No human teratology studies of dexamethasone or betamethasone have been published. These drugs are commonly used in the late second and early third trimesters to promote fetal lung maturity, preventing respiratory distress syndrome (Collaborative Group on Antenatal Steroid Therapy, 1984; Liggins, 1976; Liggins and Howie, 1974). Consistent with other corticosteroids, dexamethasone and betamethasone are reported to be a.s.sociated with an increased frequency of cleft palate in the offspring of pregnant animals that received these agents during embryogenesis (Mosier et al et al., 1982; Pinsky and DiGeorge, 1965).

Fetal body and organ weight were decreased in several animal studies with exposure to these glucocorticoids during pregnancy (Barrada et al et al., 1980; Epstein et al et al., 1977; Johnson et al et al., 1981; Mosier et al et al., 1982). As with other glucocorticoids, it is possible that a small risk for cleft palate in humans exists with dexamethasone and betamethasone use during early pregnancy. However, the risk is very likely small at less than 1 percent (Shepard et al et al., 2002).

Triamcinolone No human epidemiological studies of triamcinolone use during early pregnancy have been published. The published casecontrol studies are confounded and it is not possible to interpret them for triamcinolone exposures. The cause of concern for triamcinolone exposure during embryogenesis is an increased frequency of congenital anomalies found in offspring of three species of nonhuman primates that received this corticosteroid during embryogenesis (Bacher and Michejda, 1988; Hendrickx and Tarara, 1990; Hendrickx et al et al., 1980; Jerome and Hendrickx, 1988; Parker and Hendrickx, 1983). The collection of congenital anomalies included neural tube defects, craniofacial malformations, and skeletal anomalies. Therefore, triamcinolone should be avoided during pregnancy, especially during the first trimester (Friedman and Polifka, 2006).

Triamcinolone will most probably be a.s.sociated with an increased risk of birth defects in humans when these studies are reported. This warning is issued to attempt a reduction of the number of infants who will be damaged, i.e., exposed to this drug, before official warnings are issued.

Cortisone The risk of congenital anomalies among women who used cortisone during pregnancy and its possible adverse fetal effects cannot be a.s.sessed with the available published data. Among only 34 infants exposed to cortisone during early pregnancy, the frequency of congenital anomalies was not increased (Heinonen et al et al., 1977). Cortisone is in the drug cla.s.s (glucocorticoids) noted above to be a.s.sociated with an increased frequency of cleft palate in several animal models, including nonhuman primates (Biddle and Fraser, 1976; Walker, 1971). The nonhuman primate a.s.sociation, even with small sample sizes, is an ominous indicator. Based mostly on primate data, these agents will predictably be shown to be a.s.sociated with an increased frequency of isolated cleft palate in human 248 248 Use of dermatologics during pregnancy infants exposed to glucocorticoids during embryogenesis. However, the risk will be small at less than 1 percent (Shepard et al et al., 2002).

Glucocorticoids summary In summary, limited human data are published of adrenocorticosteroid use during early human pregnancy and possible a.s.sociation with congenital anomalies or other possible adverse fetal effects. Although these agents were used for many years in pregnant women without apparent adverse effects, no systematic studies are available. Recent a.n.a.lyses based upon reputable casecontrol studies indicate that a low risk (< 1="" percent)="" for="" cleft="" palate="" may="" be="" a.s.sociated="" with="" glucocorticoid="" exposure="" during="" the="" first="">

Triamcinolone effects are possibly more severe, suggesting that it would be prudent to avoid this drug during pregnancy especially during early gestation. However, the consequence of not treating certain conditions during pregnancy, such as systemic lupus erythematosus and asthma, generally outweigh any theoretical risk of these medications.

Failure to treat lupus and asthma during pregnancy may result in congenital heart block or maternal death, respectively.

Follow-up studies of children whose mothers received betamethasone and dexamethasone are rea.s.suring because they show no growth and development deficits. Emphasis should be placed on the <1 percent="" of="" infants="" born="" following="" exposure="" during="" the="" first="" trimester="" who="" may="" have="" isolated="" cleft="" palate.="" among="" infants="" exposed="" to="" triamcinolone="" during="" the="" first="" trimester,="" a="" cl.u.s.ter="" of="" congenital="" anomalies="" may="" occur="" given="" the="" evidence="" from="" nonhuman="" primate="" studies.="" these="" data="" suggest="" that="" a="" 'fetal="" triamcinolone="" syndrome'="" will="" be="" discovered="" that="" comprises="" debilitating="" congenital="" anomalies="" such="" as="" neural="" tube="" defects,="" characteristic="" facies,="" and="" skeletal="">

Therefore, triamcinolone and other glucocorticoids should be avoided in early pregnancy (first trimester) if possible.

OTHER AGENTS.

Anthralin Anthralin (Anthra-Derm, Drithocreme, Lisan) is a topical antipsoriatic agent. It is also used as a hair growth stimulant. No animal or human reproduction studies have been published. Based upon related medication and the a.s.sumption of topical administration, a panel of experts inferred that if there is any risk of congenital anomalies a.s.sociated with first-trimester exposure to anthralin, it must be very small (Friedman and Polifka, 2006). This may be interpreted to mean that the risk may be so small that it is indis-cernible from the background risk of congenital anomalies (3.55 percent).

Methotrexate Methotrexate, a folate antagonist, is used most frequently as an antineoplastic agent, but is effective in the treatment of psoriasis. It is similar to the well-known teratogen, aminopterin (see Chapter 7, Antineoplastic drugs during pregnancy). Anomalies a.s.sociated with methotrexate and aminopterin include ossification and skeletal anomalies, Special considerations Special considerations 249.

hydrocephalus, and cleft palate (Milunsky et al et al., 1968; Reich et al et al., 1977; Warkany, 1978). Methotrexate should not be used to treat psoriasis during pregnancy, but its benefits in the treatment of leukemia and other neoplastic diseases may outweigh its risk (especially after the first trimester). For dermatologic maladies, other less potentially dangerous therapies are available.

Podophyllin The topical chemical compound, podophyllin, is used primarily to treat condyloma ac.u.minata. The formulation used to treat condyloma is a solution of 20 percent podophyllin solution in tincture of benzoin. Use of podophyllin during pregnancy has been a.s.sociated with significant edema, skin irritation, and discomfort. The frequency of birth defects was not increased in frequency among 14 infants whose mothers used podophyllin during the first trimester (Heinonen et al et al., 1977), but this sample was too small to interpret. Several anecdotal reports of maternal and fetal toxicity include a case of fetal demise in a mother who experienced systemic toxicity following the topical application of podophyllin (Gorthey and Krebs, 1954) and others that reported similar adverse effects (Chamberlain et al et al., 1972; Slater et al et al., 1978).

One case report of major congenital anomalies a.s.sociated with podophyllin has been published (Karol et al et al., 1980), but a causal link cannot be inferred from a case report.

Nonetheless, it seems prudent to avoid use of this agent during pregnancy because safer therapies (e.g., laser removal of warts) are of equal efficacy (see Condyloma under Special Considerations below).

Trichloroacetic acid Trichloroacetic acid (TCA) is another topical chemical compound used to treat condyloma ac.u.minata. It is a caustic and astringent agent that primarily causes sloughing of the skin. Among rats fed TCA during embryogenesis, the rate of congenital heart defects was increased in one study (Smith et al et al., 1989) and replicated in another (Johnson et al et al., 1998).

SPECIAL CONSIDERATIONS.

Dermatologic diseases in most pregnant women rarely require emergency or extensive therapy during the first trimester. Most conditions can be treated with topical agents with little systemic effects.

Acne and psoriasis Acne is common in young women and young gravidas. In contrast, psoriasis occurs infrequently during pregnancy (fewer than 1 percent of gravidas), and may actually improve during pregnancy. Three vitamin A congeners, isotretinoin (for acne), acitretin (for psoriasis), and etretinate (for psoriasis) are contraindicated for use during pregnancy (Table 13.1). Women inadvertently exposed to these agents during early pregnancy should be counseled regarding the serious risk of major congenital anomalies in 250 250 Use of dermatologics during pregnancy Table 13.1 Teratogen Information System (TERIS) risk for congenital anomalies and Food and Drug Administration (FDA) pregnancy risk category Drugs Teratogen Information System (TERIS) risk for congenital anomalies and Food and Drug Administration (FDA) pregnancy risk category Drugs TERIS risk FDA pregnancy risk category rating Acitretin High Xm Aminopterin Moderate to high X.

Amphotericin B Undetermined Bm Anthralin Undetermined NA.

Bacitracin Undetermined C.

Betamethasone Undetermined C*

Butoconazole Undetermined Cm Ciclopirox Undetermined Bm Chloramphenicol Unlikely C.

Clindamycin Undetermined Bm Clioquinol Undetermined NA.

Clotrimazole Unlikely B.

Dexamethasone Minimal C*

Econazole Undetermined NA.

Erythromycin None Bm Etretinate High Xm Gentamicin Undetermined C.

Gramicidin None NA.

Griseofulvin Undetermined C.

Haloprogin Undetermined NA.

Hydrocortisone Unlikely C*

Isotretinoin High Xm Ketoconazole Undetermined Cm Mafenide Undetermined NA.

Meclocycline Undetermined NA.

Methotrexate Moderate to high Xm Metronidazole None Bm Miconazole Undetermined Cm Mupirocin Undetermined NA.

Naftifine Undetermined NA.

Neomycin None C.

Nystatin None Cm Podophyllum Undetermined C.

Prednisone/prednisolone Oral clefts: small C*

Other congenital anomalies: unlikely Terconazole Undetermined Cm Tetracycline Unlikely D.

Tolnaftate Undetermined NA.

Tretinoin Topical use: unlikely Dm Systemic administration: undetermined Triamcinolone Undetermined C *

m NA, not available.

Compiled from: Friedman et al., Obstet Gynecol 1990; 75 75: 594; Briggs et al., 2005; Friedman and Polifka, 2006.

Special considerations 251.

their babies. The patient should also be informed that even if the child does not have a major congenital anomaly at birth, intellectual development would most likely be impaired. The best counseling option is to contact TERIS (see Chapter 1, Introduction to drugs in pregnancy) and purchase the comprehensive summary on isotretinoin to (1) use in counseling, (2) place in the medical record, and (3) share with the patient. The option of pregnancy termination should be discussed. On the other hand, topical tretinoin (Retin-A) poses no known risk to the developing conceptus.

A variety of topical agents, including antibiotics (such as topical erythromycin), keratolytics, and astringents, can be used to treat acne during pregnancy. Topical steroids can generally be used safely for the treatment of psoriasis during pregnancy, except for triamcinolone.

Abnormalities of pigmentation and striae gravidarum Striae and abnormal pigmentation can be especially worrisome to the pregnant patient.

Chloasma (increased pigmentation along the linea nigra or areola of the nipple) and melasma (brownish discoloration of areas of the face) are the two most common forms of abnormal pigmentation. No specific therapy is available or required for these conditions, other than possibly cosmetic make-up. Importantly, striae and pigmentation usually regress and spontaneously disappear following delivery.

Stretch marks or striae gravidarum may be especially disconcerting to pregnant women.

Numerous creams and ointments (including 'mink oil') are available in the over-the-counter market to treat stretch marks. However, no known medical therapy has been shown to be effective. Most striae, which are hyperemic during pregnancy, will diminish in appearance (often becoming small, silvery lines). Most patients simply require rea.s.surance.

Condyloma ac.u.minata Wart-like growths, condyloma ac.u.minata, may proliferate rapidly during pregnancy. A common therapy in the nonpregnant patient is local application of a 20 percent solution of podophyllin in benzoin. Podophyllin is contraindicated in pregnancy because of the potential for maternal and fetal toxicity. Another local agent, when applied topically, TCA is a.s.sociated with no known serious maternal or fetal side effects. Unfortunately, TCA is not very effective in the eradication of condyloma, especially during pregnancy.